PubAnnotation

Id	Subject	Object	Predicate	Lexical cue
TextSentencer_T1	0-40	Sentence	denotes	Disorders of the Gastrointestinal System
TextSentencer_T2	42-50	Sentence	denotes	Abstract
TextSentencer_T3	53-305	Sentence	denotes	Examination of patients with disease of the gastrointestinal tract must include evaluation of the metabolic and cardiovascular status of the patient because acute conditions of the proximal or distal intestinal tract can lead to endotoxemia and sepsis.
TextSentencer_T4	306-624	Sentence	denotes	Examination of the cardiovascular system (heart, peripheral pulse, and mucous membranes), lungs, and abdomen is essential to detect clinical signs of systemic inflammation from endotoxemia, coagulation disorders, dehydration, ileus, shock, and other abnormalities resulting from injury to the small or large intestine.
TextSentencer_T5	625-729	Sentence	denotes	Clinical signs of systemic inflammation from endotoxemia and sepsis are described later in this chapter.
TextSentencer_T6	730-854	Sentence	denotes	The physical examination of the abdomen should include auscultation, transabdominal ballottement, and transrectal palpation.
TextSentencer_T7	855-1056	Sentence	denotes	Abdominal distention often indicates distention of the large intestine; small intestinal distention also can cause visible abdominal distention if a large proportion of the small intestine is involved.
TextSentencer_T8	1057-1112	Sentence	denotes	Abdominal palpation can be performed in neonatal foals.
TextSentencer_T9	1113-1230	Sentence	denotes	After several weeks of age the abdominal wall is too rigid to allow effective palpation of intraabdominal structures.
TextSentencer_T10	1231-1327	Sentence	denotes	Abdominal auscultation is particularly useful for assessing the motility of the large intestine.
TextSentencer_T11	1328-1458	Sentence	denotes	Progressive motility of the small intestine, conversely, is difficult to distinguish by auscultation from nonprogressive motility.
TextSentencer_T12	1459-1652	Sentence	denotes	The distinct character of the borborygmi produced during propulsive contractions of the cecum and ascending colon allows evaluation of the frequency and strength of retropulsion and propulsion.
TextSentencer_T13	1653-1815	Sentence	denotes	Propulsive contractions of the cecum and ventral colon occur every 3 to 4 minutes and give rise to prolonged rushing sounds heard over long segments of intestine.
TextSentencer_T14	1816-1912	Sentence	denotes	Retropulsive sounds presumably are similar to propulsive sounds, but they occur less frequently.
TextSentencer_T15	1913-2051	Sentence	denotes	Distinguishing between propulsion and retropulsion is not important clinically because both types of contractions signify normal motility.
TextSentencer_T16	2052-2282	Sentence	denotes	Interhaustral and intrahaustral mixing contractions produce nonspecific sounds of fluid and ingesta movement that are difficult to distinguish from other borborygmi, such as small intestinal contractions or spasmodic contractions.
TextSentencer_T17	2283-2438	Sentence	denotes	1 Auscultation over the right flank and proceeding along the caudal edge of the costal margin toward the xiphoid allows evaluation of the cecal borborygmi.
TextSentencer_T18	2439-2549	Sentence	denotes	Auscultation over a similar area on the left side allows evaluation of the pelvic flexure and ascending colon.
TextSentencer_T19	2550-2695	Sentence	denotes	Typical progressive borborygmi heard every 3 to 4 minutes on both sides of the abdomen indicate normal motility of the cecum and ascending colon.
TextSentencer_T20	2696-3148	Sentence	denotes	Less frequent progressive sounds may indicate a pathologic condition of the large intestine or may result from anorexia, nervousness (sympathetic tone), or pharmacologic inhibition of motility (i.e., α 2 -adrenergic agonists such as xylazine). [2] [3] [4] [5] Absolute absence of any auscultable borborygmi suggests abnormal motility and indicates ileus resulting from a serious pathologic condition but is not specific to any segment of the intestine.
TextSentencer_T21	3149-3338	Sentence	denotes	3, 6 If borborygmi are audible but progressive sounds are not detectable, determining whether a significant abnormality exists is difficult, and such findings should not be overinterpreted.
TextSentencer_T22	3339-3586	Sentence	denotes	6 Borborygmi heard more frequently than normal may result from increased motility following feeding; from excessive stimulation from irritation, distention, or inflammation; or after administration of parasympathomimetic drugs such as neostigmine.
TextSentencer_T23	3587-3691	Sentence	denotes	Large intestinal motility increases in the early stages of intestinal distention regardless of the site.
TextSentencer_T24	3692-3785	Sentence	denotes	7 Mild inflammation or irritation of the large intestinal mucosa also can stimulate motility.
TextSentencer_T25	3786-4006	Sentence	denotes	3 Parasympathomimetic drugs stimulate contractions and auscultable borborygmi in the large intestine; an increase in parasympathetic tone may result in segmental contractions, which actually inhibit progressive motility.
TextSentencer_T26	4007-4093	Sentence	denotes	2 Percussion of the abdomen during auscultation can reveal gas in the large intestine.
TextSentencer_T27	4094-4272	Sentence	denotes	The characteristic ping produced by simultaneous digital percussion and auscultation over a gasfilled viscus often is associated with abnormal accumulation of gas under pressure.
TextSentencer_T28	4273-4397	Sentence	denotes	This technique is particularly useful in foals, ponies, and Miniature Horses because of the limitations of rectal palpation.
TextSentencer_T29	4398-4514	Sentence	denotes	Transabdominal ballottement can be used to detect large, firm masses or an abnormal volume of peritoneal fluid (PF).
TextSentencer_T30	4515-4608	Sentence	denotes	The usefulness of this technique is usually limited to animals too small to palpate rectally.
TextSentencer_T31	4609-4701	Sentence	denotes	Soft tissue masses or fetuses can be detected by bumping the structures with a hand or fist.
TextSentencer_T32	4702-4883	Sentence	denotes	If excessive PF is present, a fluid wave can be generated by ballottement; however, this technique is not as useful in horses older than 4 weeks because the abdominal wall is rigid.
TextSentencer_T33	4884-5064	Sentence	denotes	Transrectal palpation is the most specific physical examination technique for investigation of intestinal disease and is particularly valuable when evaluating obstructive diseases.
TextSentencer_T34	5065-5309	Sentence	denotes	8 The primary objectives of transrectal palpation are to assess the size, consistency, and position of the segments of the large intestine; to determine the presence of any distention of the small intestine; and to detect intraabdominal masses.
TextSentencer_T35	5310-5485	Sentence	denotes	Evaluation of the wall thickness and texture and the mesenteric structures (blood and lymphatic vessels and lymph nodes) also may aid in diagnosis of large intestinal disease.
TextSentencer_T36	5486-5721	Sentence	denotes	The interpretation of transrectal palpation findings in light of clinical signs and laboratory results is an important diagnostic aid for developing appropriate treatment strategies for intestinal diseases manifested by abdominal pain.
TextSentencer_T37	5722-5881	Sentence	denotes	Enlargement of one or more segments of large intestine detected by transrectal palpation provides evidence of obstruction at or distal to the enlarged segment.
TextSentencer_T38	5882-5967	Sentence	denotes	By systematically evaluating each segment, the site of obstruction may be determined.
TextSentencer_T39	5968-6137	Sentence	denotes	Obstruction of the pelvic flexure, for instance, results in enlargement of the pelvic flexure and ventral colon, but the dorsal and descending colons are of normal size.
TextSentencer_T40	6138-6249	Sentence	denotes	Enlargement of a segment of the large intestine usually is accompanied by abnormal consistency of the contents.
TextSentencer_T41	6250-6360	Sentence	denotes	It is possible to distinguish among gas, fluid, and ingesta and to detect foreign bodies in palpable segments.
TextSentencer_T42	6361-6508	Sentence	denotes	Accumulation of gas and fluid suggests complete and acute obstruction, whereas accumulation of ingesta suggests chronic and incomplete obstruction.
TextSentencer_T43	6509-6555	Sentence	denotes	Accumulation of fluid usually indicates ileus.
TextSentencer_T44	6556-6771	Sentence	denotes	The practitioner must evaluate the consistency of the contents in light of the size of the segment; ingesta in the ventral colon of a dehydrated patient may be firm, but the size of the ventral colon will be normal.
TextSentencer_T45	6772-6875	Sentence	denotes	Conversely, if the ingesta is firm because of a distal obstruction, the ventral colon will be enlarged.
TextSentencer_T46	6876-7075	Sentence	denotes	Displacement of a segment of the large intestine may create an obstruction detectable by enlargement of the segment and accumulation of gas and fluid, even if the site of obstruction is not palpable.
TextSentencer_T47	7076-7278	Sentence	denotes	Torsion of the ascending colon at the sternal and diaphragmatic flexures results in acute accumulation of gas and fluid proximal to the torsion, causing distention of the left dorsal and ventral colons.
TextSentencer_T48	7279-7395	Sentence	denotes	Depending on the degree of torsion, the position of the ventral and dorsal colons may not be significantly abnormal.
TextSentencer_T49	7396-7649	Sentence	denotes	Displacement of a segment of large intestine often results in incomplete obstruction, and the diagnosis is either confirmed on detection of the displaced segment in an abnormal position or suspected when the segment is not palpable in a normal position.
TextSentencer_T50	7650-7833	Sentence	denotes	A determination should be made as to whether the segment that appears to be displaced is in a normal position but of smaller than normal size because of a decreased volume of ingesta.
TextSentencer_T51	7834-7943	Sentence	denotes	The cecum, right dorsal and ventral colons, pelvic flexure, and descending colon are palpable in most horses.
TextSentencer_T52	7944-8078	Sentence	denotes	The nephrosplenic space should be palpated to detect the presence of intestine, usually pelvic flexure, entrapped within the ligament.
TextSentencer_T53	8079-8133	Sentence	denotes	Small intestine is not normally palpable in the horse.
TextSentencer_T54	8134-8256	Sentence	denotes	Distention indicates ileus with gas or fluid retention, usually following a strangulating or nonstrangulating obstruction.
TextSentencer_T55	8257-8398	Sentence	denotes	Strangulating obstructions often are accompanied by severe pain, dehydration, PF changes, and a varying degree of gastric fluid accumulation.
TextSentencer_T56	8399-8466	Sentence	denotes	The small intestine in these cases is turgid and firm on palpation.
TextSentencer_T57	8467-8572	Sentence	denotes	The mesentery and wall thickness should be assessed in the same manner as for large intestinal disorders.
TextSentencer_T58	8573-8706	Sentence	denotes	Careful palpation of the inguinal rings in stallions with small intestinal distention is crucial for determining inguinal herniation.
TextSentencer_T59	8707-8897	Sentence	denotes	Evaluation of the wall thickness and mesenteric vessels can reveal venous congestion (mural edema and enlarged blood and lymphatic vessels) or inflammation (mural edema with normal vessels).
TextSentencer_T60	8898-9007	Sentence	denotes	Disruption of arterial blood flow does not cause venous congestion, but the arterial pulse is not detectable.
TextSentencer_T61	9008-9109	Sentence	denotes	Mesenteric tears may not be palpable, but the entrapped ischemic intestinal segment may be thickened.
TextSentencer_T62	9110-9166	Sentence	denotes	Enlargement of mesenteric lymph nodes also may be noted.
TextSentencer_T63	9167-9325	Sentence	denotes	Abnormalities in the wall or vessels should be interpreted in light of the size, consistency, and position of the segment of intestine and the clinical signs.
TextSentencer_T64	9326-9512	Sentence	denotes	Several conditions involving small intestinal strangulating lesions do not necessarily cause abnormal rectal examination findings until the disease has been present for an extended time.
TextSentencer_T65	9513-9600	Sentence	denotes	These conditions include diaphragmatic hernias and epiploic foramen entrapments (EFEs).
TextSentencer_T66	9601-9712	Sentence	denotes	PF analysis can be normal in these cases as well because the fluid is trapped in the thorax or cranial abdomen.
TextSentencer_T67	9713-9839	Sentence	denotes	Nonstrangulating causes of small intestinal distention can be divided further into intraluminal and extraluminal obstructions.
TextSentencer_T68	9840-10020	Sentence	denotes	Ileal impactions are the most common cause of intraluminal obstruction, and on rare occasions the impaction can be palpated in the upper right quadrant, near the ileocecal opening.
TextSentencer_T69	10021-10248	Sentence	denotes	Intraluminal masses caused by lymphoma, eosinophilic enteritis, foreign bodies, or ascarid impactions often lead to small intestinal distention and are usually indistinguishable from one another on the basis of palpation alone.
TextSentencer_T70	10249-10360	Sentence	denotes	Small intestine in these cases can be moderately to severely distended, depending on the degree of obstruction.
TextSentencer_T71	10361-10441	Sentence	denotes	Extraluminal obstructions include abdominal masses and large colon displacement.
TextSentencer_T72	10442-10525	Sentence	denotes	The rest of the abdomen should be carefully palpated to help rule out these causes.
TextSentencer_T73	10526-10633	Sentence	denotes	Some cases of small intestinal distention result from physiologic ileus rather than mechanical obstruction.
TextSentencer_T74	10634-10748	Sentence	denotes	The bowel is usually mildly to moderately distended and almost always is accompanied by significant gastric fluid.
TextSentencer_T75	10749-10856	Sentence	denotes	The small colon is easily distinguishable by the presence of normal fecal balls and an antimesenteric band.
TextSentencer_T76	10857-11011	Sentence	denotes	In horses with impaction of the small colon, a long, hard, tubelike structure is present in the caudal abdomen, and the band is palpable along the length.
TextSentencer_T77	11012-11156	Sentence	denotes	Fluid stool is often present in the rectum in these horses, as is tenesmus, and the rectal mucosa is often edematous and occasionally roughened.
TextSentencer_T78	11157-11230	Sentence	denotes	Rectal tears can be detected and evaluated with careful rectal palpation.
TextSentencer_T79	11231-11468	Sentence	denotes	Also detectable are mural masses in palpable segments of intestine or mesentery; if a mass causes obstruction, then it is possible to detect the result of the obstruction in proximal segments of intestine even if the mass is unreachable.
TextSentencer_T80	11469-11584	Sentence	denotes	Palpation of the mesenteric vessels may reveal thickening and thrombosis, which can lead to ischemia or infarction.
TextSentencer_T81	11585-11718	Sentence	denotes	Visual inspection of the mucosa of the rectum and descending colon can be performed with the aid of a speculum or flexible endoscope.
TextSentencer_T82	11719-11908	Sentence	denotes	A flexible endoscope is also useful for evaluation of rectal tears or perforations, mural masses, strictures, or mucosal inflammation and obtaining biopsy specimens of the mucosa or masses.
TextSentencer_T83	11909-12066	Sentence	denotes	The obvious limitations are the amount of fecal material, which can interfere with the examination, and the distance of the lesion of interest from the anus.
TextSentencer_T84	12067-12180	Sentence	denotes	These techniques offer little advantage over palpation in many cases, unless the patient is too small to palpate.
TextSentencer_T85	12181-12306	Sentence	denotes	Examination of the oral cavity in horses with dysphagia or weight loss is an important extension of the physical examination.
TextSentencer_T86	12307-12548	Sentence	denotes	The horse should be adequately sedated and a full-mouth speculum used to allow palpation and visual examination of all parts of the oral cavity and detection of abnormal dentition, foreign bodies, fractures, abscesses, or mucosal ulceration.
TextSentencer_T87	12549-12667	Sentence	denotes	The presence of fluid accumulation in the stomach indicates a functional or mechanical obstruction of gastric outflow.
TextSentencer_T88	12668-12827	Sentence	denotes	Fluid accumulation in the stomach is assessed by siphoning of the gastric contents with a nasogastric tube and examining the fluid for amount, color, and odor.
TextSentencer_T89	12828-12879	Sentence	denotes	Normal fluid is green and may contain foamy saliva.
TextSentencer_T90	12880-12947	Sentence	denotes	The net volume obtained by gastric lavage is usually less than 4 L.
TextSentencer_T91	12948-13027	Sentence	denotes	Large volumes (≥8-10 L) of foul-smelling fluid may indicate proximal enteritis.
TextSentencer_T92	13028-13245	Sentence	denotes	Horses with strangulating obstructions or luminal obstructions often accumulate moderate amounts of gastric fluid, but the amount is generally less than in horses with proximal enteritis or postoperative ileus (POI) .
TextSentencer_T93	13246-13359	Sentence	denotes	Distinction between these conditions should not be made based on the volume and character of gastric fluid alone.
TextSentencer_T94	13360-13482	Sentence	denotes	Hemorrhage in the gastric fluid usually indicates devitalized small intestine, stomach wall, or severe gastric ulceration.
TextSentencer_T95	13483-13573	Sentence	denotes	Endoscopy or contrast radiography may aid in the diagnosis of gastric outflow obstruction.
TextSentencer_T96	13574-13745	Sentence	denotes	Hematologic alterations associated with diseases of the gastrointestinal tract are often nonspecific, reflecting systemic response to inflammation, endotoxemia, or sepsis.
TextSentencer_T97	13746-13922	Sentence	denotes	Neutrophilic leukocytosis and normochromic, normocytic anemia with or without hyperfibrinogenemia commonly are associated with chronic inflammatory conditions of the intestine.
TextSentencer_T98	13923-14184	Sentence	denotes	Anemia from chronic blood loss occurs infrequently in adult horses because of the large iron stores and high concentrations of iron in their diet; anemia usually follows chronic inflammation, as do alterations in the leukon and plasma fibrinogen concentrations.
TextSentencer_T99	14185-14348	Sentence	denotes	Plasma protein concentrations vary depending on gastrointestinal losses of albumin and globulin and elevation of globulin concentration from antigenic stimulation.
TextSentencer_T100	14349-14432	Sentence	denotes	Protein-losing enteropathy may manifest as a hypoalbuminemia or panhypoproteinemia.
TextSentencer_T101	14433-14622	Sentence	denotes	Significant alterations of the hemogram do not accompany acute disease of the intestine unless severe dehydration, endotoxemia, or systemic inflammatory response syndrome (SIRS) is present.
TextSentencer_T102	14623-14797	Sentence	denotes	During the early stages of SIRS, elevations in circulating concentrations of inflammatory mediators, epinephrine, and cortisol produce characteristic changes in the hemogram.
TextSentencer_T103	14798-15018	Sentence	denotes	Leukopenia, with neutropenia and a left shift, toxic changes in the neutrophil cytoplasm, and lymphopenia commonly occur early in the disease, but neutrophilic leukocytosis is more common during the later stages of SIRS.
TextSentencer_T104	15019-15077	Sentence	denotes	Hemoconcentration and hyperfibrinogenemia are also common.
TextSentencer_T105	15078-15146	Sentence	denotes	Thrombocytopenia and other coagulopathies are also features of SIRS.
TextSentencer_T106	15147-15281	Sentence	denotes	Electrolyte imbalances and increased blood lactate are common biochemical abnormalities in horses with acute gastrointestinal disease.
TextSentencer_T107	15282-15348	Sentence	denotes	Decreased serum calcium concentrations are common and nonspecific.
TextSentencer_T108	15349-15511	Sentence	denotes	9 Mucosal inflammation can disrupt electrolyte fluxes; diarrhea or gastric reflux greatly exacerbates sodium, potassium, calcium, magnesium, and bicarbonate loss.
TextSentencer_T109	15512-15694	Sentence	denotes	Large colon ischemia causes increased lactate and potassium concentrations and metabolic acidosis in the colonic vasculature and inflammation in the colonic and systemic vasculature.
TextSentencer_T110	15695-15915	Sentence	denotes	10 Reduced perfusion of peripheral tissues from hypotensive shock and intestinal ischemia can cause increased blood lactate; intestinal obstruction during ischemia may also result in absorption of lactate from the lumen.
TextSentencer_T111	15916-16102	Sentence	denotes	Increased blood lactate can result from a variety of causes, including hypovolemia, and blood lactate alone should not be used for diagnostic or prognostic purposes in horses with colic.
TextSentencer_T112	16103-16268	Sentence	denotes	11 Increases in blood lactate over time are greater in nonsurvivors, relative to survivors, in adult equine emergencies (many of which had gastrointestinal disease).
TextSentencer_T113	16269-16479	Sentence	denotes	12 Portable lactate analyzers have demonstrated variable intraanalyzer reliability in equine blood so that caution should be exercised in interpretation and comparison of results reported from various searches.
TextSentencer_T114	16480-16648	Sentence	denotes	13, 14 Metabolic acidosis may accompany lactic acidemia, but an inconsistent association exists between the two, especially when mixed acid-base imbalances are present.
TextSentencer_T115	16649-16814	Sentence	denotes	15, 16 Increases in hepatic enzymes, specifically γ-glutamyl transferase (GGT), may occur with large colon displacements, duodenal strictures, or proximal enteritis.
TextSentencer_T116	16815-16896	Sentence	denotes	Increased GTT is more suggestive of right, rather than left, dorsal displacement.
TextSentencer_T117	16897-17070	Sentence	denotes	17 Relative polycythemia from hemoconcentration or splenic contraction and changes in red blood cell deformability from hypoxia or hypocalcemia may increase blood viscosity.
TextSentencer_T118	17071-17140	Sentence	denotes	Blood viscosity increases in patients with acute obstructive disease.
TextSentencer_T119	17141-17234	Sentence	denotes	Hyperviscosity reduces perfusion of capillary beds, exacerbating ischemia and tissue hypoxia.
TextSentencer_T120	17235-17237	Sentence	denotes	18
TextSentencer_T121	17239-17451	Sentence	denotes	Abdominocentesis and analysis of PF are performed on many patients with gastrointestinal disease and are especially helpful in differentiating strangulating from nonstrangulating disorders of the small intestine.
TextSentencer_T122	17452-17567	Sentence	denotes	Important quantifications include white and red blood cell counts and protein, lactate, and glucose concentrations.
TextSentencer_T123	17568-17671	Sentence	denotes	Cytologic evaluation can reveal cellular abnormalities, especially in horses with intestinal neoplasia.
TextSentencer_T124	17672-17861	Sentence	denotes	Results of PF analysis may help establish a specific diagnosis and, more important, may reflect inflammatory, vascular, or ischemic injury to the intestine, requiring surgical intervention.
TextSentencer_T125	17862-17949	Sentence	denotes	Alteration of PF reflects a sequence of events during acute intestinal vascular injury.
TextSentencer_T126	17950-18071	Sentence	denotes	The PF protein concentration increases first, followed by increases in red blood cell count and fibrinogen concentration.
TextSentencer_T127	18072-18352	Sentence	denotes	A transudative process resulting from vascular congestion and increased endothelial permeability allows small macromolecules (albumin) to escape into the PF, followed by larger macromolecules (globulin and fibrinogen), and finally diapedesis of cells (red then white blood cells).
TextSentencer_T128	18353-18557	Sentence	denotes	Severe ischemic intestinal inflammation or visceral peritonitis result in an exudative process, with large quantities of protein and white blood cells (WBCs), primarily neutrophils, to escape into the PF.
TextSentencer_T129	18558-18690	Sentence	denotes	19, 20 Eventually, bacteria begin to translocate across the intestinal wall and appear in the PF as the mucosal barrier breaks down.
TextSentencer_T130	18691-18870	Sentence	denotes	If perforation occurs, bacteria and particles of ingesta appear in the PF, and the neutrophils become degenerate (i.e., pyknotic), with karyorrhexis, karyolysis, and smudge cells.
TextSentencer_T131	18871-19082	Sentence	denotes	Increased PF protein concentration is an indicator of early inflammation, whereas increased red blood cell counts in the presence of normal WBC counts suggest vascular damage without significant tissue ischemia.
TextSentencer_T132	19083-19327	Sentence	denotes	20 Of note, the anticoagulant potassium ethylenediamine tetraacetic acid, but not lithium heparin, can cause an increase in total protein as measured by a refractometer, relative to the value obtained from the same sample without anticoagulant.
TextSentencer_T133	19328-19422	Sentence	denotes	21 The gross color of the PF can be helpful in detecting injury and necrosis of the intestine.
TextSentencer_T134	19423-19575	Sentence	denotes	A serosanguineous appearance indicates vascular injury, whereas orange or brown-red indicates necrosis with the release of pigments such as hemosiderin.
TextSentencer_T135	19576-19737	Sentence	denotes	Tissue hypoxia and ischemia cause rapid increases in PF lactate dehydrogenase, creatine kinase, and alkaline phosphatase (AP) activity and lactate concentration.
TextSentencer_T136	19738-19811	Sentence	denotes	22, 23 Phosphate concentration increases when cellular disruption occurs.
TextSentencer_T137	19812-19923	Sentence	denotes	24 PF enzyme activities, phosphate, and lactate concentration increase faster and higher than serum activities.
TextSentencer_T138	19924-20068	Sentence	denotes	16, [22] [23] [24] PF pH and glucose concentration tend to decrease during intestinal ischemia but not as dramatically as in septic peritonitis.
TextSentencer_T139	20069-20411	Sentence	denotes	25 Lactate concentrations in PF are commonly evaluated and are better predictors of strangulating small intestinal obstruction than blood lactate, 22 although increases in both lactate (the term by which l-lactate is commonly referred) and d-lactate are likely more accurate for predicting strangulating lesions as opposed to ruling them out.
TextSentencer_T140	20412-20666	Sentence	denotes	26 Serial sampling of blood and PF lactate may be useful in cases in which clinical and diagnostic findings at initial presentation were not conclusive for either strangulating or nonstrangulating lesions and/or a horse's clinical condition deteriorates.
TextSentencer_T141	20667-20776	Sentence	denotes	27 Cytologic examination of PF may reflect chronic inflammatory intestinal conditions or neoplastic diseases.
TextSentencer_T142	20777-20973	Sentence	denotes	28 Although culturing PF is recommended to distinguish bacterial infections from noninfectious inflammation unless bacteria are visible on cytologic examination, culturing PF is often unrewarding.
TextSentencer_T143	20974-21082	Sentence	denotes	Decreases in PF glucose concentrations (<30 mg/dL) and pH (<7.3) are early indicators of septic peritonitis.
TextSentencer_T144	21083-21175	Sentence	denotes	Glucose concentration and pH in PF should approximately equal blood values in normal horses.
TextSentencer_T145	21176-21437	Sentence	denotes	Practically, the gross appearance and the total solids of PF in conjunction with a comparison of PF to serum lactate are most useful when distinguishing between strangulating and nonstrangulating small intestinal disorders in a horse presenting for acute colic.
TextSentencer_T146	21438-21610	Sentence	denotes	Potential risks associated with performing an abdominocentesis should be considered, and this procedure is performed only if results are likely to alter the treatment plan.
TextSentencer_T147	21611-21804	Sentence	denotes	For example, if other examination findings indicate that an exploratory laparotomy is clearly indicated or not in the case of a horse with acute colic, abdominocentesis is likely not indicated.
TextSentencer_T148	21805-21916	Sentence	denotes	Gross examination of the feces can provide information about digestion and transit time in the large intestine.
TextSentencer_T149	21917-22020	Sentence	denotes	Large fiber particles in the feces represent poor mastication or poor digestion in the large intestine.
TextSentencer_T150	22021-22175	Sentence	denotes	Small, mucus-covered, hard fecal balls indicate prolonged transit through the descending colon, whereas increased fluidity implies decreased transit time.
TextSentencer_T151	22176-22237	Sentence	denotes	Feces containing sand or gravel are not necessarily abnormal.
TextSentencer_T152	22238-22331	Sentence	denotes	However, a significant amount of sand implies that large quantities are present in the colon.
TextSentencer_T153	22332-22421	Sentence	denotes	Alternatively, absence of sand in feces does not confirm an absence of sand in the colon.
TextSentencer_T154	22422-22560	Sentence	denotes	Frank blood indicates substantial bleeding into the distal colon (right dorsal colon, small colon, or both) resulting from mucosal damage.
TextSentencer_T155	22561-22636	Sentence	denotes	Laboratory analysis of the feces can be performed for horses with diarrhea.
TextSentencer_T156	22637-22744	Sentence	denotes	Fecal cytologic examination and tests for occult blood detect mucosal inflammation, erosion, or ulceration.
TextSentencer_T157	22745-22878	Sentence	denotes	Increased fecal leukocyte counts have been documented in horses with diarrhea and salmonellosis, but specificity of this test is low.
TextSentencer_T158	22879-23034	Sentence	denotes	29 Fecal occult blood tests detect blood in the feces, presumably from erosion or ulceration of the mucosa, but do not distinguish the source of the blood.
TextSentencer_T159	23035-23272	Sentence	denotes	Large volumes of blood (1-2 L) given by nasogastric tube were required to produce a positive test for occult blood in the feces, but the amount of blood originating from the large intestine required to produce a positive test is unknown.
TextSentencer_T160	23273-23482	Sentence	denotes	Despite initial reports to the contrary, 30 there does not appear to be any correlation between endoscopic evidence of glandular or nonglandular gastric ulceration and detection of fecal albumin or hemoglobin.
TextSentencer_T161	23483-23569	Sentence	denotes	31 Bacteriologic examination of the fecal flora has been used in horses with diarrhea.
TextSentencer_T162	23570-23853	Sentence	denotes	Quantitation of clostridial species may be beneficial in diagnosing clostridial infection of the large intestine, although tests to detect clostridial toxins in intestinal contents or feces are important for determining whether clostridia cultured from the feces are causing disease.
TextSentencer_T163	23854-23964	Sentence	denotes	The most common bacterial pathogens isolated from the feces of horses are Salmonella spp. and Clostridium spp.
TextSentencer_T164	23965-24126	Sentence	denotes	The number of Salmonella organisms isolated from the feces of horses with clinical salmonellosis is usually higher than from horses with asymptomatic infections.
TextSentencer_T165	24127-24330	Sentence	denotes	However, the volume of feces in many cases of acute diarrhea is high, and the concentration of Salmonella organisms may be lower than would be expected, accounting for many false-negative fecal cultures.
TextSentencer_T166	24331-24421	Sentence	denotes	The sensitivity of fecal cultures for detecting Salmonella infection may be as low as 20%.
TextSentencer_T167	24422-24525	Sentence	denotes	Culture of five consecutive daily fecal samples is recommended to increase the sensitivity of the test.
TextSentencer_T168	24526-25075	Sentence	denotes	Real-time polymerase chain reaction (PCR) assays used on fecal samples can detect DNA from Salmonella spp. and have performed well in recent validation studies; accuracy of pointof-care tests remains elusive. [32] [33] [34] [35] Currently, PCR assays can be used for detection of viral (rotavirus and coronavirus), bacterial (Cryptosporidium spp., Salmonella spp., Neorickettsia risticii, Lawsonia intracellularis), or bacterial toxin (Clostridium difficile toxins A and B, Clostridium perfringens enterotoxin A) DNA in feces or blood (N. risticii).
TextSentencer_T169	25076-25207	Sentence	denotes	Qualitative fecal examination can detect nematode and cestode ova, protozoan oocysts, parasitic larvae, and protozoan trophozoites.
TextSentencer_T170	25208-25338	Sentence	denotes	A direct smear of fecal material can rapidly detect parasite larvae and trophozoites and motility of ciliates and parasite larvae.
TextSentencer_T171	25339-25450	Sentence	denotes	Fecal flotation with zinc sulfate or sucrose solutions is often used to concentrate less dense ova and oocysts.
TextSentencer_T172	25451-25539	Sentence	denotes	Zinc sulfate produces less distortion of trophozoites and larvae than sucrose solutions.
TextSentencer_T173	25540-25638	Sentence	denotes	Fecal sedimentation is particularly appropriate for ciliates, Giardia organisms, and trichomonads.
TextSentencer_T174	25639-25821	Sentence	denotes	Quantitative techniques such as the Cornell-McMaster method allow estimation of the number of eggs per gram of feces and are most appropriate in monitoring parasite control programs.
TextSentencer_T175	25822-25888	Sentence	denotes	Survey radiography of the normal esophagus is usually unrewarding.
TextSentencer_T176	25889-26072	Sentence	denotes	It is possible to detect foreign bodies or soft tissue masses and, in cases of esophageal rupture, free air and ingesta in the tissues surrounding the esophagus and pneumomediastinum.
TextSentencer_T177	26073-26198	Sentence	denotes	Thoracic radiographs may be necessary to detect megaesophagus or cranial mediastinal masses causing extraluminal obstruction.
TextSentencer_T178	26199-26444	Sentence	denotes	Barium swallows or double-contrast esophagrams may be used after resolution of an esophageal obstruction to determine whether a stricture, diverticulum, or other underlying disorder is present, although endoscopy can provide similar information.
TextSentencer_T179	26445-26628	Sentence	denotes	Barium sulfate is the usual contrast medium and can be administered orally by way of a dose syringe or nasogastric tube (50-100 mL of a 40% barium sulfate suspension or barium paste).
TextSentencer_T180	26629-26729	Sentence	denotes	Oral administration is preferred for evaluation of swallowing and lesions in the proximal esophagus.
TextSentencer_T181	26730-26918	Sentence	denotes	Administration of contrast using a nasogastric tube (preferably cuffed) allows for delivery of larger volumes of barium (up to 500 mL) but should be performed without sedation if possible.
TextSentencer_T182	26919-27027	Sentence	denotes	Administration of contrast material can be followed with air insufflation to create a doublecontrast effect.
TextSentencer_T183	27028-27287	Sentence	denotes	If rupture of the esophagus is suspected or if the contrast material is likely to be aspirated, barium should be avoided, and iodinated organic compounds in an aqueous solution should be used as contrast material to decrease the potential for adverse effects.
TextSentencer_T184	27288-27399	Sentence	denotes	When interpreting esophageal radiographs, the veterinarian should take particular care if the horse is sedated.
TextSentencer_T185	27400-27534	Sentence	denotes	Acepromazine or detomidine administration causes esophageal dilation in normal horses, especially after passage of a nasogastric tube.
TextSentencer_T186	27535-27846	Sentence	denotes	36 Radiography of the adult equine abdomen is an effective technique in detecting radiodense material in the large intestine, such as enteroliths, sand, and metallic objects. [37] [38] [39] [40] One survey demonstrated that radiography has 76.9% sensitivity and 94.4% specificity for diagnosing enterolithiasis.
TextSentencer_T187	27847-28077	Sentence	denotes	40 Recently, an objective scoring system demonstrated greater efficacy and less interobserver variability than a subjective assessment of radiographic sand accumulation in horses with or without a clinical diagnosis of sand colic.
TextSentencer_T188	28078-28325	Sentence	denotes	38 The large size and density of the adult abdomen preclude evaluation of soft tissue structures because the detail and contrast of the radiographs are usually poor, and ultrasonography is a much more useful imaging modality in the equine abdomen.
TextSentencer_T189	28326-28851	Sentence	denotes	Administration of contrast (barium sulfate 30% at 5 mL/kg) through a nasogastric tube or retrograde (20 mL/kg) through a 24-Fr Foley catheter inserted into the rectum may be helpful for the diagnosis of gastric outflow obstruction or disorders of the rectum, small colon, or transverse colon, respectively, in foals. [41] [42] [43] [44] Y ULTRASONOGRAPHY Transcutaneous ultrasonographic evaluation of the abdomen is quick and noninvasive and can add valuable information in cases of acute or chronic gastrointestinal disease.
TextSentencer_T190	28852-28966	Sentence	denotes	Ultrasound has become a virtually indispensable tool for horses with acute or chronic gastrointestinal conditions.
TextSentencer_T191	28967-29005	Sentence	denotes	This section provides a brief summary.
TextSentencer_T192	29006-29145	Sentence	denotes	Examination of the adult horse requires a 2.5-to 5.0-MHz transducer, depending on size of the horse; a curvilinear transducer is preferred.
TextSentencer_T193	29146-29358	Sentence	denotes	A functional examination is often performed with isopropyl alcohol saturation alone, although clipping, with or without coupling gel, can be used to enhance evaluation, especially in large or overweight patients.
TextSentencer_T194	29359-29588	Sentence	denotes	A protocol for fast localized abdominal sonography (FLASH) has been described and demonstrates good predictive value of the requirement for surgical intervention in the acute abdomen, even with relatively inexperienced examiners.
TextSentencer_T195	29589-29841	Sentence	denotes	45 This examination evaluates seven locations (ventral abdomen, gastric window, splenorenal window, left middle third of the abdomen, duodenal window, right middle third of the abdomen, and thoracic window) and can be performed in less than 15 minutes.
TextSentencer_T196	29842-30030	Sentence	denotes	A complete examination requires a methodical approach to the evaluation of the entire abdomen; details of the examination can be variable based on equipment and experience of the examiner.
TextSentencer_T197	30031-30165	Sentence	denotes	A complete review of abdominal ultrasound is beyond the scope of this chapter; a thorough, detailed examination is reviewed elsewhere.
TextSentencer_T198	30166-30354	Sentence	denotes	46 In general terms, a quick examination of the acute abdomen should include estimation of gastric size and assessment of small intestinal diameter, wall thickness, motility, and location.
TextSentencer_T199	30355-30445	Sentence	denotes	Specific abnormalities, such as ascarid impaction or intussusception, may also be visible.
TextSentencer_T200	30446-30661	Sentence	denotes	Evaluation of the large colon and cecum should include estimation of mural thickening or increased fluidity of contents, and whether or not the colon obscures viewing of the left kidney in the left paralumbar fossa.
TextSentencer_T201	30662-30875	Sentence	denotes	It is important to remember that other causes of colonic distention can have the same result; thus, it is always important to combine physical, rectal, and ultrasonographic examination findings for any given case.
TextSentencer_T202	30876-31073	Sentence	denotes	Sand impactions may appear as hyperechoic bands on the ventral abdominal wall, 47 but according to the author and others, 46 ultrasound does not allow for consistent diagnosis of sand accumulation.
TextSentencer_T203	31074-31219	Sentence	denotes	Evaluation of the abdomen always should include assessment of the peritoneal space for any evidence of an increased amount or echogenicity of PF.
TextSentencer_T204	31220-31310	Sentence	denotes	Ultrasonography also can be useful in determining the ideal location for abdominocentesis.
TextSentencer_T205	31311-31579	Sentence	denotes	Nuclear scintigraphy has several proposed uses for evaluation of the gastrointestinal tract, although most have been replaced with cross-sectional imaging (dental disease 48, 49 ), ultrasonography (right dorsal colitis 50 ), or other modalities (gastric emptying 51 ).
TextSentencer_T206	31580-31859	Sentence	denotes	Computed tomography (CT) and, less commonly, magnetic resonance imaging are extremely useful for evaluating dental disease as well as tumors and masses of the head, larynx, pharynx, and proximal esophagus in adult horses [52] [53] [54] [55] and some abdominal disorders in foals.
TextSentencer_T207	31860-31965	Sentence	denotes	56 Availability, gantry size, and table weight limits provide the biggest limitations for widespread use.
TextSentencer_T208	31966-32106	Sentence	denotes	Endoscopic examination of the gastrointestinal tract begins with evaluation of the pharynx for signs of collapse, dysfunction, or dysphagia.
TextSentencer_T209	32107-32233	Sentence	denotes	The oral cavity should only be examined endoscopically with the use of heavy sedation or anesthesia and a full-mouth speculum.
TextSentencer_T210	32234-32355	Sentence	denotes	Indications include examination of the teeth, palate, and tongue for completeness, ulceration, masses, or foreign bodies.
TextSentencer_T211	32356-32504	Sentence	denotes	The most common gastrointestinal indication is evaluation of the stomach, proximal esophagus, and duodenum, typically with a 3-m flexible endoscope.
TextSentencer_T212	32505-32587	Sentence	denotes	The esophagus should be examined aborad to orad because of its collapsible nature.
TextSentencer_T213	32588-32644	Sentence	denotes	The esophageal mucosa is normally smooth and light pink.
TextSentencer_T214	32645-32777	Sentence	denotes	Erosion or ulceration can occur secondary to obstruction, reflux esophagitis, or an indwelling nasogastric tube, among other causes.
TextSentencer_T215	32778-32901	Sentence	denotes	Erosions may be punctate, linear, or circumferential, and their extent (depth, length, etc.) should be evaluated carefully.
TextSentencer_T216	32902-33033	Sentence	denotes	Distinguishing normal peristaltic contractions from areas of stricture requires observation of the area and its motility over time.
TextSentencer_T217	33034-33142	Sentence	denotes	Diverticula also may be noted as outpouchings of the mucosa, sometimes associated with a stricture distally.
TextSentencer_T218	33143-33205	Sentence	denotes	Megaesophagus, although rare, appears as generalized dilation.
TextSentencer_T219	33206-33402	Sentence	denotes	Reevaluation after resolution of an obstruction is especially important for detecting the presence of complications (ulceration and rupture) or initiating causes (strictures, diverticula, masses).
TextSentencer_T220	33403-33462	Sentence	denotes	Gastroscopy is best performed after a minimum 12-hour fast.
TextSentencer_T221	33463-33632	Sentence	denotes	Complete examination of the stomach, including the antrum and pylorus, and preferably proximal duodenum, is critical to avoid missing lesions in the more aborad regions.
TextSentencer_T222	33633-33691	Sentence	denotes	The squamous mucosa should resemble the esophageal mucosa.
TextSentencer_T223	33692-33773	Sentence	denotes	The glandular mucosa should be glistening red and may have a reticulated pattern.
TextSentencer_T224	33774-33856	Sentence	denotes	The veterinarian should carefully examine it for evidence of ulceration or masses.
TextSentencer_T225	33857-34068	Sentence	denotes	Trans endoscopic biopsy material can be easily obtained from esophageal, pharyngeal, or gastric masses, and because the biopsy size will be small, several samples should be taken for histopathologic examination.
TextSentencer_T226	34069-34209	Sentence	denotes	A complete description of gastroscopy and evaluation of gastric and gastroduodenal ulceration are available in Gastroduodenal Ulcer Disease.
TextSentencer_T227	34210-34369	Sentence	denotes	Oral Glucose Tolerance Test d-Glucose or d-xylose absorption tests are useful in determining malabsorption of carbohydrates from the small intestine in horses.
TextSentencer_T228	34370-34448	Sentence	denotes	For either test, the horse should be fasted for 14 to 18 hours before testing.
TextSentencer_T229	34449-34553	Sentence	denotes	Prolonged fasting (≥24 hours) results in a delayed and slightly lower peak plasma glucose concentration.
TextSentencer_T230	34554-34644	Sentence	denotes	57 A dosage of 1 g/kg of d-glucose is administered as a 20% solution via nasogastric tube.
TextSentencer_T231	34645-34719	Sentence	denotes	Xylazine sedation does not appear to significantly alter d-xylose results.
TextSentencer_T232	34720-34853	Sentence	denotes	58 Blood glucose or xylose concentrations are then measured 0, 30, 60, 90, 120, 150, 180, 210 , and 240 minutes after administration.
TextSentencer_T233	34854-34945	Sentence	denotes	Additional samples can be taken up to 6 hours after dosing if the results are questionable.
TextSentencer_T234	34946-35044	Sentence	denotes	Sodium fluoride and heparin are the preferred anticoagulants for glucose and xylose, respectively.
TextSentencer_T235	35045-35245	Sentence	denotes	A normal d-glucose absorption test, also known as an oral glucose tolerance test (OGTT), should peak between 90 and 120 minutes at a glucose concentration >85% above the resting glucose concentration.
TextSentencer_T236	35246-35439	Sentence	denotes	59 Complete malabsorption is defined as a peak less than 15% above the resting concentration, and partial malabsorption is defined as a peak between 15% and 85% above the resting concentration.
TextSentencer_T237	35440-35614	Sentence	denotes	Gastric emptying, gastrointestinal transit time, length of fasting, glucose and insulin metabolism, age, diet, and endocrine function can influence glucose absorption curves.
TextSentencer_T238	35615-35853	Sentence	denotes	59, 60 Higher glucose peaks are recorded from healthy animals eating grass or hay than from those eating concentrates 60 and from horses fed a pasture (clover and kikuyu) versus stable (oat hay, complete feed, and alfalfa/oat chaff) diet.
TextSentencer_T239	35854-36029	Sentence	denotes	61 Results from the OGTT can also be affected by the content of nonstructural carbohydrate and fat in the diet 62 and other disorders, such as polysaccharide storage myopathy.
TextSentencer_T240	36030-36032	Sentence	denotes	63
TextSentencer_T241	36034-36193	Sentence	denotes	The xylose absorption test is performed as per the OGTT, except 0.5 g d-xylose per kilogram body weight is administered as a 10% solution via nasogastric tube.
TextSentencer_T242	36194-36270	Sentence	denotes	The pretest period of fasting and timing of sample collection are identical.
TextSentencer_T243	36271-36423	Sentence	denotes	The laboratory to which samples will be sent should be contacted before collection to ensure that heparinized plasma is acceptable for their laboratory.
TextSentencer_T244	36424-36573	Sentence	denotes	Plasma d-xylose should peak between 20 and 25 mg/dL between 60 and 90 minutes following administration, with occasional peaks as late as 120 minutes.
TextSentencer_T245	36574-36812	Sentence	denotes	64 ,65 d-Xylose absorption testing is not confounded by hormonal effects or mucosal metabolism as is glucose, but it is altered by diet, length of fasting (which could also be influenced by recent appetite or degree of cachexia), and age.
TextSentencer_T246	36813-37010	Sentence	denotes	Horses fed a high-energy (oat chaff, oats, and corn) diet had a lower mean peak plasma d-xylose concentration (14.1 mg/ dL versus 24.9 mg/dL) than those consuming a low-energy (alfalfa chaff) diet.
TextSentencer_T247	37011-37148	Sentence	denotes	61 Healthy mares fasted for up to 96 hours had flatter curves and a slower decrease in plasma xylose than when fasted for 12 to 36 hours.
TextSentencer_T248	37149-37393	Sentence	denotes	64 Kinetic analysis indicates that prolonged food deprivation does not alter renal or nonrenal excretion of d-xylose; thus, the effect of fasting on the curve is likely related to either intestinal transit, small intestinal absorption, or both.
TextSentencer_T249	37394-37600	Sentence	denotes	66, 67 Ponies may have lower peak d-xylose concentrations than horses, although the range is wide, and diagnostic discriminatory cutoff points for peak plasma xylose concentrations have not been determined.
TextSentencer_T250	37601-37768	Sentence	denotes	Foals normally have a higher mean peak xylose concentration at 1 and 2 months of age, but mean peak falls to a level similar to that seen in adults by 3 months of age.
TextSentencer_T251	37769-37894	Sentence	denotes	68 Gastric emptying rate, intestinal motility, intraluminal bacterial overgrowth, and renal clearance can affect curve shape.
TextSentencer_T252	37895-37897	Sentence	denotes	69
TextSentencer_T253	37899-38033	Sentence	denotes	Milk intolerance is well documented in children and can result from primary or secondary lactase (neutral β-galactosidase) deficiency.
TextSentencer_T254	38034-38218	Sentence	denotes	Secondary lactase deficiency can occur when a small intestinal disorder, typically rotavirus, damages the epithelial cells, resulting in decreased brush border disaccharidase activity.
TextSentencer_T255	38219-38304	Sentence	denotes	Such an association has been reported secondary to clostridial enteritis in the foal.
TextSentencer_T256	38305-38522	Sentence	denotes	40 In horses, lactase activity peaks at birth and declines slowly, such that activity is approximately 50% at 2 years of age and rapidly decelerates after 3 years of age, and it is barely detectable by 4 years of age.
TextSentencer_T257	38523-38697	Sentence	denotes	41 The oral lactose tolerance test is performed in foals after a 4-hour fast, with a standard dose of 1 g/kg lactose monohydrate given via nasogastric tube as a 20% solution.
TextSentencer_T258	38698-38732	Sentence	denotes	Blood sampling is as per the OGTT.
TextSentencer_T259	38733-38935	Sentence	denotes	Plasma glucose typically peaks 60 minutes following lactose administration, with a range from 30 to 90 minutes, with a mean increase of 77 mg/dL, with a 35-mg/dL increase covering 2 standard deviations.
TextSentencer_T260	38936-39050	Sentence	denotes	42 Of note, older foals (12 weeks) had a more significant increase in plasma glucose relative to 1-week-old foals.
TextSentencer_T261	39051-39232	Sentence	denotes	Assessment of gastric emptying may be useful in cases of gastric and esophageal ulceration or suspected gastric outflow obstruction, although accurate assessment can be challenging.
TextSentencer_T262	39233-39275	Sentence	denotes	Contrast radiography can be used in foals.
TextSentencer_T263	39276-39362	Sentence	denotes	In the normal foal, a significant amount of liquid barium should empty within 2 hours.
TextSentencer_T264	39363-39561	Sentence	denotes	41 Nuclear scintigraphy can be used for measurement of liquid 51 or solid phase emptying 70 by use of orally administered 99m Tc pentetate (10 mCi) or a 99m Tc-labeled pelleted ration, respectively.
TextSentencer_T265	39562-39725	Sentence	denotes	Alternatively, absorption testing of glucose or xylose (discussed previously) or acetaminophen can be used as an indirect determination of liquid gastric emptying.
TextSentencer_T266	39726-39923	Sentence	denotes	Acetaminophen absorption is performed by administering 20 mg/kg of acetaminophen orally, sampling blood, then calculating the time to reach maximum serum concentrations and the absorption constant.
TextSentencer_T267	39924-40010	Sentence	denotes	71, 72 In humans the proximal small intestine absorbs almost all of the acetaminophen.
TextSentencer_T268	40011-40115	Sentence	denotes	73 The median time to reach peak plasma levels using acetaminophen absorption in horses is 47.7 minutes.
TextSentencer_T269	40116-40229	Sentence	denotes	72 The 13 C-octane acid breath test offers an easy, noninvasive method of determining gastric emptying of solids.
TextSentencer_T270	40230-40362	Sentence	denotes	70, 74 This test is performed by feeding a standard 13 C-labeled test meal and then collecting breath samples using a modified mask.
TextSentencer_T271	40363-40471	Sentence	denotes	The breath is then analyzed for the ratio of the novel isotope, 13:CO 2 , to the normally produced 12:CO 2 .
TextSentencer_T272	40472-40742	Sentence	denotes	It is often necessary to perform a histopathologic examination of tissues from the intestine to diagnose chronic inflammatory, infiltrative, or neoplastic conditions, and such an examination can be useful in evaluating the extent of injury after obstruction or ischemia.
TextSentencer_T273	40743-40811	Sentence	denotes	Rectal mucosal biopsies are easy to collect, with few complications.
TextSentencer_T274	40812-40974	Sentence	denotes	Fullthickness biopsy often provides more thorough analysis and can be directed based on serosal appearance via a flank, ventral midline, or laparoscopic approach.
TextSentencer_T275	40975-41124	Sentence	denotes	When taking gastric or duodenal biopsies endoscopically for the putative diagnosis of inflammatory bowel disorders, multiple samples are recommended.
TextSentencer_T276	41125-41276	Sentence	denotes	The likelihood of establishing an accurate diagnosis varies with tissue quality, number of samples, skill of the endoscopist, and submission technique.
TextSentencer_T277	41277-41382	Sentence	denotes	75 Laparoscopy Laparoscopic evaluation of the equine abdomen requires specialized equipment and training.
TextSentencer_T278	41383-41459	Sentence	denotes	The laparoscopic procedure can be done with the horse standing or recumbent.
TextSentencer_T279	41460-41607	Sentence	denotes	Advantages of this technique over a flank or ventral midline celiotomy include smaller incisions, shorter healing time, and shorter procedure time.
TextSentencer_T280	41608-41759	Sentence	denotes	Disadvantages include equipment and personnel needs, limited therapeutic potential, and limited visual field, especially relative to midline celiotomy.
TextSentencer_T281	41760-42083	Sentence	denotes	Potential gastrointestinal applications of abdominal laparoscopy include the correction of rectal tears; percutaneous abscess drainage, assessment of adhesions, displacements, and integrity of the serosa of various bowel segments; biopsy of abdominal masses; and closure of the nephrosplenic space. [76] [77] [78] [79] [80]
TextSentencer_T282	42085-42268	Sentence	denotes	The inflammatory response of the gastrointestinal tract is a mechanism ultimately aimed at eliminating pathogens, initiating tissue repair, and restoring the gastrointestinal barrier.
TextSentencer_T283	42269-42554	Sentence	denotes	Blood flow is altered, endothelial permeability increases, cells are rapidly recruited into the tissue, plasma protein cascades are activated, and myriad soluble products are released that coordinate the response, trigger innate and adaptive immunity, and mobilize reparative elements.
TextSentencer_T284	42555-42822	Sentence	denotes	Although the cellular and vascular response and the secreted mediators of inflammation are important for killing pathogens and limiting invasion of injured tissues by commensal organisms, they can be quite damaging to host cells and proteins if not tightly regulated.
TextSentencer_T285	42823-42950	Sentence	denotes	If the inciting stimulus is not eliminated quickly, then the inflammatory response itself will cause significant tissue injury.
TextSentencer_T286	42951-43153	Sentence	denotes	The mechanism regulating inflammation has been the focus of a great deal of research to identify therapeutic targets to modulate the damage to host tissues that occurs in many gastrointestinal diseases.
TextSentencer_T287	43154-43319	Sentence	denotes	Recent work has provided some of the molecular and cellular details of this complex physiology and has led to novel therapeutic strategies for treating inflammation.
TextSentencer_T288	43320-43451	Sentence	denotes	The gastrointestinal epithelium interfaces with a luminal environment that is inhabited by potentially hostile microbial organisms.
TextSentencer_T289	43452-43704	Sentence	denotes	The epithelium presents a physical barrier to invasion by the flora of the gastrointestinal tract, consisting of the apical cellular membrane, intercellular tight junctions (the permeability of which is highly regulated), and a secreted layer of mucus.
TextSentencer_T290	43705-43844	Sentence	denotes	When invading pathogens breach the mucosal barrier, potent soluble and neural signals are generated that initiate an inflammatory response.
TextSentencer_T291	43845-43998	Sentence	denotes	81 The epithelium can be conceptualized as a sensory organ that detects pathogen invasion to trigger an appropriate host defense and reparative response.
TextSentencer_T292	43999-44284	Sentence	denotes	Noninfectious mucosal injury or invasion of epithelial cells by pathogenic organisms such as Salmonella activates the synthesis of proinflammatory chemokines (chemoattractants) by epithelial cells that triggers a robust influx of neutrophils into the tissue within hours of the damage.
TextSentencer_T293	44285-44539	Sentence	denotes	81 Of the chemoattractants produced by epithelium, interleukin-8 (IL-8) has a particularly important role in initiating inflammation by recruiting neutrophils from blood 82 and regulating neutrophil migration through tissue matrix adjacent to epithelium.
TextSentencer_T294	44540-44880	Sentence	denotes	83, 84 Complement fragments such as C5a and bacteria-derived formylated chemotactic peptides also act as potent "end target" chemoattractants that are fully capable of stimulating a robust inflammatory response in the intestine if the epithelial barrier permits invasion of bacteria or the diffusion of bacterial peptides across the mucosa.
TextSentencer_T295	44881-45085	Sentence	denotes	Epithelial cells activated during infection produce cytokines such as tumor necrosis factor-α (TNF-α), arachidonic acid metabolites, and other proinflammatory mediators that activate recruited leukocytes.
TextSentencer_T296	45086-45279	Sentence	denotes	85 Microbial products, particularly lipopolysaccharide (LPS) and other bacterial cell wall components and microbial nucleic acids, are potent activators of leukocytes recruited into the tissue.
TextSentencer_T297	45280-45463	Sentence	denotes	86 Mast cells are key sentinel leukocytes that sense microbial invasion, releasing TNF-α, which appears to be a critical initiator and regulator of the cellular phase of inflammation.
TextSentencer_T298	45464-45661	Sentence	denotes	87 Once the inflammatory response has been initiated, TNF-α; IL-1β; and other proinflammatory products of neutrophils, monocytes, mast cells, and epithelial cells amplify the inflammatory response.
TextSentencer_T299	45662-45776	Sentence	denotes	The enteric nervous system (ENS) has a key role in sensing and regulating inflammatory responses in the intestine.
TextSentencer_T300	45777-45914	Sentence	denotes	For example, C. difficile toxin A activates a neural pathway that triggers mast cell degranulation and neutrophil influx into the tissue.
TextSentencer_T301	45915-46099	Sentence	denotes	88, 89 Blockade of this neural pathway is sufficient to abolish the profound inflammatory response induced by toxin A as well as many of the effects of toxin A on enterocyte secretion.
TextSentencer_T302	46100-46231	Sentence	denotes	Other pathogens and immune-mediated hypersensitivity reactions similarly stimulate inflammation by mechanisms that involve the ENS.
TextSentencer_T303	46232-46405	Sentence	denotes	Thus the epithelium interacts in a highly complex manner with the intestinal milieu, the ENS, and inflammatory cells to regulate the tissue response to injury and infection.
TextSentencer_T304	46406-46582	Sentence	denotes	Resident macrophages located in the lamina propria, submucosa, and intestinal lymphoid organs are among the first cells beyond the epithelium to respond to infection or injury.
TextSentencer_T305	46583-46784	Sentence	denotes	Macrophages are activated by microbial products by way of pattern recognition receptors and begin to produce proinflammatory molecules important for recruiting and activating neutrophils and monocytes.
TextSentencer_T306	46785-46952	Sentence	denotes	Pattern recognition receptors recognize microbial molecules such as LPS, lipoproteins, flagellin, peptidoglycan, and nucleic acids to signal the invasion by pathogens.
TextSentencer_T307	46953-47047	Sentence	denotes	86 Of the pattern recognition receptors, the LPS receptor complex is perhaps the best defined.
TextSentencer_T308	47048-47263	Sentence	denotes	LPS activates macrophages by way of the CD14 Toll-like receptor 4 (TLR-4) complex to initiate transcription of the inflammatory cytokines TNF-α and IL-1β, which synergize with LPS to amplify the macrophage response.
TextSentencer_T309	47264-47434	Sentence	denotes	86 LPS, particularly in concert with inflammatory cytokines, stimulates macrophages to produce copious amounts of nitric oxide, which is both microbicidal and vasoactive.
TextSentencer_T310	47435-47661	Sentence	denotes	90 Nitric oxide and other nitrogen radicals react with reactive oxygen intermediates (ROIs) generated by the activated oxidase complex to produce some of the most toxic molecules of the host defense system: the peroxynitrites.
TextSentencer_T311	47662-47713	Sentence	denotes	90 IL-8 is produced as well to recruit neutrophils.
TextSentencer_T312	47714-48047	Sentence	denotes	As the response progresses, other inflammatory mediators, particularly the arachidonic acid-derived lipids dependent on inflammationinduced cyclooxygenase (COX)-2 and 5-lipoxygenase activity, are produced that have potent vasoactive and proinflammatory effects through the activation of endothelial cells, neutrophils, and platelets.
TextSentencer_T313	48048-48424	Sentence	denotes	91 Y VASCULAR RESPONSE DURING INFLAMMATION Four important changes occur in the intestinal vasculature during inflammation: (1) alteration of blood flow; (2) increased vascular permeability; (3) increased adhesiveness of endothelial cells, leukocytes, and platelets; and (4) exposure of the basement membrane and activation of the complement, contact, and coagulation cascades.
TextSentencer_T314	48425-48744	Sentence	denotes	A wide range of mediators alter blood flow during inflammation in the intestinal tract, ranging from gases such as nitric oxide (a major vasodilator of the intestinal vasculature) to lipids (prostaglandins, leukotrienes, thromboxanes, and platelet-activating factor [PAF]), cytokines, bradykinin, histamine, and others.
TextSentencer_T315	48745-48866	Sentence	denotes	The major sources for these mediators include activated leukocytes, endothelial cells, epithelial cells, and fibroblasts.
TextSentencer_T316	48867-49106	Sentence	denotes	The primary determinant of blood flow early in inflammation is vascular caliber, which initially decreases in arterioles but then quickly changes to vasodilation coincident with the opening of new capillary beds, increasing net blood flow.
TextSentencer_T317	49107-49272	Sentence	denotes	The increase in blood flow is relatively short-lived, because the viscosity of the blood increases from fluid loss and tissue edema resulting from leaky capillaries.
TextSentencer_T318	49273-49436	Sentence	denotes	Leukocyte margination, platelet adhesion to endothelial cells and exposed matrix, and areas of coagulation protein accumulation further decrease local circulation.
T2330	49437-49547	Sentence	denotes	Increased vascular permeability is initially caused by inflammatory mediator actions on the endothelial cells.
T92561	49548-49697	Sentence	denotes	Histamine, leukotrienes, PAF, prostaglandins, bradykinin, and other mediators stimulate endothelial cell contraction, and interendothelial gaps form.
T41177	49698-49773	Sentence	denotes	92, 93 This stage of increased vascular permeability is readily reversible.
T65809	49774-49970	Sentence	denotes	Concurrently, mediators such as the cytokines TNF-α and IL-1β induce a structural reorganization of the interendothelial junctions, resulting in frank discontinuities in the endothelial monolayer.
T30831	49971-50156	Sentence	denotes	94 Cytokines also stimulate endothelial cells to express adhesion molecules that support adhesion of leukocytes and platelets, 95 leading to the next and perhaps most devastating event.
T60100	50157-50275	Sentence	denotes	Leukocytes (primarily neutrophils) and platelets adhere to exposed basement membranes and activated endothelial cells.
T26498	50276-50832	Sentence	denotes	Adherent neutrophils and platelets are then exposed to the mediators of inflammation present in the surrounding milieu, which activates the cells to release oxidants and proteases (particularly elastase) that injure the endothelium and have the potential to cause irreparable harm to the microvasculature. [96] [97] [98] Marginated neutrophils begin to transmigrate between endothelial cells (as described in later sections), which, if in sufficiently large numbers, disrupts the integrity of the interendothelial junctions, worsening the vascular leakage.
T4989	50833-51031	Sentence	denotes	97 These stages of enhanced vascular permeability can be conceptualized as a mechanism to allow plasma proteins to enter the tissues and to potentiate the critical influx of leukocytes into tissues.
T19390	51032-51207	Sentence	denotes	However, if they are not regulated precisely, alterations in both hydrostatic and oncotic forces and irreversible damage to the vascular bed may have devastating consequences.
T38667	51208-51542	Sentence	denotes	Moreover, inappropriate activation of plasma protein cascades and leukocytes by activated endothelium and exposed matrix proteins can contribute to SIRS (see the later section Gastrointestinal Ileus for more information) characterized by hypotension, generalized vascular leak syndrome, and multiorgan dysfunction, which may be fatal.
T52914	51543-51876	Sentence	denotes	Phosphodiesterase inhibitors reduce endothelial permeability in ischemiareperfusion injury and other models of inflammation-induced vascular leakage 99,100 by increasing endothelial tight junction integrity; thus, it may be a viable therapeutic strategy to prevent or reduce the permeability alterations associated with inflammation.
T74468	51877-52057	Sentence	denotes	Endothelial cells respond to products of activated epithelial cells and macrophages in the intestinal tissue to recruit cells and humoral mediators of inflammation into the tissue.
T1476	52058-52161	Sentence	denotes	Activated endothelial cells display a range of molecules critical for neutrophil and platelet adhesion.
T63702	52162-52278	Sentence	denotes	The role of endothelial cells in mediating neutrophil recruitment is discussed in more detail later in this chapter.
T51168	52279-52509	Sentence	denotes	Intercellular permeability is increased to expose basement membrane proteins that trigger humoral defense systems (complement, coagulation, and contact system cascades) and to provide access for these macromolecules to the tissue.
T350	52510-52678	Sentence	denotes	Endothelial cells are an important source of inflammatory mediators that amplify the response and vasoactive substances (particularly nitric oxide) altering blood flow.
T62871	52679-52829	Sentence	denotes	Infection or injury to the gastrointestinal mucosa causes an influx of leukocytes from the blood that lay the foundation of the inflammatory response.
T3020	52830-52927	Sentence	denotes	Neutrophils, the first to arrive during inflammation, have a dominant role in the acute response.
T45913	52928-53135	Sentence	denotes	Within minutes neutrophils are recruited into the tissue, in which they are activated to release products that not only are lethal to pathogens and proinflammatory but also may damage host cells and tissues.
T95175	53136-53280	Sentence	denotes	101 Not surprisingly, a great deal of attention has been paid to the role of neutrophils in the pathophysiology of many inflammatory conditions.
T64605	53281-53376	Sentence	denotes	102 Neutrophil depletion is protective in many models of gastrointestinal inflammatory disease.
T35871	53377-53607	Sentence	denotes	Of interest to clinicians, blockade of neutrophil migration into inflamed tissues prevents many of the pathophysiologic events associated with infectious enteritis, ischemia-reperfusion injury, and other gastrointestinal diseases.
T70702	53608-53796	Sentence	denotes	98, [103] [104] [105] [106] Neutrophil transendothelial migration is a multistep process that is temporally and spatially regulated and has a degree of cell type specificity ( Fig. 12.1 ).
T23211	53797-53927	Sentence	denotes	The predominant sites of neutrophil transendothelial migration are in the postcapillary venules and, in some tissues, capillaries.
T42173	53928-54142	Sentence	denotes	Endothelial cells in these vessels respond to cytokines and other soluble signals by expressing molecules that promote neutrophil adhesion and transmigration, including selectins and counterreceptors for integrins.
T15525	54143-54235	Sentence	denotes	As neutrophils flow through these vessels, they are first tethered to activated endothelium.
T1993	54236-54436	Sentence	denotes	Tethering is mediated by selectin molecules expressed on neutrophils (L-selectin) and on activated endothelial cells (P-and E-selectins), which bind to PSGL-1, ESL-1, and other mucin counterreceptors.
T6333	54437-54594	Sentence	denotes	107 , 108 The function of tethering is to increase the exposure of the neutrophil to activating chemokines presented on the surface of the endothelial cells.
T16326	54595-54706	Sentence	denotes	Stimulation of neutrophils by IL-8 and other chemokines activate the second step of transendothelial migration.
T10706	54707-55003	Sentence	denotes	Chemokine binding to their receptors on the neutrophil generates signals that activate the binding of integrin adhesion receptors to their ligands, called intracellular adhesion molecules (ICAMs) or vascular cell adhesion molecules, expressed on endothelial , and other proinflammatory mediators.
T79753	55004-55165	Sentence	denotes	Endothelial cells stimulated by inflammatory mediators produce chemoattractants (such as IL-8) and display adhesion molecules that promote neutrophil emigration.
T77547	55166-55450	Sentence	denotes	The three steps of neutrophil (polymorphonuclear [PMN]) emigration capture/rolling (mediated by selectins), adhesion (mediated by β 2 integrins), and transendothelial migration (mediated by integrins and platelet/endothelial cellular adhesion molecule) occur on activated endothelium.
T48091	55451-55520	Sentence	denotes	Chemoattractant molecules such as IL-8 trigger neutrophil emigration.
T78400	55521-55748	Sentence	denotes	In inflamed tissues cytokines (IL-1β and TNF-α) and a variety of other proinflammatory mediators stimulate the neutrophil oxidase complex to produce reactive oxygen intermediates (ROIs; O 2 − and H 2 O 2 and their derivatives).
T23090	55749-55909	Sentence	denotes	Activated neutrophils degranulate to release proteases and other hydrolases, cationic peptides (defensins), myeloperoxidase, and other products into the tissue.
T65059	55910-56054	Sentence	denotes	Activated neutrophils synthesize a variety of inflammatory mediators, including prostaglandins (PGE 2 ) that modulate the inflammatory response.
T74346	56055-56215	Sentence	denotes	The products of activated neutrophils (ROIs, proteases, and mediators) stimulate epithelial secretion and alter tight junction permeability, promoting diarrhea.
T25440	56216-56475	Sentence	denotes	Neutrophils eventually migrate across the infected epithelium by a mechanism that involves integrins, disrupting tight junction integrity and increasing permeability to bacterial products, thus exacerbating the inflammatory response. cells in inflamed mucosa.
T47649	56476-56583	Sentence	denotes	Integrin ligation to ICAMs arrests the tethered neutrophils, resulting in firm adhesion to the endothelium.
T12677	56584-56711	Sentence	denotes	Of the integrins expressed on neutrophils, the β 2 -integrins have a particularly important role in transendothelial migration.
T81447	56712-56870	Sentence	denotes	Calves and people with the disorder leukocyte adhesion deficiency (LAD) illustrate the requirement for β 2 -integrin-mediated adhesion in neutrophil function.
T59180	56871-56973	Sentence	denotes	LAD is a result of an autosomal recessive trait resulting in the lack of the β 2 -integrin expression.
T91347	56974-57188	Sentence	denotes	The neutrophils from affected individuals cannot migrate into most tissues and do not function normally, resulting in poor tissue healing and profound susceptibility to infection, especially at epithelial barriers.
T18018	57189-57420	Sentence	denotes	109, 110 Other integrins also have a role in transendothelial migration. β 1 -Integrins mediate transendothelial migration in some cells and seem to be particularly important for mediating emigration of monocytes into many tissues.
T22457	57421-57608	Sentence	denotes	111 Following this firm adhesion step, neutrophils migrate through the endothelium along a chemotactic gradient of IL-8 and other chemoattractants, such as C5a and leukotriene B 4 (LTB4).
T97383	57609-57932	Sentence	denotes	82, 97, 112 Neutrophils migrate across the endothelial monolayer at intercellular junctions by way of a mechanism involving a series of integrin-ligand interactions mediated by both β 2 -and β 1 -integrins and other adhesion molecules, 108 which is generally capable of maintaining the integrity of the endothelial barrier.
T31393	57933-58223	Sentence	denotes	113 However, a massive flux of neutrophils through the endothelium alters endothelial tight junctions and injures the basement membrane, resulting in increased endothelial permeability to molecules as large as plasma proteins and even endothelial cell detachment from the basement membrane.
T87252	58224-58378	Sentence	denotes	96, 97 Nonintegrin molecules such as platelet-endothelial cell adhesion molecules (PECAMs) also are involved in transendothelial migration of neutrophils.
T73787	58379-58481	Sentence	denotes	108 Homotypic binding of PECAMs on adjacent endothelial cells form part of the intercellular junction.
T40779	58482-58715	Sentence	denotes	Neutrophils express an integrin of the β 3 -family that can bind PECAMs, and through sequential binding of β 3 -integrins to PECAMs, the neutrophil can "unzip" the intercellular junction and migrate through, closing it behind itself.
T72783	58716-58911	Sentence	denotes	A key feature of neutrophils and other leukocytes is the requirement for integrin-mediated adhesion to extracellular matrix (ECM) proteins or other cells to achieve an optimal effector phenotype.
T26730	58912-59191	Sentence	denotes	114 Critical components of the ECM in inflamed tissues include fibronectin, fibrinogen, and vitronectin, deposited in tissues as a result of plasma leakage and by synthesis of new proteins by stromal cells and resident macrophages in response to inflammatory mediator activation.
T73675	59192-59399	Sentence	denotes	The changing composition of the matrix proteins deposited in tissues during inflammation serves as a clue as to the nature of the tissue environment for recruited inflammatory cells as they become activated.
T74684	59400-59756	Sentence	denotes	Individual gene expression studies have demonstrated that adhesion to matrix proteins induces the expression of cytokines and chemokines and their receptors, arachidonic acid-derived lipid mediator synthases, metalloproteinases, growth factors, transcription factors, and other genes that influence the differentiation and activation of inflammatory cells.
T17167	59757-59953	Sentence	denotes	115 ROI production, phagocytosis, degranulation, and other effector functions stimulated by inflammatory mediators and bacterial products are optimal only when neutrophils are adherent to the ECM.
T94375	59954-60261	Sentence	denotes	114 Adhesion to distinct ECM proteins selectively activates signaling pathways and gene expression of neutrophils, monocytes, and other leukocytes with differing abilities to promote certain functions such that the composition of ECM in many ways controls the development of the ultimate effector phenotype.
T30540	60262-60424	Sentence	denotes	Thus integrin-mediated adhesion provides a mechanism in which neutrophils and other leukocytes can sense the complex tissue environment and respond appropriately.
T74696	60425-60630	Sentence	denotes	Of the activators of neutrophils at sites of inflammation, complement (C3-opsonized particles), cytokines (TNF-α and IL-1β), PAF, immune complexes, and bacterial products are among the most potent stimuli.
T83388	60631-60819	Sentence	denotes	Other mediators produced during inflammation may modify neutrophil activity, particularly formylated bacterial peptides, chemokines, complement fragments (C5a), LTB 4 , and prostaglandins.
T10565	60820-61149	Sentence	denotes	Activated neutrophils are highly phagocytic; produce large amounts of ROI; degranulate to release myeloperoxidase, cationic antimicrobial peptides (defensins), serine proteases (mainly elastase), and metalloproteinases; and secrete inflammatory mediators (TNF-α, IL-1β, prostaglandins, leukotrienes, and others) (see Fig. 12 .1).
T10323	61150-61346	Sentence	denotes	Mast cells strategically reside in mucosal tissues, including the submucosa and lamina propria of the gastrointestinal tract, and constitute a crucial first line of defense at epithelial barriers.
T10643	61347-61460	Sentence	denotes	However, they are also important effector cells of the pathophysiology of inflammatory gastrointestinal diseases.
T48897	61461-61898	Sentence	denotes	116 Experimental depletion of mast cells, genetic deficiency in the development of mast cells, or pharmacologic stabilization of mast cells to prevent degranulation all have a protective effect in a variety of models of gastrointestinal inflammatory disease, including dextran sulfate sodium-induced or trinitrobenzenesulfonic acid-induced colitis, 117, 118 ischemia-reperfusion injury, 119, 120 and immediate hypersensitivity responses.
T18677	61899-61995	Sentence	denotes	121 Mast cells are activated by a wide variety of microbial products and host-derived mediators.
T23420	61996-62180	Sentence	denotes	122 Among the activators of mast cells, the so-called anaphylatoxins (complement fragments C3a, C5a, and C4a) are extremely potent stimuli causing release of mediators of inflammation.
T5590	62181-62351	Sentence	denotes	In addition, mast cells are the primary effector cells of IgE-mediated anaphylaxis (type I hypersensitivity reactions) by virtue of their high-affinity receptors for IgE.
T16773	62352-62540	Sentence	denotes	The cross-linking of a receptor-bound IgE on the mast cell surface by antigens (i.e., food antigens) causes rapid degranulation, which results in the explosive release of granule contents.
T59875	62541-62720	Sentence	denotes	123 Neural pathways in the intestine also regulate mast cells, which respond to enteric pathogen invasion via neural reflexes that stimulate the release of inflammatory mediators.
T76927	62721-62847	Sentence	denotes	Activated mast cells release preformed histamine, 5-hydroxytryptamine (5-HT), proteases, heparin, and cytokines from granules.
T24748	62848-62979	Sentence	denotes	Activation also stimulates de novo synthesis of a range of inflammatory mediators, including prostaglandins, PAF, and leukotrienes.
T28281	62980-63126	Sentence	denotes	Transcription of a number of peptide mediators, such as the cytokines TNF-α and IL-1β among many others, also increases stimulation of mast cells.
T83881	63127-63249	Sentence	denotes	Mast cell products have profound effects on the vasculature, increasing endothelial permeability and causing vasodilation.
T51174	63250-63436	Sentence	denotes	124 Moreover, mast cell-derived mediators markedly enhance epithelial secretion by a mechanism that involves the activation of neural pathways and direct stimulation of epithelial cells.
T13338	63437-63724	Sentence	denotes	123 In particular, the mast cell granule protease tryptase operating via the protease-activated receptor-2 is a key regulator of gastrointestinal physiologic responses during inflammation, including epithelial secretion and intercellular junction integrity, motility, and pain responses.
T18766	63725-63860	Sentence	denotes	125, 126 Mast cell products significantly alter intestinal motility, generally increasing transit and expulsion of intestinal contents.
T23783	63861-64130	Sentence	denotes	Mast cell-derived leukotrienes and TNF-α also have crucial roles in host defense against bacterial pathogens, acting to recruit and activate neutrophils, 127, 128 and are crucial players in the mechanism regulating dendritic cell function and adaptive immune responses.
T24491	64131-64412	Sentence	denotes	129 Mast cells have a role in host defense and inflammatory responses to bacterial pathogens, partly because of the release of proinflammatory mediators during bacterial infection, which is critical for recruiting and activating other innate host defense cells such as neutrophils.
T4230	64413-64547	Sentence	denotes	87 Mast cells are also phagocytic, have microbicidal properties, and can act as antigenpresenting cells to the adaptive immune system.
T51059	64548-64652	Sentence	denotes	87 The role for mast cells in host protective responses appears to be as a sensor of bacterial invasion.
T67419	64653-64776	Sentence	denotes	Unlike IgE-mediated responses, bacterial products seem to elicit a highly regulated and selective response from mast cells.
T40573	64777-64851	Sentence	denotes	The complement cascade is a fundamental part of the inflammatory response.
T64475	64852-65202	Sentence	denotes	Activation of the complement cascade, either by immune complexes (classical pathway) or by bacteria or bacterial products, polysaccharides, viruses, fungi, or host cells (alternative pathway), results in the deposition of complement proteins on the activating surface and the release of soluble proteolytic fragments of several complement components.
T45376	65203-65385	Sentence	denotes	130 In particular, activation of either pathway results in the deposition of various fragments of the complement protein C3, which are potent activators of neutrophils and monocytes.
T55795	65386-65511	Sentence	denotes	130 Opsonization of particles with C3 fragments constitutes a major mechanism of target recognition and phagocyte activation.
T98594	65512-65665	Sentence	denotes	131 During the activation of the complement cascade culminating in deposition of C3, soluble fragments of C3 (C3a), C5 (C5a), and C4 (C4a) are liberated.
T27395	65666-65767	Sentence	denotes	These fragments, termed anaphylatoxins, have potent effects on tissues and cells during inflammation.
T51901	65768-65962	Sentence	denotes	Perhaps most notably, they are chemotactic for neutrophils (particularly C5a), activate neutrophil and mast cell degranulation, and stimulate reactive oxygen metabolite release from neutrophils.
T40326	65963-66113	Sentence	denotes	130 The termination of the complement cascade results in the formation of a membrane attack complex in membranes at the site of complement activation.
T90722	66114-66201	Sentence	denotes	If this occurs on host cells such as endothelium, the cell may be irreversibly injured.
T49999	66202-66442	Sentence	denotes	Although the primary source of complement is plasma, epithelial cells of the gastrointestinal tract also produce C3, suggesting that local production and activation of the complement cascade during inflammation occurs in intestinal tissues.
T25249	66443-66601	Sentence	denotes	It is clear that if the regulatory mechanisms of the complement cascade fail, then the inflammatory response may be inappropriate and tissue injury can occur.
T49576	66602-66733	Sentence	denotes	The role of complement in gastrointestinal inflammation has been most extensively studied in models of ischemia-reperfusion injury.
T25299	66734-66856	Sentence	denotes	Activation of the complement cascades has a major role in altered endothelial and epithelial permeability in these models.
T68727	66857-66941	Sentence	denotes	Several lines of evidence support the importance of complement in intestinal injury.
T51658	66942-67019	Sentence	denotes	Mice deficient in C3 or C4 are protected against ischemia-reperfusion injury.
T84269	67020-67186	Sentence	denotes	132 Moreover, administration of monoclonal antibodies against C5 reduced local and remote injury and inflammation during intestinal reperfusion injury in a rat model.
T78002	67187-67476	Sentence	denotes	133 Administration of a soluble form of complement receptor 1, a regulatory protein that halts the complement cascade by dissociating C3 and C5 on host cell membranes, reduced mucosal permeability, neutrophil influx, and LTB4 production during ischemia-reperfusion injury in rats and mice.
T7919	67477-67714	Sentence	denotes	132, 134 Although neutrophils and mast cells mediate many of the pathophysiologic effects of the complement cascade, the membrane attack complex may have a primary role in altered vascular permeability during ischemia-reperfusion injury.
T14281	67715-67718	Sentence	denotes	135
T928	67719-67780	Sentence	denotes	The contact system of plasma is initiated by four components:
T94520	67781-67864	Sentence	denotes	Hageman factor (HF), prekallikrein, factor XI, and high-molecular-weight kininogen.
T58434	67865-67948	Sentence	denotes	HF is a large plasma glycoprotein that binds avidly to negatively charged surfaces.
T14391	67949-68196	Sentence	denotes	136 Bacterial cell walls, vascular basement membranes, heparin, glycosaminoglycans, and other negatively charged surfaces in the intestine capture HF and the other three important initiators of the contact system in a large multimolecular complex.
T84538	68197-68290	Sentence	denotes	Of the surfaces that bind HF, the ECM is an extremely potent activator of the contact system.
T72975	68291-68398	Sentence	denotes	Once bound, HF is converted to HF-α, which cleaves prekallikrein to kallikrein and factor XI to factor XIa.
T51654	68399-68713	Sentence	denotes	The ultimate result is further cleavage of HF by kallikrein and triggering of the contact system cascade, activation of intrinsic coagulation by factor XIa, activation of the alternative pathway by HF, and proteolytic cleavage of high-molecular-weight kininogen by kallikrein, releasing biologically active kinins.
T68761	68714-68894	Sentence	denotes	The products of the contact system, particularly bradykinin, have several important biologic properties that drive many of the vascular and leukocyte responses during inflammation.
T4439	68895-69056	Sentence	denotes	136 Bradykinin induces endothelial cell contracture and intracellular tight junction alterations that increase vascular permeability to fluid and macromolecules.
T58059	69057-69197	Sentence	denotes	Bradykinin also affects vascular smooth muscle contracture, resulting in either vasoconstriction or vasodilation, depending on the location.
T67430	69198-69337	Sentence	denotes	Bradykinin also increases intestinal motility, enhances chloride secretion by the intestinal mucosa, and intensifies gastrointestinal pain.
T99222	69338-69474	Sentence	denotes	In neutrophils kinins stimulate the release of many inflammatory mediators, including cytokines, prostaglandins, leukotrienes, and ROIs.
T30765	69475-69635	Sentence	denotes	137 Kallikrein cleaves C5 to release C5a, a potent chemotactic factor for neutrophils, and thus has a role in recruiting and activating inflammatory leukocytes.
T843	69636-69775	Sentence	denotes	The plasma kallikrein-bradykinin system is activated in a variety of acute and chronic inflammatory diseases of the gastrointestinal tract.
T80096	69776-69866	Sentence	denotes	138, 139 Blockade of the pathophysiologic effects of bradykinin has clinical applications.
T53661	69867-70084	Sentence	denotes	Oral or intravenous (IV) administration of the bradykinin receptor antagonist icatibant reduces the clinical signs, onset of diarrhea, and many of the histopathologic changes in experimental models of colitis in mice.
T60867	70085-70280	Sentence	denotes	140 Inhibition of kallikrein by oral administration of P8720 attenuated the intestinal inflammation, clinical score, and systemic manifestations in a model of chronic granulomatous enterocolitis.
T6588	70281-70386	Sentence	denotes	138 Thus the contact system is a potential therapeutic target for inflammatory diseases of the intestine.
T78123	70387-70559	Sentence	denotes	Changes in blood flow to the mucosa and other regions of the intestine that reduce perfusion of the tissues can potentiate the initial damage caused by infection or injury.
T50541	70560-70721	Sentence	denotes	For example, reperfusion of ischemic tissues is associated with platelet and neutrophil clumping in the small vessels of the mucosa, which can impede blood flow.
T84484	70722-70867	Sentence	denotes	141 Platelets are activated and adhere to exposed basement membrane and activated endothelial cells and provide a surface for leukocyte adhesion.
T46622	70868-71029	Sentence	denotes	The accumulation of platelets and leukocytes can significantly reduce vessel diameter and blood flow while potentiating local coagulation and thrombus formation.
T93747	71030-71126	Sentence	denotes	Soluble mediators released by activated leukocytes and endothelial cells also affect blood flow.
T52767	71127-71384	Sentence	denotes	Histamine and the vasoactive lipids derived from arachidonic acid (leukotrienes, prostaglandins, thromboxane, prostacyclin, and PAF) have a prominent role in regulating local perfusion during inflammation and may have systemic effects on blood flow as well.
T28884	71385-71724	Sentence	denotes	Procoagulant mediators released by inflammatory cells in response to the inflammatory process (i.e., tissue factor produced by macrophages or endothelial cells), exposed basement membrane proteins, and bacterial components can trigger the contact system and the coagulation and complement cascades, the products of which affect blood flow.
T88864	71725-71917	Sentence	denotes	Nitric oxide, whether produced by endothelial cells or leukocytes (macrophages), is a potent regulator of blood flow and has a significant role in the control of perfusion during inflammation.
T39981	71918-72062	Sentence	denotes	142 Many of the mediators that affect perfusion also affect endothelial permeability, altering osmotic and hydrostatic balance and tissue edema.
T1183	72063-72357	Sentence	denotes	In extreme cases local and systemic coagulopathies initiated by vascular injury and absorption of microbial products and inflammatory mediators induce a hypercoagulable state, leading to microthrombus formation, which can reduce blood flow or macrothrombus formation, causing tissue infarction.
T48191	72358-72463	Sentence	denotes	The cellular mediators of inflammation have the potential to inflict severe injury to intestinal tissues.
T94103	72464-72706	Sentence	denotes	Neutrophils have an important role in the pathophysiology of many intestinal diseases, including ischemia-reperfusion injury, 98 infectious enterocolitis, 105, 143 nonsteroidal antiinflammatory drug-induced mucosal ulceration, 106 and others.
T68367	72707-72877	Sentence	denotes	Depletion of neutrophils, blockade of their emigration into tissues, or inhibition of neutrophil activation reduces the severity of these and other inflammatory diseases.
T99129	72878-72999	Sentence	denotes	144 Many antiinflammatory therapies are emerging that specifically target neutrophil adhesion, migration, and activation.
T11051	73000-73191	Sentence	denotes	Migration of neutrophils through endothelium during emigration into inflamed tissues is remarkable in that the permeability of the endothelial monolayer is preserved under most circumstances.
T64567	73192-73310	Sentence	denotes	However, there is a limit above which neutrophil migration alters the permeability characteristics of the endothelium.
T81617	73311-73588	Sentence	denotes	The effect is in part physical in that the mere movement of large numbers of neutrophils through the endothelium is sufficient to mechanically disrupt the tight junctions and in part because of toxic products of neutrophils that damage endothelial cells and basement membranes.
T82700	73589-73867	Sentence	denotes	141, 145 Serine proteases (particularly elastase) and metalloproteinases released by degranulating neutrophils liquefy tissue matrix proteins and cleave cell-surface proteins that make up endothelial intercellular junctions to ease neutrophil migration to the site of infection.
T97712	73868-74075	Sentence	denotes	101 These degradative enzymes are particularly damaging to basement membranes and the cellular barriers of the endothelium, thus contributing to vascular permeability (and local tissue edema) and thrombosis.
T47682	74076-74239	Sentence	denotes	The permeability may be affected to the extent that not only water but also macromolecules (e.g., albumin, matrix proteins, complement) leak into the interstitium.
T93664	74240-74526	Sentence	denotes	Blockade of neutrophil adhesion to endothelium with anti-β 2 -integrin antibodies has a sparing effect on the microvasculature in experimental intestinal ischemia-reperfusion injury, reducing the alterations in vascular permeability and histopathologic evidence of microvascular damage.
T4275	74527-74677	Sentence	denotes	141 Similar to the endothelium of inflamed tissues, massive neutrophil transmigration occurs across the epithelium in response to infection or injury.
T95704	74678-74779	Sentence	denotes	Neutrophil transepithelial migration increases epithelial permeability by disrupting tight junctions.
T72444	74780-74903	Sentence	denotes	145 Like the endothelium, neutrophils disrupt the epithelial barrier mechanically as they migrate through (see Fig. 12 .1).
T18177	74904-75003	Sentence	denotes	Proteases, particularly elastase, degrade basement membrane components and tight junction proteins.
T9612	75004-75141	Sentence	denotes	Protease activated receptor-2 activated by neutrophil granule serine proteases alter epithelial and endothelial tight junction integrity.
T43750	75142-75279	Sentence	denotes	Proinflammatory products of activated neutrophils (TNFα and IFN-γ) increase tight junction permeability by direct effects on enterocytes.
T69968	75280-75391	Sentence	denotes	Prostaglandins released by activated neutrophils stimulate epithelial secretion, thus contributing to diarrhea.
T26012	75392-75538	Sentence	denotes	Subepithelial accumulation of neutrophils can lead to deadhesion of the epithelial cells from the basement membrane and mild to severe ulceration.
T14498	75539-75789	Sentence	denotes	The physiologic result of the effects of neutrophils and their products on the epithelial barrier includes protein-losing enteropathy and absorption of bacterial cell wall constituents, which potentiates the local and systemic inflammatory responses.
T11088	75790-75971	Sentence	denotes	Neutrophils in inflamed tissues stimulated by potent host-derived activators (such as IL-1β and TNF-α) and bacterial products (LPS) release copious amounts of ROIs (see Fig. 12 .1).
T40802	75972-76142	Sentence	denotes	Although these oxygen and oxyhalide radicals are important for killing pathogens, they are also potentially toxic to epithelial and endothelial cells and matrix proteins.
T51612	76143-76302	Sentence	denotes	Reactive nitrogen intermediates, produced primarily by macrophages during inflammation, combine with ROIs to form peroxynitrites, which are particularly toxic.
T38135	76303-76471	Sentence	denotes	90 In addition to injury to mucosal tissues, ROIs also have an as yet ill-defined role in recruiting and activating neutrophils, potentiating the inflammatory response.
T75416	76472-76714	Sentence	denotes	146 In support of the role of ROIs in inflammatory diseases of the gastrointestinal tract, administration of inhibitors of ROI production or pharmacologic ROI scavengers can be protective in many models of reperfusion injury or enterocolitis.
T22142	76715-76862	Sentence	denotes	Many therapies are aimed at inhibiting neutrophil activation, and effector functions in tissues have been evaluated for use in intestinal diseases.
T85701	76863-77072	Sentence	denotes	Phosphodiesterase inhibitors, by causing cyclic adenosine monophosphate (cAMP) accumulation in neutrophils, are antiinflammatory by virtue of their ability to suppress neutrophil activation and ROI production.
T39434	77073-77227	Sentence	denotes	New phosphodiesterase inhibitors selective for the predominant neutrophil isoform of phosphodiesterase hold promise for use in many inflammatory diseases.
T77631	77228-77339	Sentence	denotes	Subepithelial mast cells also have an important role in altering epithelial permeability in inflamed intestine.
T8210	77340-77535	Sentence	denotes	During the intestinal hypersensitivity response subepithelial mast cell release of mast cell protease tryptase by degranulation increases epithelial permeability via an effect on tight junctions.
T80603	77536-77694	Sentence	denotes	147, 148 This alteration in tight junction permeability results in enhanced transepithelial flux of macromolecules, including proteins and bacterial products.
T75762	77695-77785	Sentence	denotes	Cytokines released by mast cells and phagocytes also regulate tight junction permeability.
T92627	77786-77891	Sentence	denotes	IL-4, a product of mast cells and macrophages, has been demonstrated to increase epithelial permeability.
T37500	77892-78013	Sentence	denotes	149 Moreover, TNF-α and IFN-γ, products of many inflammatory cells, synergistically increase tight junction permeability.
T71765	78014-78131	Sentence	denotes	150 Y PATHOPHYSIOLOGY OF DIARRHEA Acute equine colitis causes rapid, severe debilitation and, often, death in horses.
T23357	78132-78386	Sentence	denotes	Diarrhea associated with acute equine colitis occurs sporadically and is characterized by intraluminal sequestration of fluid, moderate to severe colic (abdominal pain), and profuse watery diarrhea with resultant endotoxemia, leukopenia, and hypovolemia.
T41335	78387-78480	Sentence	denotes	151, 152 Causes of acute colitis and therapeutic options are discussed later in this section.
T33728	78481-79054	Sentence	denotes	Although all mechanisms responsible for fluid losses are not known, inflammatory cells likely play an integral role; colitis is characterized by granulocyte infiltration of the large intestinal mucosa. [153] [154] [155] [156] [157] Equine cecal and colonic tissues collected during the acute stages of experimentally induced acute equine colitis (Potomac horse fever, lincomycin with and without Clostridium spp. inoculation, nonsteroidal antiinflammatory drug administration) reveal the presence of numerous neutrophils and eosinophils in the lamina propria and submucosa.
T4933	79055-79224	Sentence	denotes	153, 156, 158, 159 Granulocyte-derived ROIs are crucial to antimicrobial defenses in the gut and stimulate chloride and water secretion by interactions with enterocytes.
T73723	79225-79409	Sentence	denotes	160, 161 Normal equine intestinal tissue is unique compared with that in most other mammalian species for a preponderance of eosinophils located in the intestinal mucosa and submucosa.
T26782	79410-79633	Sentence	denotes	162, 163 Production of ROIs by stimulated phagocytic granulocytes following mucosal barrier disruption may be responsible for the massive fluid secretory response that occurs during the early stages of acute equine colitis.
T76024	79634-79772	Sentence	denotes	Colitis refers to inflammation and mucosal injury of the colon and cecum (typhlocolitis) that may occur in response to a number of causes.
T82856	79773-79905	Sentence	denotes	164 The cause of the colonic injury may be well defined such as in naturally occurring infectious or experimentally induced colitis.
T92295	79906-80011	Sentence	denotes	However, many cases of human and animal diarrhea have a speculative or unknown diagnosis or no diagnosis.
T15926	80012-80262	Sentence	denotes	Irrespective of the underlying or initiating cause of colonic injury, the colon apparently has a limited repertoire of responses to damage because most forms of colitis demonstrate similarities in histopathologic appearance and clinical presentation.
T58473	80263-80504	Sentence	denotes	Various degrees of mucosal erosion and ulceration, submucosal/mucosal edema, goblet cell depletion, and the presence of an inflammatory cellular infiltrate within the mucosa and submucosa are common to many types of human and animal colitis.
T93322	80505-80670	Sentence	denotes	163, 164 Characteristic clinical manifestations include intraluminal fluid sequestration; abdominal discomfort; hypovolemia; and most often profuse, watery diarrhea.
T50991	80671-80766	Sentence	denotes	Large bowel diarrhea results from abnormal fluid and ion transport by cecal and colonic mucosa.
T79367	80767-80900	Sentence	denotes	Loss of fluid by the large intestine can result from malabsorptive or hypersecretory processes and is often a combination of the two.
T72449	80901-81042	Sentence	denotes	165 Colonic secretory processes are a function of the crypt epithelium, whereas absorptive processes are limited to surface epithelial cells.
T68967	81043-81196	Sentence	denotes	166, 167 Under normal baseline conditions, an underlying secretion by crypt epithelium is masked by a greater rate of surface epithelial cell absorption.
T48806	81197-81581	Sentence	denotes	Abnormal forces influencing the rates of secretion and absorption can result in massive, uncontrolled secretion and malabsorption by large intestinal mucosal epithelial cells, leading to rapid dehydration and death. [165] [166] [167] Two intracellular processes control colonic secretion: the cyclic nucleotide (cAMP and cyclic guanosine monophosphate [cGMP]) and the calcium systems.
T56463	81582-81781	Sentence	denotes	168, 169 Agents may activate adenyl cyclase (vasoactive intestinal peptide, prostaglandin E2 [PGE 2 ]) or guanylyl cyclase (bacterial enterotoxins) and induce increases in cAMP or cGMP, respectively.
T45968	81782-81919	Sentence	denotes	This reaction causes phosphorylation of specific protein kinases that induce the actual apical and basolateral membrane transport events.
T71785	81920-82221	Sentence	denotes	Increases in intracellular free calcium may arise from cyclic nucleotide-dependent release of stored calcium within the cell or from increased calcium entry across the cell membrane. [165] [166] [167] Calcium may act through calmodulin, which then can activate membranephosphorylating protein kinases.

TextSentencer_T1

0-40

Sentence

denotes

Disorders of the Gastrointestinal System

TextSentencer_T2

42-50

Sentence

denotes

Abstract

TextSentencer_T3

53-305

Sentence

denotes

Examination of patients with disease of the gastrointestinal tract must include evaluation of the metabolic and cardiovascular status of the patient because acute conditions of the proximal or distal intestinal tract can lead to endotoxemia and sepsis.

TextSentencer_T4

306-624

Sentence

denotes

Examination of the cardiovascular system (heart, peripheral pulse, and mucous membranes), lungs, and abdomen is essential to detect clinical signs of systemic inflammation from endotoxemia, coagulation disorders, dehydration, ileus, shock, and other abnormalities resulting from injury to the small or large intestine.

TextSentencer_T5

625-729

Sentence

denotes

Clinical signs of systemic inflammation from endotoxemia and sepsis are described later in this chapter.

TextSentencer_T6

730-854

Sentence

denotes

The physical examination of the abdomen should include auscultation, transabdominal ballottement, and transrectal palpation.

TextSentencer_T7

855-1056

Sentence

denotes

Abdominal distention often indicates distention of the large intestine; small intestinal distention also can cause visible abdominal distention if a large proportion of the small intestine is involved.

TextSentencer_T8

1057-1112

Sentence

denotes

Abdominal palpation can be performed in neonatal foals.

TextSentencer_T9

1113-1230

Sentence

denotes

After several weeks of age the abdominal wall is too rigid to allow effective palpation of intraabdominal structures.

TextSentencer_T10

1231-1327

Sentence

denotes

Abdominal auscultation is particularly useful for assessing the motility of the large intestine.

TextSentencer_T11

1328-1458

Sentence

denotes

Progressive motility of the small intestine, conversely, is difficult to distinguish by auscultation from nonprogressive motility.

TextSentencer_T12

1459-1652

Sentence

denotes

The distinct character of the borborygmi produced during propulsive contractions of the cecum and ascending colon allows evaluation of the frequency and strength of retropulsion and propulsion.

TextSentencer_T13

1653-1815

Sentence

denotes

Propulsive contractions of the cecum and ventral colon occur every 3 to 4 minutes and give rise to prolonged rushing sounds heard over long segments of intestine.

TextSentencer_T14

1816-1912

Sentence

denotes

Retropulsive sounds presumably are similar to propulsive sounds, but they occur less frequently.

TextSentencer_T15

1913-2051

Sentence

denotes

Distinguishing between propulsion and retropulsion is not important clinically because both types of contractions signify normal motility.

TextSentencer_T16

2052-2282

Sentence

denotes

Interhaustral and intrahaustral mixing contractions produce nonspecific sounds of fluid and ingesta movement that are difficult to distinguish from other borborygmi, such as small intestinal contractions or spasmodic contractions.

TextSentencer_T17

2283-2438

Sentence

denotes

1 Auscultation over the right flank and proceeding along the caudal edge of the costal margin toward the xiphoid allows evaluation of the cecal borborygmi.

TextSentencer_T18

2439-2549

Sentence

denotes

Auscultation over a similar area on the left side allows evaluation of the pelvic flexure and ascending colon.

TextSentencer_T19

2550-2695

Sentence

denotes

Typical progressive borborygmi heard every 3 to 4 minutes on both sides of the abdomen indicate normal motility of the cecum and ascending colon.

TextSentencer_T20

2696-3148

Sentence

denotes

Less frequent progressive sounds may indicate a pathologic condition of the large intestine or may result from anorexia, nervousness (sympathetic tone), or pharmacologic inhibition of motility (i.e., α 2 -adrenergic agonists such as xylazine). [2] [3] [4] [5] Absolute absence of any auscultable borborygmi suggests abnormal motility and indicates ileus resulting from a serious pathologic condition but is not specific to any segment of the intestine.

TextSentencer_T21

3149-3338

Sentence

denotes

3, 6 If borborygmi are audible but progressive sounds are not detectable, determining whether a significant abnormality exists is difficult, and such findings should not be overinterpreted.

TextSentencer_T22

3339-3586

Sentence

denotes

6 Borborygmi heard more frequently than normal may result from increased motility following feeding; from excessive stimulation from irritation, distention, or inflammation; or after administration of parasympathomimetic drugs such as neostigmine.

TextSentencer_T23

3587-3691

Sentence

denotes

Large intestinal motility increases in the early stages of intestinal distention regardless of the site.

TextSentencer_T24

3692-3785

Sentence

denotes

7 Mild inflammation or irritation of the large intestinal mucosa also can stimulate motility.

TextSentencer_T25

3786-4006

Sentence

denotes

3 Parasympathomimetic drugs stimulate contractions and auscultable borborygmi in the large intestine; an increase in parasympathetic tone may result in segmental contractions, which actually inhibit progressive motility.

TextSentencer_T26

4007-4093

Sentence

denotes

2 Percussion of the abdomen during auscultation can reveal gas in the large intestine.

TextSentencer_T27

4094-4272

Sentence

denotes

The characteristic ping produced by simultaneous digital percussion and auscultation over a gasfilled viscus often is associated with abnormal accumulation of gas under pressure.

TextSentencer_T28

4273-4397

Sentence

denotes

This technique is particularly useful in foals, ponies, and Miniature Horses because of the limitations of rectal palpation.

TextSentencer_T29

4398-4514

Sentence

denotes

Transabdominal ballottement can be used to detect large, firm masses or an abnormal volume of peritoneal fluid (PF).

TextSentencer_T30

4515-4608

Sentence

denotes

The usefulness of this technique is usually limited to animals too small to palpate rectally.

TextSentencer_T31

4609-4701

Sentence

denotes

Soft tissue masses or fetuses can be detected by bumping the structures with a hand or fist.

TextSentencer_T32

4702-4883

Sentence

denotes

If excessive PF is present, a fluid wave can be generated by ballottement; however, this technique is not as useful in horses older than 4 weeks because the abdominal wall is rigid.

TextSentencer_T33

4884-5064

Sentence

denotes

Transrectal palpation is the most specific physical examination technique for investigation of intestinal disease and is particularly valuable when evaluating obstructive diseases.

TextSentencer_T34

5065-5309

Sentence

denotes

8 The primary objectives of transrectal palpation are to assess the size, consistency, and position of the segments of the large intestine; to determine the presence of any distention of the small intestine; and to detect intraabdominal masses.

TextSentencer_T35

5310-5485

Sentence

denotes

Evaluation of the wall thickness and texture and the mesenteric structures (blood and lymphatic vessels and lymph nodes) also may aid in diagnosis of large intestinal disease.

TextSentencer_T36

5486-5721

Sentence

denotes

The interpretation of transrectal palpation findings in light of clinical signs and laboratory results is an important diagnostic aid for developing appropriate treatment strategies for intestinal diseases manifested by abdominal pain.

TextSentencer_T37

5722-5881

Sentence

denotes

Enlargement of one or more segments of large intestine detected by transrectal palpation provides evidence of obstruction at or distal to the enlarged segment.

TextSentencer_T38

5882-5967

Sentence

denotes

By systematically evaluating each segment, the site of obstruction may be determined.

TextSentencer_T39

5968-6137

Sentence

denotes

Obstruction of the pelvic flexure, for instance, results in enlargement of the pelvic flexure and ventral colon, but the dorsal and descending colons are of normal size.

TextSentencer_T40

6138-6249

Sentence

denotes

Enlargement of a segment of the large intestine usually is accompanied by abnormal consistency of the contents.

TextSentencer_T41

6250-6360

Sentence

denotes

It is possible to distinguish among gas, fluid, and ingesta and to detect foreign bodies in palpable segments.

TextSentencer_T42

6361-6508

Sentence

denotes

Accumulation of gas and fluid suggests complete and acute obstruction, whereas accumulation of ingesta suggests chronic and incomplete obstruction.

TextSentencer_T43

6509-6555

Sentence

denotes

Accumulation of fluid usually indicates ileus.

TextSentencer_T44

6556-6771

Sentence

denotes

The practitioner must evaluate the consistency of the contents in light of the size of the segment; ingesta in the ventral colon of a dehydrated patient may be firm, but the size of the ventral colon will be normal.

TextSentencer_T45

6772-6875

Sentence

denotes

Conversely, if the ingesta is firm because of a distal obstruction, the ventral colon will be enlarged.

TextSentencer_T46

6876-7075

Sentence

denotes

Displacement of a segment of the large intestine may create an obstruction detectable by enlargement of the segment and accumulation of gas and fluid, even if the site of obstruction is not palpable.

TextSentencer_T47

7076-7278

Sentence

denotes

Torsion of the ascending colon at the sternal and diaphragmatic flexures results in acute accumulation of gas and fluid proximal to the torsion, causing distention of the left dorsal and ventral colons.

TextSentencer_T48

7279-7395

Sentence

denotes

Depending on the degree of torsion, the position of the ventral and dorsal colons may not be significantly abnormal.

TextSentencer_T49

7396-7649

Sentence

denotes

Displacement of a segment of large intestine often results in incomplete obstruction, and the diagnosis is either confirmed on detection of the displaced segment in an abnormal position or suspected when the segment is not palpable in a normal position.

TextSentencer_T50

7650-7833

Sentence

denotes

A determination should be made as to whether the segment that appears to be displaced is in a normal position but of smaller than normal size because of a decreased volume of ingesta.

TextSentencer_T51

7834-7943

Sentence

denotes

The cecum, right dorsal and ventral colons, pelvic flexure, and descending colon are palpable in most horses.

TextSentencer_T52

7944-8078

Sentence

denotes

The nephrosplenic space should be palpated to detect the presence of intestine, usually pelvic flexure, entrapped within the ligament.

TextSentencer_T53

8079-8133

Sentence

denotes

Small intestine is not normally palpable in the horse.

TextSentencer_T54

8134-8256

Sentence

denotes

Distention indicates ileus with gas or fluid retention, usually following a strangulating or nonstrangulating obstruction.

TextSentencer_T55

8257-8398

Sentence

denotes

Strangulating obstructions often are accompanied by severe pain, dehydration, PF changes, and a varying degree of gastric fluid accumulation.

TextSentencer_T56

8399-8466

Sentence

denotes

The small intestine in these cases is turgid and firm on palpation.

TextSentencer_T57

8467-8572

Sentence

denotes

The mesentery and wall thickness should be assessed in the same manner as for large intestinal disorders.

TextSentencer_T58

8573-8706

Sentence

denotes

Careful palpation of the inguinal rings in stallions with small intestinal distention is crucial for determining inguinal herniation.

TextSentencer_T59

8707-8897

Sentence

denotes

Evaluation of the wall thickness and mesenteric vessels can reveal venous congestion (mural edema and enlarged blood and lymphatic vessels) or inflammation (mural edema with normal vessels).

TextSentencer_T60

8898-9007

Sentence

denotes

Disruption of arterial blood flow does not cause venous congestion, but the arterial pulse is not detectable.

TextSentencer_T61

9008-9109

Sentence

denotes

Mesenteric tears may not be palpable, but the entrapped ischemic intestinal segment may be thickened.

TextSentencer_T62

9110-9166

Sentence

denotes

Enlargement of mesenteric lymph nodes also may be noted.

TextSentencer_T63

9167-9325

Sentence

denotes

Abnormalities in the wall or vessels should be interpreted in light of the size, consistency, and position of the segment of intestine and the clinical signs.

TextSentencer_T64

9326-9512

Sentence

denotes

Several conditions involving small intestinal strangulating lesions do not necessarily cause abnormal rectal examination findings until the disease has been present for an extended time.

TextSentencer_T65

9513-9600

Sentence

denotes

These conditions include diaphragmatic hernias and epiploic foramen entrapments (EFEs).

TextSentencer_T66

9601-9712

Sentence

denotes

PF analysis can be normal in these cases as well because the fluid is trapped in the thorax or cranial abdomen.

TextSentencer_T67

9713-9839

Sentence

denotes

Nonstrangulating causes of small intestinal distention can be divided further into intraluminal and extraluminal obstructions.

TextSentencer_T68

9840-10020

Sentence

denotes

Ileal impactions are the most common cause of intraluminal obstruction, and on rare occasions the impaction can be palpated in the upper right quadrant, near the ileocecal opening.

TextSentencer_T69

10021-10248

Sentence

denotes

Intraluminal masses caused by lymphoma, eosinophilic enteritis, foreign bodies, or ascarid impactions often lead to small intestinal distention and are usually indistinguishable from one another on the basis of palpation alone.

TextSentencer_T70

10249-10360

Sentence

denotes

Small intestine in these cases can be moderately to severely distended, depending on the degree of obstruction.

TextSentencer_T71

10361-10441

Sentence

denotes

Extraluminal obstructions include abdominal masses and large colon displacement.

TextSentencer_T72

10442-10525

Sentence

denotes

The rest of the abdomen should be carefully palpated to help rule out these causes.

TextSentencer_T73

10526-10633

Sentence

denotes

Some cases of small intestinal distention result from physiologic ileus rather than mechanical obstruction.

TextSentencer_T74

10634-10748

Sentence

denotes

The bowel is usually mildly to moderately distended and almost always is accompanied by significant gastric fluid.

TextSentencer_T75

10749-10856

Sentence

denotes

The small colon is easily distinguishable by the presence of normal fecal balls and an antimesenteric band.

TextSentencer_T76

10857-11011

Sentence

denotes

In horses with impaction of the small colon, a long, hard, tubelike structure is present in the caudal abdomen, and the band is palpable along the length.

TextSentencer_T77

11012-11156

Sentence

denotes

Fluid stool is often present in the rectum in these horses, as is tenesmus, and the rectal mucosa is often edematous and occasionally roughened.

TextSentencer_T78

11157-11230

Sentence

denotes

Rectal tears can be detected and evaluated with careful rectal palpation.

TextSentencer_T79

11231-11468

Sentence

denotes

Also detectable are mural masses in palpable segments of intestine or mesentery; if a mass causes obstruction, then it is possible to detect the result of the obstruction in proximal segments of intestine even if the mass is unreachable.

TextSentencer_T80

11469-11584

Sentence

denotes

Palpation of the mesenteric vessels may reveal thickening and thrombosis, which can lead to ischemia or infarction.

TextSentencer_T81

11585-11718

Sentence

denotes

Visual inspection of the mucosa of the rectum and descending colon can be performed with the aid of a speculum or flexible endoscope.

TextSentencer_T82

11719-11908

Sentence

denotes

A flexible endoscope is also useful for evaluation of rectal tears or perforations, mural masses, strictures, or mucosal inflammation and obtaining biopsy specimens of the mucosa or masses.

TextSentencer_T83

11909-12066

Sentence

denotes

The obvious limitations are the amount of fecal material, which can interfere with the examination, and the distance of the lesion of interest from the anus.

TextSentencer_T84

12067-12180

Sentence

denotes

These techniques offer little advantage over palpation in many cases, unless the patient is too small to palpate.

TextSentencer_T85

12181-12306

Sentence

denotes

Examination of the oral cavity in horses with dysphagia or weight loss is an important extension of the physical examination.

TextSentencer_T86

12307-12548

Sentence

denotes

The horse should be adequately sedated and a full-mouth speculum used to allow palpation and visual examination of all parts of the oral cavity and detection of abnormal dentition, foreign bodies, fractures, abscesses, or mucosal ulceration.

TextSentencer_T87

12549-12667

Sentence

denotes

The presence of fluid accumulation in the stomach indicates a functional or mechanical obstruction of gastric outflow.

TextSentencer_T88

12668-12827

Sentence

denotes

Fluid accumulation in the stomach is assessed by siphoning of the gastric contents with a nasogastric tube and examining the fluid for amount, color, and odor.

TextSentencer_T89

12828-12879

Sentence

denotes

Normal fluid is green and may contain foamy saliva.

TextSentencer_T90

12880-12947

Sentence

denotes

The net volume obtained by gastric lavage is usually less than 4 L.

TextSentencer_T91

12948-13027

Sentence

denotes

Large volumes (≥8-10 L) of foul-smelling fluid may indicate proximal enteritis.

TextSentencer_T92

13028-13245

Sentence

denotes

Horses with strangulating obstructions or luminal obstructions often accumulate moderate amounts of gastric fluid, but the amount is generally less than in horses with proximal enteritis or postoperative ileus (POI) .

TextSentencer_T93

13246-13359

Sentence

denotes

Distinction between these conditions should not be made based on the volume and character of gastric fluid alone.

TextSentencer_T94

13360-13482

Sentence

denotes

Hemorrhage in the gastric fluid usually indicates devitalized small intestine, stomach wall, or severe gastric ulceration.

TextSentencer_T95

13483-13573

Sentence

denotes

Endoscopy or contrast radiography may aid in the diagnosis of gastric outflow obstruction.

TextSentencer_T96

13574-13745

Sentence

denotes

Hematologic alterations associated with diseases of the gastrointestinal tract are often nonspecific, reflecting systemic response to inflammation, endotoxemia, or sepsis.

TextSentencer_T97

13746-13922

Sentence

denotes

Neutrophilic leukocytosis and normochromic, normocytic anemia with or without hyperfibrinogenemia commonly are associated with chronic inflammatory conditions of the intestine.

TextSentencer_T98

13923-14184

Sentence

denotes

Anemia from chronic blood loss occurs infrequently in adult horses because of the large iron stores and high concentrations of iron in their diet; anemia usually follows chronic inflammation, as do alterations in the leukon and plasma fibrinogen concentrations.

TextSentencer_T99

14185-14348

Sentence

denotes

Plasma protein concentrations vary depending on gastrointestinal losses of albumin and globulin and elevation of globulin concentration from antigenic stimulation.

TextSentencer_T100

14349-14432

Sentence

denotes

Protein-losing enteropathy may manifest as a hypoalbuminemia or panhypoproteinemia.

TextSentencer_T101

14433-14622

Sentence

denotes

Significant alterations of the hemogram do not accompany acute disease of the intestine unless severe dehydration, endotoxemia, or systemic inflammatory response syndrome (SIRS) is present.

TextSentencer_T102

14623-14797

Sentence

denotes

During the early stages of SIRS, elevations in circulating concentrations of inflammatory mediators, epinephrine, and cortisol produce characteristic changes in the hemogram.

TextSentencer_T103

14798-15018

Sentence

denotes

Leukopenia, with neutropenia and a left shift, toxic changes in the neutrophil cytoplasm, and lymphopenia commonly occur early in the disease, but neutrophilic leukocytosis is more common during the later stages of SIRS.

TextSentencer_T104

15019-15077

Sentence

denotes

Hemoconcentration and hyperfibrinogenemia are also common.

TextSentencer_T105

15078-15146

Sentence

denotes

Thrombocytopenia and other coagulopathies are also features of SIRS.

TextSentencer_T106

15147-15281

Sentence

denotes

Electrolyte imbalances and increased blood lactate are common biochemical abnormalities in horses with acute gastrointestinal disease.

TextSentencer_T107

15282-15348

Sentence

denotes

Decreased serum calcium concentrations are common and nonspecific.

TextSentencer_T108

15349-15511

Sentence

denotes

9 Mucosal inflammation can disrupt electrolyte fluxes; diarrhea or gastric reflux greatly exacerbates sodium, potassium, calcium, magnesium, and bicarbonate loss.

TextSentencer_T109

15512-15694

Sentence

denotes

Large colon ischemia causes increased lactate and potassium concentrations and metabolic acidosis in the colonic vasculature and inflammation in the colonic and systemic vasculature.

TextSentencer_T110

15695-15915

Sentence

denotes

10 Reduced perfusion of peripheral tissues from hypotensive shock and intestinal ischemia can cause increased blood lactate; intestinal obstruction during ischemia may also result in absorption of lactate from the lumen.

TextSentencer_T111

15916-16102

Sentence

denotes

Increased blood lactate can result from a variety of causes, including hypovolemia, and blood lactate alone should not be used for diagnostic or prognostic purposes in horses with colic.

TextSentencer_T112

16103-16268

Sentence

denotes

11 Increases in blood lactate over time are greater in nonsurvivors, relative to survivors, in adult equine emergencies (many of which had gastrointestinal disease).

TextSentencer_T113

16269-16479

Sentence

denotes

12 Portable lactate analyzers have demonstrated variable intraanalyzer reliability in equine blood so that caution should be exercised in interpretation and comparison of results reported from various searches.

TextSentencer_T114

16480-16648

Sentence

denotes

13, 14 Metabolic acidosis may accompany lactic acidemia, but an inconsistent association exists between the two, especially when mixed acid-base imbalances are present.

TextSentencer_T115

16649-16814

Sentence

denotes

15, 16 Increases in hepatic enzymes, specifically γ-glutamyl transferase (GGT), may occur with large colon displacements, duodenal strictures, or proximal enteritis.

TextSentencer_T116

16815-16896

Sentence

denotes

Increased GTT is more suggestive of right, rather than left, dorsal displacement.

TextSentencer_T117

16897-17070

Sentence

denotes

17 Relative polycythemia from hemoconcentration or splenic contraction and changes in red blood cell deformability from hypoxia or hypocalcemia may increase blood viscosity.

TextSentencer_T118

17071-17140

Sentence

denotes

Blood viscosity increases in patients with acute obstructive disease.

TextSentencer_T119

17141-17234

Sentence

denotes

Hyperviscosity reduces perfusion of capillary beds, exacerbating ischemia and tissue hypoxia.

TextSentencer_T120

17235-17237

Sentence

denotes

18

TextSentencer_T121

17239-17451

Sentence

denotes

Abdominocentesis and analysis of PF are performed on many patients with gastrointestinal disease and are especially helpful in differentiating strangulating from nonstrangulating disorders of the small intestine.

TextSentencer_T122

17452-17567

Sentence

denotes

Important quantifications include white and red blood cell counts and protein, lactate, and glucose concentrations.

TextSentencer_T123

17568-17671

Sentence

denotes

Cytologic evaluation can reveal cellular abnormalities, especially in horses with intestinal neoplasia.

TextSentencer_T124

17672-17861

Sentence

denotes

Results of PF analysis may help establish a specific diagnosis and, more important, may reflect inflammatory, vascular, or ischemic injury to the intestine, requiring surgical intervention.

TextSentencer_T125

17862-17949

Sentence

denotes

Alteration of PF reflects a sequence of events during acute intestinal vascular injury.

TextSentencer_T126

17950-18071

Sentence

denotes

The PF protein concentration increases first, followed by increases in red blood cell count and fibrinogen concentration.

TextSentencer_T127

18072-18352

Sentence

denotes

A transudative process resulting from vascular congestion and increased endothelial permeability allows small macromolecules (albumin) to escape into the PF, followed by larger macromolecules (globulin and fibrinogen), and finally diapedesis of cells (red then white blood cells).

TextSentencer_T128

18353-18557

Sentence

denotes

Severe ischemic intestinal inflammation or visceral peritonitis result in an exudative process, with large quantities of protein and white blood cells (WBCs), primarily neutrophils, to escape into the PF.

TextSentencer_T129

18558-18690

Sentence

denotes

19, 20 Eventually, bacteria begin to translocate across the intestinal wall and appear in the PF as the mucosal barrier breaks down.

TextSentencer_T130

18691-18870

Sentence

denotes

If perforation occurs, bacteria and particles of ingesta appear in the PF, and the neutrophils become degenerate (i.e., pyknotic), with karyorrhexis, karyolysis, and smudge cells.

TextSentencer_T131

18871-19082

Sentence

denotes

Increased PF protein concentration is an indicator of early inflammation, whereas increased red blood cell counts in the presence of normal WBC counts suggest vascular damage without significant tissue ischemia.

TextSentencer_T132

19083-19327

Sentence

denotes

20 Of note, the anticoagulant potassium ethylenediamine tetraacetic acid, but not lithium heparin, can cause an increase in total protein as measured by a refractometer, relative to the value obtained from the same sample without anticoagulant.

TextSentencer_T133

19328-19422

Sentence

denotes

21 The gross color of the PF can be helpful in detecting injury and necrosis of the intestine.

TextSentencer_T134

19423-19575

Sentence

denotes

A serosanguineous appearance indicates vascular injury, whereas orange or brown-red indicates necrosis with the release of pigments such as hemosiderin.

TextSentencer_T135

19576-19737

Sentence

denotes

Tissue hypoxia and ischemia cause rapid increases in PF lactate dehydrogenase, creatine kinase, and alkaline phosphatase (AP) activity and lactate concentration.

TextSentencer_T136

19738-19811

Sentence

denotes

22, 23 Phosphate concentration increases when cellular disruption occurs.

TextSentencer_T137

19812-19923

Sentence

denotes

24 PF enzyme activities, phosphate, and lactate concentration increase faster and higher than serum activities.

TextSentencer_T138

19924-20068

Sentence

denotes

16, [22] [23] [24] PF pH and glucose concentration tend to decrease during intestinal ischemia but not as dramatically as in septic peritonitis.

TextSentencer_T139

20069-20411

Sentence

denotes

25 Lactate concentrations in PF are commonly evaluated and are better predictors of strangulating small intestinal obstruction than blood lactate, 22 although increases in both lactate (the term by which l-lactate is commonly referred) and d-lactate are likely more accurate for predicting strangulating lesions as opposed to ruling them out.

TextSentencer_T140

20412-20666

Sentence

denotes

26 Serial sampling of blood and PF lactate may be useful in cases in which clinical and diagnostic findings at initial presentation were not conclusive for either strangulating or nonstrangulating lesions and/or a horse's clinical condition deteriorates.

TextSentencer_T141

20667-20776

Sentence

denotes

27 Cytologic examination of PF may reflect chronic inflammatory intestinal conditions or neoplastic diseases.

TextSentencer_T142

20777-20973

Sentence

denotes

28 Although culturing PF is recommended to distinguish bacterial infections from noninfectious inflammation unless bacteria are visible on cytologic examination, culturing PF is often unrewarding.

TextSentencer_T143

20974-21082

Sentence

denotes

Decreases in PF glucose concentrations (<30 mg/dL) and pH (<7.3) are early indicators of septic peritonitis.

TextSentencer_T144

21083-21175

Sentence

denotes

Glucose concentration and pH in PF should approximately equal blood values in normal horses.

TextSentencer_T145

21176-21437

Sentence

denotes

Practically, the gross appearance and the total solids of PF in conjunction with a comparison of PF to serum lactate are most useful when distinguishing between strangulating and nonstrangulating small intestinal disorders in a horse presenting for acute colic.

TextSentencer_T146

21438-21610

Sentence

denotes

Potential risks associated with performing an abdominocentesis should be considered, and this procedure is performed only if results are likely to alter the treatment plan.

TextSentencer_T147

21611-21804

Sentence

denotes

For example, if other examination findings indicate that an exploratory laparotomy is clearly indicated or not in the case of a horse with acute colic, abdominocentesis is likely not indicated.

TextSentencer_T148

21805-21916

Sentence

denotes

Gross examination of the feces can provide information about digestion and transit time in the large intestine.

TextSentencer_T149

21917-22020

Sentence

denotes

Large fiber particles in the feces represent poor mastication or poor digestion in the large intestine.

TextSentencer_T150

22021-22175

Sentence

denotes

Small, mucus-covered, hard fecal balls indicate prolonged transit through the descending colon, whereas increased fluidity implies decreased transit time.

TextSentencer_T151

22176-22237

Sentence

denotes

Feces containing sand or gravel are not necessarily abnormal.

TextSentencer_T152

22238-22331

Sentence

denotes

However, a significant amount of sand implies that large quantities are present in the colon.

TextSentencer_T153

22332-22421

Sentence

denotes

Alternatively, absence of sand in feces does not confirm an absence of sand in the colon.

TextSentencer_T154

22422-22560

Sentence

denotes

Frank blood indicates substantial bleeding into the distal colon (right dorsal colon, small colon, or both) resulting from mucosal damage.

TextSentencer_T155

22561-22636

Sentence

denotes

Laboratory analysis of the feces can be performed for horses with diarrhea.

TextSentencer_T156

22637-22744

Sentence

denotes

Fecal cytologic examination and tests for occult blood detect mucosal inflammation, erosion, or ulceration.

TextSentencer_T157

22745-22878

Sentence

denotes

Increased fecal leukocyte counts have been documented in horses with diarrhea and salmonellosis, but specificity of this test is low.

TextSentencer_T158

22879-23034

Sentence

denotes

29 Fecal occult blood tests detect blood in the feces, presumably from erosion or ulceration of the mucosa, but do not distinguish the source of the blood.

TextSentencer_T159

23035-23272

Sentence

denotes

Large volumes of blood (1-2 L) given by nasogastric tube were required to produce a positive test for occult blood in the feces, but the amount of blood originating from the large intestine required to produce a positive test is unknown.

TextSentencer_T160

23273-23482

Sentence

denotes

Despite initial reports to the contrary, 30 there does not appear to be any correlation between endoscopic evidence of glandular or nonglandular gastric ulceration and detection of fecal albumin or hemoglobin.

TextSentencer_T161

23483-23569

Sentence

denotes

31 Bacteriologic examination of the fecal flora has been used in horses with diarrhea.

TextSentencer_T162

23570-23853

Sentence

denotes

Quantitation of clostridial species may be beneficial in diagnosing clostridial infection of the large intestine, although tests to detect clostridial toxins in intestinal contents or feces are important for determining whether clostridia cultured from the feces are causing disease.

TextSentencer_T163

23854-23964

Sentence

denotes

The most common bacterial pathogens isolated from the feces of horses are Salmonella spp. and Clostridium spp.

TextSentencer_T164

23965-24126

Sentence

denotes

The number of Salmonella organisms isolated from the feces of horses with clinical salmonellosis is usually higher than from horses with asymptomatic infections.

TextSentencer_T165

24127-24330

Sentence

denotes

However, the volume of feces in many cases of acute diarrhea is high, and the concentration of Salmonella organisms may be lower than would be expected, accounting for many false-negative fecal cultures.

TextSentencer_T166

24331-24421

Sentence

denotes

The sensitivity of fecal cultures for detecting Salmonella infection may be as low as 20%.

TextSentencer_T167

24422-24525

Sentence

denotes

Culture of five consecutive daily fecal samples is recommended to increase the sensitivity of the test.

TextSentencer_T168

24526-25075

Sentence

denotes

Real-time polymerase chain reaction (PCR) assays used on fecal samples can detect DNA from Salmonella spp. and have performed well in recent validation studies; accuracy of pointof-care tests remains elusive. [32] [33] [34] [35] Currently, PCR assays can be used for detection of viral (rotavirus and coronavirus), bacterial (Cryptosporidium spp., Salmonella spp., Neorickettsia risticii, Lawsonia intracellularis), or bacterial toxin (Clostridium difficile toxins A and B, Clostridium perfringens enterotoxin A) DNA in feces or blood (N. risticii).

TextSentencer_T169

25076-25207

Sentence

denotes

Qualitative fecal examination can detect nematode and cestode ova, protozoan oocysts, parasitic larvae, and protozoan trophozoites.

TextSentencer_T170

25208-25338

Sentence

denotes

A direct smear of fecal material can rapidly detect parasite larvae and trophozoites and motility of ciliates and parasite larvae.

TextSentencer_T171

25339-25450

Sentence

denotes

Fecal flotation with zinc sulfate or sucrose solutions is often used to concentrate less dense ova and oocysts.

TextSentencer_T172

25451-25539

Sentence

denotes

Zinc sulfate produces less distortion of trophozoites and larvae than sucrose solutions.

TextSentencer_T173

25540-25638

Sentence

denotes

Fecal sedimentation is particularly appropriate for ciliates, Giardia organisms, and trichomonads.

TextSentencer_T174

25639-25821

Sentence

denotes

Quantitative techniques such as the Cornell-McMaster method allow estimation of the number of eggs per gram of feces and are most appropriate in monitoring parasite control programs.

TextSentencer_T175

25822-25888

Sentence

denotes

Survey radiography of the normal esophagus is usually unrewarding.

TextSentencer_T176

25889-26072

Sentence

denotes

It is possible to detect foreign bodies or soft tissue masses and, in cases of esophageal rupture, free air and ingesta in the tissues surrounding the esophagus and pneumomediastinum.

TextSentencer_T177

26073-26198

Sentence

denotes

Thoracic radiographs may be necessary to detect megaesophagus or cranial mediastinal masses causing extraluminal obstruction.

TextSentencer_T178

26199-26444

Sentence

denotes

Barium swallows or double-contrast esophagrams may be used after resolution of an esophageal obstruction to determine whether a stricture, diverticulum, or other underlying disorder is present, although endoscopy can provide similar information.

TextSentencer_T179

26445-26628

Sentence

denotes

Barium sulfate is the usual contrast medium and can be administered orally by way of a dose syringe or nasogastric tube (50-100 mL of a 40% barium sulfate suspension or barium paste).

TextSentencer_T180

26629-26729

Sentence

denotes

Oral administration is preferred for evaluation of swallowing and lesions in the proximal esophagus.

TextSentencer_T181

26730-26918

Sentence

denotes

Administration of contrast using a nasogastric tube (preferably cuffed) allows for delivery of larger volumes of barium (up to 500 mL) but should be performed without sedation if possible.

TextSentencer_T182

26919-27027

Sentence

denotes

Administration of contrast material can be followed with air insufflation to create a doublecontrast effect.

TextSentencer_T183

27028-27287

Sentence

denotes

If rupture of the esophagus is suspected or if the contrast material is likely to be aspirated, barium should be avoided, and iodinated organic compounds in an aqueous solution should be used as contrast material to decrease the potential for adverse effects.

TextSentencer_T184

27288-27399

Sentence

denotes

When interpreting esophageal radiographs, the veterinarian should take particular care if the horse is sedated.

TextSentencer_T185

27400-27534

Sentence

denotes

Acepromazine or detomidine administration causes esophageal dilation in normal horses, especially after passage of a nasogastric tube.

TextSentencer_T186

27535-27846

Sentence

denotes

36 Radiography of the adult equine abdomen is an effective technique in detecting radiodense material in the large intestine, such as enteroliths, sand, and metallic objects. [37] [38] [39] [40] One survey demonstrated that radiography has 76.9% sensitivity and 94.4% specificity for diagnosing enterolithiasis.

TextSentencer_T187

27847-28077

Sentence

denotes

40 Recently, an objective scoring system demonstrated greater efficacy and less interobserver variability than a subjective assessment of radiographic sand accumulation in horses with or without a clinical diagnosis of sand colic.

TextSentencer_T188

28078-28325

Sentence

denotes

38 The large size and density of the adult abdomen preclude evaluation of soft tissue structures because the detail and contrast of the radiographs are usually poor, and ultrasonography is a much more useful imaging modality in the equine abdomen.

TextSentencer_T189

28326-28851

Sentence

denotes

Administration of contrast (barium sulfate 30% at 5 mL/kg) through a nasogastric tube or retrograde (20 mL/kg) through a 24-Fr Foley catheter inserted into the rectum may be helpful for the diagnosis of gastric outflow obstruction or disorders of the rectum, small colon, or transverse colon, respectively, in foals. [41] [42] [43] [44] Y ULTRASONOGRAPHY Transcutaneous ultrasonographic evaluation of the abdomen is quick and noninvasive and can add valuable information in cases of acute or chronic gastrointestinal disease.

TextSentencer_T190

28852-28966

Sentence

denotes

Ultrasound has become a virtually indispensable tool for horses with acute or chronic gastrointestinal conditions.

TextSentencer_T191

28967-29005

Sentence

denotes

This section provides a brief summary.

TextSentencer_T192

29006-29145

Sentence

denotes

Examination of the adult horse requires a 2.5-to 5.0-MHz transducer, depending on size of the horse; a curvilinear transducer is preferred.

TextSentencer_T193

29146-29358

Sentence

denotes

A functional examination is often performed with isopropyl alcohol saturation alone, although clipping, with or without coupling gel, can be used to enhance evaluation, especially in large or overweight patients.

TextSentencer_T194

29359-29588

Sentence

denotes

A protocol for fast localized abdominal sonography (FLASH) has been described and demonstrates good predictive value of the requirement for surgical intervention in the acute abdomen, even with relatively inexperienced examiners.

TextSentencer_T195

29589-29841

Sentence

denotes

45 This examination evaluates seven locations (ventral abdomen, gastric window, splenorenal window, left middle third of the abdomen, duodenal window, right middle third of the abdomen, and thoracic window) and can be performed in less than 15 minutes.

TextSentencer_T196

29842-30030

Sentence

denotes

A complete examination requires a methodical approach to the evaluation of the entire abdomen; details of the examination can be variable based on equipment and experience of the examiner.

TextSentencer_T197

30031-30165

Sentence

denotes

A complete review of abdominal ultrasound is beyond the scope of this chapter; a thorough, detailed examination is reviewed elsewhere.

TextSentencer_T198

30166-30354

Sentence

denotes

46 In general terms, a quick examination of the acute abdomen should include estimation of gastric size and assessment of small intestinal diameter, wall thickness, motility, and location.

TextSentencer_T199

30355-30445

Sentence

denotes

Specific abnormalities, such as ascarid impaction or intussusception, may also be visible.

TextSentencer_T200

30446-30661

Sentence

denotes

Evaluation of the large colon and cecum should include estimation of mural thickening or increased fluidity of contents, and whether or not the colon obscures viewing of the left kidney in the left paralumbar fossa.

TextSentencer_T201

30662-30875

Sentence

denotes

It is important to remember that other causes of colonic distention can have the same result; thus, it is always important to combine physical, rectal, and ultrasonographic examination findings for any given case.

TextSentencer_T202

30876-31073

Sentence

denotes

Sand impactions may appear as hyperechoic bands on the ventral abdominal wall, 47 but according to the author and others, 46 ultrasound does not allow for consistent diagnosis of sand accumulation.

TextSentencer_T203

31074-31219

Sentence

denotes

Evaluation of the abdomen always should include assessment of the peritoneal space for any evidence of an increased amount or echogenicity of PF.

TextSentencer_T204

31220-31310

Sentence

denotes

Ultrasonography also can be useful in determining the ideal location for abdominocentesis.

TextSentencer_T205

31311-31579

Sentence

denotes

Nuclear scintigraphy has several proposed uses for evaluation of the gastrointestinal tract, although most have been replaced with cross-sectional imaging (dental disease 48, 49 ), ultrasonography (right dorsal colitis 50 ), or other modalities (gastric emptying 51 ).

TextSentencer_T206

31580-31859

Sentence

denotes

Computed tomography (CT) and, less commonly, magnetic resonance imaging are extremely useful for evaluating dental disease as well as tumors and masses of the head, larynx, pharynx, and proximal esophagus in adult horses [52] [53] [54] [55] and some abdominal disorders in foals.

TextSentencer_T207

31860-31965

Sentence

denotes

56 Availability, gantry size, and table weight limits provide the biggest limitations for widespread use.

TextSentencer_T208

31966-32106

Sentence

denotes

Endoscopic examination of the gastrointestinal tract begins with evaluation of the pharynx for signs of collapse, dysfunction, or dysphagia.

TextSentencer_T209

32107-32233

Sentence

denotes

The oral cavity should only be examined endoscopically with the use of heavy sedation or anesthesia and a full-mouth speculum.

TextSentencer_T210

32234-32355

Sentence

denotes

Indications include examination of the teeth, palate, and tongue for completeness, ulceration, masses, or foreign bodies.

TextSentencer_T211

32356-32504

Sentence

denotes

The most common gastrointestinal indication is evaluation of the stomach, proximal esophagus, and duodenum, typically with a 3-m flexible endoscope.

TextSentencer_T212

32505-32587

Sentence

denotes

The esophagus should be examined aborad to orad because of its collapsible nature.

TextSentencer_T213

32588-32644

Sentence

denotes

The esophageal mucosa is normally smooth and light pink.

TextSentencer_T214

32645-32777

Sentence

denotes

Erosion or ulceration can occur secondary to obstruction, reflux esophagitis, or an indwelling nasogastric tube, among other causes.

TextSentencer_T215

32778-32901

Sentence

denotes

Erosions may be punctate, linear, or circumferential, and their extent (depth, length, etc.) should be evaluated carefully.

TextSentencer_T216

32902-33033

Sentence

denotes

Distinguishing normal peristaltic contractions from areas of stricture requires observation of the area and its motility over time.

TextSentencer_T217

33034-33142

Sentence

denotes

Diverticula also may be noted as outpouchings of the mucosa, sometimes associated with a stricture distally.

TextSentencer_T218

33143-33205

Sentence

denotes

Megaesophagus, although rare, appears as generalized dilation.

TextSentencer_T219

33206-33402

Sentence

denotes

Reevaluation after resolution of an obstruction is especially important for detecting the presence of complications (ulceration and rupture) or initiating causes (strictures, diverticula, masses).

TextSentencer_T220

33403-33462

Sentence

denotes

Gastroscopy is best performed after a minimum 12-hour fast.

TextSentencer_T221

33463-33632

Sentence

denotes

Complete examination of the stomach, including the antrum and pylorus, and preferably proximal duodenum, is critical to avoid missing lesions in the more aborad regions.

TextSentencer_T222

33633-33691

Sentence

denotes

The squamous mucosa should resemble the esophageal mucosa.

TextSentencer_T223

33692-33773

Sentence

denotes

The glandular mucosa should be glistening red and may have a reticulated pattern.

TextSentencer_T224

33774-33856

Sentence

denotes

The veterinarian should carefully examine it for evidence of ulceration or masses.

TextSentencer_T225

33857-34068

Sentence

denotes

Trans endoscopic biopsy material can be easily obtained from esophageal, pharyngeal, or gastric masses, and because the biopsy size will be small, several samples should be taken for histopathologic examination.

TextSentencer_T226

34069-34209

Sentence

denotes

A complete description of gastroscopy and evaluation of gastric and gastroduodenal ulceration are available in Gastroduodenal Ulcer Disease.

TextSentencer_T227

34210-34369

Sentence

denotes

Oral Glucose Tolerance Test d-Glucose or d-xylose absorption tests are useful in determining malabsorption of carbohydrates from the small intestine in horses.

TextSentencer_T228

34370-34448

Sentence

denotes

For either test, the horse should be fasted for 14 to 18 hours before testing.

TextSentencer_T229

34449-34553

Sentence

denotes

Prolonged fasting (≥24 hours) results in a delayed and slightly lower peak plasma glucose concentration.

TextSentencer_T230

34554-34644

Sentence

denotes

57 A dosage of 1 g/kg of d-glucose is administered as a 20% solution via nasogastric tube.

TextSentencer_T231

34645-34719

Sentence

denotes

Xylazine sedation does not appear to significantly alter d-xylose results.

TextSentencer_T232

34720-34853

Sentence

denotes

58 Blood glucose or xylose concentrations are then measured 0, 30, 60, 90, 120, 150, 180, 210 , and 240 minutes after administration.

TextSentencer_T233

34854-34945

Sentence

denotes

Additional samples can be taken up to 6 hours after dosing if the results are questionable.

TextSentencer_T234

34946-35044

Sentence

denotes

Sodium fluoride and heparin are the preferred anticoagulants for glucose and xylose, respectively.

TextSentencer_T235

35045-35245

Sentence

denotes

A normal d-glucose absorption test, also known as an oral glucose tolerance test (OGTT), should peak between 90 and 120 minutes at a glucose concentration >85% above the resting glucose concentration.

TextSentencer_T236

35246-35439

Sentence

denotes

59 Complete malabsorption is defined as a peak less than 15% above the resting concentration, and partial malabsorption is defined as a peak between 15% and 85% above the resting concentration.

TextSentencer_T237

35440-35614

Sentence

denotes

Gastric emptying, gastrointestinal transit time, length of fasting, glucose and insulin metabolism, age, diet, and endocrine function can influence glucose absorption curves.

TextSentencer_T238

35615-35853

Sentence

denotes

59, 60 Higher glucose peaks are recorded from healthy animals eating grass or hay than from those eating concentrates 60 and from horses fed a pasture (clover and kikuyu) versus stable (oat hay, complete feed, and alfalfa/oat chaff) diet.

TextSentencer_T239

35854-36029

Sentence

denotes

61 Results from the OGTT can also be affected by the content of nonstructural carbohydrate and fat in the diet 62 and other disorders, such as polysaccharide storage myopathy.

TextSentencer_T240

36030-36032

Sentence

denotes

63

TextSentencer_T241

36034-36193

Sentence

denotes

The xylose absorption test is performed as per the OGTT, except 0.5 g d-xylose per kilogram body weight is administered as a 10% solution via nasogastric tube.

TextSentencer_T242

36194-36270

Sentence

denotes

The pretest period of fasting and timing of sample collection are identical.

TextSentencer_T243

36271-36423

Sentence

denotes

The laboratory to which samples will be sent should be contacted before collection to ensure that heparinized plasma is acceptable for their laboratory.

TextSentencer_T244

36424-36573

Sentence

denotes

Plasma d-xylose should peak between 20 and 25 mg/dL between 60 and 90 minutes following administration, with occasional peaks as late as 120 minutes.

TextSentencer_T245

36574-36812

Sentence

denotes

64 ,65 d-Xylose absorption testing is not confounded by hormonal effects or mucosal metabolism as is glucose, but it is altered by diet, length of fasting (which could also be influenced by recent appetite or degree of cachexia), and age.

TextSentencer_T246

36813-37010

Sentence

denotes

Horses fed a high-energy (oat chaff, oats, and corn) diet had a lower mean peak plasma d-xylose concentration (14.1 mg/ dL versus 24.9 mg/dL) than those consuming a low-energy (alfalfa chaff) diet.

TextSentencer_T247

37011-37148

Sentence

denotes

61 Healthy mares fasted for up to 96 hours had flatter curves and a slower decrease in plasma xylose than when fasted for 12 to 36 hours.

TextSentencer_T248

37149-37393

Sentence

denotes

64 Kinetic analysis indicates that prolonged food deprivation does not alter renal or nonrenal excretion of d-xylose; thus, the effect of fasting on the curve is likely related to either intestinal transit, small intestinal absorption, or both.

TextSentencer_T249

37394-37600

Sentence

denotes

66, 67 Ponies may have lower peak d-xylose concentrations than horses, although the range is wide, and diagnostic discriminatory cutoff points for peak plasma xylose concentrations have not been determined.

TextSentencer_T250

37601-37768

Sentence

denotes

Foals normally have a higher mean peak xylose concentration at 1 and 2 months of age, but mean peak falls to a level similar to that seen in adults by 3 months of age.

TextSentencer_T251

37769-37894

Sentence

denotes

68 Gastric emptying rate, intestinal motility, intraluminal bacterial overgrowth, and renal clearance can affect curve shape.

TextSentencer_T252

37895-37897

Sentence

denotes

69

TextSentencer_T253

37899-38033

Sentence

denotes

Milk intolerance is well documented in children and can result from primary or secondary lactase (neutral β-galactosidase) deficiency.

TextSentencer_T254

38034-38218

Sentence

denotes

Secondary lactase deficiency can occur when a small intestinal disorder, typically rotavirus, damages the epithelial cells, resulting in decreased brush border disaccharidase activity.

TextSentencer_T255

38219-38304

Sentence

denotes

Such an association has been reported secondary to clostridial enteritis in the foal.

TextSentencer_T256

38305-38522

Sentence

denotes

40 In horses, lactase activity peaks at birth and declines slowly, such that activity is approximately 50% at 2 years of age and rapidly decelerates after 3 years of age, and it is barely detectable by 4 years of age.

TextSentencer_T257

38523-38697

Sentence

denotes

41 The oral lactose tolerance test is performed in foals after a 4-hour fast, with a standard dose of 1 g/kg lactose monohydrate given via nasogastric tube as a 20% solution.

TextSentencer_T258

38698-38732

Sentence

denotes

Blood sampling is as per the OGTT.

TextSentencer_T259

38733-38935

Sentence

denotes

Plasma glucose typically peaks 60 minutes following lactose administration, with a range from 30 to 90 minutes, with a mean increase of 77 mg/dL, with a 35-mg/dL increase covering 2 standard deviations.

TextSentencer_T260

38936-39050

Sentence

denotes

42 Of note, older foals (12 weeks) had a more significant increase in plasma glucose relative to 1-week-old foals.

TextSentencer_T261

39051-39232

Sentence

denotes

Assessment of gastric emptying may be useful in cases of gastric and esophageal ulceration or suspected gastric outflow obstruction, although accurate assessment can be challenging.

TextSentencer_T262

39233-39275

Sentence

denotes

Contrast radiography can be used in foals.

TextSentencer_T263

39276-39362

Sentence

denotes

In the normal foal, a significant amount of liquid barium should empty within 2 hours.

TextSentencer_T264

39363-39561

Sentence

denotes

41 Nuclear scintigraphy can be used for measurement of liquid 51 or solid phase emptying 70 by use of orally administered 99m Tc pentetate (10 mCi) or a 99m Tc-labeled pelleted ration, respectively.

TextSentencer_T265

39562-39725

Sentence

denotes

Alternatively, absorption testing of glucose or xylose (discussed previously) or acetaminophen can be used as an indirect determination of liquid gastric emptying.

TextSentencer_T266

39726-39923

Sentence

denotes

Acetaminophen absorption is performed by administering 20 mg/kg of acetaminophen orally, sampling blood, then calculating the time to reach maximum serum concentrations and the absorption constant.

TextSentencer_T267

39924-40010

Sentence

denotes

71, 72 In humans the proximal small intestine absorbs almost all of the acetaminophen.

TextSentencer_T268

40011-40115

Sentence

denotes

73 The median time to reach peak plasma levels using acetaminophen absorption in horses is 47.7 minutes.

TextSentencer_T269

40116-40229

Sentence

denotes

72 The 13 C-octane acid breath test offers an easy, noninvasive method of determining gastric emptying of solids.

TextSentencer_T270

40230-40362

Sentence

denotes

70, 74 This test is performed by feeding a standard 13 C-labeled test meal and then collecting breath samples using a modified mask.

TextSentencer_T271

40363-40471

Sentence

denotes

The breath is then analyzed for the ratio of the novel isotope, 13:CO 2 , to the normally produced 12:CO 2 .

TextSentencer_T272

40472-40742

Sentence

denotes

It is often necessary to perform a histopathologic examination of tissues from the intestine to diagnose chronic inflammatory, infiltrative, or neoplastic conditions, and such an examination can be useful in evaluating the extent of injury after obstruction or ischemia.

TextSentencer_T273

40743-40811

Sentence

denotes

Rectal mucosal biopsies are easy to collect, with few complications.

TextSentencer_T274

40812-40974

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denotes

Fullthickness biopsy often provides more thorough analysis and can be directed based on serosal appearance via a flank, ventral midline, or laparoscopic approach.

TextSentencer_T275

40975-41124

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denotes

When taking gastric or duodenal biopsies endoscopically for the putative diagnosis of inflammatory bowel disorders, multiple samples are recommended.

TextSentencer_T276

41125-41276

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The likelihood of establishing an accurate diagnosis varies with tissue quality, number of samples, skill of the endoscopist, and submission technique.

TextSentencer_T277

41277-41382

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75 Laparoscopy Laparoscopic evaluation of the equine abdomen requires specialized equipment and training.

TextSentencer_T278

41383-41459

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The laparoscopic procedure can be done with the horse standing or recumbent.

TextSentencer_T279

41460-41607

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denotes

Advantages of this technique over a flank or ventral midline celiotomy include smaller incisions, shorter healing time, and shorter procedure time.

TextSentencer_T280

41608-41759

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denotes

Disadvantages include equipment and personnel needs, limited therapeutic potential, and limited visual field, especially relative to midline celiotomy.

TextSentencer_T281

41760-42083

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denotes

Potential gastrointestinal applications of abdominal laparoscopy include the correction of rectal tears; percutaneous abscess drainage, assessment of adhesions, displacements, and integrity of the serosa of various bowel segments; biopsy of abdominal masses; and closure of the nephrosplenic space. [76] [77] [78] [79] [80]

TextSentencer_T282

42085-42268

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The inflammatory response of the gastrointestinal tract is a mechanism ultimately aimed at eliminating pathogens, initiating tissue repair, and restoring the gastrointestinal barrier.

TextSentencer_T283

42269-42554

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denotes

Blood flow is altered, endothelial permeability increases, cells are rapidly recruited into the tissue, plasma protein cascades are activated, and myriad soluble products are released that coordinate the response, trigger innate and adaptive immunity, and mobilize reparative elements.

TextSentencer_T284

42555-42822

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denotes

Although the cellular and vascular response and the secreted mediators of inflammation are important for killing pathogens and limiting invasion of injured tissues by commensal organisms, they can be quite damaging to host cells and proteins if not tightly regulated.

TextSentencer_T285

42823-42950

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denotes

If the inciting stimulus is not eliminated quickly, then the inflammatory response itself will cause significant tissue injury.

TextSentencer_T286

42951-43153

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denotes

The mechanism regulating inflammation has been the focus of a great deal of research to identify therapeutic targets to modulate the damage to host tissues that occurs in many gastrointestinal diseases.

TextSentencer_T287

43154-43319

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denotes

Recent work has provided some of the molecular and cellular details of this complex physiology and has led to novel therapeutic strategies for treating inflammation.

TextSentencer_T288

43320-43451

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denotes

The gastrointestinal epithelium interfaces with a luminal environment that is inhabited by potentially hostile microbial organisms.

TextSentencer_T289

43452-43704

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denotes

The epithelium presents a physical barrier to invasion by the flora of the gastrointestinal tract, consisting of the apical cellular membrane, intercellular tight junctions (the permeability of which is highly regulated), and a secreted layer of mucus.

TextSentencer_T290

43705-43844

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denotes

When invading pathogens breach the mucosal barrier, potent soluble and neural signals are generated that initiate an inflammatory response.

TextSentencer_T291

43845-43998

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81 The epithelium can be conceptualized as a sensory organ that detects pathogen invasion to trigger an appropriate host defense and reparative response.

TextSentencer_T292

43999-44284

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denotes

Noninfectious mucosal injury or invasion of epithelial cells by pathogenic organisms such as Salmonella activates the synthesis of proinflammatory chemokines (chemoattractants) by epithelial cells that triggers a robust influx of neutrophils into the tissue within hours of the damage.

TextSentencer_T293

44285-44539

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81 Of the chemoattractants produced by epithelium, interleukin-8 (IL-8) has a particularly important role in initiating inflammation by recruiting neutrophils from blood 82 and regulating neutrophil migration through tissue matrix adjacent to epithelium.

TextSentencer_T294

44540-44880

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denotes

83, 84 Complement fragments such as C5a and bacteria-derived formylated chemotactic peptides also act as potent "end target" chemoattractants that are fully capable of stimulating a robust inflammatory response in the intestine if the epithelial barrier permits invasion of bacteria or the diffusion of bacterial peptides across the mucosa.

TextSentencer_T295

44881-45085

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denotes

Epithelial cells activated during infection produce cytokines such as tumor necrosis factor-α (TNF-α), arachidonic acid metabolites, and other proinflammatory mediators that activate recruited leukocytes.

TextSentencer_T296

45086-45279

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85 Microbial products, particularly lipopolysaccharide (LPS) and other bacterial cell wall components and microbial nucleic acids, are potent activators of leukocytes recruited into the tissue.

TextSentencer_T297

45280-45463

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denotes

86 Mast cells are key sentinel leukocytes that sense microbial invasion, releasing TNF-α, which appears to be a critical initiator and regulator of the cellular phase of inflammation.

TextSentencer_T298

45464-45661

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denotes

87 Once the inflammatory response has been initiated, TNF-α; IL-1β; and other proinflammatory products of neutrophils, monocytes, mast cells, and epithelial cells amplify the inflammatory response.

TextSentencer_T299

45662-45776

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denotes

The enteric nervous system (ENS) has a key role in sensing and regulating inflammatory responses in the intestine.

TextSentencer_T300

45777-45914

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denotes

For example, C. difficile toxin A activates a neural pathway that triggers mast cell degranulation and neutrophil influx into the tissue.

TextSentencer_T301

45915-46099

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88, 89 Blockade of this neural pathway is sufficient to abolish the profound inflammatory response induced by toxin A as well as many of the effects of toxin A on enterocyte secretion.

TextSentencer_T302

46100-46231

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denotes

Other pathogens and immune-mediated hypersensitivity reactions similarly stimulate inflammation by mechanisms that involve the ENS.

TextSentencer_T303

46232-46405

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denotes

Thus the epithelium interacts in a highly complex manner with the intestinal milieu, the ENS, and inflammatory cells to regulate the tissue response to injury and infection.

TextSentencer_T304

46406-46582

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denotes

Resident macrophages located in the lamina propria, submucosa, and intestinal lymphoid organs are among the first cells beyond the epithelium to respond to infection or injury.

TextSentencer_T305

46583-46784

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denotes

Macrophages are activated by microbial products by way of pattern recognition receptors and begin to produce proinflammatory molecules important for recruiting and activating neutrophils and monocytes.

TextSentencer_T306

46785-46952

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denotes

Pattern recognition receptors recognize microbial molecules such as LPS, lipoproteins, flagellin, peptidoglycan, and nucleic acids to signal the invasion by pathogens.

TextSentencer_T307

46953-47047

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denotes

86 Of the pattern recognition receptors, the LPS receptor complex is perhaps the best defined.

TextSentencer_T308

47048-47263

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denotes

LPS activates macrophages by way of the CD14 Toll-like receptor 4 (TLR-4) complex to initiate transcription of the inflammatory cytokines TNF-α and IL-1β, which synergize with LPS to amplify the macrophage response.

TextSentencer_T309

47264-47434

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denotes

86 LPS, particularly in concert with inflammatory cytokines, stimulates macrophages to produce copious amounts of nitric oxide, which is both microbicidal and vasoactive.

TextSentencer_T310

47435-47661

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denotes

90 Nitric oxide and other nitrogen radicals react with reactive oxygen intermediates (ROIs) generated by the activated oxidase complex to produce some of the most toxic molecules of the host defense system: the peroxynitrites.

TextSentencer_T311

47662-47713

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denotes

90 IL-8 is produced as well to recruit neutrophils.

TextSentencer_T312

47714-48047

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denotes

As the response progresses, other inflammatory mediators, particularly the arachidonic acid-derived lipids dependent on inflammationinduced cyclooxygenase (COX)-2 and 5-lipoxygenase activity, are produced that have potent vasoactive and proinflammatory effects through the activation of endothelial cells, neutrophils, and platelets.

TextSentencer_T313

48048-48424

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denotes

91 Y VASCULAR RESPONSE DURING INFLAMMATION Four important changes occur in the intestinal vasculature during inflammation: (1) alteration of blood flow; (2) increased vascular permeability; (3) increased adhesiveness of endothelial cells, leukocytes, and platelets; and (4) exposure of the basement membrane and activation of the complement, contact, and coagulation cascades.

TextSentencer_T314

48425-48744

Sentence

denotes

A wide range of mediators alter blood flow during inflammation in the intestinal tract, ranging from gases such as nitric oxide (a major vasodilator of the intestinal vasculature) to lipids (prostaglandins, leukotrienes, thromboxanes, and platelet-activating factor [PAF]), cytokines, bradykinin, histamine, and others.

TextSentencer_T315

48745-48866

Sentence

denotes

The major sources for these mediators include activated leukocytes, endothelial cells, epithelial cells, and fibroblasts.

TextSentencer_T316

48867-49106

Sentence

denotes

The primary determinant of blood flow early in inflammation is vascular caliber, which initially decreases in arterioles but then quickly changes to vasodilation coincident with the opening of new capillary beds, increasing net blood flow.

TextSentencer_T317

49107-49272

Sentence

denotes

The increase in blood flow is relatively short-lived, because the viscosity of the blood increases from fluid loss and tissue edema resulting from leaky capillaries.

TextSentencer_T318

49273-49436

Sentence

denotes

Leukocyte margination, platelet adhesion to endothelial cells and exposed matrix, and areas of coagulation protein accumulation further decrease local circulation.

T2330

49437-49547

Sentence

denotes

Increased vascular permeability is initially caused by inflammatory mediator actions on the endothelial cells.

T92561

49548-49697

Sentence

denotes

Histamine, leukotrienes, PAF, prostaglandins, bradykinin, and other mediators stimulate endothelial cell contraction, and interendothelial gaps form.

T41177

49698-49773

Sentence

denotes

92, 93 This stage of increased vascular permeability is readily reversible.

T65809

49774-49970

Sentence

denotes

Concurrently, mediators such as the cytokines TNF-α and IL-1β induce a structural reorganization of the interendothelial junctions, resulting in frank discontinuities in the endothelial monolayer.

T30831

49971-50156

Sentence

denotes

94 Cytokines also stimulate endothelial cells to express adhesion molecules that support adhesion of leukocytes and platelets, 95 leading to the next and perhaps most devastating event.

T60100

50157-50275

Sentence

denotes

Leukocytes (primarily neutrophils) and platelets adhere to exposed basement membranes and activated endothelial cells.

T26498

50276-50832

Sentence

denotes

Adherent neutrophils and platelets are then exposed to the mediators of inflammation present in the surrounding milieu, which activates the cells to release oxidants and proteases (particularly elastase) that injure the endothelium and have the potential to cause irreparable harm to the microvasculature. [96] [97] [98] Marginated neutrophils begin to transmigrate between endothelial cells (as described in later sections), which, if in sufficiently large numbers, disrupts the integrity of the interendothelial junctions, worsening the vascular leakage.

T4989

50833-51031

Sentence

denotes

97 These stages of enhanced vascular permeability can be conceptualized as a mechanism to allow plasma proteins to enter the tissues and to potentiate the critical influx of leukocytes into tissues.

T19390

51032-51207

Sentence

denotes

However, if they are not regulated precisely, alterations in both hydrostatic and oncotic forces and irreversible damage to the vascular bed may have devastating consequences.

T38667

51208-51542

Sentence

denotes

Moreover, inappropriate activation of plasma protein cascades and leukocytes by activated endothelium and exposed matrix proteins can contribute to SIRS (see the later section Gastrointestinal Ileus for more information) characterized by hypotension, generalized vascular leak syndrome, and multiorgan dysfunction, which may be fatal.

T52914

51543-51876

Sentence

denotes

Phosphodiesterase inhibitors reduce endothelial permeability in ischemiareperfusion injury and other models of inflammation-induced vascular leakage 99,100 by increasing endothelial tight junction integrity; thus, it may be a viable therapeutic strategy to prevent or reduce the permeability alterations associated with inflammation.

T74468

51877-52057

Sentence

denotes

Endothelial cells respond to products of activated epithelial cells and macrophages in the intestinal tissue to recruit cells and humoral mediators of inflammation into the tissue.

T1476

52058-52161

Sentence

denotes

Activated endothelial cells display a range of molecules critical for neutrophil and platelet adhesion.

T63702

52162-52278

Sentence

denotes

The role of endothelial cells in mediating neutrophil recruitment is discussed in more detail later in this chapter.

T51168

52279-52509

Sentence

denotes

Intercellular permeability is increased to expose basement membrane proteins that trigger humoral defense systems (complement, coagulation, and contact system cascades) and to provide access for these macromolecules to the tissue.

T350

52510-52678

Sentence

denotes

Endothelial cells are an important source of inflammatory mediators that amplify the response and vasoactive substances (particularly nitric oxide) altering blood flow.

T62871

52679-52829

Sentence

denotes

Infection or injury to the gastrointestinal mucosa causes an influx of leukocytes from the blood that lay the foundation of the inflammatory response.

T3020

52830-52927

Sentence

denotes

Neutrophils, the first to arrive during inflammation, have a dominant role in the acute response.

T45913

52928-53135

Sentence

denotes

Within minutes neutrophils are recruited into the tissue, in which they are activated to release products that not only are lethal to pathogens and proinflammatory but also may damage host cells and tissues.

T95175

53136-53280

Sentence

denotes

101 Not surprisingly, a great deal of attention has been paid to the role of neutrophils in the pathophysiology of many inflammatory conditions.

T64605

53281-53376

Sentence

denotes

102 Neutrophil depletion is protective in many models of gastrointestinal inflammatory disease.

T35871

53377-53607

Sentence

denotes

Of interest to clinicians, blockade of neutrophil migration into inflamed tissues prevents many of the pathophysiologic events associated with infectious enteritis, ischemia-reperfusion injury, and other gastrointestinal diseases.

T70702

53608-53796

Sentence

denotes

98, [103] [104] [105] [106] Neutrophil transendothelial migration is a multistep process that is temporally and spatially regulated and has a degree of cell type specificity ( Fig. 12.1 ).

T23211

53797-53927

Sentence

denotes

The predominant sites of neutrophil transendothelial migration are in the postcapillary venules and, in some tissues, capillaries.

T42173

53928-54142

Sentence

denotes

Endothelial cells in these vessels respond to cytokines and other soluble signals by expressing molecules that promote neutrophil adhesion and transmigration, including selectins and counterreceptors for integrins.

T15525

54143-54235

Sentence

denotes

As neutrophils flow through these vessels, they are first tethered to activated endothelium.

T1993

54236-54436

Sentence

denotes

Tethering is mediated by selectin molecules expressed on neutrophils (L-selectin) and on activated endothelial cells (P-and E-selectins), which bind to PSGL-1, ESL-1, and other mucin counterreceptors.

T6333

54437-54594

Sentence

denotes

107 , 108 The function of tethering is to increase the exposure of the neutrophil to activating chemokines presented on the surface of the endothelial cells.

T16326

54595-54706

Sentence

denotes

Stimulation of neutrophils by IL-8 and other chemokines activate the second step of transendothelial migration.

T10706

54707-55003

Sentence

denotes

Chemokine binding to their receptors on the neutrophil generates signals that activate the binding of integrin adhesion receptors to their ligands, called intracellular adhesion molecules (ICAMs) or vascular cell adhesion molecules, expressed on endothelial , and other proinflammatory mediators.

T79753

55004-55165

Sentence

denotes

Endothelial cells stimulated by inflammatory mediators produce chemoattractants (such as IL-8) and display adhesion molecules that promote neutrophil emigration.

T77547

55166-55450

Sentence

denotes

The three steps of neutrophil (polymorphonuclear [PMN]) emigration capture/rolling (mediated by selectins), adhesion (mediated by β 2 integrins), and transendothelial migration (mediated by integrins and platelet/endothelial cellular adhesion molecule) occur on activated endothelium.

T48091

55451-55520

Sentence

denotes

Chemoattractant molecules such as IL-8 trigger neutrophil emigration.

T78400

55521-55748

Sentence

denotes

In inflamed tissues cytokines (IL-1β and TNF-α) and a variety of other proinflammatory mediators stimulate the neutrophil oxidase complex to produce reactive oxygen intermediates (ROIs; O 2 − and H 2 O 2 and their derivatives).

T23090

55749-55909

Sentence

denotes

Activated neutrophils degranulate to release proteases and other hydrolases, cationic peptides (defensins), myeloperoxidase, and other products into the tissue.

T65059

55910-56054

Sentence

denotes

Activated neutrophils synthesize a variety of inflammatory mediators, including prostaglandins (PGE 2 ) that modulate the inflammatory response.

T74346

56055-56215

Sentence

denotes

The products of activated neutrophils (ROIs, proteases, and mediators) stimulate epithelial secretion and alter tight junction permeability, promoting diarrhea.

T25440

56216-56475

Sentence

denotes

Neutrophils eventually migrate across the infected epithelium by a mechanism that involves integrins, disrupting tight junction integrity and increasing permeability to bacterial products, thus exacerbating the inflammatory response. cells in inflamed mucosa.

T47649

56476-56583

Sentence

denotes

Integrin ligation to ICAMs arrests the tethered neutrophils, resulting in firm adhesion to the endothelium.

T12677

56584-56711

Sentence

denotes

Of the integrins expressed on neutrophils, the β 2 -integrins have a particularly important role in transendothelial migration.

T81447

56712-56870

Sentence

denotes

Calves and people with the disorder leukocyte adhesion deficiency (LAD) illustrate the requirement for β 2 -integrin-mediated adhesion in neutrophil function.

T59180

56871-56973

Sentence

denotes

LAD is a result of an autosomal recessive trait resulting in the lack of the β 2 -integrin expression.

T91347

56974-57188

Sentence

denotes

The neutrophils from affected individuals cannot migrate into most tissues and do not function normally, resulting in poor tissue healing and profound susceptibility to infection, especially at epithelial barriers.

T18018

57189-57420

Sentence

denotes

109, 110 Other integrins also have a role in transendothelial migration. β 1 -Integrins mediate transendothelial migration in some cells and seem to be particularly important for mediating emigration of monocytes into many tissues.

T22457

57421-57608

Sentence

denotes

111 Following this firm adhesion step, neutrophils migrate through the endothelium along a chemotactic gradient of IL-8 and other chemoattractants, such as C5a and leukotriene B 4 (LTB4).

T97383

57609-57932

Sentence

denotes

82, 97, 112 Neutrophils migrate across the endothelial monolayer at intercellular junctions by way of a mechanism involving a series of integrin-ligand interactions mediated by both β 2 -and β 1 -integrins and other adhesion molecules, 108 which is generally capable of maintaining the integrity of the endothelial barrier.

T31393

57933-58223

Sentence

denotes

113 However, a massive flux of neutrophils through the endothelium alters endothelial tight junctions and injures the basement membrane, resulting in increased endothelial permeability to molecules as large as plasma proteins and even endothelial cell detachment from the basement membrane.

T87252

58224-58378

Sentence

denotes

96, 97 Nonintegrin molecules such as platelet-endothelial cell adhesion molecules (PECAMs) also are involved in transendothelial migration of neutrophils.

T73787

58379-58481

Sentence

denotes

108 Homotypic binding of PECAMs on adjacent endothelial cells form part of the intercellular junction.

T40779

58482-58715

Sentence

denotes

Neutrophils express an integrin of the β 3 -family that can bind PECAMs, and through sequential binding of β 3 -integrins to PECAMs, the neutrophil can "unzip" the intercellular junction and migrate through, closing it behind itself.

T72783

58716-58911

Sentence

denotes

A key feature of neutrophils and other leukocytes is the requirement for integrin-mediated adhesion to extracellular matrix (ECM) proteins or other cells to achieve an optimal effector phenotype.

T26730

58912-59191

Sentence

denotes

114 Critical components of the ECM in inflamed tissues include fibronectin, fibrinogen, and vitronectin, deposited in tissues as a result of plasma leakage and by synthesis of new proteins by stromal cells and resident macrophages in response to inflammatory mediator activation.

T73675

59192-59399

Sentence

denotes

The changing composition of the matrix proteins deposited in tissues during inflammation serves as a clue as to the nature of the tissue environment for recruited inflammatory cells as they become activated.

T74684

59400-59756

Sentence

denotes

Individual gene expression studies have demonstrated that adhesion to matrix proteins induces the expression of cytokines and chemokines and their receptors, arachidonic acid-derived lipid mediator synthases, metalloproteinases, growth factors, transcription factors, and other genes that influence the differentiation and activation of inflammatory cells.

T17167

59757-59953

Sentence

denotes

115 ROI production, phagocytosis, degranulation, and other effector functions stimulated by inflammatory mediators and bacterial products are optimal only when neutrophils are adherent to the ECM.

T94375

59954-60261

Sentence

denotes

114 Adhesion to distinct ECM proteins selectively activates signaling pathways and gene expression of neutrophils, monocytes, and other leukocytes with differing abilities to promote certain functions such that the composition of ECM in many ways controls the development of the ultimate effector phenotype.

T30540

60262-60424

Sentence

denotes

Thus integrin-mediated adhesion provides a mechanism in which neutrophils and other leukocytes can sense the complex tissue environment and respond appropriately.

T74696

60425-60630

Sentence

denotes

Of the activators of neutrophils at sites of inflammation, complement (C3-opsonized particles), cytokines (TNF-α and IL-1β), PAF, immune complexes, and bacterial products are among the most potent stimuli.

T83388

60631-60819

Sentence

denotes

Other mediators produced during inflammation may modify neutrophil activity, particularly formylated bacterial peptides, chemokines, complement fragments (C5a), LTB 4 , and prostaglandins.

T10565

60820-61149

Sentence

denotes

Activated neutrophils are highly phagocytic; produce large amounts of ROI; degranulate to release myeloperoxidase, cationic antimicrobial peptides (defensins), serine proteases (mainly elastase), and metalloproteinases; and secrete inflammatory mediators (TNF-α, IL-1β, prostaglandins, leukotrienes, and others) (see Fig. 12 .1).

T10323

61150-61346

Sentence

denotes

Mast cells strategically reside in mucosal tissues, including the submucosa and lamina propria of the gastrointestinal tract, and constitute a crucial first line of defense at epithelial barriers.

T10643

61347-61460

Sentence

denotes

However, they are also important effector cells of the pathophysiology of inflammatory gastrointestinal diseases.

T48897

61461-61898

Sentence

denotes

116 Experimental depletion of mast cells, genetic deficiency in the development of mast cells, or pharmacologic stabilization of mast cells to prevent degranulation all have a protective effect in a variety of models of gastrointestinal inflammatory disease, including dextran sulfate sodium-induced or trinitrobenzenesulfonic acid-induced colitis, 117, 118 ischemia-reperfusion injury, 119, 120 and immediate hypersensitivity responses.

T18677

61899-61995

Sentence

denotes

121 Mast cells are activated by a wide variety of microbial products and host-derived mediators.

T23420

61996-62180

Sentence

denotes

122 Among the activators of mast cells, the so-called anaphylatoxins (complement fragments C3a, C5a, and C4a) are extremely potent stimuli causing release of mediators of inflammation.

T5590

62181-62351

Sentence

denotes

In addition, mast cells are the primary effector cells of IgE-mediated anaphylaxis (type I hypersensitivity reactions) by virtue of their high-affinity receptors for IgE.

T16773

62352-62540

Sentence

denotes

The cross-linking of a receptor-bound IgE on the mast cell surface by antigens (i.e., food antigens) causes rapid degranulation, which results in the explosive release of granule contents.

T59875

62541-62720

Sentence

denotes

123 Neural pathways in the intestine also regulate mast cells, which respond to enteric pathogen invasion via neural reflexes that stimulate the release of inflammatory mediators.

T76927

62721-62847

Sentence

denotes

Activated mast cells release preformed histamine, 5-hydroxytryptamine (5-HT), proteases, heparin, and cytokines from granules.

T24748

62848-62979

Sentence

denotes

Activation also stimulates de novo synthesis of a range of inflammatory mediators, including prostaglandins, PAF, and leukotrienes.

T28281

62980-63126

Sentence

denotes

Transcription of a number of peptide mediators, such as the cytokines TNF-α and IL-1β among many others, also increases stimulation of mast cells.

T83881

63127-63249

Sentence

denotes

Mast cell products have profound effects on the vasculature, increasing endothelial permeability and causing vasodilation.

T51174

63250-63436

Sentence

denotes

124 Moreover, mast cell-derived mediators markedly enhance epithelial secretion by a mechanism that involves the activation of neural pathways and direct stimulation of epithelial cells.

T13338

63437-63724

Sentence

denotes

123 In particular, the mast cell granule protease tryptase operating via the protease-activated receptor-2 is a key regulator of gastrointestinal physiologic responses during inflammation, including epithelial secretion and intercellular junction integrity, motility, and pain responses.

T18766

63725-63860

Sentence

denotes

125, 126 Mast cell products significantly alter intestinal motility, generally increasing transit and expulsion of intestinal contents.

T23783

63861-64130

Sentence

denotes

Mast cell-derived leukotrienes and TNF-α also have crucial roles in host defense against bacterial pathogens, acting to recruit and activate neutrophils, 127, 128 and are crucial players in the mechanism regulating dendritic cell function and adaptive immune responses.

T24491

64131-64412

Sentence

denotes

129 Mast cells have a role in host defense and inflammatory responses to bacterial pathogens, partly because of the release of proinflammatory mediators during bacterial infection, which is critical for recruiting and activating other innate host defense cells such as neutrophils.

T4230

64413-64547

Sentence

denotes

87 Mast cells are also phagocytic, have microbicidal properties, and can act as antigenpresenting cells to the adaptive immune system.

T51059

64548-64652

Sentence

denotes

87 The role for mast cells in host protective responses appears to be as a sensor of bacterial invasion.

T67419

64653-64776

Sentence

denotes

Unlike IgE-mediated responses, bacterial products seem to elicit a highly regulated and selective response from mast cells.

T40573

64777-64851

Sentence

denotes

The complement cascade is a fundamental part of the inflammatory response.

T64475

64852-65202

Sentence

denotes

Activation of the complement cascade, either by immune complexes (classical pathway) or by bacteria or bacterial products, polysaccharides, viruses, fungi, or host cells (alternative pathway), results in the deposition of complement proteins on the activating surface and the release of soluble proteolytic fragments of several complement components.

T45376

65203-65385

Sentence

denotes

130 In particular, activation of either pathway results in the deposition of various fragments of the complement protein C3, which are potent activators of neutrophils and monocytes.

T55795

65386-65511

Sentence

denotes

130 Opsonization of particles with C3 fragments constitutes a major mechanism of target recognition and phagocyte activation.

T98594

65512-65665

Sentence

denotes

131 During the activation of the complement cascade culminating in deposition of C3, soluble fragments of C3 (C3a), C5 (C5a), and C4 (C4a) are liberated.

T27395

65666-65767

Sentence

denotes

These fragments, termed anaphylatoxins, have potent effects on tissues and cells during inflammation.

T51901

65768-65962

Sentence

denotes

Perhaps most notably, they are chemotactic for neutrophils (particularly C5a), activate neutrophil and mast cell degranulation, and stimulate reactive oxygen metabolite release from neutrophils.

T40326

65963-66113

Sentence

denotes

130 The termination of the complement cascade results in the formation of a membrane attack complex in membranes at the site of complement activation.

T90722

66114-66201

Sentence

denotes

If this occurs on host cells such as endothelium, the cell may be irreversibly injured.

T49999

66202-66442

Sentence

denotes

Although the primary source of complement is plasma, epithelial cells of the gastrointestinal tract also produce C3, suggesting that local production and activation of the complement cascade during inflammation occurs in intestinal tissues.

T25249

66443-66601

Sentence

denotes

It is clear that if the regulatory mechanisms of the complement cascade fail, then the inflammatory response may be inappropriate and tissue injury can occur.

T49576

66602-66733

Sentence

denotes

The role of complement in gastrointestinal inflammation has been most extensively studied in models of ischemia-reperfusion injury.

T25299

66734-66856

Sentence

denotes

Activation of the complement cascades has a major role in altered endothelial and epithelial permeability in these models.

T68727

66857-66941

Sentence

denotes

Several lines of evidence support the importance of complement in intestinal injury.

T51658

66942-67019

Sentence

denotes

Mice deficient in C3 or C4 are protected against ischemia-reperfusion injury.

T84269

67020-67186

Sentence

denotes

132 Moreover, administration of monoclonal antibodies against C5 reduced local and remote injury and inflammation during intestinal reperfusion injury in a rat model.

T78002

67187-67476

Sentence

denotes

133 Administration of a soluble form of complement receptor 1, a regulatory protein that halts the complement cascade by dissociating C3 and C5 on host cell membranes, reduced mucosal permeability, neutrophil influx, and LTB4 production during ischemia-reperfusion injury in rats and mice.

T7919

67477-67714

Sentence

denotes

132, 134 Although neutrophils and mast cells mediate many of the pathophysiologic effects of the complement cascade, the membrane attack complex may have a primary role in altered vascular permeability during ischemia-reperfusion injury.

T14281

67715-67718

Sentence

denotes

135

T928

67719-67780

Sentence

denotes

The contact system of plasma is initiated by four components:

T94520

67781-67864

Sentence

denotes

Hageman factor (HF), prekallikrein, factor XI, and high-molecular-weight kininogen.

T58434

67865-67948

Sentence

denotes

HF is a large plasma glycoprotein that binds avidly to negatively charged surfaces.

T14391

67949-68196

Sentence

denotes

136 Bacterial cell walls, vascular basement membranes, heparin, glycosaminoglycans, and other negatively charged surfaces in the intestine capture HF and the other three important initiators of the contact system in a large multimolecular complex.

T84538

68197-68290

Sentence

denotes

Of the surfaces that bind HF, the ECM is an extremely potent activator of the contact system.

T72975

68291-68398

Sentence

denotes

Once bound, HF is converted to HF-α, which cleaves prekallikrein to kallikrein and factor XI to factor XIa.

T51654

68399-68713

Sentence

denotes

The ultimate result is further cleavage of HF by kallikrein and triggering of the contact system cascade, activation of intrinsic coagulation by factor XIa, activation of the alternative pathway by HF, and proteolytic cleavage of high-molecular-weight kininogen by kallikrein, releasing biologically active kinins.

T68761

68714-68894

Sentence

denotes

The products of the contact system, particularly bradykinin, have several important biologic properties that drive many of the vascular and leukocyte responses during inflammation.

T4439

68895-69056

Sentence

denotes

136 Bradykinin induces endothelial cell contracture and intracellular tight junction alterations that increase vascular permeability to fluid and macromolecules.

T58059

69057-69197

Sentence

denotes

Bradykinin also affects vascular smooth muscle contracture, resulting in either vasoconstriction or vasodilation, depending on the location.

T67430

69198-69337

Sentence

denotes

Bradykinin also increases intestinal motility, enhances chloride secretion by the intestinal mucosa, and intensifies gastrointestinal pain.

T99222

69338-69474

Sentence

denotes

In neutrophils kinins stimulate the release of many inflammatory mediators, including cytokines, prostaglandins, leukotrienes, and ROIs.

T30765

69475-69635

Sentence

denotes

137 Kallikrein cleaves C5 to release C5a, a potent chemotactic factor for neutrophils, and thus has a role in recruiting and activating inflammatory leukocytes.

T843

69636-69775

Sentence

denotes

The plasma kallikrein-bradykinin system is activated in a variety of acute and chronic inflammatory diseases of the gastrointestinal tract.

T80096

69776-69866

Sentence

denotes

138, 139 Blockade of the pathophysiologic effects of bradykinin has clinical applications.

T53661

69867-70084

Sentence

denotes

Oral or intravenous (IV) administration of the bradykinin receptor antagonist icatibant reduces the clinical signs, onset of diarrhea, and many of the histopathologic changes in experimental models of colitis in mice.

T60867

70085-70280

Sentence

denotes

140 Inhibition of kallikrein by oral administration of P8720 attenuated the intestinal inflammation, clinical score, and systemic manifestations in a model of chronic granulomatous enterocolitis.

T6588

70281-70386

Sentence

denotes

138 Thus the contact system is a potential therapeutic target for inflammatory diseases of the intestine.

T78123

70387-70559

Sentence

denotes

Changes in blood flow to the mucosa and other regions of the intestine that reduce perfusion of the tissues can potentiate the initial damage caused by infection or injury.

T50541

70560-70721

Sentence

denotes

For example, reperfusion of ischemic tissues is associated with platelet and neutrophil clumping in the small vessels of the mucosa, which can impede blood flow.

T84484

70722-70867

Sentence

denotes

141 Platelets are activated and adhere to exposed basement membrane and activated endothelial cells and provide a surface for leukocyte adhesion.

T46622

70868-71029

Sentence

denotes

The accumulation of platelets and leukocytes can significantly reduce vessel diameter and blood flow while potentiating local coagulation and thrombus formation.

T93747

71030-71126

Sentence

denotes

Soluble mediators released by activated leukocytes and endothelial cells also affect blood flow.

T52767

71127-71384

Sentence

denotes

Histamine and the vasoactive lipids derived from arachidonic acid (leukotrienes, prostaglandins, thromboxane, prostacyclin, and PAF) have a prominent role in regulating local perfusion during inflammation and may have systemic effects on blood flow as well.

T28884

71385-71724

Sentence

denotes

Procoagulant mediators released by inflammatory cells in response to the inflammatory process (i.e., tissue factor produced by macrophages or endothelial cells), exposed basement membrane proteins, and bacterial components can trigger the contact system and the coagulation and complement cascades, the products of which affect blood flow.

T88864

71725-71917

Sentence

denotes

Nitric oxide, whether produced by endothelial cells or leukocytes (macrophages), is a potent regulator of blood flow and has a significant role in the control of perfusion during inflammation.

T39981

71918-72062

Sentence

denotes

142 Many of the mediators that affect perfusion also affect endothelial permeability, altering osmotic and hydrostatic balance and tissue edema.

T1183

72063-72357

Sentence

denotes

In extreme cases local and systemic coagulopathies initiated by vascular injury and absorption of microbial products and inflammatory mediators induce a hypercoagulable state, leading to microthrombus formation, which can reduce blood flow or macrothrombus formation, causing tissue infarction.

T48191

72358-72463

Sentence

denotes

The cellular mediators of inflammation have the potential to inflict severe injury to intestinal tissues.

T94103

72464-72706

Sentence

denotes

Neutrophils have an important role in the pathophysiology of many intestinal diseases, including ischemia-reperfusion injury, 98 infectious enterocolitis, 105, 143 nonsteroidal antiinflammatory drug-induced mucosal ulceration, 106 and others.

T68367

72707-72877

Sentence

denotes

Depletion of neutrophils, blockade of their emigration into tissues, or inhibition of neutrophil activation reduces the severity of these and other inflammatory diseases.

T99129

72878-72999

Sentence

denotes

144 Many antiinflammatory therapies are emerging that specifically target neutrophil adhesion, migration, and activation.

T11051

73000-73191

Sentence

denotes

Migration of neutrophils through endothelium during emigration into inflamed tissues is remarkable in that the permeability of the endothelial monolayer is preserved under most circumstances.

T64567

73192-73310

Sentence

denotes

However, there is a limit above which neutrophil migration alters the permeability characteristics of the endothelium.

T81617

73311-73588

Sentence

denotes

The effect is in part physical in that the mere movement of large numbers of neutrophils through the endothelium is sufficient to mechanically disrupt the tight junctions and in part because of toxic products of neutrophils that damage endothelial cells and basement membranes.

T82700

73589-73867

Sentence

denotes

141, 145 Serine proteases (particularly elastase) and metalloproteinases released by degranulating neutrophils liquefy tissue matrix proteins and cleave cell-surface proteins that make up endothelial intercellular junctions to ease neutrophil migration to the site of infection.

T97712

73868-74075

Sentence

denotes

101 These degradative enzymes are particularly damaging to basement membranes and the cellular barriers of the endothelium, thus contributing to vascular permeability (and local tissue edema) and thrombosis.

T47682

74076-74239

Sentence

denotes

The permeability may be affected to the extent that not only water but also macromolecules (e.g., albumin, matrix proteins, complement) leak into the interstitium.

T93664

74240-74526

Sentence

denotes

Blockade of neutrophil adhesion to endothelium with anti-β 2 -integrin antibodies has a sparing effect on the microvasculature in experimental intestinal ischemia-reperfusion injury, reducing the alterations in vascular permeability and histopathologic evidence of microvascular damage.

T4275

74527-74677

Sentence

denotes

141 Similar to the endothelium of inflamed tissues, massive neutrophil transmigration occurs across the epithelium in response to infection or injury.

T95704

74678-74779

Sentence

denotes

Neutrophil transepithelial migration increases epithelial permeability by disrupting tight junctions.

T72444

74780-74903

Sentence

denotes

145 Like the endothelium, neutrophils disrupt the epithelial barrier mechanically as they migrate through (see Fig. 12 .1).

T18177

74904-75003

Sentence

denotes

Proteases, particularly elastase, degrade basement membrane components and tight junction proteins.

T9612

75004-75141

Sentence

denotes

Protease activated receptor-2 activated by neutrophil granule serine proteases alter epithelial and endothelial tight junction integrity.

T43750

75142-75279

Sentence

denotes

Proinflammatory products of activated neutrophils (TNFα and IFN-γ) increase tight junction permeability by direct effects on enterocytes.

T69968

75280-75391

Sentence

denotes

Prostaglandins released by activated neutrophils stimulate epithelial secretion, thus contributing to diarrhea.

T26012

75392-75538

Sentence

denotes

Subepithelial accumulation of neutrophils can lead to deadhesion of the epithelial cells from the basement membrane and mild to severe ulceration.

T14498

75539-75789

Sentence

denotes

The physiologic result of the effects of neutrophils and their products on the epithelial barrier includes protein-losing enteropathy and absorption of bacterial cell wall constituents, which potentiates the local and systemic inflammatory responses.

T11088

75790-75971

Sentence

denotes

Neutrophils in inflamed tissues stimulated by potent host-derived activators (such as IL-1β and TNF-α) and bacterial products (LPS) release copious amounts of ROIs (see Fig. 12 .1).

T40802

75972-76142

Sentence

denotes

Although these oxygen and oxyhalide radicals are important for killing pathogens, they are also potentially toxic to epithelial and endothelial cells and matrix proteins.

T51612

76143-76302

Sentence

denotes

Reactive nitrogen intermediates, produced primarily by macrophages during inflammation, combine with ROIs to form peroxynitrites, which are particularly toxic.

T38135

76303-76471

Sentence

denotes

90 In addition to injury to mucosal tissues, ROIs also have an as yet ill-defined role in recruiting and activating neutrophils, potentiating the inflammatory response.

T75416

76472-76714

Sentence

denotes

146 In support of the role of ROIs in inflammatory diseases of the gastrointestinal tract, administration of inhibitors of ROI production or pharmacologic ROI scavengers can be protective in many models of reperfusion injury or enterocolitis.

T22142

76715-76862

Sentence

denotes

Many therapies are aimed at inhibiting neutrophil activation, and effector functions in tissues have been evaluated for use in intestinal diseases.

T85701

76863-77072

Sentence

denotes

Phosphodiesterase inhibitors, by causing cyclic adenosine monophosphate (cAMP) accumulation in neutrophils, are antiinflammatory by virtue of their ability to suppress neutrophil activation and ROI production.

T39434

77073-77227

Sentence

denotes

New phosphodiesterase inhibitors selective for the predominant neutrophil isoform of phosphodiesterase hold promise for use in many inflammatory diseases.

T77631

77228-77339

Sentence

denotes

Subepithelial mast cells also have an important role in altering epithelial permeability in inflamed intestine.

T8210

77340-77535

Sentence

denotes

During the intestinal hypersensitivity response subepithelial mast cell release of mast cell protease tryptase by degranulation increases epithelial permeability via an effect on tight junctions.

T80603

77536-77694

Sentence

denotes

147, 148 This alteration in tight junction permeability results in enhanced transepithelial flux of macromolecules, including proteins and bacterial products.

T75762

77695-77785

Sentence

denotes

Cytokines released by mast cells and phagocytes also regulate tight junction permeability.

T92627

77786-77891

Sentence

denotes

IL-4, a product of mast cells and macrophages, has been demonstrated to increase epithelial permeability.

T37500

77892-78013

Sentence

denotes

149 Moreover, TNF-α and IFN-γ, products of many inflammatory cells, synergistically increase tight junction permeability.

T71765

78014-78131

Sentence

denotes

150 Y PATHOPHYSIOLOGY OF DIARRHEA Acute equine colitis causes rapid, severe debilitation and, often, death in horses.

T23357

78132-78386

Sentence

denotes

Diarrhea associated with acute equine colitis occurs sporadically and is characterized by intraluminal sequestration of fluid, moderate to severe colic (abdominal pain), and profuse watery diarrhea with resultant endotoxemia, leukopenia, and hypovolemia.

T41335

78387-78480

Sentence

denotes

151, 152 Causes of acute colitis and therapeutic options are discussed later in this section.

T33728

78481-79054

Sentence

denotes

Although all mechanisms responsible for fluid losses are not known, inflammatory cells likely play an integral role; colitis is characterized by granulocyte infiltration of the large intestinal mucosa. [153] [154] [155] [156] [157] Equine cecal and colonic tissues collected during the acute stages of experimentally induced acute equine colitis (Potomac horse fever, lincomycin with and without Clostridium spp. inoculation, nonsteroidal antiinflammatory drug administration) reveal the presence of numerous neutrophils and eosinophils in the lamina propria and submucosa.

T4933

79055-79224

Sentence

denotes

153, 156, 158, 159 Granulocyte-derived ROIs are crucial to antimicrobial defenses in the gut and stimulate chloride and water secretion by interactions with enterocytes.

T73723

79225-79409

Sentence

denotes

160, 161 Normal equine intestinal tissue is unique compared with that in most other mammalian species for a preponderance of eosinophils located in the intestinal mucosa and submucosa.

T26782

79410-79633

Sentence

denotes

162, 163 Production of ROIs by stimulated phagocytic granulocytes following mucosal barrier disruption may be responsible for the massive fluid secretory response that occurs during the early stages of acute equine colitis.

T76024

79634-79772

Sentence

denotes

Colitis refers to inflammation and mucosal injury of the colon and cecum (typhlocolitis) that may occur in response to a number of causes.

T82856

79773-79905

Sentence

denotes

164 The cause of the colonic injury may be well defined such as in naturally occurring infectious or experimentally induced colitis.

T92295

79906-80011

Sentence

denotes

However, many cases of human and animal diarrhea have a speculative or unknown diagnosis or no diagnosis.

T15926

80012-80262

Sentence

denotes

Irrespective of the underlying or initiating cause of colonic injury, the colon apparently has a limited repertoire of responses to damage because most forms of colitis demonstrate similarities in histopathologic appearance and clinical presentation.

T58473

80263-80504

Sentence

denotes

Various degrees of mucosal erosion and ulceration, submucosal/mucosal edema, goblet cell depletion, and the presence of an inflammatory cellular infiltrate within the mucosa and submucosa are common to many types of human and animal colitis.

T93322

80505-80670

Sentence

denotes

163, 164 Characteristic clinical manifestations include intraluminal fluid sequestration; abdominal discomfort; hypovolemia; and most often profuse, watery diarrhea.

T50991

80671-80766

Sentence

denotes

Large bowel diarrhea results from abnormal fluid and ion transport by cecal and colonic mucosa.

T79367

80767-80900

Sentence

denotes

Loss of fluid by the large intestine can result from malabsorptive or hypersecretory processes and is often a combination of the two.

T72449

80901-81042

Sentence

denotes

165 Colonic secretory processes are a function of the crypt epithelium, whereas absorptive processes are limited to surface epithelial cells.

T68967

81043-81196

Sentence

denotes

166, 167 Under normal baseline conditions, an underlying secretion by crypt epithelium is masked by a greater rate of surface epithelial cell absorption.

T48806

81197-81581

Sentence

denotes

Abnormal forces influencing the rates of secretion and absorption can result in massive, uncontrolled secretion and malabsorption by large intestinal mucosal epithelial cells, leading to rapid dehydration and death. [165] [166] [167] Two intracellular processes control colonic secretion: the cyclic nucleotide (cAMP and cyclic guanosine monophosphate [cGMP]) and the calcium systems.

T56463

81582-81781

Sentence

denotes

168, 169 Agents may activate adenyl cyclase (vasoactive intestinal peptide, prostaglandin E2 [PGE 2 ]) or guanylyl cyclase (bacterial enterotoxins) and induce increases in cAMP or cGMP, respectively.

T45968

81782-81919

Sentence

denotes

This reaction causes phosphorylation of specific protein kinases that induce the actual apical and basolateral membrane transport events.

T71785

81920-82221

Sentence

denotes

Increases in intracellular free calcium may arise from cyclic nucleotide-dependent release of stored calcium within the cell or from increased calcium entry across the cell membrane. [165] [166] [167] Calcium may act through calmodulin, which then can activate membranephosphorylating protein kinases.

T44515

82222-82374

Sentence

denotes

At least four central systems control intestinal secretion: (1) the hormonal system, (2) the ENS, (3) bacterial enterotoxins, and (4) the immune system.

T28796

82375-82502

Sentence

denotes

169, 170 Hormonal control of colonic electrolyte transport is exerted primarily through the renin-angiotensin-aldosterone axis.

T79632

82503-82638

Sentence

denotes

171 The ENS controls transport through three separate components: (1) extrinsic nerves of the parasympathetic and sympathetic pathways;

T97208

82639-82894

Sentence

denotes

(2) intrinsic ganglia and nerves, secreting a variety of neurotransmitters including peptides; and (3) neuroendocrine cells (intraepithelial lymphocytes) that reside in the epithelium and release messengers onto the epithelial cells in a paracrine manner.

T55565

82895-83014

Sentence

denotes

165, [169] [170] [171] Many bacterial enterotoxins can induce intestinal secretion by cAMP or cGMP signal transduction.

T61584

83015-83207

Sentence

denotes

172 Bacterial enterotoxins can stimulate release of mediators (such as substance P) from primary afferent neurons, which then affect enteric neurons, often propagating neurogenic inflammation.

T16513

83208-83623

Sentence

denotes

173 Preformed inflammatory mediators such as histamine, serotonin, or adenosine and newly synthesized mediators such as prostaglandins, leukotrienes, PAF, various cytokines, the inducible form of nitric oxide, and reactive oxygen metabolites can initiate intestinal secretion by directly stimulating the enterocyte and by acting on enteric nerves indirectly to induce neurotransmitter-mediator intestinal secretion.

T19656

83624-83753

Sentence

denotes

170 Prostaglandins of the E and F series can cause an increase in chloride secretion in intact tissue and isolated colonic cells.

T74147

83754-84343

Sentence

denotes

174, 175 Leukotrienes, PAF, and a number of cytokines have been shown to have no effect on T84 cell secretion but have a significant effect on electrolyte transport in intact tissue, suggesting that intermediate cell types may be involved in these secretory responses. [176] [177] [178] The epithelial cell chloride secretory response occurs via prostaglandin-mediated and adenosine-mediated increases in cellular cAMP, whereas histamine acts by H 1 receptor induction of phosphatidylinositol turnover, production of inositol triphosphate, and mobilization of intracellular calcium stores.

T54693

84344-84508

Sentence

denotes

170 Lipoxygenase products (leukotrienes) are capable of activating a colonic secretory response and do not appear to involve the cyclic nucleotides or calcium ions.

T69642

84509-84703

Sentence

denotes

176 Phagocytederived reactive oxygen mediators (ROMs) can induce colonic electrolyte secretion in vitro, suggesting that oxidants may contribute directly to the diarrhea associated with colitis.

T31410

84704-85126

Sentence

denotes

179 Reactive oxygen species initiate the secretory response by increasing cellular cAMP or stimulating mesenchymal release of PGE 2 or prostacyclin, which in turn stimulates the epithelial cell or enteric neuron, respectively. [179] [180] [181] [182] Sodium nitroprusside, an exogenous source of nitric oxide, stimulated an increase in chloride secretion in rat colon that was mediated by COX products and enteric neurons.

T73352

85127-85130

Sentence

denotes

183

T78878

85132-85282

Sentence

denotes

Acute colitis rarely develops by a simple cause or effect phenomenon but is influenced by many extrinsic and intrinsic host and microorganism factors.

T88755

85283-85469

Sentence

denotes

Inflammatory mediators released from mast cells and monocytic or granulocytic phagocytes cause intestinal chloride and water secretion and inhibit neutral sodium and chloride absorption.

T39459

85470-85616

Sentence

denotes

169, 170, 184 Inflammatory cells, particularly the phagocytic granulocytes, play an important role in mucosal pathophysiology in cases of colitis.

T13197

85617-85749

Sentence

denotes

161, 185 Large numbers of these cells are observed on histopathologic examination of tissues from human and animal cases of colitis.

T77635

85750-85860

Sentence

denotes

Products of cell activation stimulate direct and indirect secretory responses in intestinal cells and tissues.

T61937

85861-86033

Sentence

denotes

169, 170 Products of phagocyte secretion may amplify the inflammatory signal or have effects on other target cells in intestine such as enterocytes and smooth muscle cells.

T77900

86034-86287

Sentence

denotes

The nicotinamide adenine dinucleotide phosphate (NADPH)-NADPH oxidase system of phagocytes (neutrophils, eosinophils, and monocytes/macrophages) is a potent inducer of superoxide radicals used as a host defense mechanism to kill invading microorganisms.

T37249

86288-86478

Sentence

denotes

161 During inappropriate stimulation such as inflammation, trauma, or ischemia followed by reperfusion, increased levels of toxic oxygen species are produced, causing damage to host tissues.

T56355

86479-86660

Sentence

denotes

Engagement of any of several receptor and nonreceptor types including phagocytosis mediators, chemotactic agents, various cytokines, and microbial products can stimulate phagocytes.

T12053

86661-86873

Sentence

denotes

161 Resident phagocytes or those recruited to colonic mucosa early in the disease process are considered to augment mechanisms causing fluid and electrolyte secretory processes, a so-called amplification process.

T31280

86874-87016

Sentence

denotes

104, 186 Activation of the respiratory burst results in the production and release of large amounts of superoxide anion (O 2 − ) and H 2 O 2 .

T43579

87017-87202

Sentence

denotes

187 In addition to these ROMs, activated phagocytes secrete peroxidase enzyme (myeloperoxidase from neutrophils and eosinophil peroxidase from eosinophils) into the extracellular space.

T8442

87203-87327

Sentence

denotes

The peroxidases catalyze the oxidation of Cl − by H 2 O 2 to yield HOCl, the active ingredient in household bleach products.

T50581

87328-87472

Sentence

denotes

The peroxidase-H 2 O 2halide system is the most cytotoxic system of the phagocytes; HOCl is 100 to 1000 times more toxic than O 2 − or H 2 O 2 .

T21974

87473-87679

Sentence

denotes

HOCl is a nonspecific oxidizing and chlorinating agent that reacts rapidly with a variety of biologic compounds including DNA, sulfhydryls, nucleotides, amino acids, and other nitrogen-containing compounds.

T35689

87680-87757

Sentence

denotes

It reacts rapidly with primary amines to produce the cytotoxic N-chloramines.

T79093

87758-88007

Sentence

denotes

The mechanisms by which these substances damage cells and tissue remain speculative, but possibilities include direct sulfhydryl oxidation, hemoprotein inactivation, protein and amino acid degradation, and inactivation of metabolic cofactors of DNA.

T30673

88008-88147

Sentence

denotes

188 Luminal perfusion of specific ROMs increased mucosal permeability, and serosal application caused increases in Cl − secretion in vitro.

T79982

88148-88287

Sentence

denotes

189 Tissue myeloperoxidase activity, an index of tissue granulocyte infiltration, is used experimentally to assess intestinal inflammation.

T27713

88288-88681

Sentence

denotes

190 Myeloperoxidase activity is elevated in acute flare-ups of human inflammatory bowel disease and various animal models of acute colitis. [190] [191] [192] The acute inflammatory response in these conditions is characterized predominantly by neutrophils, although this assay measures total hemoprotein peroxidase, which includes monocyte and eosinophil peroxidase in addition to neutrophils.

T63088

88682-88867

Sentence

denotes

193 Moreover, levels of peroxidase activity in equine circulating eosinophils are greater than in circulating neutrophils, 194 and this may apply to resident tissue eosinophils as well.

T61417

88868-88972

Sentence

denotes

Arachidonic acid metabolites are thought to play a role in intestinal inflammation in diarrheal disease.

T28759

88973-89167

Sentence

denotes

170 Elevated levels of these intermediate metabolites have been demonstrated in natural disease and experimental models of colitis and appear to parallel increases in ROMs in inflamed intestine.

T40052

89168-89293

Sentence

denotes

195 The addition of H 2 O 2 or HOCl to rat colonic tissue in Ussing chambers induces PGE 2 release and active Cl − secretion.

T89851

89294-89436

Sentence

denotes

182, 196 Prostaglandins can stimulate increases in Cl − secretion in intact intestinal tissue 181, 196, 197 and in isolated colonic T84 cells.

T61843

89437-89580

Sentence

denotes

180, 182 Interactions between ROMs and mesenchymal release of PGE 2 /PGI 2 may be relevant to the mechanisms producing the diarrheic condition.

T34451

89581-89735

Sentence

denotes

Fibroblasts cocultured or juxtaposed to colonic T84 cells greatly increased the Cl − secretory response to H 2 O 2 in vitro through the release of PGE 2 .

T97176

89736-89916

Sentence

denotes

180 In addition, equine colonic mucosa has an increased sensitivity to endogenously released prostaglandin by exhibiting a significant secretory response under in vitro conditions.

T80194

89917-90196

Sentence

denotes

198 194, 198 The intact bowel forms an effective barrier to the transport of significant amounts of these highly antigenic toxins, but the diseased gut absorbs these macromolecules in large amounts, causing the subsequent adverse systemic effects that are often life-threatening.

T74934

90197-90269

Sentence

denotes

199 A complete review of endotoxemia is presented later in this chapter.

T76367

90270-90379

Sentence

denotes

Endotoxins trigger mucosal immune cells and subsequent release of inflammatory mediators in cases of colitis.

T7847

90380-90588

Sentence

denotes

In vitro studies on the effects of endotoxin on intestinal water and electrolyte transport in adult male rats showed a significant decrease in net colonic sodium absorption and increased colonic permeability.

T79396

90589-90722

Sentence

denotes

200 In horses, endotoxin negatively affects gastrointestinal motility, including in the cecum and right ventral colon, and perfusion.

T16236

90723-90726

Sentence

denotes

201

T33820

90727-90877

Sentence

denotes

The importance of a normal immune system to the defense of the mucosal surface of the gastrointestinal tract is evident in the immunosuppressed state.

T68651

90878-90962

Sentence

denotes

Primary immunodeficiencies affecting the gastrointestinal tract are well documented.

T87861

90963-91123

Sentence

denotes

Common agammaglobulinemia is the most frequently reported gastrointestinal immunodeficiency and causes B-cell deficiency-associated giardiasis in other species.

T67581

91124-91266

Sentence

denotes

202 In horses, severe combined immunodeficiency can result in diarrhea secondary to adenovirus, coronavirus, and/or Cryptosporidium infection.

T53328

91267-91429

Sentence

denotes

203, 204 Interestingly, selective immunoglobulin A (IgA) deficiency rarely results in intestinal disease because of a speculated increase in mucosal IgM response.

T57087

91430-91525

Sentence

denotes

However, combined IgA and IgM deficiencies with a higher incidence of intestinal disease occur.

T73840

91526-91631

Sentence

denotes

A selective deficiency of secretory IgA has been associated with intestinal candidiasis in other species.

T56471

91632-91717

Sentence

denotes

Certain mucosal pathogens may enhance their pathogenicity by producing IgA proteases.

T35596

91718-91944

Sentence

denotes

202 Acquired immunodeficiency or immunosuppression in adults can result from infectious diseases (particularly viral), nutritional deficiencies, aging phenomena, and drugs (corticosteroids, azathioprine, and cyclophosphamide).

T22777

91945-92044

Sentence

denotes

Chronic salmonellosis was documented secondary to adult-onset B-cell deficiency in a Quarter Horse.

T86174

92045-92048

Sentence

denotes

205

T39395

92049-92141

Sentence

denotes

Nutrition is a critical determinant of immunocompetence and risk of illness in many species.

T71322

92142-92304

Sentence

denotes

206 Impaired systemic and mucosal immunity contributes to an increased frequency and severity of intestinal infections observed in patients with undernourishment.

T83316

92305-92451

Sentence

denotes

Abnormalities occur in cell-mediated immunity, complement system, phagocytic function, mucosal secretory antibody response, and antibody affinity.

T87445

92452-92586

Sentence

denotes

Morbidity caused by diarrheal disease is increased, particularly among individuals with stunted growth rate because of malnourishment.

T67631

92587-92704

Sentence

denotes

207 The interaction between nutritional deficiency and intestinal health in the horse requires further investigation.

T66317

92705-92793

Sentence

denotes

Recently knowledge regarding the equine intestinal microbiota has expended dramatically.

T33166

92794-92896

Sentence

denotes

The intestinal microbiome is complex, and additional discussion is provided in Chapter 1 of this text.

T9073

92897-93050

Sentence

denotes

Briefly, fecal microbiota varies widely between healthy horses and those with colitis, 208 and changes can precede episodes of colic in postpartum mares.

T47467

93051-93281

Sentence

denotes

209 The intestinal microbiota is affected by antimicrobial administration, 210 transport, fasting and anesthesia, 211 and dietary starch, 212 among other factors; many of these have been associated with the development of colitis.

T62609

93282-93450

Sentence

denotes

Disturbances in motility patterns occur during inflammatory diseases of the colon, but the role of motility alterations in the pathogenesis of diarrhea remains unclear.

T8577

93451-93628

Sentence

denotes

Invasive bacteria cause characteristic motor patterns in the colon consisting of rapid bursts of motor activity that appear to decrease transit time through the large intestine.

T91072

93629-93753

Sentence

denotes

The result is reduced clearance of bacteria from the large intestine, which may contribute to the virulence of the organism.

T77172

93754-94024

Sentence

denotes

213 Absorption of endotoxin and the release of inflammatory mediators such as prostaglandins disrupts the motility patterns of the large intestine, resulting in less coordinated contractions, and may contribute to the alterations in motility seen with invasive bacteria.

T37511

94025-94185

Sentence

denotes

Although the effect of endotoxin and prostaglandins on transit time is not profound, the disruption of coordinated activity may play a role in causing diarrhea.

T43423

94186-94362

Sentence

denotes

214 Thorough mixing and prolonged retention time of ingesta are important not only in microbial digestion of nutrients but also in absorption of microbial byproducts and fluid.

T92395

94363-94485

Sentence

denotes

171 The ingesta is viscous and therefore must be mixed to bring luminal ingesta in contact with the mucosa for absorption.

T74175

94486-94631

Sentence

denotes

In addition, poor mixing increases the thickness of the unstirred layer, decreasing contact of ingesta with the mucosa and decreasing absorption.

T96546

94632-94716

Sentence

denotes

171 Progressive motility must be present, however, if a diarrheal state is to occur.

T95563

94717-94859

Sentence

denotes

171 Ileus may be accompanied by increased fluid in the lumen of the large intestine, but without progressive motility the fluid is not passed.

T87657

94860-95021

Sentence

denotes

Acute colitis is often associated with a period of ileus characterized by scant stool, which may be the reason for signs of colic in the early stages of colitis.

T17082

95022-95070

Sentence

denotes

Diarrhea is apparent only when motility returns.

T67196

95071-95277

Sentence

denotes

Increased progressive motility has been suggested to contribute to diarrhea by decreasing transit time; this is thought to play a role in irritant catharsis and in the mechanism of action of some laxatives.

T62069

95278-95373

Sentence

denotes

3 Endotoxemia Endotoxemia is literally defined as the presence of endotoxin in the bloodstream.

T51404

95374-95523

Sentence

denotes

Most often, however, the term is used to refer to the associated clinical manifestations caused by an excessive and unbalanced inflammatory reaction.

T96802

95524-95682

Sentence

denotes

Endotoxemia is not a disease in its own right; rather, it is a complication of many septic and nonseptic disease processes affecting horses and other animals.

T95095

95683-95799

Sentence

denotes

Its diagnosis and management must therefore be discussed in the context of underlying primary pathologic conditions.

T68920

95800-95987

Sentence

denotes

In its pathophysiologic consequences the innate immune response to endotoxin (LPS) is similar to the response to other stimuli (e.g., bacterial infection, viral infection, severe trauma).

T72354

95988-96297

Sentence

denotes

Moreover, the clinical presentation and clinical pathologic abnormalities of patients suffering from severe systemic inflammation are consistent regardless of the etiologic cause, and outcome may be predicted more accurately by the severity of the inflammatory response than the nature of the inciting insult.

T20955

96298-96566

Sentence

denotes

215 In 1992, therefore, the term systemic inflammatory response syndrome (SIRS) was introduced in a consensus statement of chest physicians and critical care physicians to account for these similarities and provide a case definition for clinical and research purposes.

T36342

96567-96867

Sentence

denotes

Fairly soon thereafter, however, the 1992 SIRS definition was criticized as being too sensitive while providing little specificity, 216 and its usefulness for clinical practice was challenged because it failed to predict outcome and to discriminate patients at a high risk of morbidity and mortality.

T1668

96868-97002

Sentence

denotes

217 The definition of SIRS may therefore be valuable from a conceptual standpoint, but it has little value in daily clinical practice.

T23988

97003-97563

Sentence

denotes

Sepsis was defined as the systemic inflammatory response to infection, and septic shock as "sepsis-induced hypotension, persisting despite adequate fluid resuscitation, along with the presence of hypoperfusion abnormalities or organ dysfunction. " 215 According to these definitions the diagnosis of sepsis requires documentation of infection by culture in addition to two or more of the following findings: hypothermia or hyperthermia; tachycardia; tachypnea or hypocapnia; and leukocytosis, leukopenia, or an increased proportion of immature leukocyte forms.

T22658

97564-97783

Sentence

denotes

Organ failure is a common sequela of endotoxic or septic shock, and the term multiple organ dysfunction syndrome describes insufficiency of two or more organ systems, as evident by clinical or clinicopathologic changes.

T98220

97784-97882

Sentence

denotes

In horses the laminae of the feet should be included in the list of organs susceptible to failure.

T86109

97883-98203

Sentence

denotes

German scientist Richard Pfeiffer (1858 Pfeiffer ( -1945 , in working with Vibrio cholerae, first described endotoxin as a toxin "closely attached to, and probably integral of, the bacterial body. " 218 He observed this toxin to be distinct from the actively secreted, heat-labile, and proteinaceous bacterial exotoxins.

T50358

98204-98332

Sentence

denotes

Endotoxin later was found to be a heat-stable LPS structure, and the terms endotoxin and LPS now are often used interchangeably.

T79189

98333-98454

Sentence

denotes

LPS is a major structural cell wall component of all gramnegative bacteria, including noninfectious species (Fig. 12.2) .

T45585

98455-98696

Sentence

denotes

With 3 to 4 × 10 6 molecules per cell, LPS makes up about 75% of the outer layer of the outer cell membrane and is a key functional molecule for the bacterial outer membrane, serving as a permeability barrier against external noxious agents.

T60833

98697-98802

Sentence

denotes

The LPS molecule consists of four domains that are essential for the virulence of gram-negative bacteria.

T31810

98803-99024

Sentence

denotes

219 Three of the domains (inner core, outer core, and O-specific chain) represent the hydrophilic polysaccharide portion of the molecule, whereas the lipid A portion represents the hydrophobic lipid portion ( Fig. 12.3) .

T98651

99025-99178

Sentence

denotes

Combined, these domains confer the overall amphiphilic properties of the molecule that lead to the formation of micellar aggregates in aqueous solutions.

T25986

99179-99360

Sentence

denotes

O-specific chains (also called O-antigen polysaccharides or O-chains) are characteristic of any given type of LPS and show enormous structural variability among bacterial serotypes.

T48545

99361-99511

Sentence

denotes

220 O-chains are synthesized by the addition of preformed oligosaccharide blocks to a growing polymer chain and therefore have a repetitive structure.

T8048

99512-99710

Sentence

denotes

O-specific chains determine part of the immunospecificity of bacterial cells 221 and, on interaction with the host immune system, serve as antigens for the production of species-specific antibodies.

T5507

99711-99919

Sentence

denotes

222 O-specific chains are further responsible for the smooth appearance of gram-negative bacterial colonies on culture plates, 219 and LPS molecules containing an O-chain are termed smooth lipopolysaccharide.

T96770

99920-100101

Sentence

denotes

The inner (lipid A-proximal) and outer (O-chain-proximal) core oligosaccharide portion is more conserved among different strains of gram-negative bacteria than the O-specific chain.

T8667

100102-100264

Sentence

denotes

220 The core of all LPS molecules contains the unusual sugar 3-deoxy-d-manno-oct-2-ulopyranosonic acid (KDO), which links the core region to the lipid A molecule.

T50832

100265-100419

Sentence

denotes

Synthesis of a minimal core is essential for the survival of bacteria, 223 and the smallest naturally occurring LPS structure consists of lipid A and KDO.

T51190

100420-100613

Sentence

denotes

224 In contrast to the S-form colonies, colonies of gram-negative bacteria with LPS molecules that lack the O-specific chain but contain a core region show a rough appearance on culture plates.

T21881

100614-100717

Sentence

denotes

Rough LPS molecules are denoted further as Ra, Rb, and so on to indicate the length of the core region.

T2459

100718-100802

Sentence

denotes

In Re-LPS (also called deep rough LPS), the core region is reduced to a KDO residue.

T11033

100803-100954

Sentence

denotes

Re-mutants often are used to raise antibodies against the core region in an attempt to provide cross-protection against a variety of bacterial species.

T3257

100955-101171

Sentence

denotes

The lipid A portion, which serves to anchor the LPS molecule in the bacterial outer membrane, has been identified as the toxic principle of LPS, 225 and its structure is highly conserved among gram-negative bacteria.

T70100

101172-101359

Sentence

denotes

The common structure shared by lipid A molecules is a 1,4′-bisphosphorylated β1,6linked d-glucosamine disaccharide backbone (lipid A backbone), which is acylated by up to six fatty acids.

T22248

101360-101427

Sentence

denotes

220 Fig. 12.4 shows the acylation pattern for Escherichia coli LPS.

T87979

101428-101633

Sentence

denotes

Variation in the lipid A structure between gram-negative bacteria affects the number, length, and position of fatty acids and the backbone structure and the substitution of phosphate by other polar groups.

T42703

101634-101637

Sentence

denotes

222

T72280

101639-101785

Sentence

denotes

According to its nature as a structural cell wall component, the presence of endotoxin implies the presence of gram-negative bacteria as a source.

T88591

101786-102065

Sentence

denotes

Depending on the nature of the underlying disease, these bacteria may circulate in the bloodstream in their intact form (i.e., bacteremia), may be confined to a localized infectious process, or may be part of the endogenous bacterial florae colonizing the gastrointestinal tract.

T16988

102066-102205

Sentence

denotes

In any of these scenarios endotoxin molecules are released as a byproduct of bacterial growth and in large numbers on bacterial cell death.

T43400

102206-102495

Sentence

denotes

226 Common infectious conditions associated with endotoxemia in horses include neonatal gram-negative sepsis, bacterial pneumonia and pleuropneumonia, endometritis, peritonitis, and infectious colitis with bacteria such as Salmonella spp. that are not part of the normal intestinal florae.

T52860

102496-102604

Sentence

denotes

In one study, for example, endotoxin was detectable in plasma of 50% of foals evaluated for presumed sepsis.

T97883

102605-102768

Sentence

denotes

227 The term translocation describes entry of endogenous bacteria and bacterial products from the gastrointestinal tract into tissues and the systemic circulation.

T97877

102769-102958

Sentence

denotes

228 The natural intestinal flora of horses consists mainly of gram-negative, anaerobic bacteria; thus, large amounts of endotoxin normally exist in the lumen of the equine intestinal tract.

T48816

102959-103101

Sentence

denotes

229 Even in healthy horse small amounts of endotoxin probably cross the intact mucosal barrier and reach the portal circulation and the liver.

T6336

103102-103275

Sentence

denotes

230 These molecules are cleared, however, by the mononuclear phagocytic system in the liver and lead only to a localized and restricted activation of the host immune system.

T3962

103276-103496

Sentence

denotes

For endotoxin translocation to become detrimental, excessive amounts have to cross the intestinal barrier and overwhelm the mononuclear phagocytic system, or the capacity of the liver to detoxify LPS must be compromised.

T38657

103497-103613

Sentence

denotes

The latter may be a concern in conditions such as hepatitis, cholangiohepatitis, or portosystemic shunting of blood.

T85017

103614-103725

Sentence

denotes

Permeability of the intestinal mucosal barrier frequently increases in cases of acute gastrointestinal disease.

T12842

103726-103871

Sentence

denotes

Colic patients are prime candidates for developing endotoxemia, and plasma endotoxin was detectable in 10% to 40% of colic patients on admission.

T6900

103872-104089

Sentence

denotes

231, 232 The studies differed in their inclusion criteria, and the higher percentage of horses testing positive for plasma endotoxin was observed when only patients presenting for surgical intervention were evaluated.

T31187

104090-104462

Sentence

denotes

232 Aside from gastrointestinal rupture, increased permeability to intact bacteria or free endotoxin molecules is thought to be associated most commonly with ischemic insults such as strangulating obstruction and bowel infarction; severe inflammation, as in proximal enteritis and colitis; bacterial overgrowth; and intraluminal acidosis, which occurs with grain overload.

T66440

104463-104659

Sentence

denotes

233, 234 One study, however, found no difference in plasma endotoxin detection among disease groups, emphasizing the fact that any disease of the abdominal cavity can induce endotoxemia in horses.

T92102

104660-104780

Sentence

denotes

In the same study endotoxin was approximately three times more likely to be detected in PF as opposed to plasma samples.

T60251

104781-104863

Sentence

denotes

Similarly, higher cytokine concentrations have been measured in PF than in plasma.

T88967

104864-105069

Sentence

denotes

The likely explanation for these findings is a local inflammatory response in the peritoneal cavity elicited by translocated bacteria or LPS molecules before their absorption into the systemic circulation.

T88463

105070-105257

Sentence

denotes

231 Although gastrointestinal disease is likely the most important cause of endotoxin translocation in horses, other conditions may also result in translocation of endotoxin and bacteria.

T38970

105258-105614

Sentence

denotes

In experimental studies using laboratory animals, entry of gut-associated bacteria into the lymphatic system was demonstrated after hypovolemic shock, burn injuries, trauma, malnutrition, and starvation. [235] [236] [237] Furthermore, endotoxin itself caused bacterial translocation into mesenteric lymph nodes after intraperitoneal administration to mice.

T12766

105615-105813

Sentence

denotes

238 These findings have received much attention in the literature concerning human patients because they serve to explain cases of endotoxic shock in the absence of demonstrable bacterial infection.

T1947

105814-106014

Sentence

denotes

The veterinarian should keep in mind the possibility of translocation when evaluating cases of presumed SIRS in horses, in which bacterial infection or gastrointestinal disease cannot be demonstrated.

T53104

106015-106176

Sentence

denotes

Endotoxin translocation also may be associated with strenuous exercise, which results in reduced splanchnic blood flow, hypoxemia, and a higher body temperature.

T9658

106177-106318

Sentence

denotes

In fit racehorses a significantly increased mean plasma LPS concentration was found after racing, whereas anti-LPS IgG levels were decreased.

T89898

106319-106521

Sentence

denotes

Fit horses showed significantly higher anti-LPS IgG concentrations at rest than sedentary controls, suggesting leakage of small amounts of endotoxin from the intestinal lumen during training and racing.

T60082

106522-106784

Sentence

denotes

239 A study in endurance horses demonstrated detectable LPS concentration in approximately 50% of horses, and correlation between plasma endotoxin and lactate concentration suggested that plasma endotoxin concentration may be reflective of the vigor of exercise.

T64233

106785-107085

Sentence

denotes

240 Surprisingly, the latter study failed to show a correlation between plasma endotoxin concentration and levels of inflammatory mediators such as TNF-α and IL-6, 240 experimentally, however, alterations in innate immune function during and after strenuous exercise in horses have been demonstrated.

T72291

107086-107089

Sentence

denotes

241

T50308

107090-107296

Sentence

denotes

The initiating event in the pathophysiology of endotoxemia is the activation of LPS-responsive cells by endotoxin, resulting in altered cellular functions and increased expression of inflammatory mediators.

T49591

107297-107461

Sentence

denotes

Immune cells such as macrophages respond to minute amounts of LPS, which usually allows them to eliminate gram-negative bacteria and free LPS molecules efficiently.

T54039

107462-107563

Sentence

denotes

An important factor in the exquisite sensitivity to LPS is the presence of LPS-binding protein (LBP).

T40629

107564-107713

Sentence

denotes

220 LBP is an approximately 60-kDa plasma glycoprotein 242 synthesized primarily by hepatocytes 243 and belongs to the family of lipid transfer/LBPs.

T34359

107714-107895

Sentence

denotes

LBP is an acute phase protein, and inflammatory agents and cytokines such as IL-1 increase LBP plasma concentration 10-to 100-fold within 24 to 48 hours of an inflammatory stimulus.

T95338

107896-108067

Sentence

denotes

244 , 245 The main function of LBP is to transfer LPS to endotoxin-responsive cells, which include mononuclear phagocytes, neutrophils, lymphocytes, and endothelial cells.

T43828

108068-108312

Sentence

denotes

The importance of a highly sensitive response to LPS for protection against gram-negative bacterial infection is demonstrated in experiments using LBP knockout micethat is, mice that lack the LBP gene and are therefore unable to synthesize LBP.

T76924

108313-108460

Sentence

denotes

Although these animals are resistant to the effects of purified LPS, they are unable to control infection with viable bacteria and rapidly succumb.

T20604

108461-108661

Sentence

denotes

246 Despite its crucial importance for an effective host defense, LBP is not essential for LPS-receptor interaction per se, because high concentrations of LPS can activate cells in the absence of LBP.

T84266

108662-108838

Sentence

denotes

247 Aside from its role as a catalyst of cellular activation by LPS, LBP has opsonizing activity 248 and participates in the phagocytosis of LPS by macrophages and neutrophils.

T53184

108839-109008

Sentence

denotes

249, 250 Although phagocytosis of LPS is receptor dependent, it appears to be uncoupled from intracellular signaling events and occurs in the absence of cell activation.

T47723

109009-109133

Sentence

denotes

251 LBP further catalyzes transfer of LPS to lipoproteins, such as high-density lipoprotein, which neutralizes LPS activity.

T68356

109134-109221

Sentence

denotes

252 This detoxifying effect may become important when large amounts of LPS are present.

T94972

109222-109428

Sentence

denotes

A protective effect of LBP against LPS challenge and infection has been demonstrated in a murine model of septic shock, 253 and further studies investigating potential therapeutic uses of LBP are under way.

T26510

109429-109628

Sentence

denotes

More recently, LBP has also been investigated as a diagnostic and prognostic indicator in human patients, in which it may differentiate between SIRS and sepsis and predict outcome of septic patients.

T4210

109629-109857

Sentence

denotes

245 One study investigating serum amyloid A (SAA) and LBP in horses with colic 254 found no correlation between serum concentration of LBP with outcome, type of disease process, or affected portion of the gastrointestinal tract.

T1714

109858-109951

Sentence

denotes

The most important LPS receptors are cluster differentiation antigen 14 (CD14) 247 and TLR-4.

T63531

109952-110109

Sentence

denotes

255 Both are classified as pattern-recognition receptors, 256 which means that they recognize LPS as a structural motif common to all gram-negative bacteria.

T53957

110110-110253

Sentence

denotes

CD14 is a 53-kDa protein that in its membranebound form (mCD14) is inserted into the cell membrane via a glycosyl-phosphatidyl-inositol anchor.

T20566

110254-110360

Sentence

denotes

257 CD14 is expressed primarily on monocytes and tissue macrophages and to a lesser extent on neutrophils.

T58873

110361-110510

Sentence

denotes

258 It also is found in a soluble form (sCD14) 259 that can bind to cell types lacking CD14, such as endothelial cells, and make them LPS responsive.

T99360

110511-110617

Sentence

denotes

In addition to this proinflammatory effect, high concentrations of sCD14 can sequester and neutralize LPS.

T32024

110618-110758

Sentence

denotes

260 The amount of circulating sCD14 greatly increases during inflammation, which makes it a useful marker of acute and chronic inflammation.

T55391

110759-110918

Sentence

denotes

258 Although CD14 is known to be crucial for cellular activation, it cannot transmit signals to the inside of the cell because it lacks a transmembrane domain.

T20939

110919-111041

Sentence

denotes

The missing link between CD14 and the cytosolic environment is a Toll-like receptor in association with the molecule MD-2.

T72394

111042-111245

Sentence

denotes

261 The name Toll-like receptor stems from the homology of the mammalian receptor with a receptor type in Drosophila (Toll) that is important for dorsoventral orientation and immune responses in the fly.

T95869

111246-111407

Sentence

denotes

A number of Toll-like receptors have been identified in mammalian species thus far, but TLR4 appears to be the receptor subtype most important for LPS signaling.

T70846

111408-111525

Sentence

denotes

255 The importance of CD14 and TLR4 in the cellular response to LPS has been demonstrated in a number of experiments.

T76240

111526-111887

Sentence

denotes

Mice deficient in CD14 are incapable of mounting a normal inflammatory response to LPS, 260 whereas mutation or deletion of the gene encoding for TLR4 causes LPS hyporesponsiveness. [262] [263] [264] After binding of LPS to cellular receptors, TLR4 undergoes oligomerization and recruits downstream adaptor proteins to activate intracellular signaling pathways.

T67311

111888-112087

Sentence

denotes

265 Signaling pathways are characterized by sequential phosphorylation and activation of enzymatic activities and ultimately result in the alterations of cellular metabolism known as cell activation.

T72633

112088-112241

Sentence

denotes

A typical result of intracellular signaling is the activation of transcription factors-that is, proteins that bind to DNA and promote gene transcription.

T62550

112242-112301

Sentence

denotes

Translational mechanisms are activated in a similar manner.

T45258

112302-112450

Sentence

denotes

TLR4-dependent cell signaling pathways can be differentiated according to the use of adaptor proteins that bind to the intracellular domain of TLR4.

T23146

112451-112696

Sentence

denotes

265 The myeloid differentiation primary response gene 88 (MyD88)-dependent pathway results in activation of IKK (Iκβ kinase) and mitogen-activated protein kinase (MAPK) pathways and ultimately in the expression of proinflammatory cytokine genes.

T12898

112697-112866

Sentence

denotes

IKK activates the well-described transcription factor NF-κβ by phosphorylating an inhibitor protein complex (IκB) that sequesters and inactivates NF-κβ in the cytoplasm.

T80997

112867-112996

Sentence

denotes

On phosphorylation IκB is ubiquitinated and degraded, and NF-κβ is translocated to the nucleus, in which it unfolds its activity.

T68594

112997-113185

Sentence

denotes

266 The MyD88independent pathway, on the other hand, is activated by interaction of TLR4 with the adaptor protein Toll-IL-1 receptor domain-containing adaptor inducing interferon-β (TRIF).

T67545

113186-113438

Sentence

denotes

Although the MyD88-independent pathway also activates MAPK and NF-κβ (in addition to a transcription factor called IRF3), this pathway primarily results in activation of type I interferons, which are important for antiviral and antibacterial responses.

T6625

113439-113605

Sentence

denotes

265 Despite the characterization of seemingly separate and "ordered" pathways, one should recognize that interaction and synergy between pathways are likely to occur.

T89003

113606-113735

Sentence

denotes

Similarly, inhibitory pathways are required for regulation of the cell response and can target multiple levels of TLR4 signaling.

T46192

113736-113851

Sentence

denotes

265 The potential manipulation of signaling pathways for therapeutic use in septic patients is under investigation.

T97406

113852-113950

Sentence

denotes

Although endotoxin can exert some direct effects, cytokines are a primary mediator of LPS effects.

T53402

113951-114072

Sentence

denotes

Cytokines are glycoprotein molecules that regulate inflammatory and immune responses by acting as a signal between cells.

T54593

114073-114258

Sentence

denotes

267 Cytokines of major interest in the pathogenesis of endotoxemia include TNF-α, the interleukins, chemokines, and growth factors such as granulocytemonocyte colony-stimulating factor.

T58383

114259-114339

Sentence

denotes

TNF-α is thought of as the most "proximal" cytokine released in response to LPS.

T45053

114340-114538

Sentence

denotes

Studies corroborate this by showing that administration of recombinant TNF-α mimics the effects of LPS 268 and that antibodies directed against TNF-α protect against the lethal effects of endotoxin.

T23590

114539-114693

Sentence

denotes

269 Increased plasma activity of TNF is associated with increased mortality in equine patients with acute gastrointestinal disease and in septic neonates.

T86088

114694-114874

Sentence

denotes

231 Despite being a structurally diverse group of proteins, cytokines share several characteristics that allow them to execute their complex functions in the inflammatory response.

T33422

114875-115034

Sentence

denotes

267 Any individual cytokine generally is produced by several different cell types, can act on different cell types, and has multiple effects on any given cell.

T24612

115035-115139

Sentence

denotes

Furthermore, cytokine effects are redundant, meaning that different cytokines can share the same effect.

T97096

115140-115215

Sentence

denotes

In endotoxemia this is particularly true for the effects of IL-1 and TNF-α.

T28354

115216-115353

Sentence

denotes

270 Many of the biologic activities of cytokines in vivo result from synergistic or antagonistic actions involving two or more cytokines.

T10746

115354-115593

Sentence

denotes

271 Within itself the cytokine response is highly regulated: cytokines induce or suppress synthesis of other cytokines, including their own (feedback regulation); regulate expression of cytokine receptors; and regulate cytokine activities.

T94642

115594-115892

Sentence

denotes

Additional regulatory mechanisms include the release of specific cytokine inhibitors such as soluble IL-1 and TNF-α receptors; cytokine receptor antagonists such as the IL-1 receptor antagonist; and antiinflammatory cytokines, including IL-10, IL-4, IL-13, and transforming growth factor-β (TGF-β).

T49323

115893-116009

Sentence

denotes

Glucocorticoids, which are produced increasingly in response to endotoxin, also inhibit the production of cytokines.

T89019

116010-116274

Sentence

denotes

272 During a "controlled" inflammatory response, therefore, cytokine secretion is a self-limited event, whereas excessive stimulation of cytokine production can lead to the perpetuation of the inflammatory response even after the initial stimulus has been removed.

T84987

116275-116560

Sentence

denotes

Aberrations from the controlled, self-regulated inflammatory response have been described as predominantly proinflammatory (SIRS), antiinflammatory or hypoinflammatory (compensatory antiinflammatory response syndrome [CARS]), or combined (mixed antagonist response syndrome) responses.

T23330

116561-116743

Sentence

denotes

273 That these responses may not represent a continuum in response to infection was demonstrated in a recent study investigating cytokine profiles in an experimental model of sepsis.

T3855

116744-116988

Sentence

denotes

274 Here, increased plasma concentration of antiinflammatory mediators such as IL-1 receptor antagonist and IL-10 in the early phase of sepsis predicted early mortality almost as accurately as the typical proinflammatory cytokines such as IL-6.

T3923

116989-117150

Sentence

denotes

Cytokine profiles failed to predict mortality in the later stages of sepsis, thereby suggesting that late outcome is not "preprogrammed" early on in the disease.

T8560

117151-117271

Sentence

denotes

A progression from proinflammatory (SIRS) to antiinflammatory (CARS), as previously proposed, could not be demonstrated.

T79604

117272-117566

Sentence

denotes

274 The authors concluded that use of biomarkers may be helpful in determining the inflammatory status of clinical patients suffering from sepsis and that the success of treatments aimed at suppressing or stimulating immune responses may depend on the individual patient's inflammatory profile.

T96353

117567-117645

Sentence

denotes

Interestingly, tolerance to endotoxin develops after repeated exposure to LPS.

T43337

117646-117786

Sentence

denotes

275 Tolerance can be demonstrated in vitro and in vivo and encompasses decreased production of cytokines and a diminished clinical response.

T63418

117787-117992

Sentence

denotes

275, 276 Tolerance may be a protective mechanism and was shown to reduce mortality in some experimental models; however, impaired resistance to infectious processes was demonstrated by other investigators.

T29557

117993-118225

Sentence

denotes

277 Mechanisms that likely are responsible for the development of endotoxin tolerance include receptor downregulation, 278 downregulation of intracellular signaling pathways, 277, 279 and mediators such as glucocorticoids and IL-10.

T3500

118226-118297

Sentence

denotes

277 The development of endotoxin tolerance in horses has been reported.

T22654

118298-118450

Sentence

denotes

280, 281 More recently, the term cellular reprogramming has been introduced to describe altered inflammatory cell functions in septic and SIRS patients.

T97705

118451-118692

Sentence

denotes

This term better accounts for the observation that cellular LPS-sensing ability appears to be maintained, whereas intracellular signaling and cytokine production are modified toward an antiinflammatory rather than a proinflammatory response.

T18266

118693-118898

Sentence

denotes

277 Aside from cytokines, a number of other molecules function as inflammatory mediators in the pathogenesis of endotoxemia, the synthesis and release of which are stimulated by endotoxin and by cytokines.

T44363

118899-119065

Sentence

denotes

These mediators include the arachidonic acid metabolites or prostanoids, PAF, oxygenderived free radicals, nitric oxide, histamine, kinins, and complement components.

T85882

119066-119212

Sentence

denotes

Table 12 .2 summarizes the origins, targets, and effects of the most important inflammatory mediators involved in the pathogenesis of endotoxemia.

T2450

119213-119299

Sentence

denotes

Fig. 12 .5 shows the pathways of arachidonic acid metabolism by COX and lipoxygenase.

T87459

119300-119424

Sentence

denotes

COX products are the prostaglandins, prostacyclin (PGI 2 ) and thromboxanes, and the lipoxygenase produces the leukotrienes.

T93794

119426-119638

Sentence

denotes

The innate immune response to LPS is an efficient defense mechanism that provides maintenance of homeostasis and therefore health in the face of an almost continuous exposure to microorganisms and their products.

T45318

119639-119914

Sentence

denotes

282 Detrimental consequences of this immune response occur only if excessive and uncontrolled mediator output results in endothelial damage, neutrophil-mediated tissue damage, and uncontrolled activation of the coagulation and fibrinolytic cascades and the complement system.

T36925

119915-120054

Sentence

denotes

Ultimately, the combination of these events culminates in cardiovascular instability, impaired hemostasis, organ failure, shock, and death.

T46098

120055-120209

Sentence

denotes

The following discussion addresses the various pathophysiologic events in the development of endotoxemia and shock and the role of inflammatory mediators.

T84273

120210-120350

Sentence

denotes

Normal endothelium plays an important role in regulating blood pressure and regional tissue perfusion and provides an anticoagulant surface.

T23857

120351-120549

Sentence

denotes

Endothelial dysfunction and damage result in a decreased responsiveness to vasoactive agents (vasoplegia), increased vascular permeability, and a tendency for clot formation in the microvasculature.

T26757

120550-120649

Sentence

denotes

If the basement membrane and underlying matrix are compromised, microvascular hemorrhage can occur.

T62071

120650-120707

Sentence

denotes

Endothelial cell damage is primarily neutrophil mediated.

T20296

120708-120992

Sentence

denotes

More specifically, damage is caused by oxygen-derived free radicals, which are produced within endothelial cells through reactions involving neutrophil-derived elastase and hydrogen peroxide molecules, endothelial cell enzymes such as xanthine oxidase, and endothelial cytosolic iron.

T79371

120993-121106

Sentence

denotes

The hypochloric anion radical (HO˙) is thought to be responsible most directly for endothelial cell cytotoxicity.

T7174

121107-121355

Sentence

denotes

Nitric oxide, which is produced by constitutively expressed nitric oxide synthase in endothelial cells and scavenges superoxide radicals in a reaction to form peroxynitrite, may afford protection from oxygen radical-induced endothelial cell damage.

T97678

121356-121515

Sentence

denotes

Variations in the ability to produce nitric oxide may explain why vascular beds in different organs vary in their susceptibility to neutrophil-mediated damage.

T48491

121516-121771

Sentence

denotes

283 Excessive production of nitric oxide by an inducible form of nitric oxide synthase (iNOS), however, contributes to tissue damage, and increased peroxynitrite concentrations may be responsible in part for PAF-induced increases in vascular permeability.

T25102

121772-121912

Sentence

denotes

284 In addition to oxygen-derived free radicals, activated neutrophils release matrix metalloproteinases, which contribute to tissue damage.

T90413

121913-121916

Sentence

denotes

272

T36489

121918-122121

Sentence

denotes

Neutrophil activation by LPS and cytokines results in stimulation of phagocytosis and the respiratory burst, release of lysosomal enzymes and inflammatory mediators, and expression of adhesion molecules.

T93021

122122-122296

Sentence

denotes

Perhaps the single most specific clinicopathologic indicator of endotoxemia is pronounced neutropenia, 286 which temporally correlates with peak plasma concentrations of TNF.

T76731

122297-122555

Sentence

denotes

287 Neutropenia is caused primarily by margination of neutrophils in the vasculature, especially of the lungs, 288 whereas significant loss through active migration into peripheral tissues likely is limited to the presence of a localized source of infection.

T96843

122556-122699

Sentence

denotes

In fact, neutrophils exposed to endotoxin or inflammatory mediators exhibit reduced capacity to respond to chemotactic stimuli and extravasate.

T69230

122700-122881

Sentence

denotes

288 Margination is made possible by adhesion molecules on endothelial cells and leukocytes that interact and allow sticking of leukocytes to the endothelial lining of blood vessels.

T15472

122882-122979

Sentence

denotes

The details of neutrophil margination and transmigration are reviewed in several excellent texts.

T82458

122980-123240

Sentence

denotes

289, 290 Recent evidence demonstrates a role for TLR-4 in neutrophil margination in the lung microvasculature during endotoxemia, and suggests that activation and TLR-4 expression of endothelial cells may be more important than that of circulating neutrophils.

T68153

123241-123523

Sentence

denotes

288 Although neutrophil activation during infections provides the body with an effective defense system against microbial invaders, margination and reduced migratory ability of neutrophils during endotoxemia results in the accumulation of activated cells at the endothelial surface.

T72570

123524-123687

Sentence

denotes

These cells are then positioned to effect endothelial injury, increase vascular permeability, and in some cases cause parenchymal cell death and organ dysfunction.

T9497

123688-123853

Sentence

denotes

291 In addition, inhibition of transmigration deprives the body of phagocytic cells at sites of infection, resulting in reduced ability to fight bacterial infection.

T2279

123854-124058

Sentence

denotes

This latter complication of endotoxemia may have significant clinical impact, because defective neutrophil recruitment has been demonstrated at low endotoxin doses that do not yet result in tissue damage.

T83466

124059-124206

Sentence

denotes

291, 292 In human patients endotoxemia and impaired neutrophil migration have been associated with infectious complications of surgical procedures.

T42840

124207-124439

Sentence

denotes

291 Decreased phagocytic function and oxidative burst activity have also been suggested in sick and septic hospitalized foals, 293, 294 in which a beneficial effect of plasma transfusion on neutrophil function could be demonstrated.

T53769

124440-124711

Sentence

denotes

The mechanisms of migration inhibition during endotoxemia are incompletely understood but may include occupation of neutrophil chemotactic receptors by cytokines and complement components, resulting in an inability of activated cells to respond to a chemotactic gradient.

T59468

124712-125012

Sentence

denotes

291 Rebound neutrophilia, which is observed frequently following episodes of endotoxemia, is caused by neutrophil release from the bone marrow reserve pool and by stimulation of myeloid cell proliferation via granulocyte-macrophage colony-stimulating factor and is mediated primarily by TNF and IL-1.

T56939

125013-125016

Sentence

denotes

270

T94051

125017-125153

Sentence

denotes

In health coagulation and fibrinolysis underlie stringent control mechanisms that allow appropriate clot formation and their resolution.

T70461

125154-125295

Sentence

denotes

Coagulopathies frequently are observed in horses with colic 233,295,296 and foals with sepsis 227 and are likely attributable to endotoxemia.

T93355

125296-125525

Sentence

denotes

In human medicine virtually all septic patients are considered to have some degree of coagulopathy, which may range from subclinical abnormalities of the clotting profile to fulminant disseminated intravascular coagulation (DIC).

T22138

125526-125660

Sentence

denotes

297, 298 DIC results from a widespread activation of the coagulation and fibrinolytic systems and failure of their control mechanisms.

T81721

125661-125845

Sentence

denotes

Ultimately, this leads to disseminated fibrin deposition in the microvasculature, consumption of platelets and clotting factors, and accumulation of fibrin degradation products (FDPs).

T51386

125846-126127

Sentence

denotes

Depending on the underlying disease process and the relative impairment of the coagulation and fibrinolytic systems, DIC can manifest as a diffuse thrombotic syndrome leading to ischemic organ failure, a fibrinolytic syndrome with uncontrolled hemorrhage, or a combination of both.

T83339

126128-126239

Sentence

denotes

299 A procoagulant state characterized by clinicopathologic abnormalities of the clotting profile precedes DIC.

T64482

126240-126329

Sentence

denotes

The intrinsic and extrinsic arms of the coagulation cascade are activated in endotoxemia.

T71799

126330-126496

Sentence

denotes

The intrinsic pathway is initiated by activation of coagulation factor XII (HF), prekallikrein, and high-molecular-weight kininogen, which compose the contact system.

T49964

126497-126703

Sentence

denotes

300 Although direct activation of coagulation factor XII by endotoxin has been demonstrated, 301 the extrinsic pathway likely is more important for the development of coagulopathy in endotoxemia and sepsis.

T80162

126704-126890

Sentence

denotes

300 Activation of the extrinsic pathway depends on the interaction of coagulation factor VII with tissue factor, which is the only coagulation factor not constitutively present in blood.

T83133

126891-127065

Sentence

denotes

Tissue factor is present in subendothelial tissues and is exposed on vascular injury but also is expressed on endothelial cells and mononuclear phagocytes in response to LPS.

T40214

127066-127261

Sentence

denotes

302, 303 Increased expression of monocyte tissue factor (also described as increased procoagulant activity) was significantly associated with coagulopathy and poor prognosis in horses with colic.

T28870

127262-127416

Sentence

denotes

304 Furthermore, LPS-induced tissue factor expression by equine peritoneal macrophages may be associated with the development of intraabdominal adhesions.

T39352

127417-127562

Sentence

denotes

280 Regulatory mechanisms of the coagulation cascade include tissue factor pathway inhibitor, antithrombin III (AT III) and the protein C system.

T84669

127563-127726

Sentence

denotes

300 Protein C acts as an anticoagulant by inactivating clotting factors V and VIII and promotes fibrinolysis by inactivating plasminogen activator inhibitor (PAI).

T23827

127727-128296

Sentence

denotes

305 Protein C activation by thrombin-thrombomodulin complexes is important for the anticoagulative properties of normal endothelium, 300 and downregulation of endothelial thrombomodulin expression by TNF and IL-1 along with decreased expression of AT III and tissue factor pathway inhibitor by damaged endothelial cells contribute to the procoagulant state in endotoxemia and sepsis. [306] [307] [308] In addition, activation of vascular endothelial cells leads to a loss of prostacyclin and nitric oxide production and an increased release of thromboxane A 2 (TXA 2 ).

T22886

128297-128408

Sentence

denotes

As a result, platelets are stimulated to aggregate and release TXA 2 and PAF, further promoting clot formation.

T87296

128409-128529

Sentence

denotes

234 The crucial step in the fibrinolytic cascade is the conversion of plasminogen to plasmin, a fibrin-degrading enzyme.

T66928

128530-128709

Sentence

denotes

300 Tissue-type (tPA) and urokinase-type (uPA) plasminogen activator are the major initiators of fibrinolysis, whereas PAI and α 2 -antiplasmin are the main regulatory components.

T59218

128710-128810

Sentence

denotes

309, 310 TNF and IL-1 have been shown to induce the release of uPA and tPA and the synthesis of PAI.

T25928

128811-129061

Sentence

denotes

300 Activation of fibrinolysis leads to consumption of α 2 -antiplasmin and accumulation of FDPs, which if present in high concentrations can interfere with platelet aggregation, fibrin polymerization, and thrombin formation and can promote bleeding.

T32426

129062-129126

Sentence

denotes

Additionally, FDPs mediate an increase in vascular permeability.

T12763

129127-129299

Sentence

denotes

LPS infusion in rabbits 311 and humans 312 resulted in an early increase in plasma tPA activity, followed by a later profound rise in PAI activity and fall in tPA activity.

T77941

129300-129396

Sentence

denotes

Increased plasma PAI concentrations also were found in horses with colic compared with controls.

T23845

129397-129538

Sentence

denotes

313, 314 Although fibrinolysis may compensate initially for accelerated coagulation, its subsequent inhibition contributes to clot formation.

T23835

129539-129794

Sentence

denotes

Cross-activation between the inflammatory and coagulation cascades plays an important role in endotoxemia and sepsis, and the presence of coagulopathies has been associated with an increased risk of organ failure and poor outcome in septic human patients.

T96876

129795-129867

Sentence

denotes

297, 298 Activated protein C reduces mortality in septic human patients.

T59715

129868-130024

Sentence

denotes

315 Activated protein C reduces inflammation by inhibiting leukocyte activation and cytokine production and was shown to lower plasma concentration of IL-6.

T46493

130025-130158

Sentence

denotes

315 Although bleeding complications were increased in treated patients, incidence of severe bleeding was not increased significantly.

T83471

130159-130274

Sentence

denotes

Activation of the complement system in endotoxemia occurs via the alternative pathway through interaction with LPS.

T80381

130275-130471

Sentence

denotes

Increased concentrations of plasmin and kallikrein (caused by activation of the fibrinolytic and contact system) further promote this pathway by directly activating complement factors C3a and C5a.

T19362

130472-130636

Sentence

denotes

Aside from being key molecules in the complement cascade, C3a and C5a are anaphylatoxins and cause an increase in vascular permeability via mast cell degranulation.

T13420

130637-130819

Sentence

denotes

C5a further activates the lipoxygenase pathway in neutrophils and monocytes, acts as a chemotaxin for leukocytes and monocytes, and promotes neutrophil adhesion to endothelial cells.

T63099

130820-130999

Sentence

denotes

In response to acute inflammation, synthesis and secretion of a number of proteins called the acute phase proteins increase in hepatocytes, whereas synthesis of albumin decreases.

T32783

131000-131104

Sentence

denotes

The primary function of this acute phase response may be to suppress and contain inflammatory processes.

T84081

131105-131331

Sentence

denotes

272 IL-6 and IL-1 are the most important cytokines that induce the acute phase response, 316 which typically begins within a few hours of the insult and subsides within 24 to 48 hours, 317 unless the initiating cause persists.

T9657

131332-131601

Sentence

denotes

In horses fibrinogen (the most commonly evaluated acute phase protein), haptoglobin, transferrin, ferritin, ceruloplasmin, coagulation factor VIII:C, SAA, C-reactive protein, α 1 -acid glycoprotein, and phospholipase A 2 are considered part of the acute phase response.

T60331

131602-131828

Sentence

denotes

318 SAA is a sensitive indicator of experimentally induced inflammation 319 and may be helpful in the diagnosis of inflammatory gastrointestinal disease, 254 neonatal weakness and diarrhea, 320 and various infectious diseases.

T2709

131829-131931

Sentence

denotes

A commercially available turbidimetric immunoassay for human SAA is reliable for measuring equine SAA.

T29540

131932-132083

Sentence

denotes

321 The effect of acute inflammation on the serum concentration of several coagulation factors must be considered when evaluating coagulation profiles.

T59436

132084-132251

Sentence

denotes

Serum fibrinogen concentration is determined primarily by the acute phase response, although fibrinogen is consumed increasingly on activation of the clotting cascade.

T17205

132252-132472

Sentence

denotes

Shock is characterized by a loss of homeostasis attributable to the breakdown of hemodynamic control mechanisms, decreases in cardiac output and the effective circulating volume, and inadequate perfusion of vital organs.

T21509

132473-132607

Sentence

denotes

Shock caused by endotoxemia is classified as distributive shock 322 and is largely initiated by vascular dysfunction in the periphery.

T13239

132608-132779

Sentence

denotes

Peripheral vascular beds are of major importance for the regulation of local tissue perfusion and affect systemic blood pressure by regulating total peripheral resistance.

T39250

132780-132954

Sentence

denotes

Normally, vascular smooth muscle tone is regulated by endothelin-1 (vasoconstriction), nitric oxide, and prostacyclin (vasodilation) released from vascular endothelial cells.

T33633

132955-133136

Sentence

denotes

323 Detrimental effects of nitric oxide are attributable to overproduction of nitric oxide by iNOS in macrophages and other cell types, rather than endothelial-derived nitric oxide.

T12378

133137-133294

Sentence

denotes

Peripheral vasomotor effects of endotoxin manifest as vasodilation and vasoplegia and are mediated by PGI 2 , nitric oxide, and mediators such as bradykinin.

T9279

133295-133481

Sentence

denotes

Widespread vasodilation leads to vascular blood pooling, decentralization of blood flow, decreased venous return, and in effect decreased effective circulating volume and cardiac output.

T73340

133482-133727

Sentence

denotes

322 Compensatory responses in the form of an initial hyperdynamic phase include tachycardia, increased cardiac output and central venous pressure, pulmonary hypertension, peripheral vasoconstriction, and increased peripheral vascular resistance.

T12736

133728-134027

Sentence

denotes

322, 324, 325 The early vasoconstrictive phase corresponds to an increased serum concentration of TXA 2 , 234 but additional vasoconstrictors such as arginine vasopressin, angiotensin II, serotonin, endothelin, and norepinephrine likely are implicated in the pathogenesis of shock and organ failure.

T64380

134028-134240

Sentence

denotes

272 With progression of disease the animal enters a stage of decompensated shock and progressive systemic hypotension, which corresponds to increased plasma concentrations of prostacyclin, PGE 2 , and bradykinin.

T46774

134241-134596

Sentence

denotes

234, 272 Inadequate blood flow and oxygen delivery to tissues caused by hypotension are confounded by direct myocardial suppression via nitric oxide, 322 increased vascular permeability, 234 intravascular microthrombosis, and impaired tissue oxygen extraction 322 and results in progressive metabolic acidosis and inhibition of normal cellular metabolism.

T79837

134597-134655

Sentence

denotes

Quantification of endotoxin in plasma samples is possible.

T50646

134656-134816

Sentence

denotes

The Limulus amebocyte lysate assay is an activity assay based on the endotoxin-sensitive hemolymph coagulation cascade in the horseshoe crab Limulus polyphemus.

T86156

134817-134912

Sentence

denotes

In Limulus, this reaction is thought to be a defense mechanism against gram-negative infection.

T61942

134913-135031

Sentence

denotes

326 Although frequently used as a research tool, the assay is not convenient enough to become a routine clinical test.

T46244

135032-135222

Sentence

denotes

The clinician therefore must appreciate the primary disease processes associated with a high risk of endotoxemia and rely on clinical signs and clinicopathologic data to achieve a diagnosis.

T45926

135223-135512

Sentence

denotes

In a survey of board-certified internal medicine specialists and surgeons, colitis/enteritis, small intestinal strangulation and obstruction, retained fetal membranes/metritis, grain overload, and pleuropneumonia were among the most frequently cited conditions associated with endotoxemia.

T57422

135513-135652

Sentence

denotes

327 In some cases, endotoxemia may be the first indication of disease or may be the most overt of otherwise subtle clinical manifestations.

T18757

135653-135867

Sentence

denotes

With colitis or proximal enteritis, for example, one may detect signs of endotoxemia before the development of colic, diarrhea, or gastric reflux, which more specifically indicate the nature of the primary illness.

T42130

135868-135968

Sentence

denotes

The presence of neutropenia should always prompt the clinician to investigate causes of endotoxemia.

T18237

135969-136148

Sentence

denotes

In vivo LPS challenge experiments in horses clearly show that many of the clinical signs associated with acute gastrointestinal disease and sepsis are attributable to endotoxemia.

T5735

136149-136301

Sentence

denotes

On administration of sublethal doses of LPS, the clinical response can be divided into the early hyperdynamic and the later hypodynamic or shock phases.

T85579

136302-136525

Sentence

denotes

Clinical signs during the first phase, which begins within 15 to 45 minutes after LPS administration, include anorexia, yawning, sweating, depression, evidence of abdominal discomfort, muscle fasciculations, and recumbency.

T11127

136526-136603

Sentence

denotes

Heart and respiratory rates increase, and decreased borborygmi suggest ileus.

T60115

136604-136711

Sentence

denotes

Hyperemia of the mucous membranes and an accelerated capillary refill time indicate the hyperdynamic state.

T76674

136712-136877

Sentence

denotes

286 If large amounts of LPS are administered or if exposure is ongoing, depression worsens progressively, anorexia persists, and feces develop a diarrheic character.

T12566

136878-136933

Sentence

denotes

Signs of colic typically abate after the initial stage.

T85813

136934-137087

Sentence

denotes

Fever develops as a result of direct action of TNF on the thermoregulatory center and IL-1-induced local production of PGE 2 in or near the hypothalamus.

T33648

137088-137264

Sentence

denotes

328, 329 Because of compromised peripheral perfusion, mucous membrane color changes to brick red or purple, a dark "toxic" line appears, and capillary refill time is prolonged.

T97481

137265-137381

Sentence

denotes

286 Inadequate peripheral perfusion and compromised organ function finally characterize the hypodynamic shock phase.

T76746

137382-137483

Sentence

denotes

Body temperature may become subnormal, and the skin, especially on extremities, is cool to the touch.

T65208

137484-137541

Sentence

denotes

The arterial pulse weakens, and venous fill is decreased.

T67584

137542-137677

Sentence

denotes

Vascular endothelial damage and increased capillary permeability result in a muddy mucous membrane color and diffuse scleral reddening.

T58699

137678-137775

Sentence

denotes

Similar changes are evident in horses suffering from endotoxemia associated with natural disease.

T49660

137776-137961

Sentence

denotes

In the previously mentioned survey, 327 tachycardia, fever, abnormal mucous membrane color, and increased capillary refill time were named by most specialists as indicating endotoxemia.

T90124

137962-138144

Sentence

denotes

Hemostatic abnormalities can manifest in the form of thrombosis or increased bleeding tendency with mucosal petechiation or ecchymoses and prolonged bleeding from venipuncture sites.

T89139

138145-138263

Sentence

denotes

299 Bleeding also may occur in the form of spontaneous epistaxis or prolonged hemorrhage after nasogastric intubation.

T19594

138264-138345

Sentence

denotes

234 Additional clinical signs typically reflect the development of organ failure.

T12514

138346-138645

Sentence

denotes

Renal failure and laminitis 327 appear to be common complications of endotoxemia in horses, and endotoxemia was identified as the only clinical condition significantly associated with the development of acute laminitis in one retrospective case-control study of horses admitted to a referral center.

T8724

138646-138836

Sentence

denotes

330 Other potential complications include liver failure, 299 respiratory failure, colic and ischemia-induced gastrointestinal ulceration, 234 cardiac failure, and abortion in pregnant mares.

T17669

138837-138990

Sentence

denotes

331, 332 Renal failure results from ischemic cortical necrosis and acute tubular necrosis caused by coagulopathy-induced afferent arteriolar obstruction.

T96507

138991-139076

Sentence

denotes

Clinical signs may include oliguria, anuria, or hematuria caused by renal infarction.

T82642

139077-139222

Sentence

denotes

Laminitis may lead to lameness, increased digital arterial pulsation, increased warmth of the hoof wall, and sensitivity to hoof tester pressure.

T11704

139223-139399

Sentence

denotes

The exact nature of the association between endotoxemia and laminitis is not understood, and, interestingly, experimental endotoxin infusion does not reliably induce laminitis.

T15057

139400-139599

Sentence

denotes

Studies have shown, however, that endotoxin administration decreases digital blood flow and laminar perfusion 333 coincident with increased plasma concentrations of 5-HT and thromboxane B 2 (TXB 2 ).

T26940

139600-139731

Sentence

denotes

334 In addition, in vitro vascular reactivity of digital vessels is altered following sublethal endotoxin administration to horses.

T51666

139732-139892

Sentence

denotes

335 In addition to the response to circulating mediators, LPS exposure also alters the production of vasoactive mediators by digital vascular endothelial cells.

T45294

139893-140093

Sentence

denotes

336 Alterations in vascular reactivity are, therefore, likely responsible for development of laminitis in endotoxemia; however, other mechanisms may apply depending on the underlying clinical disease.

T98121

140094-140203

Sentence

denotes

Leukopenia caused by neutropenia may be the most specific indicator of acute bacterial sepsis or endotoxemia.

T83625

140204-140319

Sentence

denotes

286 In prolonged cases an increased proportion of immature neutrophil forms (bands) and toxic changes are observed.

T23968

140320-140456

Sentence

denotes

Toxic changes resulting from neutrophil activation include vacuolation, cytoplasmic granulation, basophilic cytoplasm, and Döhle bodies.

T67

140457-140589

Sentence

denotes

Because neutropenia occurs early in the development of endotoxemia, it also may be a useful parameter for monitoring horses at risk.

T24532

140590-140677

Sentence

denotes

286 On recovery neutropenia typically is followed by a pronounced rebound neutrophilia.

T91756

140678-140824

Sentence

denotes

Other alterations in the hemogram and serum biochemical profile mainly reflect the underlying disease process and the occurrence of organ failure.

T96822

140825-141111

Sentence

denotes

An elevated hematocrit and total serum protein concentration are frequently interpreted as evidence of dehydration; however, splenic contraction caused by increased sympathetic stimulation, increased production of acute phase proteins, or protein losses also influence these parameters.

T59590

141112-141332

Sentence

denotes

Hyperproteinemia may be observed as a result of increases in the fibrinogen or globulin concentration, and determination of protein fractions, including protein electrophoresis, is indicated in hyperproteinemic patients.

T38875

141333-141483

Sentence

denotes

Hypoproteinemia and hypoalbuminemia can occur because of loss via the gastrointestinal or urinary tract or with pleural or peritoneal cavity effusion.

T9578

141484-141566

Sentence

denotes

Increased vascular permeability and edema formation contribute to hypoproteinemia.

T16872

141567-141713

Sentence

denotes

Serum electrolyte abnormalities primarily depend on the nature and duration of underlying disease processes and need to be evaluated individually.

T51888

141714-141866

Sentence

denotes

In human patients, gram-negative sepsis frequently is associated with hypocalcemia, more specifically a decrease in serum ionized calcium concentration.

T60

141867-142141

Sentence

denotes

Endotoxin is thought to be a causative factor, and proposed mechanisms include acquired parathyroid gland insufficiency, dietary vitamin D deficiency, impaired calcium mobilization, and renal 1-hydroxylase insufficiency, leading to decreased 1,25-hydroxylation of vitamin D.

T15913

142142-142229

Sentence

denotes

Hypocalcemia in septic human patients was associated with hypotension and poor outcome.

T21048

142230-142444

Sentence

denotes

337 In horses with surgically managed gastrointestinal disease, decreased serum ionized calcium concentration was a common finding and was most severe in patients with strangulating or nonstrangulating infarctions.

T98394

142445-142528

Sentence

denotes

In some horses, ionized calcium concentration decreased further throughout surgery.

T31623

142529-142641

Sentence

denotes

Treatment with calcium gluconate resulted in normalization of serum ionized calcium concentrations in all cases.

T5660

142642-142917

Sentence

denotes

338 Septic neonatal patients are frequently hypoglycemic, which may be attributable to decreased oral intake, generally increased metabolism, glucose use by the infecting bacteria, inhibition of gluconeogenesis by endotoxin, and insulin-like activity produced by macrophages.

T30927

142918-143077

Sentence

denotes

234 Interestingly, experimental endotoxin administration results in transient hyperglycemia in adult horses, 324 whereas profound hypoglycemia occurs in foals.

T38263

143078-143227

Sentence

denotes

339 Because of the high incidence of coagulopathies in endotoxemic and septic patients, clinicians should consider monitoring coagulation parameters.

T52066

143228-143436

Sentence

denotes

The most significant changes can be expected with severe inflammatory disease such as colitis, 295,296 devitalized intestine as with strangulating obstruction, 296, 340 and with increased duration of disease.

T89909

143437-143550

Sentence

denotes

In 30 horses with acute gastrointestinal disease, coagulation profiles were considered normal in only two horses.

T506

143551-144035

Sentence

denotes

295 Although coagulation times may be shortened during the procoagulant state, commonly observed abnormalities with developing DIC include an increased concentration of FDPs and soluble fibrin monomer, prolonged prothrombin time indicative of factor VII consumption, prolonged activated partial thromboplastin time indicative of factor VIII:C and IX consumption, prolonged thrombin time, decreased AT III activity, thrombocytopenia, and decreased protein C and plasminogen activities.

T76700

144036-144181

Sentence

denotes

Fibrinogen concentration appears to reflect the acute phase response rather than coagulation abnormalities in horses and is frequently increased.

T35824

144182-144517

Sentence

denotes

304 Some clinicians make a diagnosis of DIC if three or more coagulation parameters (specifically AT III, FDPs, platelet count, prothrombin time, and activated partial thromboplastin time) are abnormal, 340 whereas others require overt clinical signs of hemorrhage and concomitant thrombosis in addition to classic laboratory findings.

T42039

144518-144588

Sentence

denotes

296 The prognostic value of coagulation parameters has been evaluated.

T96715

144589-144768

Sentence

denotes

233, 296, 314 Overall, persistence or worsening of abnormalities in the face of treatment appears to be more indicative of poor outcome than alterations in any specific parameter.

T33926

144769-144909

Sentence

denotes

In one study decreased serum AT III concentration was the parameter most commonly associated with fatal outcome in mature horses with colic.

T614

144910-145138

Sentence

denotes

295 Hypoxemia observed in response to endotoxin infusion is thought to be caused by an increase in ventilation-perfusion mismatch rather than pulmonary edema, as occurs in human patients with acute respiratory distress syndrome.

T37600

145139-145229

Sentence

denotes

Pulmonary edema may occur in patients with associated sepsis or complications such as DIC.

T17397

145230-145233

Sentence

denotes

341

T75626

145235-145285

Sentence

denotes

The ideal treatment for endotoxemia is prevention.

T11841

145286-145539

Sentence

denotes

Recognition and close monitoring of patients at risk are crucial because doing so allows institution of timely, possibly proactive treatment, which may reverse the effects of endotoxin before the inflammatory response has developed a dynamic of its own.

T28673

145540-145786

Sentence

denotes

Unfortunately, endotoxemia can develop rapidly, and horses are exquisitely sensitive to the effects of endotoxin; therefore, many equine patients are not presented for evaluation until they have reached more severe stages of endotoxemia or shock.

T7803

145787-145901

Sentence

denotes

Prognosis and patient outcome then frequently depend on the severity of complications associated with endotoxemia.

T11903

145902-146324

Sentence

denotes

234 Treatment of endotoxemia involves multiple aspects, and the following strategies have been proposed 342 : • Inhibition of endotoxin release into the circulation • Scavenging of LPS molecules to prevent direct effects and interaction with inflammatory cells • Inhibition of cellular activation by LPS • Inhibition of mediator synthesis • Interference with the effects of inflammatory mediators • General supportive care

T37920

146325-146423

Sentence

denotes

In addition, treatment must also address the primary disease process as well as any complications.

T28924

146424-146619

Sentence

denotes

When evaluating reports concerning the efficacy of any one treatment, the clinician should keep in mind differences in underlying disease processes and the complexity of the inflammatory cascade.

T78369

146620-146777

Sentence

denotes

A "one for all" treatment most likely will not be found; similarly, any one treatment can address only a few pathophysiologic aspects of endotoxemia at most.

T57288

146778-146860

Sentence

denotes

Inhibition of endotoxin release requires identification and removal of its source.

T17014

146861-147073

Sentence

denotes

Identification of responsible microorganisms and their antimicrobial sensitivity spectrum are crucial steps toward effective therapy; however, one should not necessarily delay treatment to obtain culture results.

T81987

147074-147215

Sentence

denotes

Specimen containers with antimicrobial removal devices may be useful in cases for which initiation of treatment precedes specimen collection.

T13291

147216-147299

Sentence

denotes

Once a diagnosis is reached, correction of the primary disease process is critical.

T47142

147300-147520

Sentence

denotes

Examples are removal of devitalized sections of bowel or infected umbilical remnants, drainage of infected pleural or PF, and gastric lavage followed by administration of intestinal adsorbents in cases of grain overload.

T9734

147521-147727

Sentence

denotes

Di-tri-octahedral smectite (DTO; Bio-Sponge, Platinum Performance Inc., Buellton, CA) was shown to remove endotoxin in an in vitro assay 343 and may be useful in preventing endotoxemia of intestinal origin.

T12371

147728-147862

Sentence

denotes

Septic processes must be addressed with appropriate antimicrobial therapy, and principles of antimicrobial therapy should be followed.

T19534

147863-148058

Sentence

denotes

Regarding endotoxemia specifically, antimicrobial therapy has been suggested to increase the amount of circulating endotoxin by inducing endotoxin release on cell death of gram-negative bacteria.

T6010

148059-148294

Sentence

denotes

An in vitro study comparing endotoxin release and inflammatory mediator activity among antimicrobials commonly used to treat E. coli bacteremia in foals evaluated amikacin, ampicillin, amikacin plus ampicillin, ceftiofur, and imipenem.

T55445

148295-148503

Sentence

denotes

Although these antimicrobials showed no difference in the ability to kill bacteria, amikacin and the amikacinampicillin combination resulted in the lowest, and ceftiofur in the greatest, release of endotoxin.

T50951

148504-148628

Sentence

denotes

Endotoxin release appeared to be dose dependent in that lesser amounts were released at higher antimicrobial concentrations.

T34324

148629-148835

Sentence

denotes

344 On the basis of these results and clinical experience, combining antimicrobial therapy with endotoxin-binding agents such as polymyxin B may be beneficial, especially when using β-lactam antimicrobials.

T15789

148836-148995

Sentence

denotes

Endotoxin typically has a short plasma half-life and is removed rapidly by mononuclear phagocytes or neutralized by binding to serum proteins and lipoproteins.

T55862

148996-149134

Sentence

denotes

Many conditions responsible for the development of endotoxemia in horses, however, may be associated with an ongoing release of endotoxin.

T99371

149135-149265

Sentence

denotes

Examples include severe gastrointestinal inflammation as in proximal enteritis or colitis, grain overload, or uncontrolled sepsis.

T92283

149266-149402

Sentence

denotes

Therapy directed against endotoxin itself may be able to interrupt the continuous activation of the inflammatory cascade in these cases.

T58107

149403-149554

Sentence

denotes

Further benefits of antiendotoxin treatment may be derived if large amounts of endotoxin have been released before the inciting cause can be addressed.

T17499

149555-149692

Sentence

denotes

An important consideration regarding the efficacy of immunotherapy is the region of the LPS molecule against which antibodies are raised.

T38838

149693-149914

Sentence

denotes

The O-chain of LPS acts as a potent antigen 222 ; however, antibodies directed against the O-chain are serotype specific and cannot afford significant cross-protection against heterologous gram-negative bacterial strains.

T45275

149915-150098

Sentence

denotes

The core and lipid A region, both of which show a much higher degree of homology between LPS derived from different bacterial strains, offer a more promising target for immunotherapy.

T49255

150099-150167

Sentence

denotes

Active immunization against endotoxins has been reported for horses.

T2497

150168-150391

Sentence

denotes

Vaccination with a bacterin-toxoid vaccine prepared from rough mutants of Salmonella typhimurium or S. enteritidis protected horses against homologous and heterologous endotoxin challenge 345, 346 and carbohydrate overload.

T65617

150392-150603

Sentence

denotes

346 Despite these encouraging results and the availability of a vaccine for use in horses (Endovac-Equi, Immvac Inc., Columbia, MO), active immunization against endotoxin does not appear to be a common practice.

T49685

150604-150680

Sentence

denotes

In comparison, passive immunization with anti-LPS antibodies is used widely.

T62341

150681-150850

Sentence

denotes

Rough bacterial mutants, most commonly J5 of E. coli O111:B4 and S. minnesota Re595, are used to immunize donor horses and subsequently prepare serum or plasma products.

T61390

150851-151159

Sentence

denotes

Proposed mechanisms of action after binding of the antibodies to LPS include steric blockade of lipid A interaction with cellular receptors and enhanced bacterial clearance by opsonization. [347] [348] [349] Studies concerning the efficacy of antibody administration in equine patients vary in their results.

T63674

151160-151590

Sentence

denotes

Beneficial effects have been described in experimental models of endotoxemia, acute gastrointestinal disease, and neonates with sepsis, 346, [350] [351] [352] [353] whereas in other studies antibodies failed to protect foals and horses against endotoxin effects. [354] [355] [356] Administration of an S. typhimurium antiserum to foals was associated with an increased respiratory rate and higher serum activities of IL-6 and TNF.

T62384

151591-151663

Sentence

denotes

354 Various equine serum and plasma products are commercially available.

T8878

151664-151863

Sentence

denotes

An antiserum raised against the LPS core of S. typhimurium (Endoserum, Immvac Inc., Columbia, MO) is available for administration to endotoxemic horses at a recommended dosage of 1.5 mL/kg body mass.

T30214

151864-152031

Sentence

denotes

Diluting the serum 10-to 20-fold in crystalloid IV solutions, administering it slowly over 1 to 2 hours, and monitoring the patient for adverse reactions is advisable.

T11046

152032-152217

Sentence

denotes

Although the product is marketed for use in foals with failure of passive transfer, adverse effects have been reported, 354 and one should use caution when administering it to neonates.

T51317

152218-152384

Sentence

denotes

Plasma from donors inoculated with J5 (E. coli) and S. typhimurium (Re-mutant) is available under a California license (Equiplas J, Plasvacc USA Inc., Templeton, CA).

T87744

152385-152473

Sentence

denotes

The manufacturer recommends administration of at least 1 to 2 L in cases of endotoxemia.

T12400

152474-152810

Sentence

denotes

Hyperimmune plasma, which has a guaranteed minimum IgG content but does not contain specific antiendotoxin antibodies (HiGamm Equi, Lake Immunogenics, Inc., Ontario, NY; Equiplas and Equiplas Plus, Plasvacc USA Inc.,), is marketed for treatment of failure of passive transfer, and many clinicians use it to treat endotoxemia and sepsis.

T92407

152811-153054

Sentence

denotes

In addition to antibodies and protein, plasma contains active constituents such as complement components, fibronectin, clotting factors, and AT III 351 and therefore may be particularly useful in patients with endotoxemia-induced coagulopathy.

T32288

153055-153166

Sentence

denotes

Volumes of 2 to 10 mL/kg body mass of hyperimmune plasma have been recommended for use in endotoxemic patients.

T58027

153167-153175

Sentence

denotes

272, 357

T87046

153177-153314

Sentence

denotes

Polymyxin B is a cationic polypeptide antibiotic that binds to the anionic lipid A portion of LPS and neutralizes its endotoxin capacity.

T42779

153315-153547

Sentence

denotes

358 At dosages required for antimicrobial activity, polymyxin B carries the risk of respiratory paralysis and ototoxic, nephrotoxic, and neurotoxic side effects; however, a much lower dose is required for endotoxin-binding activity.

T80848

153548-153638

Sentence

denotes

The effects of polymyxin B in horses have been evaluated in different experimental models.

T43902

153639-153943

Sentence

denotes

354, 358, 359 In an in vivo study in foals, treatment with polymyxin B at a dosage of 6000 U/kg body mass before infusion with S. typhimurium LPS resulted in significantly less severe elevations of body temperature, respiratory rate, and serum activities of TNF and IL-6 compared with untreated controls.

T42414

153944-154074

Sentence

denotes

354 Similarly, polymyxin B treatment of adult horses given endotoxin ameliorated clinical signs and decreased plasma TNF activity.

T40142

154075-154281

Sentence

denotes

360 In the latter study benefits of treatment were also evident at lower dosages of polymyxin B (1000 and 5000 U/kg body mass) and administration of polymyxin B 1 hour after the start of endotoxin infusion.

T26780

154282-154469

Sentence

denotes

Conversely, polymyxin B failed to ameliorate clinical signs of endotoxemia or prevent the development of coagulopathy, acidosis, lameness, and shock in experimental carbohydrate overload.

T87120

154470-154671

Sentence

denotes

361 Adverse effects suggestive of neurotoxicity appeared after repeated administration of 5 mg/kg body mass (36,000 U/kg) and in a milder form after administration of 2.5 mg/kg body mass (18,000 U/kg).

T98483

154672-154704

Sentence

denotes

Nephrotoxicity was not observed.

T52369

154705-154860

Sentence

denotes

Currently, use of polymyxin B in equine patients is recommended at dosages of 1000 to 6000 U/kg body mass every 8 to 12 hours administered as a slow bolus.

T98601

154861-155104

Sentence

denotes

362, 363 Treatment should be initiated as early in the disease process as possible because the beneficial effects of LPS scavenging may be limited to the first 24 to 48 hours after the onset of endotoxemia, before endotoxin tolerance develops.

T77658

155105-155266

Sentence

denotes

Adverse effects in the form of neuromuscular blockade and apnea, which necessitate slow infusion of the drug in human patients, have not been observed in horses.

T40400

155267-155478

Sentence

denotes

If treating horses with hypovolemia, dehydration, or azotemia, the clinician should attempt to improve peripheral tissue perfusion, minimize the polymyxin B dose, and closely monitor patients for nephrotoxicity.

T1440

155479-155653

Sentence

denotes

Close monitoring is also important if medications such as aminoglycoside antibiotics, which share a similar spectrum of potential side effects, are administered concurrently.

T60280

155654-155753

Sentence

denotes

Azotemic neonates are more susceptible to the nephrotoxic effects of polymyxin B than adult horses.

T14201

155754-155919

Sentence

denotes

360 In an attempt to decrease the risk for adverse effects while preserving the LPS-neutralizing ability, a conjugate of polymyxin B with dextran has been developed.

T49504

155920-156070

Sentence

denotes

364 In conjugated form, polymyxin B is prevented from extravasation into tissues, in which it exerts toxic effects by interaction with cell membranes.

T63895

156071-156214

Sentence

denotes

In addition, conjugation increases the residence time of polymyxin B in the circulation; therefore, it should prolong the antiendotoxic effect.

T6854

156215-156410

Sentence

denotes

The polymyxin B-dextran combination was evaluated at a total dose of 5 mg/kg body mass of polymyxin B in 6.6 g/kg body mass dextran, given 15 minutes before administration of endotoxin in horses.

T87207

156411-156647

Sentence

denotes

365 Treatment blocked the development of tachycardia, tachypnea, fever, and neutropenia completely and prevented increases in serum concentrations of TNF, IL-6, TXB 2 (a TXA 2 metabolite), and the prostacyclin metabolite 6-keto-PGF 1 α.

T80707

156648-156843

Sentence

denotes

Although mild adverse effects in the form of tachypnea, sweating, and increased systolic blood pressure were observed, these were transient and could be prevented by pretreatment with ketoprofen.

T32571

156844-156950

Sentence

denotes

To the author's knowledge, the polymyxin B-dextran combination is not commercially available at this time.

T51761

156951-157058

Sentence

denotes

Natural endotoxin-binding proteins such as LBP, lipoproteins, and sCD14 have been evaluated experimentally.

T70003

157059-157159

Sentence

denotes

Results of these studies are somewhat contradictory, and detrimental effects occurred in some cases.

T93893

157160-157309

Sentence

denotes

366 A protein receiving a great deal of attention regarding potential therapeutic efficacy is the bactericidal permeability-increasing (BPI) protein.

T20725

157310-157443

Sentence

denotes

This protein is structurally similar to LBP but is expressed exclusively in myeloid precursors of polymorphonuclear (PMN) leukocytes.

T89058

157444-157613

Sentence

denotes

367 BPI is stored in primary granules of mature neutrophils and during inflammation is expressed on their cell membranes and secreted into the extracellular environment.

T94488

157614-157740

Sentence

denotes

368 BPI has an even higher affinity for LPS than LBP 369 and shows antibacterial activity specific for gram-negative bacteria.

T45633

157741-157904

Sentence

denotes

219 Binding of BPI to the gram-negative bacterial membrane results in growth arrest and is an important factor in the antibacterial activity of intact neutrophils.

T13524

157905-158056

Sentence

denotes

Furthermore, BPI binding disrupts normal membrane organization and makes bacteria more susceptible to hydrophobic substances, including antimicrobials.

T42543

158057-158281

Sentence

denotes

370 Experimentally, recombinant BPI protects against the toxic and lethal effects of isolated LPS and intact gram-negative bacteria, and clinical trials in human patients show promising results regarding its therapeutic use.

T64543

158282-158356

Sentence

denotes

371 The biology and potential use of BPI in horses has not been evaluated.

T90915

158357-158471

Sentence

denotes

Phospholipid emulsions have recently been evaluated for treatment of experimentally induced endotoxemia in horses.

T68070

158472-158632

Sentence

denotes

Phospholipid infusion improved clinical parameters, ameliorated neutropenia, and reduced inflammatory mediator production in response to an endotoxin challenge.

T97927

158633-158863

Sentence

denotes

372, 373 Because hemolysis was a complication of phospholipid infusion in some horses in these studies, optimization of dose and time of administration will be necessary before evaluating this treatment for potential clinical use.

T32045

158864-158994

Sentence

denotes

Treatments aimed at inhibiting LPS interaction with cells or turning off intracellular signaling pathways are under investigation.

T85020

158995-159182

Sentence

denotes

Nontoxic LPS or lipid A structures can act as endotoxin antagonists, if they competitively inhibit binding to LBP or cellular receptors or inhibit cellular activation by other mechanisms.

T19457

159183-159622

Sentence

denotes

Of the potential antagonists that have been evaluated experimentally, LPS and lipid A of the phototrophic bacterium Rhodobacter sphaeroides and the synthetic compounds E5531 and E5564 have been most promising. [373] [374] [375] [376] [377] [378] [379] Unfortunately, species differences exist regarding cellular response to these structures, and R. sphaeroides LPS as well as E5531 have been found to have agonist activity in equine cells.

T56248

159623-159759

Sentence

denotes

380, 381 In cell transfection experiments, TLR-4 was shown to be responsible for this phenotypic variation regarding R. sphaeroides LPS.

T75969

159760-159858

Sentence

denotes

382 Given these results, any future potential LPS antagonists must be evaluated in equine systems.

T84976

159859-159977

Sentence

denotes

Nonsteroidal antiinflammatory drugs (NSAIDs) are probably the most commonly used drugs to treat endotoxemia in horses.

T97984

159978-160082

Sentence

denotes

The rationale for their use is inhibition of COX, which inhibits prostanoid production (see Fig. 12 .5).

T97778

160083-160265

Sentence

denotes

Additional beneficial effects may include scavenging of oxygen-derived free radicals and iron chelation; however, side effects may occur at dosages required to achieve these effects.

T66956

160266-160451

Sentence

denotes

374 Prostanoids have been identified as important mediators in the inflammatory response in a number of studies, and inhibition of their synthesis is associated with beneficial effects.

T90928

160452-160556

Sentence

denotes

Generally speaking, two COX isoforms are recognized: constitutively expressed COX-1 and inducible COX-2.

T73022

160557-160667

Sentence

denotes

Upregulation of COX-2 expression results from various proinflammatory stimuli, including LPS, TNF-α, and IL-1.

T99461

160668-160899

Sentence

denotes

383 Constitutively expressed COX products are likely important for maintenance of homeostasis, whereas increased production of prostanoids by COX-2 is thought to be responsible for detrimental effects during inflammation and shock.

T43887

160900-160983

Sentence

denotes

In horses, the most commonly used NSAID to treat endotoxemia is flunixin meglumine.

T98508

160984-161123

Sentence

denotes

Beneficial effects of flunixin meglumine have been described in experimental models of endotoxemia [384] [385] [386] and in clinical cases.

T8319

161124-161327

Sentence

denotes

In equine colic patients treatment with flunixin meglumine before exploratory surgery resulted in reduced plasma concentrations of TXB 2 and PGE 2 and had a favorable effect on cardiovascular parameters.

T18016

161328-161551

Sentence

denotes

387 Flunixin meglumine was shown further to maintain cardiac output and systemic arterial blood pressure, improve blood flow to vital organs, reduce pulmonary endothelial damage, and improve survival on endotoxin challenge.

T17383

161552-161800

Sentence

denotes

285, [388] [389] [390] Conversely, in vitro studies have suggested that flunixin meglumine impairs recovery of intestinal barrier function in intestinal segments subjected to ische miareperfusion injury and may increase mucosal permeability to LPS.

T15902

161801-161921

Sentence

denotes

391, 392 This effect may be reduced or eliminated by concurrent administration of continuous rate infusion of lidocaine.

T8983

161922-162108

Sentence

denotes

NSAID use in horses carries the risk of adverse effects, the most significant of which are development of gastrointestinal ulceration and renal papillary necrosis (renal crest necrosis).

T28060

162109-162234

Sentence

denotes

Differences may exist among NSAIDs in their propensity to induce adverse effects, 393 but all NSAIDs must be used cautiously.

T8379

162235-162463

Sentence

denotes

Because of the potential concerns for masking of cardiovascular effects of endotoxin in horses with colic, a reduced dose of flunixin meglumine (0.25 mg/kg body mass thrice daily) has been suggested and is used widely in horses.

T77171

162464-162579

Sentence

denotes

327 At this dosage flunixin meglumine inhibits eicosanoid synthesis efficiently in an in vivo model of endotoxemia.

T84596

162580-162759

Sentence

denotes

394 Reduction of clinical signs, however, was dose dependent, and lower doses provide minimal, if any, analgesia (see Chapter 2 for further discussion of NSAID therapy in horses).

T64750

162760-163003

Sentence

denotes

Some researchers have suggested that ketoprofen offers superior effects because of a proposed dual inhibitory effect on COX and lipoxygenase and may carry a decreased risk of adverse effects compared with flunixin meglumine and phenylbutazone.

T24844

163004-163266

Sentence

denotes

A comparison of cytokine and eicosanoid production by LPS-stimulated isolated monocytes in vitro, however, showed no significant difference between horses pretreated with flunixin meglumine (1.1 mg/kg body mass) or ketoprofen (2.2 mg/kg body mass), respectively.

T4318

163267-163550

Sentence

denotes

395 Given 15 minutes before LPS infusion, eltenac at a dosage of 0.5 mg/kg protected against changes in clinical, hemodynamic, and hematologic parameters and blunted the LPSinduced rise in plasma cytokine concentrations compared with controls in an experimental model of endotoxemia.

T86009

163551-163686

Sentence

denotes

396 Some parameters, however, including heart rate, leukocyte count, lactate concentration, and plasma TNF activity, were not improved.

T34721

163687-163865

Sentence

denotes

Ibuprofen may have beneficial effects superior to those of the other NSAIDs because it may be possible to achieve tissue concentrations safely that allow iron chelation to occur.

T6368

163866-163992

Sentence

denotes

According to a study in healthy foals, dosages of ibuprofen up to 25 mg/kg every 8 hours can be given safely for up to 6 days.

T75229

163993-164121

Sentence

denotes

397 To the author's knowledge, the COX-2 inhibitor firocoxib has not yet been evaluated critically for treatment of endotoxemia.

T43329

164122-164360

Sentence

denotes

The use of corticosteroids for antiinflammatory therapy in sepsis and endotoxemia has been controversial in human and equine patients, and beneficial effects superior to the ones achieved by NSAIDs have not been demonstrated consistently.

T76436

164361-164569

Sentence

denotes

Corticosteroids inhibit the activity of phospholipase A 2 and the release of arachidonic acid from cell membrane phospholipids, as well as the production of TNF, IL-1, and IL-6 in response to an LPS stimulus.

T24351

164570-164667

Sentence

denotes

Experimentally, beneficial effects of dexamethasone in equine endotoxemia have been demonstrated.

T1556

164668-164913

Sentence

denotes

398, 399 To inhibit TNF production by equine peritoneal macrophages, however, the required concentration of dexamethasone was high and corresponded to an in vivo dosage (approximately 3 mg/kg body mass) greatly exceeding current recommendations.

T91459

164914-165128

Sentence

denotes

398 Although single doses of corticosteroids are unlikely to carry a disproportionate risk of adverse effects, the clinician should consider the suggested association of laminitis with corticosteroid use in horses.

T30545

165129-165200

Sentence

denotes

In cases of sepsis immunosuppressive effects could also be detrimental.

T83757

165201-165395

Sentence

denotes

In human patients with certain types of septic shock, dysfunction of the hypothalamic-pituitary-adrenal axis has been recognized and successfully treated with hydrocortisone replacement therapy.

T59460

165396-165600

Sentence

denotes

400 Hypothalamic-pituitary-adrenal axis dysfunction has been suggested to occur in septic foals 401 ; however, the use of low-dose corticosteroids for this indication remains to be investigated in horses.

T32415

165601-165862

Sentence

denotes

Pentoxifylline, a methylxanthine derivative and phosphodiesterase inhibitor, has been suggested for use in endotoxemia because of its effects on neutrophil function and its ability to inhibit the production of various cytokines, interferons, and thromboplastin.

T89170

165863-165987

Sentence

denotes

Decreased production of TNF, IL-6, TXB 2 , and thromboplastin in response to endotoxin was shown in an equine ex vivo model.

T48625

165988-166195

Sentence

denotes

402 In horses given endotoxin followed by treatment with pentoxifylline (7.5 mg/kg body mass followed by continuous infusion of 3 mg/kg/h for 3 hours), however, only minimal beneficial effects were observed.

T90752

166196-166456

Sentence

denotes

403 Treatment significantly improved body temperature, respiratory rate, and whole blood recalcification time, but no effect was observed regarding heart rate, blood pressure, leukocyte count, plasma fibrinogen concentration, and serum cytokine concentrations.

T13036

166457-166642

Sentence

denotes

The conclusion was that benefits of treatment with pentoxifylline might be restricted to administration of high bolus doses or continuous infusion early in the pathophysiologic process.

T10689

166643-166836

Sentence

denotes

In an in vivo endotoxemia model in horses, the combination of pentoxifylline (8 mg/kg body mass) and flunixin meglumine (1.1 mg/kg body mass) had greater benefit than each treatment on its own.

T58738

166837-167163

Sentence

denotes

404 Because of its rheologic properties (i.e., the ability to increase erythrocyte deformability and microvascular blood flow), pentoxifylline has been suggested for use in endotoxemic patients showing evidence of laminitis; however, no effect on blood flow to the hoof was demonstrated after administration to healthy horses.

T52926

167164-167234

Sentence

denotes

405 An IV preparation of pentoxifylline is not commercially available.

T16279

167235-167338

Sentence

denotes

Dimethyl sulfoxide (DMSO) is used by some clinicians in an attempt to scavenge oxygen-derived radicals.

T25356

167339-167494

Sentence

denotes

However, DMSO failed to show beneficial effects in an experimental model of intestinal ischemia when administered on reperfusion of the ischemic intestine.

T46022

167495-167711

Sentence

denotes

406 DMSO at a dosage of 1 g/kg body mass increased mucosal loss after ischemia and reperfusion of the large colon, 407 and a reduced dosage of 0.1 g/kg body mass has been proposed for horses with intestinal ischemia.

T26549

167712-167892

Sentence

denotes

DMSO failed to show significant benefit in an experimental model of endotoxemia in horses, although it ameliorated the effect on fever, and many clinicians do not advocate its use.

T11880

167893-168022

Sentence

denotes

408 The xanthine oxidase inhibitor allopurinol has been suggested as a treatment to prevent oxygen radical-induced tissue damage.

T19729

168023-168183

Sentence

denotes

During periods of ischemia tissue xanthine dehydrogenase is converted to xanthine oxidase, which on reperfusion catalyzes the generation of superoxide radicals.

T95816

168184-168322

Sentence

denotes

409, 410 Evaluation in horses showed beneficial effects of allopurinol 5 mg/kg body mass administered 12 hours before endotoxin challenge.

T532

168323-168484

Sentence

denotes

411 In another study mucosal damage attributable to oxygen-derived free radicals was not attenuated by allopurinol in an experimental ischemia-reperfusion model.

T64715

168485-168488

Sentence

denotes

407

T91509

168489-168583

Sentence

denotes

Lidocaine given IV has been suggested as an antiinflammatory, analgesic, and prokinetic agent.

T19866

168584-168752

Sentence

denotes

In an experimental endotoxemia model in rabbits, lidocaine inhibited hemodynamic and cytokine responses to endotoxin profoundly if given immediately after LPS infusion.

T67350

168753-168914

Sentence

denotes

412 Lidocaine further ameliorated the inhibitory effects of flunixin on recovery of mucosal barrier function following ischemic injury in equine small intestine.

T6444

168915-168985

Sentence

denotes

413 Use of lidocaine therefore may have merit in endotoxemic patients.

T58432

168986-169155

Sentence

denotes

A common regimen for lidocaine use in horses is the administration of an initial bolus (1.3 mg/kg body mass) followed by continuous infusion at a rate of 0.05 mg/kg/min.

T23311

169156-169405

Sentence

denotes

High concentrations of ω-3 fatty acids can alter the phospholipid composition of cellular membranes toward a decreased ratio of ω-6 to ω-3, affecting membrane functions such as phagocytosis, receptor binding, and activities of membranebound enzymes.

T9980

169406-169640

Sentence

denotes

286 Most important for the treatment of endotoxemia, ω-3 fatty acid incorporation into cell membranes decreases the availability of arachidonic acid (an ω-6 fatty acid) for eicosanoid synthesis 414 and provides alternative substrates.

T90019

169641-169896

Sentence

denotes

Metabolism of ω-3 fatty acids via the COX and lipoxygenase pathway leads to the production of 3-series prostaglandins and 5-series leukotrienes, which have less biologic activity than their 2-series and 4-series counterparts derived from arachidonic acid.

T66834

169897-170071

Sentence

denotes

Aside from these mechanisms, ω-3 fatty acids prevent LPS-induced upregulation of CD14 in monocytic cells; therefore, they may be able to block transmembrane signaling of LPS.

T17219

170072-170289

Sentence

denotes

415 Cells from horses given linseed oil (high in ω-3 fatty acids) for 8 weeks before blood collection showed significantly decreased expression of procoagulant activity, TXB 2 , and TNF in response to LPS stimulation.

T61428

170290-170617

Sentence

denotes

416, 417 In an in vivo experimental model of endotoxemia in horses, treatment resulted in prolonged activated partial thromboplastin time and whole blood recalcification time, suggesting an anticoagulant effect; however, a significant beneficial effect on clinical response and serum eicosanoid concentrations was not observed.

T40869

170618-170803

Sentence

denotes

418 Because dietary addition of ω-3 fatty acids requires several weeks of treatment, IV infusion was evaluated and shown to alter the composition of cell membrane phospholipids rapidly.

T8587

170804-170927

Sentence

denotes

419 Further evaluation of this treatment for use in horses is necessary before specific dosage recommendations can be made.

T4583

170928-171266

Sentence

denotes

Monoclonal and polyclonal antibodies against equine TNF have been evaluated in horses. [420] [421] [422] Administration of a monoclonal antibody preparation before LPS infusion resulted in significantly reduced plasma TNF activity, improved clinical abnormality scores, lower heart rate, and higher leukocyte count compared with controls.

T51575

171267-171391

Sentence

denotes

421 Plasma concentrations of lactate and 6-keto-PGF1α were reduced significantly, whereas TXA 2 production was not affected.

T15927

171392-171655

Sentence

denotes

420 In another study 422 administration of a rabbit polyclonal antibody against recombinant human TNF did not improve clinical and hematologic parameters when given shortly (15 minutes) after LPS infusion, although inhibition of TNF activity was present in vitro.

T84336

171656-171838

Sentence

denotes

422, 423 Findings in horses are in agreement with studies in other species and suggest that beneficial effects of TNF inhibition may be limited to administration before LPS exposure.

T21720

171839-171904

Sentence

denotes

Widespread clinical use therefore is unlikely to become feasible.

T33845

171905-172008

Sentence

denotes

Clinical trials in septic human patients have not shown significant benefits of TNF antibody treatment.

T75100

172009-172017

Sentence

denotes

424, 425

T60662

172019-172089

Sentence

denotes

The effects of selective PAF receptor antagonists have been evaluated.

T18075

172090-172307

Sentence

denotes

PAF is implicated in the development of systemic hypotension, 426 LPS-induced platelet aggregation, 427 ileus, 428 and increased vascular permeability 429 and may mediate recruitment of leukocytes to inflamed tissues.

T69822

172308-172520

Sentence

denotes

430, 431 A study in horses using the PAF receptor antagonist SRI 63-441 before LPS infusion showed significant decreases in heart rate and shorter elevation of lactate concentrations in response to the treatment.

T87427

172521-172700

Sentence

denotes

Although not statistically significant, additional beneficial effects included delayed onset of fever, a shortened period of neutropenia, and reduced maximal platelet aggregation.

T91787

172701-172704

Sentence

denotes

432

T31150

172705-172840

Sentence

denotes

Fluid therapy is a mainstay of therapy of most endotoxemic patients suffering from the cardiovascular effects of systemic inflammation.

T36377

172841-173018

Sentence

denotes

Many endotoxemic equine patients require fluid therapy for treatment of the underlying disease process and correction of dehydration and electrolyte and acid-base abnormalities.

T7547

173019-173087

Sentence

denotes

Principles of fluid therapy are discussed in Chapter 4 of this text.

T28524

173088-173291

Sentence

denotes

Patients with severe hypovolemia and shock present management challenges, especially because increased vascular permeability in endotoxemic patients requires careful consideration of fluid therapy plans.

T4302

173292-173497

Sentence

denotes

A rapid increase in total body fluid volume may be detrimental in patients with compromised cardiac and peripheral vasomotor function and may increase the severity of vascular pooling in peripheral organs.

T39934

173498-173640

Sentence

denotes

In these patients hypertonic solutions or colloids may be more appropriate means of stabilization than large volumes of crystalloid solutions.

T88262

173641-173798

Sentence

denotes

Hypertonic saline solution (7.5% sodium chloride) is the most commonly used hypertonic solution in horses and has beneficial effects in endotoxemic patients.

T50658

173799-173990

Sentence

denotes

433 A dosage of 4 mL/kg is recommended, which should be given as a bolus infusion over 10 to 15 minutes, followed by administration of an isotonic solution to restore total body fluid volume.

T19169

173991-174187

Sentence

denotes

The clinician should use hypertonic saline with caution in patients with sodium or chloride derangements and should monitor serum electrolyte concentrations in the case of repeated administration.

T56500

174188-174304

Sentence

denotes

Failure of urination despite appropriate fluid resuscitation should result in critical evaluation of renal function.

T30905

174305-174487

Sentence

denotes

In one recent study small-volume resuscitation with hypertonic saline plus hydroxyethyl starch failed to alleviate hemodynamic responses in experimental endotoxin infusion in horses.

T96581

174488-174609

Sentence

denotes

434 Plasma is an ideal colloid and should be administered to maintain a serum total protein concentration above 4.2 g/dL.

T90169

174610-174832

Sentence

denotes

357 To raise plasma protein concentration and colloid osmotic pressure significantly, however, horses often require large volumes of plasma (7-10 L or more in a 450-kg horse), and alternative colloids should be considered.

T56106

174833-174988

Sentence

denotes

High-molecular-weight polymers are thought to provide superior oncotic effects in cases of sepsis and endotoxemia, when vascular permeability is increased.

T64885

174989-175101

Sentence

denotes

Hetastarch, or hydroxyethyl starch (Hespan), is commercially available as a 6% solution in 0.9% sodium chloride.

T64837

175102-175208

Sentence

denotes

Hetastarch molecules have a very high molecular weight, and degradation must occur before renal excretion.

T27905

175209-175412

Sentence

denotes

435 These properties result in a longer plasma half-life and prolonged oncotic effects compared with other colloids; persistence of the oncotic effect for 24 hours was observed in hypoproteinemic horses.

T30454

175413-175550

Sentence

denotes

436 A dosage of 5 to 15 mL/kg given by slow IV infusion along with an equal or greater volume of crystalloid fluids has been recommended.

T15712

175551-175759

Sentence

denotes

435, 437 In human patients prolonged activated partial thromboplastin time, decreased factor VIII activity, and decreased serum fibrinogen concentration have been described in association with hetastarch use.

T40550

175760-175928

Sentence

denotes

438 In the limited number of equine studies, bleeding times were not affected 439, 440 ; however, patients treated with hetastarch should be monitored for coagulopathy.

T42979

175929-176034

Sentence

denotes

Metabolic acidosis in endotoxic shock is attributable to lactic acidemia and inadequate tissue perfusion.

T7507

176035-176246

Sentence

denotes

441 Acid-base balance often improves considerably after fluid resuscitation alone; however, additional sodium bicarbonate may be required in cases in which serum bicarbonate concentration remains below 15 mEq/L.

T98217

176247-176363

Sentence

denotes

Foals with sepsis are frequently hypoglycemic, and 5% dextrose solutions are useful as initial resuscitation fluids.

T73142

176364-176512

Sentence

denotes

The clinician should reduce the glucose concentration of IV solutions according to the blood glucose concentration to avoid prolonged hyperglycemia.

T20418

176513-176670

Sentence

denotes

Administration of hyperimmune plasma (20-40 mL/kg body mass) is highly recommended in foals with evidence of partial or complete failure of passive transfer.

T59989

176671-176789

Sentence

denotes

One should consider positive inotropic and vasomotor agents in patients with persistently inadequate tissue perfusion.

T98764

176790-177109

Sentence

denotes

Lower dosages of dopamine (0.5-2 μg/kg/min) result in vasodilation of the renal, mesenteric, coronary, and intracerebral vasculature via dopaminergic effects, whereas higher dosages (up to 10 μg/kg/min) also exert stimulation of α 1 -adrenergic receptors, resulting in increased myocardial contractility and heart rate.

T66275

177110-177224

Sentence

denotes

442 Dobutamine is a direct α 1 -adrenergic agonist and does not appear to have significant vasodilator properties.

T29871

177225-177336

Sentence

denotes

Dosages for dobutamine of 1 to 5 μg/kg/min as a continuous IV infusion have been recommended for use in horses.

T26695

177337-177465

Sentence

denotes

Norepinephrine was evaluated in hypotensive critically ill foals that were refractory to the effects of dopamine and dobutamine.

T74358

177466-177650

Sentence

denotes

443 At dosages up to 1.5 μg/kg/min administered concurrently with dobutamine, six of seven foals showed an increase in mean arterial pressure, and all foals had increased urine output.

T200

177651-177777

Sentence

denotes

Because of the risk of cardiac side effects, close monitoring of heart rate and rhythm should accompany infusion of inotropes.

T83557

177778-177881

Sentence

denotes

Indirect blood pressure measurements using a tail cuff may be used to monitor the effects of treatment.

T30292

177882-178038

Sentence

denotes

More frequently than overt thrombosis or bleeding attributable to DIC, hemostatic abnormalities occur in the form of alterations in the coagulation profile.

T59211

178039-178175

Sentence

denotes

A procoagulant state with shortened bleeding times or prolonged bleeding times caused by consumption of clotting factors may be evident.

T74917

178176-178335

Sentence

denotes

One should address abnormalities in the coagulation profile as early as possible but especially if they persist more than 24 hours after initiation of therapy.

T85297

178336-178571

Sentence

denotes

Because of the complex interactions of coagulation and fibrinolysis during endotoxemia, it might be necessary to combine anticoagulant therapy with the administration of fresh frozen plasma to replace clotting and fibrinolytic factors.

T45340

178572-178774

Sentence

denotes

Heparin acts as an anticoagulant by activation of AT III and subsequent inhibition of thrombin, release of tissue factor pathway inhibitor from endothelial cells, and inhibition of platelet aggregation.

T20978

178775-178965

Sentence

denotes

444 Because endogenous AT III levels frequently are decreased in patients with coagulopathy, the addition of heparin to fresh frozen plasma may be the most effective route of administration.

T68215

178966-179078

Sentence

denotes

An initial dosage of 100 IU/kg body mass followed by 40 to 80 IU/kg body mass thrice daily has been recommended.

T85180

179079-179268

Sentence

denotes

357 Anemia caused by erythrocyte agglutination occurs in some patients during therapy with unfractionated heparin 445, 446 but typically resolves within 96 hours if therapy is discontinued.

T74664

179269-179500

Sentence

denotes

357 Because of the risk of microthrombosis associated with erythrocyte agglutination, use of low-molecular-weight heparin (50 IU/kg body mass subcutaneously [SC] every 24 hours) has been recommended 447 but may be cost prohibitive.

T64311

179501-179672

Sentence

denotes

Aspirin can be given orally (10-20 mg/kg body mass every 48 hours), which irreversibly inhibits platelet COX activity, to inhibit platelet aggregation and microthrombosis.

T72535

179673-179866

Sentence

denotes

Platelet hyperaggregability has been implicated in the pathogenesis of carbohydrate-induced laminitis, 448 and heparin and aspirin have been recommended to prevent the development of laminitis.

T19988

179867-179961

Sentence

denotes

In an in vitro study, however, aspirin did not inhibit endotoxin-induced platelet aggregation.

T94041

179962-179965

Sentence

denotes

449

T52391

179966-180116

Sentence

denotes

Luteolysis caused by increased concentrations of PGF 2 α may lead to pregnancy loss in endotoxemic mares before day 55 of pregnancy (see Chapter 19) .

T8468

180117-180324

Sentence

denotes

450 Daily administration of altrenogest (Regu-Mate, Hoechst-Roussel Agri-Vet, Somerville, NJ) at a dosage of 44 mg orally consistently prevented fetal loss in mares if administered until day 70 of pregnancy.

T25540

180325-180473

Sentence

denotes

331 Treatment with flunixin meglumine, by blockade of PGF 2 α release, 332 also may contribute to the maintenance of pregnancy in endotoxemic mares.

T90935

180474-180618

Sentence

denotes

The pathogenesis of fetal loss and abortion caused by endotoxemia, surgery, or systemic disease later in gestation is not understood completely.

T63042

180619-180733

Sentence

denotes

Proposed mechanisms include direct effects on the fetus, placental function, or placental progesterone production.

T15970

180734-180993

Sentence

denotes

451 Decreased nitric oxide production by vascular endothelial cells in response to endotoxin has been suggested as a mechanism for vasoconstriction and decreased blood flow leading to laminitis) 452 ; however, use of nitric oxide donors remains controversial.

T88899

180994-181160

Sentence

denotes

Maintenance of adequate peripheral perfusion and anticoagulant and antiinflammatory therapy may be helpful in preventing and treating laminitis caused by endotoxemia.

T13869

181161-181365

Sentence

denotes

Digital cryotherapy is a critical component of supportive care in the equine patient with suspected endotoxemia, including those suffering from many of the inflammatory diseases discussed in this chapter.

T40747

181366-181536

Sentence

denotes

Cryotherapy has been shown to reduce the severity of laminitis lesions in the oligofructose model, [453] [454] [455] including when initiated after the onset of lameness.

T44135

181537-181636

Sentence

denotes

456 It has also been shown to decrease the incidence of laminitis in horses diagnosed with colitis.

T21959

181637-181740

Sentence

denotes

457 When initiated, digital cryotherapy should include immersion of the hoof and pastern, at a minimum.

T77501

181741-181789

Sentence

denotes

458 Inflammatory Diseases of the Small Intestine

T54171

181790-182095

Sentence

denotes

Duodenitis-proximal jejunitis (DPJ) is an inflammatory condition affecting the upper small intestine and resulting in distention, abdominal pain, gastric reflux caused by excessive fluid and electrolyte secretion, and increased PF protein concentration without a significant elevated nucleated cell count.

T31197

182096-182173

Sentence

denotes

Other terms for this condition are anterior enteritis and proximal enteritis.

T69458

182174-182242

Sentence

denotes

Clinical signs of DPJ mimic those of a small intestinal obstruction.

T50403

182243-182396

Sentence

denotes

The clinical syndrome of DPJ was well described in the 1980s, 19,459-461 but the severity of clinical signs, especially duration of disease, is variable.

T13877

182397-182496

Sentence

denotes

Although not typical, DPJ can occur in conjunction with gastritis, ileitis, typhlitis, and colitis.

T39003

182497-182613

Sentence

denotes

Typical pathologic findings in horses with DPJ include involvement of the duodenum and usually the proximal jejunum.

T75220

182614-182670

Sentence

denotes

19 The ileum and large colon usually are grossly normal.

T7264

182671-182789

Sentence

denotes

Gastric distention is common because of hypersecretion in the proximal small intestine combined with functional ileus.

T66425

182790-182889

Sentence

denotes

Small intestinal diameter often measures 5 to 7 cm, filled with malodorous, red to brown-red fluid.

T29639

182890-183061

Sentence

denotes

Duodenal and jejunal serosal surfaces may have varying degrees and distribution of bright red to dark red petechial and ecchymotic hemorrhages and yellow to white streaks.

T38178

183062-183165

Sentence

denotes

The enteric mucosal surfaces are usually hyperemic with varying degrees of petechiation and ulceration.

T29996

183166-183362

Sentence

denotes

Microscopically, the most severe lesions are located in the duodenum and proximal jejunum but may extend proximally to the gastric mucosa and aborally to the large intestinal mucosa and submucosa.

T77622

183363-183544

Sentence

denotes

19 Microscopic lesions include varying degrees of mucosal and submucosal hyperemia and edema, villous degeneration with necrosis and, more severely, sloughing of villous epithelium.

T38489

183545-183734

Sentence

denotes

The lamina propria, mucosa, and submucosa may have varying degrees of granulocyte infiltration (predominantly neutrophils), and the muscular layers and serosa may contain small hemorrhages.

T38452

183735-183980

Sentence

denotes

Proximal small intestinal serosal fibrinopurulent exudate is a common finding in the more severe cases; therefore the term hemorrhagic fibrinonecrotic duodenitis-proximal jejunitis has been suggested as a more descriptive name for this syndrome.

T59351

183981-184194

Sentence

denotes

461 Horses with DPJ can have hepatic changes including hepatocellular vacuolization, cholestasis, inflammatory infiltrate (either in association with centrilobular necrosis or periportal), and biliary hyperplasia.

T79100

184195-184447

Sentence

denotes

462 Hepatic disease is thought to result from ascending infection via the common bile duct, local absorption of endotoxin via the portal circulation, systemic consequences of endotoxin absorption, metabolic imbalances, and hypoperfusion or hypovolemia.

T48618

184448-184507

Sentence

denotes

In most cases, an underlying etiology cannot be determined.

T13873

184508-184606

Sentence

denotes

In some cases, Salmonella spp. or Clostridium spp. can be isolated from culture of gastric reflux.

T54921

184607-184765

Sentence

denotes

Salmonellosis has never been consistently identified in a majority of cases, and many horses with documented infections by these organisms do not develop DPJ.

T11540

184766-184948

Sentence

denotes

Alternatively, toxigenic strains of C. difficile were isolated from the reflux of five of five horses with DPJ and none of six control horses with other causes of nasogastric reflux.

T11527

184949-185054

Sentence

denotes

463 To the author's knowledge, such an association has not been identified in other geographic locations.

T95558

185055-185106

Sentence

denotes

Another suspected infectious agent is Fusarium spp.

T85108

185107-185484

Sentence

denotes

464 Alteration of the gastrointestinal microflora caused by recent dietary change has been suggested as a predisposing cause for DPJ; in one report, horses with DPJ were fed significantly more grain and were more likely to have grazed pasture, relative to horses with other forms of colic, but these associations were not deemed strong enough to allow clinical differentiation.

T93550

185485-185605

Sentence

denotes

465 Two intracellular processes control intestinal secretion: the cyclic nucleotide (cAMP and cGMP) and calcium systems.

T46252

185606-185829

Sentence

denotes

169 Inflammatory mediators, microorganisms, and toxins can activate adenyl cyclase (vasoactive intestinal peptide and PGE 2 ) or guanylyl cyclase (bacterial enterotoxins) and induce increases in cAMP and cGMP, respectively.

T31871

185830-185954

Sentence

denotes

This reaction causes phosphorylation of specific protein kinases, which induce the actual mucosal membrane transport events.

T42691

185955-186137

Sentence

denotes

Increases in intracellular free calcium may arise from cyclic nucleotide-dependent release of stored calcium within the cell or from increased calcium entry across the cell membrane.

T81910

186138-186239

Sentence

denotes

Calcium may act through calmodulin, which then can activate membrane-phosphorylating protein kinases.

T53298

186240-186409

Sentence

denotes

The net effect is increased movement of sodium and chloride into the mucosal cell from the interstitium, with secretion of sodium and chloride into the intestinal lumen.

T10730

186410-186514

Sentence

denotes

Water follows the directional flux of sodium and chloride through highly permeable intercellular spaces.

T5796

186515-186651

Sentence

denotes

Several bacterial toxins and endogenous mediators can cause active secretion and contribute to a synergistic mucosal secretory response.

T70915

186652-186837

Sentence

denotes

Passive secretion of protein-rich fluid into the lumen occurs after damage to the mucosal epithelium, capillary endothelium, and submucosal inflammation in the proximal small intestine.

T83141

186838-187021

Sentence

denotes

The clinically relevant events that result from active and passive fluid secretion are proximal small intestinal distention and nasogastric reflux, dehydration, and circulatory shock.

T34371

187022-187153

Sentence

denotes

466 The concentration of protein in the PF from horses with DPJ is usually higher than in horses with small intestinal obstruction.

T94999

187154-187376

Sentence

denotes

A disproportionate increase in total protein concentration relative to nucleated cell count occurs, probably by leakage of blood or plasma into the peritoneal cavity without a significant stimulus for leukocyte chemotaxis.

T53474

187377-187638

Sentence

denotes

Suggested mechanisms for increased abdominal fluid protein concentration include serositis associated with inflamed intestine and small intestinal distention causing passive congestion and increased capillary hydrostatic pressure of visceral peritoneal vessels.

T67643

187639-187878

Sentence

denotes

467 Small intestinal ileus is another hallmark sign of DPJ, and the pathophysiology is complicated, involving primary and secondary dysfunction of the central, autonomic, and ENSs and their purported roles in governing intestinal motility.

T63247

187879-188041

Sentence

denotes

Further detail regarding the effect of inflammation on small intestinal motility is provided in Inflammatory Disease of the Small Intestine later in this chapter.

T43712

188042-188250

Sentence

denotes

Differentiating horses with DPJ from horses with small intestinal obstructive lesions can be challenging because there is no single distinguishing feature, and all information must be considered collectively.

T24638

188251-188415

Sentence

denotes

Horses with obstructive lesions of the small intestine usually show consistent signs of abdominal pain until the affected viscus is repaired surgically or ruptures.

T25318

188416-188547

Sentence

denotes

In contrast, signs of acute abdominal pain typically subside after gastric decompression and volume replacement in horses with DPJ.

T15791

188548-188607

Sentence

denotes

They are replaced by signs of lethargy and general malaise.

T38506

188608-188782

Sentence

denotes

On rectal examination the degree of small intestinal distention may be subjectively less with DPJ than with obstructive lesions, particularly following gastric decompression.

T49013

188783-188978

Sentence

denotes

Although the color and odor of gastric reflux can be similar, horses with DPJ tend to have a larger volume (≥4-20 L with each decompressive effort) of reflux than horses with obstructive lesions.

T99606

188979-189140

Sentence

denotes

Horses with DPJ often have a mild fever of 38.6°C to 39.1°C (101.5°F-102.5°F), whereas horses with obstructive lesions are typically normothermic or hypothermic.

T34880

189141-189245

Sentence

denotes

Abnormalities in the leukogram are more common in horses with DPJ than with an acute obstructive lesion.

T58683

189246-189411

Sentence

denotes

19, 460 In addition, hyponatremia, hypochloremia, hypokalemia, prerenal azotemia, and elevated hepatic enzymes (GGT, alanine transaminase, and AP) are often evident.

T84100

189412-189504

Sentence

denotes

462 Hyperlactemia from poor tissue perfusion and hypovolemia is common with both conditions.

T12977

189505-189581

Sentence

denotes

PF analysis may be helpful in distinguishing DPJ from an obstructive lesion.

T1441

189582-189870

Sentence

denotes

The typical findings with DPJ include an increased PF protein concentration (often ≥3.5 g/dL) and a mild to moderate elevation of the peritoneal WBC count, although the count usually is less than 10,000 cells/μL; PF lactate concentration typically mirrors peripheral blood concentrations.

T50583

189871-190049

Sentence

denotes

The disproportionate increase in PF total protein compared with peritoneal nucleated cell count may be caused by leakage of blood or plasma without a marked leukotactic response.

T73346

190050-190170

Sentence

denotes

19 The PF is usually yellow and turbid, but in severe cases, diapedesis can occur, resulting in a serosanguineous color.

T62412

190171-190243

Sentence

denotes

Strangulating lesions typically result in more severe changes in the PF.

T30730

190244-190337

Sentence

denotes

Serosanguineous PF with increased protein, lactate, and white and red blood cells is typical.

T65129

190338-190502

Sentence

denotes

Horses with intraluminal obstructions such as ileal impactions typically have grossly normal PF with a mildly elevated protein resulting from intestinal distention.

T30762

190503-190684

Sentence

denotes

419, 460, 466 Ultrasonographic findings in horses with DPJ typically include gastric and duodenal distention and segments of small intestine containing hypoechoic to anechoic fluid.

T44042

190685-190754

Sentence

denotes

The wall of the small intestine can be normal or thickened with time.

T75750

190755-190806

Sentence

denotes

Peristalsis can be decreased, normal, or increased.

T4322

190807-190884

Sentence

denotes

Differentiation from a small intestinal obstructive lesion remains difficult.

T59642

190885-191110

Sentence

denotes

More long-standing obstructions typically result in increased wall thickness, sedimentation of ingesta within the small intestinal lumen, and distended small intestine proximal to the lesion with collapsed intestine distally.

T40524

191111-191441

Sentence

denotes

In most cases, the diagnosis is suspected on the basis of clinical and clinicopathologic signs and response to therapy; a definitive diagnosis of DPJ requires gross examination of the duodenum and proximal jejunum at surgery or at necropsy Y TREATMENT Horses with DPJ appear to share a common characteristic clinical presentation.

T10029

191442-191665

Sentence

denotes

Treatment is supportive and should include volume replacement, analgesic and antiinflammatory therapy, gastric decompression, antiendotoxin therapy, antimicrobial therapy if indicated, nutritional support, and nursing care.

T41768

191666-191777

Sentence

denotes

Although the signs of abdominal pain usually resolve after gastric decompression, most horses remain lethargic.

T66447

191778-191895

Sentence

denotes

Horses with DPJ often require gastric decompression at 2-hour intervals, with 2 to 10 L of fluid recovered each time.

T65331

191896-192111

Sentence

denotes

Nasogastric tubes left in place for long periods cause varying degrees of pharyngitis ( Fig. 12.6) , laryngitis, and esophagitis, and maintenance of an indwelling nasogastric tube may further delay gastric emptying.

T48011

192112-192258

Sentence

denotes

466, 468, 469 Thus one should use the smallest, softest nasogastric tube needed for gastric decompression and remove the tube as soon as possible.

T55886

192259-192427

Sentence

denotes

Much of the supportive care for horses with DPJ mirrors that described for other cases of endotoxemia and is discussed in detail in Endotoxemia earlier in this chapter.

T6597

192428-192516

Sentence

denotes

Specific fluid replacement should take ongoing losses through reflux into consideration.

T99329

192517-192605

Sentence

denotes

Horses should not receive food or water until they remain comfortable and reflux ceases.

T67674

192606-192678

Sentence

denotes

Occasional sips of water or rinsing of the mouth may decrease halitosis.

T48017

192679-192763

Sentence

denotes

The refeeding plan should be conservative, because horses refed quickly may relapse.

T56371

192764-192977

Sentence

denotes

NSAIDs are the most frequently used group of drugs for treatment of abdominal pain in horses (flunixin meglumine 0.25-1.1 mg/kg IV every 8-12 hours, with the higher dose given only at the least frequent interval).

T57765

192978-193055

Sentence

denotes

These agents also have beneficial antiinflammatory and antiendotoxic effects.

T10012

193056-193185

Sentence

denotes

The clinician must weigh the benefit of these drugs against their negative effects on gastrointestinal mucosa and renal function.

T12309

193186-193373

Sentence

denotes

Another popular analgesic option is butorphanol, an opioid agonist-antagonist, given at 0.02 to 0.1 mg/kg intramuscularly every 6 to 8 hours or as a constant rate infusion at 13 μg/ kg/h.

T21783

193374-193450

Sentence

denotes

470 This route appears to have minimal effects on gastrointestinal motility.

T51334

193451-193658

Sentence

denotes

Because Clostridium spp. are suspected as a causative agent of DPJ, penicillin, metronidazole, or both may be administered to affected horses in geographic locations in which said organisms appear prevalent.

T62090

193659-193761

Sentence

denotes

Broad-spectrum antimicrobial therapy may be considered for horses with DPJ and significant leukopenia.

T37612

193762-193836

Sentence

denotes

The veterinarian should consider the nutritional needs of horses with DPJ.

T20539

193837-193933

Sentence

denotes

Most horses have a total body protein loss because of cachexia and a protein-losing enteropathy.

T62961

193934-194047

Sentence

denotes

Total or partial parenteral nutrition may be indicated in horses that remain anorectic for more than 3 to 4 days.

T67845

194048-194290

Sentence

denotes

Parenterally administered solutions containing glucose, balanced amino acid solutions, lipid emulsions, balanced electrolyte and trace minerals, and vitamins have been administered to adult horses with small intestinal ileus or enterocolitis.

T85901

194291-194437

Sentence

denotes

Based on a small number of horses, this therapy has proved promising in terms of minimizing protein losses and decreasing the duration of illness.

T14237

194438-194595

Sentence

denotes

Postoperative parenteral nutrition ameliorates clinicopathologic evidence of starvation following small intestinal resection and anastomosis in adult horses.

T1293

194596-194766

Sentence

denotes

471, 472 Providing for part of the nutritional requirements of the horse (8000-12,000 kcal/day) is possible with glucose-amino acid solutions, which are of moderate cost.

T94208

194767-194931

Sentence

denotes

It is reasonable to suppose that providing nutritional support to an anorectic, severely ill horse will facilitate healing and even shorten the duration of illness.

T56215

194932-195183

Sentence

denotes

Thus the overall cost of providing parenteral nutritional supplementation to horses with DPJ may be offset by quicker recovery and diminished requirements for other, expensive treatments, but further data are necessary to accurately assess this point.

T52199

195184-195284

Sentence

denotes

Normal (healthy) intestine is necessary for optimal performance of most prokinetic agents in horses.

T75225

195285-195354

Sentence

denotes

Many motilitymodifying agents likely are ineffective in cases of DPJ.

T16369

195355-195520

Sentence

denotes

Inflamed jejunal tissue has been shown to have downregulation and decreased production of motilin receptors, which may alter the prokinetic response to erythromycin.

T62379

195521-195704

Sentence

denotes

473 However, some benefit may come of the judicious use of prokinetic agents in inflammatory conditions of the equine intestine, particularly if the agent provides additional effects.

T86207

195705-195757

Sentence

denotes

Lidocaine has shown particular promise for this use.

T86622

195758-195960

Sentence

denotes

Although the exact mechanism of action is unknown, the beneficial effects in horses with ileus are likely caused by antiinflammatory effects because a direct prokinetic effect has not been demonstrated.

T36458

195961-196361

Sentence

denotes

474 In horses with nasogastric reflux attributable to POI or enteritis, a constant rate infusion of lidocaine was shown to reduce the hourly The horse was diagnosed with duodenitis-proximal jejunitis (DPJ) and developed mild respiratory stridor and gagging and retching behavior after an indwelling nasogastric tube had been in place for 48 hours to allow for intermittent drainage of gastric reflux.

T23731

196362-196442

Sentence

denotes

The horse responded well to medical therapy for DPJ and pharyngitis-esophagitis.

T61891

196443-196525

Sentence

denotes

volume of reflux and shorten the time to cessation of reflux compared with saline.

T91753

196526-196635

Sentence

denotes

475 Prokinetic therapy with erythromycin lactobionate, metoclopramide, or bethanechol can also be considered.

T72217

196636-196784

Sentence

denotes

476, 477 Motility-modifying agents and the influence of inflammation on their effects are discussed in Gastrointestinal Ileus later in this chapter.

T19130

196785-196836

Sentence

denotes

Medical therapy is successful in most cases of DPJ.

T7549

196837-197044

Sentence

denotes

For horses with DPJ that continue to produce copious enterogastric reflux despite aggressive medical treatment, or when a mechanical obstruction cannot be satisfactorily ruled out, surgery may be considered.

T89610

197045-197249

Sentence

denotes

Refractory cases have improved with surgical intervention; however, some horses with refractory DPJ have been observed to recover after prolonged (up to 20 days) supportive care and gastric decompression.

T97124

197250-197307

Sentence

denotes

The latter is not recommended in the author's experience.

T10346

197308-197521

Sentence

denotes

For a horse exhibiting abdominal discomfort with small intestinal distention palpable per rectum and more than 2 L of gastric reflux, the veterinarian should recommend referral to an appropriate surgical facility.

T94015

197522-197706

Sentence

denotes

Typically, the main determinants for surgical intervention are degree and duration of abdominal pain, PF analysis, and results of (often repeated) rectal palpation and ultrasonography.

T403

197707-197926

Sentence

denotes

Short-term mortality rates have been reported to be 37% for horses in which manual evacuation of the small intestine into the cecum was performed surgically, compared with 40% for horses that received medical treatment.

T13517

197927-198182

Sentence

denotes

478 A 95% recovery rate was reported in horses with DPJ that underwent laparotomy and manual evacuation of the small intestine into the cecum, combined with treatment for C. perfringens consisting of IV metronidazole and intramuscular procaine penicillin.

T11833

198183-198317

Sentence

denotes

479 Drawbacks of surgery include the expense, risks of anesthesia, prolonged return to training, and risk of incisional complications.

T41051

198318-198408

Sentence

denotes

However, when an obstruction cannot be ruled out, these concerns are of minor consequence.

T55053

198409-198412

Sentence

denotes

466

T9938

198414-198467

Sentence

denotes

Survival rates for DPJ range between 25% 460 and 94%.

T56631

198468-198684

Sentence

denotes

19, 460 At present the survival of horses with DPJ that undergo surgery is much greater than previously described, and certainly greater than that of horses with small intestinal obstruction that do not have surgery.

T56942

198685-198823

Sentence

denotes

478, 479 Horses with DPJ that receive appropriate therapy have a reasonably good chance of making a full recovery, and recurrence is rare.

T61127

198824-198986

Sentence

denotes

Horses that continue to have frequent episodes of voluminous nasogastric reflux and systemic signs of endotoxemia and sepsis have a poorer prognosis for recovery.

T72429

198987-199070

Sentence

denotes

Frequent complications of DPJ include laminitis, thrombophlebitis, and weight loss.

T14302

199071-199220

Sentence

denotes

There appears to be geographic variation in the severity and prognosis for DPJ, with horses in the southeastern United States most severely affected.

T34950

199221-199573

Sentence

denotes

Equine coronavirus (ECoV) is classified as a betacoronavirus and is associated with fever, lethargy, anorexia, and enteric disease (colic and/or alteration in fecal consistency) in some horses. [480] [481] [482] A definitive association between ECoV and diarrhea in foals was not recognized before the year 2000 483, 484 or in adult horses before 2011.

T68248

199574-199620

Sentence

denotes

480, 481 Diagnosis is confirmed via fecal PCR.

T27485

199621-199795

Sentence

denotes

480, 482 Mortality is typically low (7%), 480, 482 with death caused by suspected 482 or confirmed 485 hyperammonemia and neurologic disease or severe endotoxemia and sepsis.

T32539

199796-199910

Sentence

denotes

482, 485 In some outbreaks, the fatality rate has been higher (27%), with fecal viral load higher in nonsurvivors.

T26173

199911-200091

Sentence

denotes

486 Histologically, ECoV is associated with necrotizing enteritis, particularly in the jejunum and ileum, with hemorrhage in the ventral colon in nonsurviving horses in one report.

T82701

200092-200095

Sentence

denotes

485

T9565

200097-200244

Sentence

denotes

Malabsorption and maldigestion are commonly recognized clinical problems in humans and small animals and documented clinical entities in the horse.

T37276

200245-200455

Sentence

denotes

The term malabsorption implies impairment of digestive and absorptive processes arising from functional or structural disorders of the small intestine and related organs, the pancreas, liver, and biliary tract.

T668

200456-200593

Sentence

denotes

The condition can affect absorption of carbohydrates, proteins, fats, vitamins, minerals, and to a lesser extent, water and electrolytes.

T36310

200594-200808

Sentence

denotes

In horses, the resulting pathophysiologic changes may influence large intestinal function adversely through alterations in the substrate presented for fermentation or through direct infiltration of the large colon.

T87926

200809-200989

Sentence

denotes

Differentiation between carbohydrate, protein, or fat malabsorption is not possible in the horse because of the herbivorous diet and the contribution of large intestinal functions.

T81771

200990-201395

Sentence

denotes

The rarity of pancreatic problems, such as exocrine pancreatic insufficiency, in horses along with their herbivorous diet makes maldigestion less problematic, but maldigestion can contribute to chronic weight loss in horses with severe infiltrative small intestinal disease and exacerbate diarrhea in the suckling foal through reduced intestinal bile salt concentrations from hepatic or ileal dysfunction.

T57390

201396-201478

Sentence

denotes

Malabsorption is not synonymous with diarrhea, although diarrhea may be a feature.

T74268

201479-201598

Sentence

denotes

Adult horses rarely exhibit diarrhea with small intestinal problems unless large intestinal involvement is concomitant.

T8158

201599-201771

Sentence

denotes

Chronic diarrhea is predominantly a large intestinal disorder that reflects an overload of water and electrolytes and thus may be considered a state of impaired absorption.

T16231

201772-201857

Sentence

denotes

Primary small intestinal disease is more likely to occur in neonates and young foals.

T86837

201858-202031

Sentence

denotes

For example, acquired small intestinal brush border lactase deficiency may result in increased lactose fermentation in the large intestine and induction of osmotic diarrhea.

T58169

202032-202325

Sentence

denotes

487 The clinical signs of chronic wasting and poor body condition, although nonspecific for a diagnosis of malabsorption antemortem, can typically be attributed to proliferative or inflammatory intestinal disorders, often collectively referred to as chronic inflammatory bowel diseases (CIBD).

T25230

202326-202329

Sentence

denotes

488

T22915

202330-202455

Sentence

denotes

The primary clinical sign associated with diseases of malabsorption and maldigestion is weight loss with or without diarrhea.

T43371

202456-202624

Sentence

denotes

Physical, ultrasonographic, and laboratory assessment is as described for other gastrointestinal diseases and detailed in Diagnostic Evaluation earlier in this chapter.

T88758

202625-202801

Sentence

denotes

Rectal biopsy is easy to perform and may provide an indication of cellular infiltration that could be present at more proximal locations, but interpretation is often difficult.

T47247

202802-202930

Sentence

denotes

In one retrospective study, inflammatory bowel disease was diagnosed from rectal biopsy specimens in approximately 50% of cases.

T67639

202931-203134

Sentence

denotes

489 In that report, simple proctitis (neutrophils in the crypt or surface epithelium) was associated with inflammatory disorders, whereas only mild scattered neutrophil infiltration was seen in controls.

T58235

203135-203280

Sentence

denotes

Rectal biopsy aided diagnosis for 3 of 7 horses with lymphocytic-plasmacytic enterocolitis 490 and 1 of 2 horses with eosinophilic enterocolitis.

T8477

203281-203420

Sentence

denotes

491 Tables 12.3 and 12.4 present the clinicopathologic and pathologic features of the diseases most commonly associated with malabsorption.

T63477

203421-203642

Sentence

denotes

In the same animal the extent and severity of pathologic changes differ in different regions of the small and large intestines, influencing the severity of clinical signs and abnormalities in tests of intestinal function.

T81737

203643-203770

Sentence

denotes

Early diagnosis remains a challenge, and even multiple intestinal biopsies taken at exploratory laparotomy may prove unhelpful.

T15292

203771-203981

Sentence

denotes

Biopsies of skin, liver, lymph node, or lung may reveal evidence of multisystemic disease and can be easily obtained in the standing horse, with organ biopsies typically obtained with ultrasonographic guidance.

T78141

203982-204039

Sentence

denotes

Duodenal mucosal biopsies can be obtained endoscopically.

T57644

204040-204213

Sentence

denotes

Exploratory laparotomy facilitates rigorous inspection of the gastrointestinal tract and associated organs to obtain multiple biopsies from intestinal sites and lymph nodes.

T4474

204214-204305

Sentence

denotes

Cost and potential postoperative complications may limit surgical procedures for diagnosis.

T10313

204306-204474

Sentence

denotes

Laparoscopy may provide an alternative means to facilitate biopsy of certain tissues but is typically more helpful from a diagnostic rather than therapeutic standpoint.

T3213

204475-204603

Sentence

denotes

From this perspective, surgical exploration should be considered as an option early in the process rather than as a last resort.

T62560

204604-204800

Sentence

denotes

Carbohydrate absorption tests, described in Diagnostic Evaluation earlier in this chapter, can provide a practical and inexpensive means to assess the absorptive capability of the small intestine.

T44518

204801-204960

Sentence

denotes

Pathologic changes in the mucosa and submucosa must be extensive and widely distributed to greatly affect the peak plasma concentration and shape of the curve.

T31684

204961-205204

Sentence

denotes

In one report of 42 mature horses with chronic weight loss, a normal OGTT (peak glucose concentration at 120 minutes >85% baseline) was not associated with abnormal small intestinal morphology in any of the 5 horses in which it was documented.

T70098

205205-205537

Sentence

denotes

When peak glucose concentration was between 15% and 85% of baseline at 120 minutes (considered partial malabsorption), approximately 72% had small intestinal infiltrative disease, and when peak concentration at 120 minutes was less than 15% above baseline (total malabsorption), all had severe small intestinal infiltrative disease.

T95183

205538-205684

Sentence

denotes

59 Other reports have documented horses with flat OGTT curves that subsequently showed more normal OGTT responses and resolved clinical condition.

T92455

205685-205876

Sentence

denotes

492 Carbohydrate absorption tests probably have poor diagnostic sensitivity to detect small intestinal involvement in horses with chronic diarrhea and predominantly large intestinal problems.

T27683

205877-206036

Sentence

denotes

493 An abnormal absorption test and weight loss can occur in the horse as a transient event and without significant morphologic changes in the small intestine.

T5365

206037-206223

Sentence

denotes

The intestinal sugar active transport system has a low affinity for d-xylose in the equine jejunum in vitro, hence d-xylose absorption likely occurs primarily by convection or diffusion.

T97373

206224-206414

Sentence

denotes

494 An abnormal d-xylose absorption test likely indicates abnormal mucosal surface area or permeability and has been observed in horses with CIBD, parasitism, and idiopathic villous atrophy.

T74347

206415-206637

Sentence

denotes

488, 495 Abnormal absorption curves have been detected in the absence of small intestinal histologic changes, 496 and interpretation is clouded further by findings from small intestinal resection studies in healthy ponies.

T13086

206638-206836

Sentence

denotes

One study demonstrated a progressive decline in mean peak xylose concentration after 70% distal small intestinal resection in ponies despite their normal clinical appearance and absence of diarrhea.

T48755

206837-207017

Sentence

denotes

497 In another study, a similar decline in peak xylose concentration following extensive (≥60%) small intestinal resection was accompanied by weight loss, diarrhea, and ill thrift.

T590

207018-207250

Sentence

denotes

498 Peak xylose concentrations were much lower in horses with granulomatous enteritis than those with eosinophilic granulomatosis (EG), whereas in EG the absorption curve shifted to the right, with the peak occurring at 240 minutes.

T88879

207251-207337

Sentence

denotes

499 This is not surprising given the typical lesion distribution with these disorders.

T44472

207338-207424

Sentence

denotes

As with the OGTT, results of the xylose absorption test can improve following therapy.

T47877

207425-207428

Sentence

denotes

500

T40093

207429-207682

Sentence

denotes

Alimentary lymphosarcoma of the horse may represent a primary neoplasia of the gut-associated lymphoid tissue with significant cellular infiltration of the small intestine and associated lymph nodes with minimal large intestinal or systemic involvement.

T92875

207683-207927

Sentence

denotes

Case series and pathology reports indicate that young horses 2 to 4 years of age primarily are affected, although the age range can be broad. [501] [502] [503] No breed or sex predilection has been documented, and disease prevalence is unknown.

T30102

207928-208050

Sentence

denotes

Despite the progressive nature of lymphomata, onset of clinical signs can be rapid, and the animal may become acutely ill.

T10886

208051-208170

Sentence

denotes

As with all adult cases of CIBD, antemortem diagnosis is by a process of exclusion and usually is confirmed postmortem.

T66745

208171-208353

Sentence

denotes

Frequent abnormalities include anemia, thrombocytopenia, neutrophilia or neutropenia, and hypoalbuminemia with hyperglobulinemia, resulting in either a normal elevated serum protein.

T39317

208354-208376

Sentence

denotes

Lymphocytosis is rare.

T18820

208377-208466

Sentence

denotes

Intraabdominal masses such as enlarged mesenteric lymph nodes may be palpated per rectum.

T98489

208467-208570

Sentence

denotes

Abdominocentesis and rectal biopsy can provide a diagnosis but are not sensitive indicators of disease.

T74382

208571-208791

Sentence

denotes

Carbohydrate absorption tests usually reveal partial to total malabsorption indicative of the severely reduced surface area resulting from significant villous atrophy and the extensive mucosal or transmural infiltration.

T70285

208792-208958

Sentence

denotes

Confirmation of a diagnosis requires exploratory laparotomy to obtain multiple intestinal and lymph node biopsies if rectal biopsy and/or abdominocentesis are normal.

T89313

208959-209055

Sentence

denotes

Prognosis is poor, especially because most horses are presented in an advanced state of disease.

T98277

209056-209166

Sentence

denotes

Immunosuppressive drugs or chemotherapy may afford temporary improvement, but long-term outcome is unaffected.

T2105

209167-209296

Sentence

denotes

Granulomatous enteritis was first described as a chronic wasting condition in 1974 504 ; 9 of 10 horses were young Standardbreds.

T13811

209297-209342

Sentence

denotes

Most affected horses are 2 to 3 years of age.

T67084

209343-209457

Sentence

denotes

Case reports from many countries revealed a predominance of Standardbred over Thoroughbred horses by three to one.

T4953

209458-209574

Sentence

denotes

499, 505 Some of the Standardbreds were related, implicating a genetic predisposition, but this has not been proven.

T28655

209575-209609

Sentence

denotes

Prevalence of this disease is low.

T55585

209610-209697

Sentence

denotes

The condition is sporadic and has an insidious onset, and the course can be protracted.

T26170

209698-209975

Sentence

denotes

Significant diagnostic features include anemia, slight increases or decreases in WBC counts, hypoalbuminemia, normal serum protein or hypoproteinemia, occasional increases in serum AP activity, normal serum GGT activity, and enlarged mesenteric lymph nodes on rectal palpation.

T14992

209976-210070

Sentence

denotes

Partial or complete malabsorption is typically documented via carbohydrate absorption testing.

T78512

210071-210223

Sentence

denotes

One can attribute the low proportion of horses exhibiting diarrhea to the preferential distribution of inflammatory infiltration in the small intestine.

T69117

210224-210275

Sentence

denotes

506 Rectal biopsy can be a useful aid to diagnosis.

T60643

210276-210328

Sentence

denotes

489 The cause of granulomatous enteritis is unknown.

T35436

210329-210407

Sentence

denotes

Several infectious agents have been implicated, including Mycobacterium avium.

T11918

210408-210482

Sentence

denotes

507 The condition may represent a granulomatous hypersensitivity reaction.

T18252

210483-210589

Sentence

denotes

Immunomediated responses to dietary, parasitic, or bacterial antigens may be important initiating factors.

T88979

210590-210791

Sentence

denotes

488 Six horses purported to have granulomatous enteritis were linked to environmental contamination with aluminum, 508 although problems existed regarding the case definition, data, and interpretation.

T31013

210792-210964

Sentence

denotes

509 Treatment of horses with granulomatous enteritis with a variety of drugs, particularly corticosteroids, has not affected the long-term outcome in the majority of cases.

T34953

210965-211184

Sentence

denotes

510 Prolonged (5 months) corticosteroid administration produced clinical remission and a favorable athletic outcome in a 6-year-old Standardbred gelding based on improvement in clinical signs and in d-xylose absorption.

T85204

211185-211237

Sentence

denotes

500 Surgery may be indicated with localized disease.

T71038

211238-211420

Sentence

denotes

Two young horses underwent resection of the thickened terminal small intestine; one horse died 4 months after surgery, and the other remained clinically normal for at least 10 years.

T3491

211421-211424

Sentence

denotes

505

T35155

211425-211728

Sentence

denotes

Multisystemic eosinophilic epitheliotropic disease (MEED) encompasses disorders characterized by a predominant eosinophilic infiltrate in the gastrointestinal tract, associated lymph nodes, liver, pancreas, skin, and other structures accompanied by some degree of malabsorption and enteric protein loss.

T23581

211729-211876

Sentence

denotes

The disorders include chronic eosinophilic gastroenteritis, 511 EG, 499 chronic eosinophilic dermatitis, 512 and probably basophilic enterocolitis.

T7834

211877-211969

Sentence

denotes

513 Although prevalence is low, MEED appears to be more common than granulomatous enteritis.

T20016

211970-212080

Sentence

denotes

Most affected horses are 2 to 4 years of age, and Standardbreds and Thoroughbreds are reported to predominate.

T64749

212081-212188

Sentence

denotes

The condition is sporadic, has an insidious onset, and often a protracted course (duration of 1-10 months).

T30269

212189-212208

Sentence

denotes

Diarrhea is common.

T91991

212209-212348

Sentence

denotes

Severe skin lesions with exudative dermatitis and ulcerative coronitis are prominent and frequently are the principal presenting complaint.

T20406

212349-212467

Sentence

denotes

Despite extensive tissue eosinophilia, systemic eosinophilia is rare, and hematologic values are usually unremarkable.

T59737

212468-212555

Sentence

denotes

Notable features include hypoalbuminemia and elevations in serum GGT and AP activities.

T10274

212556-212691

Sentence

denotes

Most reports of carbohydrate absorption test findings indicate a reduced or normal peak concentration delayed for at least 180 minutes.

T38665

212692-212883

Sentence

denotes

Morphologic changes are less pronounced in the small intestine than in the large intestine, 514 and small intestinal lesions predominate segmentally in the proximal duodenum and distal ileum.

T13761

212884-212988

Sentence

denotes

Significant hyperkeratosis of the fundic region may contribute to gastric muscle contractile disruption.

T19181

212989-213166

Sentence

denotes

Diarrhea can be a consequence of the severe segmental or multifocal granulomatous lesions in the large intestine with mucosal and transmural thickening and extensive ulceration.

T80774

213167-213222

Sentence

denotes

Abundant fibrosis is a feature of all affected tissues.

T29245

213223-213446

Sentence

denotes

The cause of MEED is unknown, and the disease may represent a chronic ongoing immediate hypersensitivity reaction against undefined antigens ingested or excreted into the lumen from parasitic, bacterial, or dietary sources.

T40575

213447-213490

Sentence

denotes

Infectious agents have not been identified.

T62856

213491-213642

Sentence

denotes

511, 512 Eosinophilia is a feature of parasitism in the equine intestinal tract, although nematodes rarely have been identified in any lesions of MEED.

T47019

213643-213807

Sentence

denotes

511, 515 Failure to detect larval structures in these lesions, however, may be attributable to chronicity of the disease and destruction of the parasites in tissue.

T78489

213808-213927

Sentence

denotes

505 Biopsies of the rectal mucosa 489 or of the skin, liver, intestinal tract, and lymph nodes may assist in diagnosis.

T21471

213928-214122

Sentence

denotes

Unlike the other conditions associated with malabsorption/ maldigestion in horses, MEED has definitive liver and pancreatic involvement; thus, maldigestion may contribute to the wasting disease.

T42221

214123-214260

Sentence

denotes

Treatment has been attempted with a variety of drugs, including antibiotics, corticosteroids, and anthelmintics with larvicidal activity.

T90052

214261-214335

Sentence

denotes

Although some horses can improve briefly, the long-term prognosis is poor.

T9319

214336-214496

Sentence

denotes

Idiopathic eosinophilic enterocolitis affects segmental lesions in the small or large intestine, inducing signs of colic, often requiring surgical intervention.

T53876

214497-214608

Sentence

denotes

505, 516, 517 This problem may not involve evidence of malabsorption and does not have multisystem involvement.

T27649

214609-214834

Sentence

denotes

Because the problem is often associated with signs of colic and not signs of malabsorption, eosinophilic enterocolitis differs from the other conditions discussed in this section and is often diagnosed at the time of surgery.

T95148

214835-214913

Sentence

denotes

It carries a much better prognosis than the other inflammatory bowel diseases.

T50204

214914-215072

Sentence

denotes

The morphologic findings in lymphocytic-plasmacytic enterocolitis reflect the predominant infiltrative cellular elements of this rarely encountered condition.

T15851

215073-215213

Sentence

denotes

No specific clinical or clinicopathologic features differentiate this condition antemortem from other inflammatory diseases of adult horses.

T48563

215214-215392

Sentence

denotes

In a retrospective study of 14 horses, carbohydrate absorption was abnormal or delayed in 9 of 12 horses, consistent with the predominance of small intestinal pathologic changes.

T19818

215393-215516

Sentence

denotes

490 Rectal biopsies were abnormal in 3 of 7 horses, two of which were reported as having lymphocytic-plasmacytic proctitis.

T85621

215517-215642

Sentence

denotes

Prognosis is typically reported as poor, likely caused by the advanced nature of the condition at the beginning of treatment.

T59549

215643-215902

Sentence

denotes

In the author's experience, some horses with small intestinal mural thickening, lymphocytic-plasmacytic infiltrate evident on duodenal biopsy, and signs of abdominal pain and/ or weight loss may improve with dietary modification and/or corticosteroid therapy.

T23523

215903-216225

Sentence

denotes

Proliferative enteropathy (PE) typically affects weanling foals from 3 to 8 months of age and has been reported in North America, Europe, and Australia, causing disease in individuals or outbreaks of multiple affected animals on the same premise. [518] [519] [520] [521] [522] PE is uncommon in yearlings and adult horses.

T30769

216226-216451

Sentence

denotes

518 , 523 The disease affects many other species, namely swine, and is caused by L. intracellularis, an obligate intracellular bacterium found in the cytoplasm of proliferative crypt epithelial cells of the jejunum and ileum.

T25798

216452-216510

Sentence

denotes

518, 524, 525 Like pigs, horses are affected as weanlings.

T7564

216511-216610

Sentence

denotes

The incubation period is 2 to 3 weeks in nonequine species and is presumed to be similar in horses.

T98342

216611-216757

Sentence

denotes

In some epidemiologic investigations, close proximity to swine operations was apparent, but in most instances such an association was not evident.

T23838

216758-217035

Sentence

denotes

518, 523 Comparisons of epidemiologic findings from the swine disease indicated that overcrowding, feed changes, antibiotic usage, and mixing and transportation were potential risk factors at two of the farms in one study, and recent weaning appears to be a common risk factor.

T41346

217036-217130

Sentence

denotes

518 The window for exposure appears narrow, 526 and multiple cases on a given farm are common.

T70703

217131-217228

Sentence

denotes

Affected animals shedding the organism in the feces serve as a source of infection for herdmates.

T9293

217229-217328

Sentence

denotes

It is possible that nonequine species serve as reservoirs contributing to outbreaks on horse farms.

T36474

217329-217547

Sentence

denotes

Profound hyperplasia of the mucosa associated with proliferation of crypt epithelium and crypt hyperplasia is induced locally in infected islands of tissue that eventually extend to the entire distal jejunum and ileum.

T5039

217548-217660

Sentence

denotes

L. intracellularis preferentially infects proliferating cells; thus, it is the tropism for the crypt epithelium.

T12562

217661-217872

Sentence

denotes

Infected cells proliferate far more rapidly than uninfected cells, suggesting that L. intracellularis directly induces the proliferative response, but the molecular basis for enhanced proliferation is not known.

T90152

217873-218063

Sentence

denotes

L. intracellularis penetrates epithelial cells in a membrane-bound vesicle but eventually escapes the vacuole and is found free in the cytoplasm, concentrated at the apical pole of the cell.

T33260

218064-218131

Sentence

denotes

The gross pathologic lesions of equine PE are quite characteristic.

T74563

218132-218272

Sentence

denotes

518 Lesions may be segmental and are most commonly found in the ileum and terminal jejunum in horses, but the duodenum may also be affected.

T70290

218273-218372

Sentence

denotes

Severe mucosal hypertrophy is often observed but may wane during the chronic stages of the disease.

T57839

218373-218436

Sentence

denotes

The mucosa may become corrugated with focal erosions or ulcers.

T9024

218437-218519

Sentence

denotes

Submucosal edema is often readily identified on cut sections of affected segments.

T47350

218520-218614

Sentence

denotes

Moderate to severe crypt hyperplasia with atrophy of intestinal villi is a consistent feature.

T50098

218615-218684

Sentence

denotes

Hyperplastic crypts are branched and may herniate into the submucosa.

T53311

218685-218876

Sentence

denotes

Necrosis, edema of the submucosal and lamina propria, hemorrhage, mononuclear inflammation, and muscular hypertrophy have been reported in affected intestinal segments but are not consistent.

T45833

218877-218960

Sentence

denotes

Special stains such as silver stain are required to detect intracellular organisms.

T85559

218961-219080

Sentence

denotes

The organisms are curved or comma-shaped rods found clustered in the apical cytoplasm of hyperplastic crypt epithelium.

T38948

219081-219369

Sentence

denotes

The proliferative response of the intestinal mucosa alters absorption of nutrients and fluid secretion by disrupting the architecture of the villi and by altering the maturation of epithelial cells into absorptive cells, accounting for the secretory diarrhea and often severe weight loss.

T61119

219370-219505

Sentence

denotes

The combined effects of the inflammatory response and malabsorption may account for the clinically observed protein-losing enteropathy.

T23498

219506-219603

Sentence

denotes

Clinical signs include depression, rapid and significant weight loss, edema, diarrhea, and colic.

T73657

219604-219690

Sentence

denotes

518 Poor body condition, a rough hair coat, and potbelly appearance are also reported.

T41110

219691-219816

Sentence

denotes

Not all clinical signs are present in all cases, and diarrhea has only been observed in approximately half of reported cases.

T60824

219817-219952

Sentence

denotes

Other problems often were concurrent, including respiratory tract infection, dermatitis, intestinal parasitism, and gastric ulceration.

T79774

219953-220104

Sentence

denotes

The most significant laboratory finding is profound hypoproteinemia, predominantly characterized by hypoalbuminemia; panhypoproteinemia can also occur.

T76385

220105-220314

Sentence

denotes

518, 521, 527 Leukocytosis and hyperfibrinogenemia are also common, with occasional alterations in electrolytes (hyponatremia, hypokalemia, and hypochloremia) and elevated serum creatine kinase concentrations.

T6912

220315-220396

Sentence

denotes

Abdominal ultrasound commonly reveals increased small intestinal mural thickness.

T49748

220397-220593

Sentence

denotes

521, 527 Although small intestinal mural thickness >3 mm, in conjunction with clinical and clinicopathologic signs, is highly suggestive, PE should not be ruled out in the absence of this finding.

T32686

220594-220650

Sentence

denotes

Colloid oncotic pressure, if measured, is typically low.

T20010

220651-220800

Sentence

denotes

527 PE should be considered in a weanling foal with compatible clinical signs and severe hypoalbuminemia with exclusion of common enteric infections.

T45666

220801-220892

Sentence

denotes

Fecal PCR has very high specificity but variable sensitivity for confirmation of diagnosis.

T12113

220893-221262

Sentence

denotes

528 Serum immunoperoxidase monolayer assay or indirect enzyme-linked immunosorbent assay (ELISA) are highly specific for exposure; submission of fecal PCR and serologic testing is recommended, although both tests are quite specific, because they can lack sensitivity, especially early in the course of disease (serology) or with prior antimicrobial therapy (fecal PCR).

T81147

221263-221373

Sentence

denotes

518, 527, 529 Of note, fecal PCR can become negative in affected foals within 4 days of antimicrobial therapy.

T40923

221374-221460

Sentence

denotes

530 PE is not typically associated with abnormal carbohydrate absorption test results.

T65894

221461-221539

Sentence

denotes

518, 530 In horses with diarrhea, other infectious causes should be ruled out.

T87660

221540-221794

Sentence

denotes

A definitive postmortem diagnosis can be confirmed by identifying characteristic mural thickening and intracellular bacteria within the apical cytoplasm of proliferating crypt epithelial cells using silver stains, PCR, and/or immunohistochemical testing.

T63961

221795-221976

Sentence

denotes

518 Antimicrobial therapy with erythromycin, alone or with rifampin, azithromycin, clarithromycin, oxytetracycline, doxycycline, metronidazole, or chloramphenicol has been reported.

T6555

221977-222086

Sentence

denotes

518, 519, 527 Macrolides should not be used in adults or older foals because of an increased risk of colitis.

T15464

222087-222210

Sentence

denotes

529 Recent reports favor the use of IV oxytetracycline, followed by oral doxycycline or minocycline, with apparent success.

T30488

222211-222266

Sentence

denotes

519, 527 Duration of therapy is typically 2 to 3 weeks.

T19558

222267-222402

Sentence

denotes

Affected foals often need supportive therapy including crystalloid fluid and electrolyte replacement and, potentially, colloid support.

T86210

222403-222487

Sentence

denotes

Nonsteroidal antiinflammatory therapy can be used as needed for significant pyrexia.

T63262

222488-222590

Sentence

denotes

Corticosteroid therapy is not indicated, because inflammation is not a significant pathologic finding.

T66306

222591-222675

Sentence

denotes

Response to therapy has been good, with reported survival rates between 82% and 93%.

T7584

222676-222799

Sentence

denotes

518, 519, 527 Rapid improvement in clinical signs, even within 24 hours, precedes the rise in plasma protein concentration.

T27627

222800-222972

Sentence

denotes

Foals with PE should be isolated from unaffected animals for at least 1 week after institution of antimicrobial therapy to avoid shedding of organisms into the environment.

T52277

222973-223149

Sentence

denotes

Intrarectal vaccination with an avirulent live vaccine marketed for use in pigs has demonstrated a protective effect in foals experimentally challenged with L. intracellularis.

T4636

223150-223153

Sentence

denotes

531

T2077

223154-223380

Sentence

denotes

Abnormal d-xylose absorption has also been noted in association with AA amyloid-associated gastroenteropathy in an 18-year-old Morgan stallion 532 and a horse with a gastric mass and secondary small intestinal villous atrophy.

T14960

223381-223384

Sentence

denotes

533

T75264

223385-223516

Sentence

denotes

The chronic wasting horse with suspected malabsorption and probable enteric protein loss generally has a guarded to poor prognosis.

T65242

223517-223586

Sentence

denotes

Diseases with a good prognosis include eosinophilic enteritis and PE.

T11343

223587-223679

Sentence

denotes

Prognosis may be improved through early and aggressive investigation to achieve a diagnosis.

T59583

223680-223885

Sentence

denotes

The owner must be cognizant from the start that the outcome may not be altered, even after protracted therapy; only a few case reports of successful responses with long-term follow-up have been documented.

T37948

223886-223976

Sentence

denotes

Some level of digestive and absorptive capability remains in the diseased small intestine.

T88632

223977-224058

Sentence

denotes

Interval feeding of small quantities of easily digestible food may be beneficial.

T25685

224059-224126

Sentence

denotes

Diet may include feeds with a high fiber, but potentially low bulk.

T74060

224127-224241

Sentence

denotes

Some commercially available complete pelleted feeds offer high-fiber rations based on beet pulp and soybean hulls.

T52539

224242-224298

Sentence

denotes

Some affected horses may tolerate increased dietary fat.

T26916

224299-224443

Sentence

denotes

Consultation with an equine nutritionist may provide additional options for a given horse and, in the author's experience, can prove beneficial.

T3098

224444-224558

Sentence

denotes

The objective for an affected horse is to sustain, and preferably increase, dietary intake, value, and efficiency.

T46257

224559-224696

Sentence

denotes

The owner of an affected horse must be prepared to experiment with feeds slowly and deliberately, must be patient, and must keep records.

T50089

224697-224809

Sentence

denotes

Exposure to a feed component may contribute to the problem as an allergen eliciting a hypersensitivity reaction.

T50980

224810-224957

Sentence

denotes

Identifying the potential allergen through immunologic testing or by stepwise removal and outcome assessment over a longer period may be difficult.

T16710

224958-225115

Sentence

denotes

Immunosuppressive agents have produced the most promising responses to ameliorate the effects of conditions associated with malabsorption, particularly CIBD.

T61056

225116-225317

Sentence

denotes

Short-duration, and in some cases more prolonged and sustained, improvements in body condition, weight gain, demeanor, energy, and activity levels have occurred following corticosteroid administration.

T14720

225318-225394

Sentence

denotes

Treatment should be initiated as early as possible in the course of disease.

T21846

225395-225628

Sentence

denotes

Initial parenteral (intramuscular or IV) loading doses of dexamethasone (sodium phosphate) should be followed with a series of depot injections, or orally administered prednisolone, on a tapered dose protocol over a period of months.

T59994

225629-225718

Sentence

denotes

Interval low-dose therapy may be necessary if clinical signs return after treatment ends.

T40384

225719-225817

Sentence

denotes

The lowest dose necessary to control the clinical signs with alternate-day therapy should be used.

T36248

225818-225889

Sentence

denotes

Clinical benefits far outweigh concerns over potential adverse effects.

T27330

225890-226166

Sentence

denotes

Chemotherapeutic agents such as vincristine, cytosine, cyclophosphamide, and hydroxyurea have been tried in a few cases of CIBD or lymphosarcoma with no apparent success, probably related to the advanced stage of the disease when treatment was initiated and the dose selected.

T7880

226167-226442

Sentence

denotes

Resection of a segment of intestine that is edematous, hemorrhagic, or constricted is an option in localized forms of CIBD, 505,517 particularly if gross changes are not discernible in adjacent or distant parts of the intestinal tract-that is, malabsorption is not a feature.

T90561

226443-226480

Sentence

denotes

Long-term outcome has been favorable.

T52400

226481-226720

Sentence

denotes

Removal of a substantial proportion of the diseased small intestine may be indicated in a horse with malabsorption, considering that resection of 70% distal small intestine was performed in healthy animals without inducing adverse effects.

T39528

226721-226871

Sentence

denotes

497 Because pathologic changes may exist in normal-appearing small or large intestine that is not resected or biopsied, the prognosis remains guarded.

T86961

226872-227072

Sentence

denotes

Two young horses with granulomatous enteritis had the thickened terminal small intestine resected with positive outcomes; one survived 4 months, the other has a follow-up extending more than 10 years.

T33931

227073-227076

Sentence

denotes

505

T77807

227078-227373

Sentence

denotes

Acute diarrhea caused by colitis in adult or young horses is a potentially life-threatening disorder with a variety of possible etiologies (Table 12 .5) characterized by hypersecretion of fluid, motility disturbances, and an impaired mucosal barrier resulting from direct injury or inflammation.

T80979

227374-227473

Sentence

denotes

Many of the clinical and clinicopathologic features are similar regardless of the underlying cause.

T45678

227474-227681

Sentence

denotes

Severe dehydration with profound electrolyte abnormalities is common, as is systemic inflammation secondary to absorption of endotoxin or other bacterial products through compromised gastrointestinal mucosa.

T19417

227682-227849

Sentence

denotes

Severe cases may be complicated by serosal inflammation and mural ischemia and infarction as a direct extension of mucosal inflammation or secondary to coagulopathies.

T84588

227850-228175

Sentence

denotes

The diagnostic approach for horses with acute diarrhea is aimed at determining the underlying etiology but must be accompanied by clinical and laboratory assessment of hydration, electrolyte and acid-base balance, organ function, and evaluation of the degree of systemic inflammation and the integrity of the intestinal wall.

T66868

228176-228386

Sentence

denotes

The therapeutic approach for horses with colitis, regardless of cause, consists primarily of controlling local and systemic inflammation, maintaining fluid and electrolyte balance, and promoting mucosal repair.

T46961

228387-228489

Sentence

denotes

In addition, some horses with acute colitis require specific therapy aimed at the underlying etiology.

T58396

228490-228618

Sentence

denotes

S. enterica is a species of gram-negative facultatively anaerobic bacteria that is a common gastrointestinal pathogen in horses.

T27590

228619-228795

Sentence

denotes

Many serovars of S. enterica have been reported to infect horses, but those classified in group B appear to be more commonly associated with disease than those in other groups.

T38592

228796-228829

Sentence

denotes

Group B includes S. enterica var.

T67069

228830-228862

Sentence

denotes

Typhimurium and S. enterica var.

T78200

228863-228926

Sentence

denotes

Agona, two of the species most frequently isolated from horses.

T84850

228927-228951

Sentence

denotes

534-536 S. enterica var.

T60696

228952-229092

Sentence

denotes

Typhimurium is the most pathogenic serotype in horses and is associated with a higher case fatality rate than other serovars of S. enterica.

T68489

229093-229365

Sentence

denotes

534 The number of horses that are inapparently infected with and actively shed S. enterica in their feces has been reported to be as high as 10% to 20%, but actual prevalence of S. enterica shedding in the general horse population is likely to be much lower, less than 2%.

T25231

229366-229605

Sentence

denotes

537 Horses shedding S. enterica are a potential source of infection to susceptible horses, 534, 538 as are environmental reservoirs. [539] [540] [541] For these reasons salmonellosis is one of the most common nosocomial diseases in horses.

T3744

229606-229700

Sentence

denotes

Nosocomial salmonellosis significantly affects morbidity and mortality in hospitalized horses.

T92941

229701-229952

Sentence

denotes

542 The emergence of multidrug resistance in equine S. enterica isolates has been a cause of concern because of the importance of salmonellosis as a nosocomial disease and because a number of serovars of S. enterica are significant zoonotic pathogens.

T61631

229953-230090

Sentence

denotes

540, [543] [544] [545] [546] The virulence of the bacteria varies tremendously with serotype and even among strains of the same serotype.

T72745

230091-230197

Sentence

denotes

This is because of the important role of host susceptibility in the pathogenicity of particular organisms.

T57007

230198-230660

Sentence

denotes

The infective dose is generally on the order of millions of organisms inoculated orally, but various environmental and host factors can reduce the infective dose to a few thousand or even hundreds of organisms. [547] [548] [549] Environmental factors or stresses that increase susceptibility to S. enterica infection are not well defined, but it is known that high ambient temperature, for example, can greatly increase the prevalence of salmonellosis in horses.

T70903

230661-230760

Sentence

denotes

539, 548, 549 Indeed, the peak incidence of salmonellosis in horses occurs in late summer and fall.

T86796

230761-231229

Sentence

denotes

539, 548, 549 Other environmental and host factors that are associated with salmonellosis or shedding of S. enterica organisms in feces include transportation, antibiotic administration before or during hospitalization, gastrointestinal or abdominal surgery, general anesthesia, preexisting gastrointestinal disease (e.g., colic, diarrhea), the presence of leukopenia or laminitis during hospitalization, prolonged hospital stay, change in diet, and immunosuppression.

T57626

231230-231407

Sentence

denotes

534, 541, [549] [550] [551] Interestingly, foals with gastrointestinal disease are more likely to shed S. enterica organisms than are adult horses with gastrointestinal disease.

T27686

231408-231618

Sentence

denotes

548 Host factors that restrict gastrointestinal colonization and invasion by pathogens include gastric pH, commensal gastrointestinal flora, gastrointestinal motility, the mucosal barrier, and mucosal immunity.

T84519

231619-231736

Sentence

denotes

534, 552 Gastric acidity is an important defense mechanism for preventing live organisms from reaching the intestine.

T43790

231737-231861

Sentence

denotes

552 Altering the gastric pH, with histamine H 2 receptor antagonists, for example, may increase susceptibility to infection.

T3161

231862-232054

Sentence

denotes

Gastrointestinal flora inhibit the proliferation and colonization of S. enterica by secreting bacteriocins, short-chain fatty acids (SCFAs), and other substances that are toxic to S. enterica.

T48533

232055-232146

Sentence

denotes

552 Elements of the normal flora compete for nutrients and space, especially on the mucosa.

T52230

232147-232341

Sentence

denotes

552 Being predominantly anaerobic, the normal flora maintain a low oxidation-reduction potential in the environment of the large intestine, which inhibits the growth of many bacterial pathogens.

T61449

232342-232668

Sentence

denotes

553 The importance of normal host gastrointestinal ecology is illustrated by the fact that disturbances of the colonic flora with antibiotics, changes in feed, ileus, or other underlying gastrointestinal disease markedly increases the susceptibility of the host to infection by S. enterica, often resulting in serious disease.

T62890

232669-232878

Sentence

denotes

The immune status of the host may be one of the most important factors determining not only the susceptibility to S. enterica infections but also the degree of invasion and subsequent outcome of the infection.

T46896

232879-233008

Sentence

denotes

Local immunity, such as mucosal antibody secretion and enterocyte-derived cationic peptides, prevents colonization of the mucosa.

T20589

233009-233226

Sentence

denotes

552, 554, 555 Opsonizing antibodies and activation of the complement cascade are important in fighting systemic invasion by S. enterica by increasing the efficiency of phagocytosis and by direct bactericidal activity.

T15844

233227-233394

Sentence

denotes

Humoral immunity, however, is often ineffective in preventing disease and dissemination once invasion occurs and S. enterica is established in its intracellular niche.

T14565

233395-233550

Sentence

denotes

Following invasion, S. enterica is capable of surviving and multiplying within macrophages, rendering the humoral (noncellular) immune systems ineffective.

T88945

233551-233711

Sentence

denotes

556, 557 Specific cellular immunity may be the most effective defense mechanism in the host arsenal against dissemination and systemic infection by S. enterica.

T8290

233712-233885

Sentence

denotes

557, 558 Protective immunity in horses and calves may be induced by oral inoculation with small numbers of virulent organisms, but the duration of the immunity is not known.

T56021

233886-234300

Sentence

denotes

559, 560 Oral and parenteral vaccines using killed or attenuated organisms and bacterial products have been promising but are effective only against homologous organisms and are usually not cross-protective among different serogroups. [559] [560] [561] In adult horses S. enterica primarily infects the cecum and proximal colon, causing enterocolitis, with limited likelihood of dissemination beyond the intestine.

T53928

234301-234370

Sentence

denotes

In foals, however, salmonellosis is often associated with septicemia.

T19983

234371-234498

Sentence

denotes

The ability of S. enterica to cause enterocolitis depends on the ability of the bacteria to invade the gastrointestinal mucosa.

T48497

234499-234703

Sentence

denotes

552, 556 Invasion of the gastrointestinal mucosa occurs preferentially through specialized enterocytes called M cells that overlie intestinal lymphoid tissues such as Peyer's patches in nonequine species.

T95656

234704-234798

Sentence

denotes

M cells are exploited by a variety of enteric pathogens during infection of intestinal tissue.

T5992

234799-234937

Sentence

denotes

562 Invasion of the epithelium occurs by self-induced uptake via the apical membrane of the M cell, often killing the cell in the process.

T79584

234938-235106

Sentence

denotes

556 S. enterica then invades neighboring cells via the basolateral membrane, eventually spreading the destruction of the epithelium beyond the principal area of attack.

T87529

235107-235326

Sentence

denotes

Virulent S. enterica have a welldeveloped invasion mechanism that involves the generation of an apparatus called a type III secretory system that enables virulence gene products to be injected directly into enterocytes.

T12138

235327-235484

Sentence

denotes

563 Virulence proteins injected by S. enterica into enterocytes engage the cellular machinery and induce the cell to engulf the bacteria by macropinocytosis.

T87234

235485-235717

Sentence

denotes

S. enterica virulence gene products also induce enterocyte chloride and fluid secretion and upregulate enterocyte transcription of inflammatory cytokines (TNF-α and IL-1β) and chemokines that trigger a mucosal inflammatory response.

T38844

235718-235888

Sentence

denotes

81, 556, 563 Once S. enterica has invaded the mucosa, organisms are quickly phagocytosed by macrophages and dendritic cells in the lamina propria and in lymphoid tissues.

T92147

235889-236041

Sentence

denotes

The ability of S. enterica to disseminate systemically and cause enteric fever is associated with the ability to survive and proliferate in macrophages.

T75009

236042-236142

Sentence

denotes

Indeed, phagocytes have an important role in dissemination to blood, lymph nodes, liver, and spleen.

T24552

236143-236318

Sentence

denotes

564 The majority of S. enterica in the blood and tissues of animals infected with a strain of S. enterica that is competent to cause enteric fever are within phagocytic cells.

T46330

236319-236486

Sentence

denotes

564 In adult horses with salmonellosis, dissemination appears to be limited to the intestine and mesenteric lymph nodes, and S. enterica is rarely cultured from blood.

T41322

236487-236645

Sentence

denotes

However, in foals and in some adults, S. enterica causes an enteric fever-like disease with dissemination to mesenteric lymph nodes, liver, spleen, and blood.

T85649

236646-236870

Sentence

denotes

Specific virulence gene clusters called pathogenicity islands encoded on the chromosome or on plasmids confer the main virulence traits of S. enterica: invasion, enteropathogenesis, intracellular survival, and proliferation.

T89920

236871-237095

Sentence

denotes

556 Some of the genes encoded within these islands or virulence factors are sensors that signal to the bacteria that it has entered an intracellular environment and to turn on other genes required for intracellular survival.

T18561

237096-237335

Sentence

denotes

Others, such as invasion genes, are transported from the bacteria and injected into macrophage cytosol by a type III secretory system apparatus to prevent phagosome-lysosome fusion and subvert other essential macrophage-killing mechanisms.

T20757

237336-237567

Sentence

denotes

Virulent S. enterica may also possess multiple genes that enable adhesion to target cells or confer resistance to reactive oxygen and nitrogen metabolites, which is, perhaps, the most lethal antimicrobial mechanisms of macrophages.

T32736

237568-237631

Sentence

denotes

565 Diarrhea associated with salmonellosis has multiple causes.

T78526

237632-237754

Sentence

denotes

An S. enterica cytotoxin inhibits protein synthesis in mucosal cells, causing morphologic damage and altered permeability.

T70670

237755-237874

Sentence

denotes

566 Virulent S. enterica also produce an enterotoxin that is similar to the heat-labile (LT) toxin produced by E. coli.

T13478

237875-237970

Sentence

denotes

567, 568 This enterotoxin contributes to, but is not required, in the pathogenesis of diarrhea.

T70628

237971-238153

Sentence

denotes

569,570 S. enterica enterotoxin increases secretion of chloride and water by colonic mucosal cells in many species, including horses, by increasing intracellular cAMP concentrations.

T88813

238154-238364

Sentence

denotes

567, 568, 571 The ability of virulent S. enterica to cause diarrhea appears to be most closely associated with the ability to invade enterocytes and to trigger an inflammatory reaction in the intestinal tissue.

T25489

238365-238517

Sentence

denotes

103, 556 Gene products injected into enterocyte cytosol by the type III secretory system of invading S. enterica stimulate chloride and fluid secretion.

T22512

238518-238760

Sentence

denotes

563 S. enterica invasion of enterocytes is also a potent activator of inflammatory chemokine and cytokine production, resulting in the recruitment of leukocytes, particularly neutrophils, and activation of resident macrophages and mast cells.

T82208

238761-238959

Sentence

denotes

Products of these activated leukocytes, including prostaglandins, leukotrienes, reactive oxygen metabolites, and histamine, are potent stimulators of chloride secretion in the colon of many species.

T69810

238960-239130

Sentence

denotes

213, 552, 572, 573 The ENS integrates the diverse processes of pathogen recognition, triggering of the inflammatory response, and induction of enterocyte fluid secretion.

T3294

239131-239347

Sentence

denotes

213 Many of the inflammatory mediators studied stimulate colonic secretion by prostaglandin-dependent mechanisms, resulting in either increased intracellular cAMP or calcium concentrations, or both, in mucosal cells.

T1677

239348-239664

Sentence

denotes

213 These mediators and the ENS may also stimulate secretion by prostaglandinindependent mechanisms, inhibit sodium and water absorption, cause motility disturbances, and potentiate tissue injury, all of which enhance the pathogenicity and dissemination of S. enterica and contribute to the pathogenesis of diarrhea.

T35930

239665-239896

Sentence

denotes

213, 573 Neutrophils recruited to the mucosa by signals generated by the infected enterocytes physically contribute to mucosal injury by producing a variety of products that are lethal to pathogens but are also toxic to host cells.

T58553

239897-240037

Sentence

denotes

84, 574 Neutrophils attracted to infected epithelial cells accumulate beneath the monolayer, lifting it off the basement membrane in sheets.

T97111

240038-240196

Sentence

denotes

Neutrophils also migrate across the epithelial monolayer in potentially massive numbers-enough to be detectable in feces as a marker of inflammatory diarrhea.

T41226

240197-240529

Sentence

denotes

Although the transepithelial migration of neutrophils has a benefit, positioning the host defense cell at the apical membrane to ward off attacks by invading bacteria, the mechanical disruption to the epithelial barrier may be significant enough to increase the permeability to macromolecules, bacterial products, and even bacteria.

T97772

240530-240648

Sentence

denotes

574 Potentially massive losses of electrolytes, water, and protein can occur, depending on bacterial and host factors.

T10735

240649-240833

Sentence

denotes

Perhaps most devastatingly, mucosal injury and altered permeability allow systemic absorption of bacterial products and dissemination of bacteria, resulting in life-threatening sepsis.

T21929

240834-241019

Sentence

denotes

Four clinical syndromes of S. enterica infection have been documented clinically and reproduced experimentally in horses: (1) inapparent infections with latent or active carrier states;

T90367

241020-241211

Sentence

denotes

(2) depression, fever, anorexia, and neutropenia without diarrhea or colic; (3) fulminant or peracute enterocolitis with diarrhea; and (4) septicemia (enteric fever) with or without diarrhea.

T4513

241212-241403

Sentence

denotes

575 Inapparent infections can be activated to clinical disease in compromised horses, such as horses with colic or horses being treated with antibiotics, causing mild to severe enterocolitis.

T8834

241404-241557

Sentence

denotes

Latent infections (nonshedding) can become active infections (shedding) under certain conditions, such as transportation stress and antibiotic treatment.

T50247

241558-241719

Sentence

denotes

Horses with depression, anorexia, fever, and neutropenia without diarrhea generally have a good prognosis and recover in several days without specific treatment.

T34995

241720-241815

Sentence

denotes

575 The septicemic form is mostly restricted to neonatal foals and is uncommon in adult horses.

T67559

241816-241868

Sentence

denotes

The focus of this discussion is acute enterocolitis.

T23315

241869-242058

Sentence

denotes

Acute enterocolitis is characterized by severe fibrinonecrotic typhlocolitis, with interstitial edema and variable degrees of intramural vascular thrombosis that may progress to infarction.

T67690

242059-242162

Sentence

denotes

534 Severe ulceration of the large intestinal mucosa may occur, with serosal ecchymoses and congestion.

T82808

242163-242230

Sentence

denotes

The earliest signs of enterocolitis are usually fever and anorexia.

T75796

242231-242334

Sentence

denotes

534, 549 Signs of colic may be seen early in the course of the disease, especially if ileus is present.

T43896

242335-242537

Sentence

denotes

Clinical signs of endotoxemia are common and range from fever, elevated heart and respiratory rates, poor peripheral perfusion, and ileus to fulminant and rapidly progressive signs of endotoxemic shock.

T59291

242538-242688

Sentence

denotes

Oral mucous membranes are often pale with perigingival hyperemia (a toxic rim) but may be brick red or cyanotic, with prolonged capillary refill time.

T68856

242689-242937

Sentence

denotes

Weakness, muscle fasciculations, cold extremities, and other signs suggestive of hypotensive shock; synchronous diaphragmatic flutter; abdominal pain; and marked metabolic and electrolyte abnormalities may be noted in severe cases of enterocolitis.

T8398

242938-243004

Sentence

denotes

Signs of mild dehydration may be observed before diarrhea is seen.

T87600

243005-243069

Sentence

denotes

Once diarrhea is evident, dehydration may rapidly become severe.

T88860

243070-243135

Sentence

denotes

Occasionally, horses die peracutely, without developing diarrhea.

T50481

243136-243242

Sentence

denotes

Diarrhea may not occur for several days but usually is evident by 24 to 48 hours after the onset of fever.

T88654

243243-243298

Sentence

denotes

534, 549 The duration of diarrhea may be days to weeks.

T59120

243299-243441

Sentence

denotes

The character of the first diarrheal feces is usually watery, with particles of roughage, but may rapidly become fluid without solid material.

T97810

243442-243497

Sentence

denotes

Finding frank blood and fibrin in the feces is unusual.

T91593

243498-243559

Sentence

denotes

The volume of feces is often large, with frequent defecation.

T74329

243560-243679

Sentence

denotes

Straining or signs of colic may be observed when the patient is defecating, and rectal prolapse may occasionally occur.

T46383

243680-243756

Sentence

denotes

Persistent straining and rectal prolapse may be signs of colonic infarction.

T56271

243757-243902

Sentence

denotes

Abdominal borborygmi are often absent early in the course of the disease because of ileus but become evident later, usually when diarrhea begins.

T32950

243903-244007

Sentence

denotes

Fluid and gas sounds are commonly auscultated, but normal progressive motility is less frequently heard.

T18077

244008-244110

Sentence

denotes

Transrectal palpation may reveal edematous rectal and colonic mucosa and fluid-filled colon and cecum.

T55560

244111-244197

Sentence

denotes

Gastric reflux may be obtained, especially early in the course, when ileus is evident.

T86782

244198-244396

Sentence

denotes

Hematologic abnormalities early in the course of the disease include moderate to severe neutropenia, lymphopenia, and leukopenia; a mild to moderate left shift; and toxic changes in the neutrophils.

T28308

244397-244502

Sentence

denotes

534, 549 Thrombocytopenia, moderate to severe hemoconcentration, and hyperfibrinogenemia are also common.

T92980

244503-244624

Sentence

denotes

Neutropenia is an early but nonspecific indicator of salmonellosis, often occurring concurrently with the onset of fever.

T21984

244625-244720

Sentence

denotes

534 Later in the course of disease, neutrophilic leukocytosis may be seen, indicating recovery.

T94002

244721-244839

Sentence

denotes

A degenerating left shift, with metamyelocytes and myelocytes seen in the peripheral blood, is a poor prognostic sign.

T93542

244840-245019

Sentence

denotes

Serum biochemical analysis may reveal azotemia, increases in serum sorbitol dehydrogenase and γ-glutamine aminotransferase activity, and increased blood lactic acid concentration.

T13148

245020-245152

Sentence

denotes

Azotemia is often prerenal, but acute hemodynamic renal failure may be seen in severely dehydrated, endotoxemic, or septic patients.

T90389

245153-245259

Sentence

denotes

Indeed, elevation of creatinine concentration is a poor prognostic indicator in horses with acute colitis.

T79280

245260-245375

Sentence

denotes

576 Hemodynamic renal disease may be complicated by toxic injury caused by the administration of nephrotoxic drugs.

T77726

245376-245430

Sentence

denotes

Hyponatremia may also contribute to prerenal azotemia.

T56196

245431-245643

Sentence

denotes

Elevations in hepatocellular enzymes are usually mild and reflect damage to the hepatocytes from absorbed toxins, such as endotoxin, and from poor perfusion resulting from hypotensive shock, dehydration, or both.

TextSentencer_T319

245644-245709

Sentence

denotes

Lactic acidemia may be present, reflecting poor tissue perfusion.

TextSentencer_T320

245710-245858

Sentence

denotes

Plasma protein drops rapidly as protein is lost in the gastrointestinal tract, resulting in moderate to severe hypoalbuminemia and hypoglobulinemia.

TextSentencer_T321

245859-246031

Sentence

denotes

Peripheral or organ edema (vascular leak syndrome) may occur if hypoproteinemia is severe, coupled with systemic inflammation-induced increases in endothelial permeability.

TextSentencer_T322

246032-246159

Sentence

denotes

Hypokalemia, hyponatremia, hypochloremia, and hypocalcemia are common electrolyte abnormalities in patients with enterocolitis.

TextSentencer_T323

246160-246218

Sentence

denotes

Metabolic acidosis may also be present, and DIC is common.

TextSentencer_T324

246219-246354

Sentence

denotes

Urinalysis may reveal isosthenuria, proteinuria, hematuria, cylindruria, or glucosuria if hemodynamic or toxic renal injury is present.

TextSentencer_T325

246355-246448

Sentence

denotes

The number of leukocytes in the feces is usually increased, and occult blood may be detected.

TextSentencer_T326

246449-246537

Sentence

denotes

PF is usually normal except when severe mural inflammation or colonic infarction occurs.

TextSentencer_T327

246538-246678

Sentence

denotes

S. enterica in feces is routinely detected by analyzing five daily cultures of large samples (10-30 g) of feces using enrichment techniques.

TextSentencer_T328

246679-246814

Sentence

denotes

534, 577, 578 The sensitivity of fecal culture can be as low as 30% to 50%, even if several fecal samples collected daily are cultured.

TextSentencer_T329

246815-246937

Sentence

denotes

578 Concurrent culture of rectal biopsy specimens and feces increases the sensitivity of culture techniques to 60% to 75%.

TextSentencer_T330

246938-247033

Sentence

denotes

578 Currently, the PCR test is the most sensitive and rapid way to detect S. enterica in feces.

TextSentencer_T331

247034-247283

Sentence

denotes

A single PCR test applied early in the course of disease is a more sensitive test for the presence of S. enterica than repeated fecal cultures, 579, 580 with as high as 100% sensitivity and 98% specificity for detection of organisms in some reports.

TextSentencer_T332

247284-247508

Sentence

denotes

581 Although detection of S. enterica organisms in feces does not prove a diagnosis of salmonellosis, the positive predictive value of either a positive PCR or culture result is high in horses with compatible clinical signs.

TextSentencer_T333

247509-247691

Sentence

denotes

Culture of peripheral blood may allow isolation of the organism if bacteremia or septicemia is present, but blood cultures are not a sensitive test for salmonellosis in adult horses.

TextSentencer_T334

247692-247818

Sentence

denotes

Foals are more likely than adults to become septicemic, and so blood culture is recommended in all foals with signs of sepsis.

TextSentencer_T335

247819-247937

Sentence

denotes

Increased numbers of fecal leukocytes suggest an invasive process in the colon but are not specific for salmonellosis.

T16315

247938-248073

Sentence

denotes

Early in the course of the disease, dehydration, electrolyte and acid-base imbalances, endotoxemia, and sepsis may be life-threatening.

T35414

248074-248250

Sentence

denotes

Aggressive treatment during the acute stages to replace fluids lost in the diarrhea and to control sepsis and endotoxemia is often effective in controlling the primary disease.

T8848

248251-248300

Sentence

denotes

Weight loss and hypoproteinemia are often severe.

T58556

248301-248607

Sentence

denotes

Possible complications include multiorgan dysfunction, vascular leak syndrome with peripheral and organ edema, laminitis, acute renal failure, venous thrombosis and septic phlebitis, irreversible protein-losing enteropathy or chronic malabsorption, pulmonary aspergillosis, and gastrointestinal infarction.

T68589

248608-248764

Sentence

denotes

The reader is referred to the section Endotoxemia in this chapter for additional information regarding treatment of horses with severe endotoxemia and SIRS.

T19468

248765-249013

Sentence

denotes

In many instances horses recover from acute salmonellosis with aggressive treatment, only to succumb to complications of the disease, which partially explains the high fatality rate of equine salmonellosis compared with that of human salmonellosis.

T48492

249014-249157

Sentence

denotes

Chronic mild to moderate diarrhea is occasionally seen in horses after a bout of severe salmonellosis, usually with protein-losing enteropathy.

T91165

249158-249272

Sentence

denotes

If the chronic diarrhea persists beyond 4 to 5 weeks after the onset of signs, the prognosis for recovery is poor.

T2298

249273-249276

Sentence

denotes

549

T47362

249277-249538

Sentence

denotes

Potomac horse fever is caused by the obligate intracellular rickettsial organism N. risticii (formerly called Ehrlichia risticii). [582] [583] [584] [585] [586] The disease is most common from late summer to early fall, with a peak incidence in July and August.

T5880

249539-249768

Sentence

denotes

583, 584 Potomac horse fever was first described in the northeastern United States but has since been described now in most areas of the continental United States, with a particularly high prevalence in the Northeast and Midwest.

T49411

249769-249893

Sentence

denotes

The geographic distribution is characterized by a significantly higher percentage of cases found along waterways and rivers.

T91477

249894-250012

Sentence

denotes

583 , 584 The disease occurs sporadically, both temporally and geographically, and can affect any age group of horses.

T67405

250013-250058

Sentence

denotes

The case fatality rate ranges from 5% to 30%.

T76916

250059-250181

Sentence

denotes

583 Transmission of N. risticii has been reproduced experimentally by oral, intramuscular, intradermal, SC, and IV routes.

T76756

250182-250331

Sentence

denotes

583, 587 Attempts to transmit the disease experimentally with ticks (Dermacentor variabilis) or biting flies (Stomoxys calcitrans) were unsuccessful.

T3317

250332-250474

Sentence

denotes

588 [590] [591] [592] [593] Infected virgulate cercariae have been identified in aquatic snails collected in other parts of the world as well.

T51389

250475-250860

Sentence

denotes

594 Although the trematode species infected with N. risticii remain to be definitively identified, at least two species have been identified as potential vectors, 595 and at least two potential definitive hosts were identified when N. risticii DNA was detected in the blood, liver, or spleen of 23 of 53 little and big brown bats harboring gravid trematodes in their intestinal tracts.

T92660

250861-251030

Sentence

denotes

596 Aquatic snails release large numbers of infected cercariae into water, in which they seek their next intermediate host, which is any of a variety of aquatic insects.

T55017

251031-251182

Sentence

denotes

593, 597 Successful transmission of N. risticii to horses was accomplished experimentally using trematode stages collected from Juga yrekaensis snails.

T73569

251183-251327

Sentence

denotes

598 The number of PCR-positive snails in endemic regions corresponds to the seasonal incidence of Potomac horse fever and may be as high as 26%.

T1503

251328-251474

Sentence

denotes

599 Preliminary studies suggest that N. risticii may in fact be naturally transmitted to horses through the ingestion of caddisflies and mayflies.

T46564

251475-251546

Sentence

denotes

593 , 600 The pathogenesis of N. risticii is not completely understood.

T49913

251547-251771

Sentence

denotes

The organism infects and survives in monocytes and monocyte-derived leukocytes and can be found in blood monocytes during natural infections, but the sequence of events resulting in enterocolitis remains open to speculation.

T71993

251772-251904

Sentence

denotes

The organism appears first to infect blood monocytes in experimentally infected horses, which may be the vehicle of organ infection.

T83977

251905-252040

Sentence

denotes

585, 601 It is unclear whether leukocytes of the monocytic lineage or epithelial cells are infected first in naturally infected horses.

T34672

252041-252148

Sentence

denotes

The target organ is the gastrointestinal mucosa, with the most severe lesions found in the large intestine.

T39562

252149-252261

Sentence

denotes

156, 601 Infection of human colonic cells in vitro does not cause major cytopathologic effects for several days.

T86480

252262-252427

Sentence

denotes

602 Disruption of the microvilli in the region of the plasma membrane in which sodium chloride channels are located has been observed in human colonic cell cultures.

T91977

252428-252510

Sentence

denotes

602 Infection in horses is associated with variable degrees of morphologic damage.

T7892

252511-252776

Sentence

denotes

156, 601 Mild morphologic damage and mononuclear cell infiltration of the lamina propria occur early during the infection, but fibrinous, necrotizing typhlocolitis with severe mucosal ulceration and inflammation of the lamina propria may occur later in the disease.

T10592

252777-252890

Sentence

denotes

Vasculitis and intravascular coagulation are consistent features in the large intestine, with perivascular edema.

T88334

252891-252993

Sentence

denotes

156 N. risticii can be observed in mucosal cells and macrophages and mast cells of the lamina propria.

T64662

252994-253424

Sentence

denotes

156, 601 N. risticii can survive and multiply in macrophages by inhibiting the production of ROIs and avoiding lysosomal digestion by blocking phagosome-lysosome fusion. [603] [604] [605] Some researchers have suggested that impaired sodium chloride absorption in the colon contributes to diarrhea in infected horses and may be related to destruction of the enterocyte membrane structure in the region of sodium chloride channels.

T47132

253425-253591

Sentence

denotes

602, 606 Direct injury to the mucosa by N. risticii and colonic inflammation are likely to be prominent features leading to diarrhea, especially later in the disease.

T36238

253592-253749

Sentence

denotes

156 Loss of fluid, protein, and electrolyte is likely caused by mucosal injury and effects on enterocyte fluid secretion caused by the inflammatory response.

T18690

253750-254024

Sentence

denotes

Like other inflammatory conditions of the colon, systemic inflammation caused by absorption of bacteria and bacterial products is a potential complication of N. risticii infections if mucosal injury is severe, which contributes to the clinical signs seen during the disease.

T41128

254025-254157

Sentence

denotes

N. risticii infection is clinically similar to other forms of enterocolitis and is characterized by anorexia, depression, and fever.

T57847

254158-254290

Sentence

denotes

156, 583, 607 Experimental infections produce a biphasic fever in which the second febrile phase occurs 6 to 7 days after the first.

T71472

254291-254432

Sentence

denotes

607, 608 Decreased gastrointestinal motility, manifested as reduced borborygmi, occurs during the early stages, before the onset of diarrhea.

T68157

254433-254546

Sentence

denotes

Diarrhea is seen in 75% of cases and occurs 2 days after the second fever episode during experimental infections.

T12747

254547-254611

Sentence

denotes

607, 608 The diarrhea can be moderate to severe and dehydrating.

T14747

254612-254706

Sentence

denotes

Ileus can develop at any stage of the disease and can cause signs of moderate to severe colic.

T82751

254707-254829

Sentence

denotes

Systemic signs of endotoxemia, shock, and peripheral edema may occur and are similar to those described for salmonellosis.

T67744

254830-254939

Sentence

denotes

Experimental and natural infection with N. risticii can cause abortion of infected fetuses in pregnant mares.

T98384

254940-255040

Sentence

denotes

609, 610 Laminitis is a complication in 20% to 30% of naturally occurring cases and is often severe.

T93406

255041-255162

Sentence

denotes

584 Other complications include proteinlosing enteropathy, thrombosis, and renal failure, as described for salmonellosis.

T97951

255163-255301

Sentence

denotes

Hematologic abnormalities reflect endotoxemia, dehydration, and sepsis and are essentially identical to those described for salmonellosis.

T27956

255302-255421

Sentence

denotes

Neutropenia with a left shift is a consistent feature and occurs concurrently with or soon after the onset of diarrhea.

T77534

255422-255470

Sentence

denotes

608 Thrombocytopenia is common and often severe.

T1184

255471-255543

Sentence

denotes

608 Neutrophilic leukocytosis occurs later in the course of the disease.

T10145

255544-255625

Sentence

denotes

Hyperfibrinogenemia is usually more pronounced than that seen with salmonellosis.

T74480

255626-255740

Sentence

denotes

Serum electrolyte, acid-base, and biochemical abnormalities are also similar to those described for salmonellosis.

T99920

255741-255850

Sentence

denotes

Coagulopathies are commonly seen during N. risticii infection and reflect activation of coagulation pathways.

T59138

255851-255965

Sentence

denotes

DIC is not uncommon and may be the cause of the high frequency of laminitis associated with N. risticii infection.

T34896

255966-256120

Sentence

denotes

611 Diagnosis of N. risticii infection cannot be based solely on clinical signs because the disease is clinically similar to other forms of enterocolitis.

T15494

256121-256303

Sentence

denotes

In endemic areas, acute colitis is likely to be caused by N. risticii; thus, the clinical signs of acute inflammatory colitis may in fact have a high predictive value in these areas.

T97606

256304-256506

Sentence

denotes

Serologic evidence of infection, such as rising antibody titers to N. risticii detected by indirect immunofluorescence (IFA) or ELISA in paired serum samples, may be helpful in establishing a diagnosis.

T41722

256507-256654

Sentence

denotes

584, 612 Care should be taken when interpreting the IFA serologic test for N. risticii because the test appears to have a high false-positive rate.

T55962

256655-256776

Sentence

denotes

613 Culture of the organism from blood is possible but difficult and is generally useful only in the research laboratory.

T31760

256777-257136

Sentence

denotes

Recently developed PCR tests for N. risticii DNA are rapid, highly sensitive (as sensitive as culture), and there are specific tests for N. risticii infection that can be applied to blood or feces. [614] [615] [616] Prevention Prevention of the disease by reducing exposure to the etiologic organism is difficult because the mode of transmission is not known.

T90938

257137-257318

Sentence

denotes

A killed vaccine has been developed that is relatively effective in preventing clinical illness other than fever in 80% of experimentally challenged horses using the vaccine strain.

T48666

257319-257443

Sentence

denotes

Field studies, however, suggest the vaccine has limited benefit for preventing natural infection or decreasing its severity.

T52452

257444-257574

Sentence

denotes

617, 618 Vaccine failures have been attributed to strain differences in antigenicity or to poor antibody responses to the vaccine.

T56019

257575-257583

Sentence

denotes

617, 618

T82796

257585-257670

Sentence

denotes

Clostridiosis is an important cause of acute enterocolitis in foals and adult horses.

T93677

257671-258082

Sentence

denotes

C. perfringens and C. difficile are most commonly associated with intestinal clostridiosis in horses, but other clostridial species, including C. septicum, C. cadaveris, and C. sordellii have also been isolated from horses with enterocolitis. [619] [620] [621] [622] [623] [624] In horses of all ages, clostridial enterocolitis appears to be a common antibiotic-associated and nosocomial cause of enterocolitis.

T39639

258083-258247

Sentence

denotes

623, 625, 626 Hemorrhagic enterocolitis caused by C. perfringens in neonatal foals is a distinct clinical entity and will be discussed in more detail in Chapter 20.

T61893

258248-258306

Sentence

denotes

This discussion focuses on adult intestinal clostridiosis.

T28131

258307-258458

Sentence

denotes

Clostridium organisms are obligate anaerobic to aerotolerant spore-forming gram-positive rods that are ubiquitous in the environment in the spore form.

T58310

258459-258577

Sentence

denotes

624 They are elements of the normal flora of horses of all ages and are among the first bacteria acquired after birth.

T5406

258578-258709

Sentence

denotes

Clostridium organisms inhabiting the gastrointestinal tract are normally found in very low numbers and do not produce enterotoxins.

T57842

258710-258886

Sentence

denotes

Clostridiosis is associated with an increase in the number of a particular species of Clostridia in the gastrointestinal tract and, perhaps most important, exotoxin production.

T14475

258887-259045

Sentence

denotes

Although the conditions resulting in exotoxin production are not fully understood, several factors increase clostridial numbers in the gastrointestinal tract.

T36519

259046-259124

Sentence

denotes

Dietary factors affect the numbers of Clostridium species shed in horse feces.

T30818

259125-259236

Sentence

denotes

619 Experimental induction of colic increases fecal shedding of Clostridium species in the absence of diarrhea.

T57189

259237-259442

Sentence

denotes

627 Antibiotics, particularly those administered orally or recycled via the enterohepatic system, increase the recovery of Clostridia colony-forming units (CFUs) in equine feces and clinical clostridiosis.

T1148

259443-259604

Sentence

denotes

620, 622, [628] [629] [630] Clostridiosis associated with C. difficile is likely to be the most important cause of antibiotic-induced enterocolitis in the horse.

T84152

259605-259629

Sentence

denotes

Clostridium perfringens.

T90415

259630-259765

Sentence

denotes

C. perfringens includes many genetically distinct strains of variable virulence that produce one or more of a large group of exotoxins.

T71719

259766-259871

Sentence

denotes

The pattern of exotoxin production is used to classify C. perfringens into five types: A, B, C, D, and E.

T60025

259872-259979

Sentence

denotes

C. perfringens type A is the most common clostridial isolate from healthy and diarrheic horses of all ages.

T52802

259980-260163

Sentence

denotes

C. perfringens types A, B, C, and D have all been associated with hemorrhagic enteritis in foals younger than 10 days of age, with type C being the most common cause in North America.

T84392

260164-260385

Sentence

denotes

The primary toxin produced by C. perfringens type A is α-toxin (phospholipase C), which interferes with glucose uptake and energy production and activates arachidonic acid metabolism and signaling pathways in enterocytes.

T63814

260386-260517

Sentence

denotes

624 Oral administration of α-toxin does not cause tissue necrosis but causes increased secretion by small intestinal mucosal cells.

T98893

260518-260678

Sentence

denotes

631 , 632 The β-toxin of types B and C is a cytotoxin that causes enterocyte necrosis, ulceration, and ultimately severe intestinal inflammation and hemorrhage.

T16458

260679-260770

Sentence

denotes

624, 632 A novel toxin designated β 2 may also have a role in C. perfringens enterocolitis.

T22404

260771-260911

Sentence

denotes

633 The biologic activity of the β 2 -toxin is similar to that of β-toxin, but β 2 -toxin is not related to β-toxin in its genetic sequence.

T47512

260912-261016

Sentence

denotes

The β 2 -toxin was prevalent in two groups of horses with acute enterocolitis but not in healthy horses.

T96176

261017-261185

Sentence

denotes

634 It is predominantly associated with C. perfringens that would have otherwise been classified as type A but that may in fact represent a previously undescribed type.

T92138

261186-261284

Sentence

denotes

Virulent strains of C. perfringens type A and, to a lesser extent, type C may produce enterotoxin.

T58500

261285-261454

Sentence

denotes

Enterotoxin is a cytotoxin that inserts into cell membranes to form pores, which alter permeability to water and macromolecules and ultimately lead to cellular necrosis.

T89480

261455-261647

Sentence

denotes

635 Massive desquamation of the intestinal mucosa that is a result of enterotoxin cytotoxicity triggers an inflammatory response, intestinal edema, mural hemorrhage, and systemic inflammation.

T43005

261648-261779

Sentence

denotes

158 Enterotoxin also alters tight junction integrity, resulting in increased paracellular permeability by a noncytotoxic mechanism.

T49390

261780-261806

Sentence

denotes

636 Clostridium difficile.

T23788

261807-261913

Sentence

denotes

C. difficile produces several toxins, only two of which, toxin A and toxin B, have been studied in detail.

T42602

261914-262019

Sentence

denotes

Toxin B is a potent cytotoxin in vitro, but its role in enterocolitis is less clear than that of toxin A.

T37231

262020-262125

Sentence

denotes

It does not induce fluid secretion, inflammation, or characteristic alterations in intestinal morphology.

T97106

262126-262232

Sentence

denotes

C. difficile toxin A is an enterotoxin that induces an inflammatory response with hypersecretory diarrhea.

T24083

262233-262414

Sentence

denotes

637 Toxin A induces neutrophil influx into intestinal tissue, mast cell degranulation, and secretion of prostaglandins, histamine, cytokines, and 5-HT by these activated leukocytes.

T79266

262415-262586

Sentence

denotes

142,637, 638 The products of neutrophils and mast cells have a significant role in the vasodilatory and secretory responses in the intestine during C. difficile infection.

T96228

262587-262683

Sentence

denotes

The ENS is central to the induction of intestinal inflammation and mucosal secretion by toxin A.

T67642

262684-262927

Sentence

denotes

A model for toxin A-induced secretory diarrhea has emerged in which toxin A stimulates substance P-containing afferent sensory nerve fibers, which in turn stimulate mast cell degranulation, recruitment and activation of PMNs, and vasodilation.

T10549

262928-263117

Sentence

denotes

88, 89, 639 Toxin A-induced stimulation of enterocyte secretion can occur via secretomotor neuronal stimulation by substance P-containing sensory neurons or products of mast cells and PMNs.

T47278

263118-263245

Sentence

denotes

Mast cell degranulation, PMN influx, and enterocyte secretion are all abolished by neural blockade or depletion of substance P.

T31977

263246-263453

Sentence

denotes

How toxin A triggers the sensory component of the ENS remains unknown, but it is likely that toxin A-induced necrosis of enterocytes exposes afferent neurons to the noxious milieu of the intestinal contents.

T40392

263454-263556

Sentence

denotes

Equine intestinal clostridiosis is clinically similar to other forms of acute enterocolitis in horses.

T3423

263557-263657

Sentence

denotes

619, 624 Although the clinical course is usually acute, peracute colitis with rapid death may occur.

T96530

263658-263721

Sentence

denotes

Occasionally, a milder, more prolonged clinical course is seen.

T63061

263722-263864

Sentence

denotes

Fever, anorexia, and depression may be observed before the onset of gastrointestinal signs, but the absence of prodromal signs is more common.

T87229

263865-263964

Sentence

denotes

Signs of endotoxemia and shock may accompany acute signs of colic and severe, dehydrating diarrhea.

T45903

263965-264022

Sentence

denotes

Diarrhea may not be profuse but is usually dark and foul.

T68700

264023-264264

Sentence

denotes

Like the clinical signs, hematologic and serum biochemical abnormalities are similar to those associated with other forms of enterocolitis and reflect fluid, protein, and electrolyte loss and systemic inflammation resulting from endotoxemia.

T63351

264265-264323

Sentence

denotes

Neutropenia, leukopenia, and hemoconcentration are common.

T6458

264324-264356

Sentence

denotes

Hypoproteinemia may be profound.

T23387

264357-264515

Sentence

denotes

Hyponatremia, hypokalemia, hypochloremia, hypocalcemia, and a mixed prerenal-renal azotemia are often noted, as well as metabolic acidosis and coagulopathies.

T47404

264516-264647

Sentence

denotes

Serum concentrations of hepatocellular enzymes, such as sorbitol dehydrogenase, may be elevated, and liver function may be reduced.

T35682

264648-264884

Sentence

denotes

Preliminary diagnosis of equine intestinal clostridiosis caused by C. perfringens is based on the isolation of greater than 100 CFUs of C. perfringens type A per gram of feces from patients with diarrhea and signs suggestive of toxemia.

T13056

264885-264981

Sentence

denotes

619, 640 Similar criteria are used to screen human patients for C. perfringens type A infection.

T58105

264982-265109

Sentence

denotes

Normal horses shed less than 100 CFU/g of feces, and usually horses with intestinal clostridiosis shed greater than 10 6 CFU/g.

T93754

265110-265257

Sentence

denotes

619, 640 Identification of high numbers of Clostridium organisms in the feces does not prove infection as the cause of the observed clinical signs.

T69474

265258-265496

Sentence

denotes

Detection of C. perfringens toxins in feces or intestinal contents in horses with high numbers of fecal CFUs and clinical signs of enterocolitis is more conclusive evidence of an enterotoxigenic infection than that based on culture alone.

T47373

265497-265648

Sentence

denotes

624 Immunoassays are available to detect C. perfringens enterotoxin, 624 but the reliability (specificity) of some immunoassays has come into question.

T4801

265649-266049

Sentence

denotes

PCR multiplex and gene probe assays are now available for detection of the major lethal toxins in bacterial isolates or fecal samples to determine the pattern of toxin production and are currently the preferred methods of detection. [641] [642] [643] Like C. perfringens, diagnosis of C. difficile infection depends on the culture of the organism from feces and identification of toxins in the feces.

T84415

266050-266160

Sentence

denotes

Bacterial culture of C. difficile may be difficult; therefore, it is an insensitive diagnostic test in horses.

T95673

266161-266246

Sentence

denotes

644, 645 Enrichment techniques and culture of multiple fecal samples may be required.

T61738

266247-266415

Sentence

denotes

645, 646 Detection of toxin A or B (or both) in feces by cell cytotoxicity assay or immunoassay is the preferred test for diagnosis of C. difficile infection in humans.

T24235

266416-266529

Sentence

denotes

624 These tests are more sensitive than bacterial culture for identifying C. difficile infection in adult horses.

T47110

266530-266654

Sentence

denotes

644, 645 Sensitive PCR methods may also be used to identify genes for toxins A and B in fecal samples from diarrheic horses.

T37717

266655-266658

Sentence

denotes

624

T61384

266659-266792

Sentence

denotes

Strongyle infections in horses are caused by two groups of nematodes: large and small strongyles (see later section Cyathostomiasis).

T24727

266793-266898

Sentence

denotes

Large strongyles that are pathogenic in horses include Strongylus vulgaris, S. edentatus, and S. equinus.

T18146

266899-267054

Sentence

denotes

Of these species S. vulgaris is by far the most important cause of disease in the large intestine and is the most pathogenic parasitic infection in horses.

T52634

267055-267133

Sentence

denotes

647 S. vulgaris infection in horses is manifested as acute or chronic disease.

T18692

267134-267298

Sentence

denotes

647 The age and resistance of the host, the infective dose, and the size and function of the affected arteries influence the type and degree of disease that occurs.

T5781

267299-267528

Sentence

denotes

Sudden ingestion of large numbers of infective larvae by a naive host causes acute strongylosis, whereas ingestion of fewer infective larvae over a long period of time by an older, more resistant host causes chronic strongylosis.

T66861

267529-267617

Sentence

denotes

Acute strongylosis is more likely to cause colic than diarrhea and may be rapidly fatal.

T64341

267618-267714

Sentence

denotes

Chronic strongylosis tends to cause debilitation and signs of colic but may also cause diarrhea.

T11951

267715-267881

Sentence

denotes

Diarrhea associated with acute strongylosis occurs within several days of infection and is likely to be caused by migration of the larvae through the intestinal wall.

T53055

267882-268053

Sentence

denotes

Fourth-stage larvae migrate through the mucosa and submucosa into the arterioles of the intestine, causing mural edema, hemorrhage, and infiltration of inflammatory cells.

T86325

268054-268265

Sentence

denotes

647, 648 Increased secretion and decreased absorption of fluid and electrolytes, stimulated by inflammatory mediators such as prostaglandins and histamine, may play a role in the diarrhea induced by S. vulgaris.

T14205

268266-268458

Sentence

denotes

Interstitial edema and damage to the interstitial matrix and mucosa may occur as a result of inflammation and migration of the parasites, causing increased secretion of fluid and albumin loss.

T94249

268459-268546

Sentence

denotes

Abnormal gastrointestinal motility may also play a role in the development of diarrhea.

T96542

268547-268755

Sentence

denotes

Migration of larvae through the intestinal wall early in the course of infection affects myoelectrical activity and motility in the large intestine and may affect retention of ingesta and absorption of fluid.

T65333

268756-268963

Sentence

denotes

649, 650 The cause of death in acute strongylosis has not been addressed, but it may be related to massive migration through the vasculature, causing thrombosis with ischemia and infarction of the intestine.

T15019

268964-269110

Sentence

denotes

Chronic strongylosis causes typical verminous arteritis and is more commonly associated with natural infections in horses than acute strongylosis.

T15639

269111-269328

Sentence

denotes

647 Lesions of the large intestinal vasculature caused by migration of larvae through the intima are characterized by thrombus formation, narrowing of the arterial lumen, fibrosis, and thickening of the arterial wall.

T69133

269329-269524

Sentence

denotes

647, 648 Embolization may occur, causing acute segmental infarction of the large intestine, but more commonly, reduced blood flow without embolization causes ischemia and occasionally infarction.

T62329

269525-269659

Sentence

denotes

648, 651 Postmortem examination of horses with colonic infarction failed to reveal embolization as the cause in the majority of cases.

T42206

269660-269852

Sentence

denotes

651 Reduced blood flow in the tissues of the intestine usually results from narrowing of the arterial lumen by the thrombus and formation of microthrombi at sites independent of the parasites.

T30877

269853-270070

Sentence

denotes

Release of vasoconstrictive inflammatory mediators, such as leukotrienes, from platelets, neutrophils, and eosinophils, as well as elaboration of parasitic antigens or toxins, may cause vasoconstriction and ische mia.

T53684

270071-270174

Sentence

denotes

652 Horses with experimental strongylosis had a 50% reduction of blood flow in the colonic vasculature.

T70248

270175-270319

Sentence

denotes

653 Clearly, reduced blood flow is an important effect of chronic strongylosis, but the relationship between blood flow and diarrhea is unclear.

T71647

270320-270445

Sentence

denotes

Disrupted motility resulting from ischemia may lead to diarrhea by reducing the retention of ingesta and absorption of fluid.

T63181

270446-270546

Sentence

denotes

Acute infarction and mucosal ulceration cause severe, chronic diarrhea in naturally infected horses.

T88588

270547-270777

Sentence

denotes

654 Release of inflammatory mediators, such as prostaglandins, histamine, and kinins, from inflammatory cells associated with thrombi and inflamed intestine may also affect secretion, absorption, and motility, leading to diarrhea.

T15303

270778-270907

Sentence

denotes

The clinical signs of acute strongylosis caused by S. vulgaris infection include depression, moderate to severe colic, and fever.

T48650

270908-270978

Sentence

denotes

655 Diarrhea is less often a feature of acute strongylosis than colic.

T26340

270979-271133

Sentence

denotes

647 Most cases of acute strongylosis occur in young naive horses introduced to an infested environment or inoculated experimentally with infective larvae.

T65105

271134-271194

Sentence

denotes

This form of strongylosis is not often recognized naturally.

T35145

271195-271264

Sentence

denotes

Chronic strongylosis is most commonly observed as a natural syndrome.

T99405

271265-271386

Sentence

denotes

Weight loss or poor weight gain; chronic, intermittent colic; fever; poor appetite; and diarrhea are frequently observed.

T92810

271387-271478

Sentence

denotes

647, 648 Diarrhea may be profuse and watery, or the feces may be soft but of normal volume.

T77723

271479-271569

Sentence

denotes

Transrectal palpation may reveal thickening and fremitus in the cranial mesenteric artery.

T46729

271570-271644

Sentence

denotes

Young horses are most commonly affected, but older horses may also be too.

T72630

271645-271844

Sentence

denotes

Horses with acute infarction or large intestinal ulceration secondary to chronic strongylosis may have signs of severe abdominal pain, sepsis, and endotoxemia, and profuse, watery diarrhea is common.

T88442

271845-272085

Sentence

denotes

Hematologic abnormalities associated with strongylosis include neutrophilic leukocytosis and eosinophilia. [655] [656] [657] Neutrophilia appears to be an early event during the course of the disease, and eosinophilia tends to appear later.

T43150

272086-272177

Sentence

denotes

655, 657 Hyperfibrinogenemia may also occur, especially later in the course of the disease.

T64812

272178-272268

Sentence

denotes

Serum α-globulin and β-globulin and IgG(T) concentrations are characteristically elevated.

T71597

272269-272378

Sentence

denotes

656, 658 Horses with chronic ulcerative colitis secondary to strongylosis may develop severe hypoalbuminemia.

T23333

272379-272457

Sentence

denotes

654 PF analysis may reveal an elevated protein concentration and eosinophilia.

T58606

272458-272558

Sentence

denotes

656, 657 Tentative diagnosis is based on clinical signs, hematologic abnormalities, and PF analysis.

T65808

272559-272662

Sentence

denotes

Elevated serum α-globulin and β-globulin concentrations and IgG(T) concentration support the diagnosis.

T32056

272663-272794

Sentence

denotes

658 Fecal analysis may reveal strongyle eggs, but fecal egg counts are often unreliable because nonpatent larvae cause the disease.

T43622

272795-273024

Sentence

denotes

Appropriate preventive measures are important in controlling this disease, including such management procedures as preventing overcrowding, reducing exposure of susceptible individuals, and instituting proper deworming schedules.

T47183

273025-273105

Sentence

denotes

Ivermectin is the preferred anthelmintic used to control strongylosis in horses.

T26917

273106-273216

Sentence

denotes

Monitoring fecal egg counts as a means of evaluating the efficacy of parasite control measures is recommended.

T83514

273217-273511

Sentence

denotes

Infection with small strongyles (cyathostomiasis) is well recognized as a cause of diarrhea and large intestinal disease in horses of all ages. [659] [660] [661] [662] [663] [664] Clinical disease is caused by intramural larval stages of more than 50 species of small strongyles (cyathostomes).

T81897

273512-273751

Sentence

denotes

The cyathostome life cycle requires migration by fourth-stage larvae through the mucosa of the large intestine and may include a period of hypobiosis, during which the larvae remain encysted within the mucosal layer of the large intestine.

T95319

273752-273846

Sentence

denotes

659 After a period of hypobiosis, the larvae emerge in response to a largely unknown stimulus.

T57501

273847-274069

Sentence

denotes

Most cases occur when larval emergence takes place, classically in the late winter and spring in the northern temperate zones and in the late fall or winter months in the southeastern United States and subtropical regions.

T44921

274070-274230

Sentence

denotes

659 Sudden emergence of encysted larvae causes mucosal injury, ulceration, and an inflammatory reaction, which are largely responsible for the clinical disease.

T47915

274231-274378

Sentence

denotes

659, 665 Migration of the larvae as they penetrate the mucosa affects motility patterns and can cause inflammation that may contribute to diarrhea.

T61787

274379-274655

Sentence

denotes

659 Chronic, eosinophilic, granulomatous colitis and diarrhea with histopathologic evidence of hypobiotic cyathostome larvae in the large intestine have been reported in two horses during a period in which the emergence of larvae would not be expected to occur (early winter).

T29979

274656-274884

Sentence

denotes

659 Natural emergence of cyathostome larvae causes fibrinous inflammation of the large intestine, focal necrosis, mural hemorrhage, and ulceration of the large intestinal mucosa, which may even result in bleeding into the lumen.

T33613

274885-274983

Sentence

denotes

648, 665 Mild to moderate eosinophilic and mononuclear inflammation of the lamina propria is seen.

T28735

274984-275054

Sentence

denotes

648, 665 Moderate to severe interstitial edema is frequently observed.

T16454

275055-275275

Sentence

denotes

648, 665 Colonic inflammation and interstitial edema may contribute to diarrhea, in conjunction with the loss of the mucosal barrier, by causing increased active and passive secretion of fluid, electrolytes, and protein.

T25268

275276-275397

Sentence

denotes

Protein loss is often significant, resulting in profound hypoalbuminemia and interstitial edema of skin and other organs.

T43113

275398-275636

Sentence

denotes

Chronic granulomatous colitis has been reported to occur in response to encysted larvae and may cause diarrhea by increased secretion secondary to granulomatous inflammation or disruption of the interstitium by granulomatous infiltration.

T26805

275637-275821

Sentence

denotes

Administration of an anthelmintic to horses with a heavy load of encysted larvae may also cause rapid larval death and acute and often severe inflammation similar to natural emergence.

T81578

275822-275913

Sentence

denotes

Cyathostomiasis may be the most commonly identified cause of chronic diarrhea in the horse.

T8557

275914-276001

Sentence

denotes

493, 666, 667 However, an acute syndrome has also been associated with cyathostomiasis.

T80559

276002-276505

Sentence

denotes

664 Clinical signs of cyathostomiasis are characterized by moderate to severe weight loss or poor weight gain, ill thrift, ventral edema, intermittent fever, and intermittent mild colic. [659] [660] [661] [662] [663] [664] 667 Acute onset of diarrhea is typically profuse and progresses to chronic diarrhea that is often mild, the consistency of bovine feces, and may be intermittent. [659] [660] [661] [662] [663] [664] 667 Appetite is usually normal, but some affected horses have a ravenous appetite.

T56814

276506-276570

Sentence

denotes

Transrectal palpation usually does not reveal any abnormalities.

T76351

276571-276748

Sentence

denotes

Horses of any age may be affected, and clinical signs are more common during periods of emergence of larvae, corresponding to late winter and spring in northern temperate zones.

T27374

276749-276797

Sentence

denotes

The deworming history may appear to be adequate.

T81765

276798-277027

Sentence

denotes

Neutrophilic leukocytosis is typically evident, but the WBC count may be normal. [659] [660] [661] [662] [663] [664] Profound hypoalbuminemia is a characteristic feature of cyathostomiasis, manifested clinically by ventral edema.

T44132

277028-277347

Sentence

denotes

Plasma α-globulin and β-globulin concentrations may be elevated, which can result in a normal total plasma protein concentration in spite of hypoalbuminemia. [658] [659] [660] The serum IgG(T) concentration, however, has been reported to be normal, which may help distinguish cyathostomiasis from S. vulgaris infection.

T24201

277348-277464

Sentence

denotes

659,661,662 PF analysis does not usually reveal any abnormalities, in contrast to horses with S. vulgaris infection.

T67357

277465-277574

Sentence

denotes

Fecal analysis may be unrewarding because the infection is often not patent when clinical signs are apparent.

T56999

277575-277704

Sentence

denotes

Measurement of plasma fructosamine may provide a measure of protein catabolism or protein loss in the absence of hypoalbuminemia.

T33018

277705-277908

Sentence

denotes

667, 668 Plasma fructosamine concentrations are significantly lower in horses with experimental cyathostomiasis than in normal controls, 667,668 suggesting that this test may be a useful diagnostic tool.

T64511

277909-278041

Sentence

denotes

However, the test has not yet been validated in naturally occurring cases, and neither the specificity nor the sensitivity is known.

T32643

278042-278128

Sentence

denotes

Rectal scrapings or rectal mucosal biopsies may reveal evidence of cyathostome larvae.

T75374

278129-278278

Sentence

denotes

659, 662 Definitive diagnosis usually requires microscopic examination of biopsy specimens of the cecum and ascending colon, collected by laparotomy.

T20350

278279-278414

Sentence

denotes

Examination of biopsy specimens collected from the small intestine is recommended to rule out other causes of weight loss and diarrhea.

T63740

278415-278561

Sentence

denotes

Appropriate diagnostic tests, such as culture of feces for pathogenic bacteria, should be included in the workup to further rule out other causes.

T57432

278562-278676

Sentence

denotes

Preventive measures are appropriate for other horses on the premises known to have a problem with cyathostomiasis.

T26059

278677-278889

Sentence

denotes

These include frequent deworming (every 6 weeks) during times of high infectivity (spring and summer in the north and fall, winter, and early spring in the south) to eliminate parasites before they become patent.

T26209

278890-279176

Sentence

denotes

659 Because of high levels of resistance to benzimidazoles, avermectins (ivermectin or moxidectin) are often the drugs of choice for cyathostome control. [669] [670] [671] Resistance to ivermectin has been demonstrated, but the prevalence of ivermectin resistance appears to remain low.

T8778

279177-279462

Sentence

denotes

669 Although daily pyrantel pamoate administration has also been reported to effectively reduce worm burdens and pasture infectivity in young and mature horses, 672 cyathostome resistance has been reported and is a concern for the use of this drug as a routine preventive anthelmintic.

T88361

279463-279716

Sentence

denotes

670, 673, 674 Because of the rapid emergence of resistant strains to even ivermectin, targeted treatment, based on fecal egg counts and careful monitoring for the development of resistance to any anthelmintics used for cyathostome control, is warranted.

T30952

279717-279720

Sentence

denotes

674

T3082

279721-279804

Sentence

denotes

Antibiotic-associated diarrhea has been reported in many species, including horses.

T71456

279805-280039

Sentence

denotes

675 Certain antibiotics, such as trimethoprim-sulfonamide combinations, erythromycin, penicillins, tetracyclines, clindamycin, and lincomycin, are associated with naturally occurring and experimental enterocolitis syndromes in horses.

T14084

280040-280233

Sentence

denotes

620, [675] [676] [677] [678] In some cases, such as those seen with trimethoprim-sulfonamide combinations, the geographic incidence of antibiotic-associated diarrhea appears to differ markedly.

T77223

280234-280374

Sentence

denotes

C. perfringens, C. difficile, and serovars of S. enterica are apparently the most common causes of antibiotic-associated diarrhea in horses.

T29305

280375-280474

Sentence

denotes

Outbreaks of C. difficile have been reported in hospitalized horses being treated with antibiotics.

T41395

280475-280641

Sentence

denotes

622, 626 In Sweden accidental erythromycin ingestion has been associated with C. difficile enterocolitis in mares in which their foals were being treated for R. equi.

T30344

280642-280915

Sentence

denotes

629, 677, 679 Tetracycline administration has been associated with an increase in the numbers of gram-negative enteric bacteria and C. perfringens in the feces of horses as well as reactivation of salmonellosis and prolongation of fecal shedding of serovars of S. enterica.

T70744

280916-281031

Sentence

denotes

619, 680 The most common mechanism by which antibiotics cause diarrhea is disruption of the gastrointestinal flora.

T40809

281032-281193

Sentence

denotes

The normal large intestinal flora, composed of mainly obligate anaerobes and streptococci, protects the host from pathogenic bacteria by colonization resistance.

T94095

281194-281265

Sentence

denotes

553 Ecologic factors play an important role in colonization resistance.

T75473

281266-281402

Sentence

denotes

For example, surface bacteria in the large intestine interact with receptors on the mucosal cells, facilitating adherence to the mucosa.

T75138

281403-281497

Sentence

denotes

545, 681 In doing so, the normal organisms compete more successfully for this important niche.

T26227

281498-281624

Sentence

denotes

Competition for space and nutrients is an important means of preventing colonization and proliferation of pathogenic bacteria.

T78094

281625-281796

Sentence

denotes

552, 553, 681 Anaerobic bacteria produce SCFAs and other metabolites that are toxic to facultative anaerobic bacteria, especially in the conditions of the large intestine.

T68971

281797-281905

Sentence

denotes

552, 553, 681 Organisms of the normal flora produce bacteriocins that inhibit growth of potential pathogens.

T49344

281906-282034

Sentence

denotes

552 Antibiotics that deplete the population of obligate anaerobes and streptococci efficiently decrease colonization resistance.

T60470

282035-282131

Sentence

denotes

552 Production of fatty acids is diminished, and competition for space and nutrients is reduced.

T98949

282132-282201

Sentence

denotes

As a result, gram-negative enteric bacteria, such as S. enterica var.

T25109

282202-282239

Sentence

denotes

Typhimurium, are able to proliferate.

T73771

282240-282312

Sentence

denotes

Pathogenic anaerobes normally found in low numbers can also proliferate.

T40618

282313-282544

Sentence

denotes

Antibiotic-resistant strains of bacteria, especially gram-negative enteric bacteria and possibly clostridia, may be selected by antibiotic administration, allowing proliferation of pathogenic bacteria resistant to many antibiotics.

T58038

282545-282862

Sentence

denotes

682 Obligate anaerobic commensal organisms, perhaps the most critical group of microbes for maintaining colonization resistance, are usually susceptible to macrolides, tetracyclines, β-lactams, and lincosamides, which may explain the high incidence of diarrhea associated with the administration of these antibiotics.

T28375

282863-283191

Sentence

denotes

624 In addition to reduction of colonization resistance, depletion of the normal anaerobic microbial population in the intestine decreases carbohydrate fermentation and production of SCFAs, which contributes to the pathogenesis of antibioticassociated diarrhea by decreasing absorption of sodium and water by the colonic mucosa.

T83286

283192-283265

Sentence

denotes

171 Ampicillin decreases colonic fermentation of carbohydrates in humans.

T44964

283266-283398

Sentence

denotes

683 Human patients with antibiotic-associated diarrhea have markedly impaired colonic fermentation and very low production of SCFAs.

T37475

283399-283543

Sentence

denotes

684 Erythromycin, ampicillin, or metronidazole treatment is associated with decreased production of SCFAs in patients with and without diarrhea.

T29377

283544-283780

Sentence

denotes

684 Absorption of sodium and water is stimulated by absorption of SCFAs in the equine colon, suggesting that reduction of colonic SCFA content by antibioticinduced depletion of anaerobic flora has similar effects in horses as in humans.

T86868

283781-283904

Sentence

denotes

171 Broad-spectrum antibiotics exert a more profound effect on the gastrointestinal flora than narrow-spectrum antibiotics.

T38954

283905-284062

Sentence

denotes

685 Antibiotics administered orally, especially those that are poorly absorbed, are more likely to cause diarrhea than parenterally administered antibiotics.

T52421

284063-284187

Sentence

denotes

685 For instance, clindamycin is less likely to cause diarrhea in humans when administered IV than when administered orally.

T34162

284188-284444

Sentence

denotes

685 Antibiotics with extensive enterohepatic circulation, such as tetracyclines and erythromycin, are excreted in high concentrations in the bile and are more commonly associated with diarrhea than antibiotics that do not undergo enterohepatic circulation.

T60099

284445-284531

Sentence

denotes

685 Antibiotics may cause diarrhea by other means than by disrupting the normal flora.

T35511

284532-284649

Sentence

denotes

Direct toxic effects may play a role in producing irritation, increasing secretion, and disrupting motility patterns.

T80829

284650-284760

Sentence

denotes

Tetracyclines are irritating to the gastrointestinal mucosa and may cause inflammation and increase secretion.

T66606

284761-284852

Sentence

denotes

685 Erythromycin interacts with smooth muscle cells, stimulating gastrointestinal motility.

T97226

284853-284975

Sentence

denotes

685, 686 Normal peristalsis plays an important role in suppressing the population size of potentially pathogenic bacteria.

T95207

284976-285129

Sentence

denotes

Normally, bacteria that are prevented from adhering to the mucosa by colonization resistance are swept aborally by peristalsis and excreted in the feces.

T19128

285130-285268

Sentence

denotes

Disruption of normal motility patterns may prevent clearance of pathogenic bacteria, contributing to the colonization of mucosal surfaces.

T55698

285269-285440

Sentence

denotes

Diarrhea induced by antibiotics usually occurs within 7 days of initiation of antibiotic administration but may occur several days after cessation of antibiotic treatment.

T8239

285441-285571

Sentence

denotes

The clinical syndrome of antibiotic-associated diarrhea varies from mild diarrhea to fulminant enterocolitis with severe diarrhea.

T14793

285572-285737

Sentence

denotes

Mild diarrhea is common, especially in foals receiving erythromycin, trimethoprim-sulfa combinations, or rifampin 677,687 and are usually not clinically significant.

T12413

285738-285848

Sentence

denotes

Acute, severe enterocolitis can occur in horses of all ages receiving antibiotics and can be life-threatening.

T32688

285849-285938

Sentence

denotes

Clinical signs are identical to those resulting from other causes of acute enterocolitis.

T1790

285939-286010

Sentence

denotes

Severe, dehydrating diarrhea; endotoxemia; sepsis; and shock may occur.

T45959

286011-286112

Sentence

denotes

Hemoconcentration, neutropenia, hypoproteinemia, and electrolyte and acid-base imbalances are common.

T5759

286113-286262

Sentence

denotes

Severe hyponatremia may occur in foals with antibiotic-associated diarrhea, especially if trimethoprim-sulfa and rifampin combinations are the cause.

T2519

286263-286353

Sentence

denotes

687 More detailed descriptions of the clinical and laboratory findings were given earlier.

T72515

286354-286456

Sentence

denotes

Diagnosis is presumptive because definitive diagnosis of antibiotic-associated diarrhea is impossible.

T87871

286457-286539

Sentence

denotes

Fecal culture or PCR testing may reveal S. enterica or Clostridium spp. infection.

T51320

286540-286809

Sentence

denotes

Toxicity resulting from NSAID administration has been well documented in several species, including horses, and is discussed in Chapter 2. [688] [689] [690] [691] [692] [693] [694] In horses and humans NSAID toxicity is manifested by renal and gastrointestinal disease.

T1590

286810-286982

Sentence

denotes

Foals are considered to be more susceptible than adult horses to gastrointestinal disease secondary to NSAID administration, and ponies may be more susceptible than horses.

T24151

286983-287134

Sentence

denotes

NSAID toxicity varies primarily as a result of properties that influence distribution to sensitive tissues and relative selectivity for COX-1 or COX-2.

T62038

287135-287241

Sentence

denotes

All nonselective NSAIDs are capable of inducing gastrointestinal and renal damage at toxic concentrations.

T16873

287242-287404

Sentence

denotes

Aspirin has been suggested to be more toxic than other NSAIDs because it irreversibly inactivates COX by acetylation, whereas other NSAIDs reversibly inhibit COX.

T69862

287405-287685

Sentence

denotes

688 Phenylbutazone is the drug most commonly reported to cause gastrointestinal toxicity in horses, perhaps because of its widespread usage by veterinarians and horse owners or perhaps because of bona fide differences in toxicity in horses compared with other nonselective NSAIDs.

T95484

287686-288057

Sentence

denotes

Acute phenylbutazone toxicity in horses resulting from overdose is characterized by mucosal ulceration throughout the gastrointestinal tract, oral ulceration, renal papillary necrosis, vasculopathy, thrombosis, and protein-losing enteropathy with hypoalbuminemia. [690] [691] [692] COX-2-selective NSAIDs appear to be much less toxic in the equine gastrointestinal tract.

T2757

288058-288237

Sentence

denotes

392, 695 The focus of this discussion is on the toxic effects of NSAIDs on the large intestine, but this necessarily includes elements of upper gastrointestinal and renal disease.

T33396

288238-288482

Sentence

denotes

Horses with large intestinal disease resulting from NSAID toxicity generally are receiving inappropriately large doses or have underlying disorders that predispose the large intestine to the toxic effects of NSAIDs, even at appropriate dosages.

T52726

288483-288621

Sentence

denotes

The dosage regimen recommended for phenylbutazone (4.4 mg/ kg every 12 hours for 1 day, then 2.2 mg/kg every 12 hours) is considered safe.

T74429

288622-288788

Sentence

denotes

Experimental studies in horses, however, have shown toxicity to occur when amounts exceeding the recommended dosage (6.6 mg/kg/day) are administered for several days.

T44692

288789-288907

Sentence

denotes

688, 689 Most reported cases of phenylbutazone toxicosis occurred in horses receiving higher than recommended dosages.

T2440

288908-289104

Sentence

denotes

692, 694, 696 Regardless, administration of phenylbutazone at the recommended dosage has been reported to cause a significant decrease in plasma protein concentration and gastrointestinal disease.

T36892

289105-289239

Sentence

denotes

691, 697 Moreover, signs of NSAID toxicity have been reported in normovolemic horses treated with appropriate doses of phenylbutazone.

T28623

289240-289396

Sentence

denotes

697, 698 Dehydration, sepsis, endotoxemia, and other conditions that alter hemodynamic homeostasis exacerbate renal and gastrointestinal toxicity of NSAIDs.

T19683

289397-289532

Sentence

denotes

688 Underlying inflammation of the intestinal tissues may increase the likelihood of gastrointestinal ulceration resulting from NSAIDs.

T80833

289533-289667

Sentence

denotes

Gastrointestinal disease induced by NSAIDs is manifested by mucosal ulceration, inflammation, bleeding, and proteinlosing enteropathy.

T20762

289668-289905

Sentence

denotes

690, 691, 694, 697 In addition to direct effects on the mucosal barrier, NSAID administration causes an acute relapse of preexisting colonic inflammatory disease and worsens colonic inflammation in humans with inflammatory bowel disease.

T66798

289906-289999

Sentence

denotes

688, 699, 700 It is not clear whether the previously mentioned NSAID effects occur in horses.

T58190

290000-290079

Sentence

denotes

The mechanism by which NSAIDs induce mucosal damage is probably multifactorial.

T36497

290080-290251

Sentence

denotes

Direct irritation may play a role in oral and gastric irritation and ulceration; however, parenteral administration of NSAIDs produces oral and gastric ulceration as well.

T83414

290252-290389

Sentence

denotes

Inhibition of prostaglandin synthesis by inhibition of both COX-1 and COX-2 appears to be the most important mechanism of mucosal injury.

T75690

290390-290493

Sentence

denotes

Prostaglandins, particularly PGE 2 and PGI 2 , are critical for mucosal health and repair after injury.

T22769

290494-290757

Sentence

denotes

701,702 PGE 2 increases mucosal blood flow; increases secretion of mucus, water, and bicarbonate; increases mucosal cell turnover rate and migration; stimulates adenyl cyclase activity; and exerts other protective effects in the gastric mucosa of several species.

T22819

290758-290959

Sentence

denotes

688, 701, 702 Perhaps most important, PGE 2 and PGI 2 have roles in maintaining epithelial tight junction integrity, which is indispensable for mucosal barrier function and repair after mucosal injury.

T53645

290960-291284

Sentence

denotes

701 In spite of the overwhelming amount of information about the role of prostaglandins in maintaining the mucosal barrier in other species and clear clinical and experimental evidence that NSAIDs injure the equine colonic mucosa, the role of prostaglandins in mucosal protection in the equine colon is not yet well defined.

T20627

291285-291573

Sentence

denotes

Inhibition of COX-1 and COX-2 in equine colonic mucosa with flunixin meglumine results in reduced electrical resistance of the mucosa and increased permeability to macromolecules in vitro, 703 suggesting that flunixin treatment disrupts the epithelial tight junctions in the equine colon.

T68745

291574-291678

Sentence

denotes

This was correlated with a profound inhibition of PGE 2 and PGI 2 concentrations in the treated tissues.

T81362

291679-291795

Sentence

denotes

Administration of a PGE 2 analog prevents the gastrointestinal manifestations of phenylbutazone toxicosis in ponies.

T54573

291796-292009

Sentence

denotes

691 The recent development of NSAIDs that specifically inhibit COX-2 has markedly reduced the frequency and severity of gastrointestinal side effects in humans taking NSAIDs for chronic musculoskeletal conditions.

T99701

292010-292165

Sentence

denotes

704 COX-2-specific NSAIDs such as firocoxib hold promise for use in horses to treat arthritis 705 and other conditions, with reduced incidence of toxicity.

T3366

292166-292322

Sentence

denotes

For example, the relatively COX-2-specific inhibitors meloxicam and firocoxib are less harmful to equine intestinal mucosa than flunixin meglumine in vitro.

T69411

292323-292545

Sentence

denotes

392, 695 Moreover, COX-2-selective inhibitors are significantly more permissive than flunixin for recovery of the mucosa in equine ischemicinjured intestinal tissues; recovery is no different from that for control tissues.

T25394

292546-292686

Sentence

denotes

392, 695 NSAID-induced mucosal injury is associated with a marked inflammatory response to microbial products exposed to the lamina propria.

T85745

292687-292783

Sentence

denotes

706 This inflammation exacerbates mucosal dysfunction and injury associated with NSAID toxicity.

T90287

292784-293048

Sentence

denotes

For example, depletion of neutrophils or blockade of neutrophil influx into gastrointestinal tissues or inhibition of neutrophil activation and release of toxic products prevents many of the pathophysiologic effects of NSAID toxicity in the gastrointestinal tract.

T40990

293049-293270

Sentence

denotes

106, [707] [708] [709] The inflammatory response alone may result in moderate to severe gastrointestinal ulceration, mural vascular thrombosis and edema, fluid secretion, proteinlosing enteropathy, and mucosal hemorrhage.

T6763

293271-293392

Sentence

denotes

NSAID colitis manifests as two clinical syndromes: right dorsal ulcerative colitis (RDUC) and generalized NSAID toxicity.

T38695

293393-293493

Sentence

denotes

As its name implies, RDUC is a disorder isolated to the right dorsal segment of the large intestine.

T18915

293494-293583

Sentence

denotes

693,694, 698 The most prominent clinical signs of RDUC are anorexia, lethargy, and colic.

T42652

293584-293669

Sentence

denotes

Anorexia, depression, diarrhea, fever, and signs of endotoxemia may also be features.

T29320

293670-293816

Sentence

denotes

If RDUC is chronic, weight loss, intermittent colic, lethargy, anorexia, and ventral edema are common clinical signs with soft and unformed feces.

T74326

293817-293971

Sentence

denotes

Ulceration of the right dorsal colonic mucosa results in proteinlosing enteropathy and significant hypoproteinemia attributable mainly to hypoalbuminemia.

T67779

293972-294122

Sentence

denotes

Hypoproteinemia may be one of the earliest clinical manifestations of RDUC and can be sufficiently severe to cause peripheral (usually ventral) edema.

T83445

294123-294336

Sentence

denotes

In some horses, dehydration, electrolyte abnormalities, neutropenia or anemia, azotemia, and biochemical abnormalities may be noted if the ulceration and diarrhea are severe or if systemic inflammation is present.

T16252

294337-294539

Sentence

denotes

Clinical signs of generalized NSAID toxicity vary from mild diarrhea with no systemic signs to severe dehydrating diarrhea with anorexia, fever, depression, peripheral edema, oral ulceration, and colic.

T90857

294540-294764

Sentence

denotes

691, 692, 696 Clinical signs of systemic inflammation caused by endotoxemia may occur, manifested as poor peripheral perfusion, tachycardia and tachypnea, weakness, trembling, and cyanotic or hyperemic oral mucous membranes.

T95026

294765-294825

Sentence

denotes

Hematuria or oliguria may be present with renal involvement.

T23672

294826-294964

Sentence

denotes

Complications associated with other forms of severe enterocolitis, such as laminitis, thrombophlebitis, and severe weight loss, may occur.

T59257

294965-295274

Sentence

denotes

Although phenylbutazone has been associated specifically with bone marrow depression resulting in abnormalities in one or more blood cell lines, 710 hematologic abnormalities of generalized NSAID toxicity are usually nonspecific and include neutropenia with a left shift or leukocytosis and hemoconcentration.

T92209

295275-295385

Sentence

denotes

Serum biochemical analysis is characterized by profound hypoproteinemia, hyponatremia, and metabolic acidosis.

T94185

295386-295500

Sentence

denotes

696, 697 Hypocalcemia, hypokalemia, hypochloremia, and elevated hepatocellular enzyme activities may also be seen.

T20619

295501-295553

Sentence

denotes

Hypoproteinemia may occur without signs of diarrhea.

T76218

295554-295747

Sentence

denotes

Azotemia may be prerenal as a result of dehydration, but it is frequently caused by renal failure that results from a combination of hemodynamic effects of NSAIDs and direct toxic renal injury.

T52995

295748-295832

Sentence

denotes

Urinalysis frequently reveals hematuria, proteinuria, cylindruria, and isosthenuria.

T82069

295833-295875

Sentence

denotes

Fecal occult blood is frequently detected.

T80479

295876-296017

Sentence

denotes

Diagnosis of either form of NSAID colitis is often presumptive, with a history of overdose of NSAIDs being strong evidence of NSAID toxicity.

T27326

296018-296192

Sentence

denotes

As discussed earlier, toxicity may occur with dosage regimens that are not considered inappropriate, particularly if the horse experiences a concurrent period of dehydration.

T50567

296193-296345

Sentence

denotes

Ultrasonographic examination of the right dorsal colon can be used to confirm a diagnosis of RDUC, but the sensitivity of this method appears to be low.

T14144

296346-296600

Sentence

denotes

711 Ultrasonography (3.5-to 5-MHz transducer at the right twelfth through fifteenth intercostal spaces below the margin of the lung axial to the liver) may reveal a thickened right dorsal colon (>0.5 cm) and evidence of colonic edema in horses with RDUC.

T80878

296601-296751

Sentence

denotes

711, 712 Nuclear scintigraphy of horses after infusion with technetium-99-labeled WBCs can be used to document inflammation of the right dorsal colon.

T63334

296752-296869

Sentence

denotes

50 Laparotomy or laparoscopic examination of the right dorsal colon may be required for definitive diagnosis of RDUC.

T46146

296870-297014

Sentence

denotes

Other causes of enterocolitis, such as salmonellosis, Potomac horse fever, clostridiosis, and antibiotic-associated diarrhea, must be ruled out.

T94064

297015-297246

Sentence

denotes

Cantharidin is the toxic substance found in beetles of the genus Epicauta, commonly known as blister beetles. [713] [714] [715] Ingestion of the beetles causes release of the toxin and absorption through the gastrointestinal tract.

T94395

297247-297316

Sentence

denotes

Transcutaneous absorption may occur but appears to be rare in horses.

T66248

297317-297600

Sentence

denotes

Blister beetles feed on the flowers of alfalfa and may be incorporated into processed alfalfa hay if the hay is cut and processed simultaneously, as by crimping. [713] [714] [715] The beetles often swarm, and large numbers of beetles may be found in relatively small portions of hay.

T13388

297601-297749

Sentence

denotes

The lethal dose of cantharidin is less than 1 mg/kg, but the concentration of cantharidin varies among species of blister beetles and between sexes.

T39575

297750-297811

Sentence

denotes

713, 714 As many as 100 to as few as 6 beetles may be lethal.

T64611

297812-297947

Sentence

denotes

Usually, only one or a few horses fed contaminated hay will ingest beetles because they are concentrated in a small portion of the hay.

T9253

297948-298013

Sentence

denotes

However, outbreaks involving many horses on a farm have occurred.

T21767

298014-298192

Sentence

denotes

Most cases have occurred in Texas and Oklahoma, but horses in other states may be affected as well, especially if hay is imported from states in which blister beetles are common.

T52095

298193-298235

Sentence

denotes

Peak incidence is in late summer and fall.

T40014

298236-298352

Sentence

denotes

716 The fatality rate may be 50% or greater, 713,717 but if the patient survives several days, recovery is probable.

T63622

298353-298437

Sentence

denotes

Cantharidin is absorbed from the gastrointestinal tract and excreted by the kidneys.

T51187

298438-298529

Sentence

denotes

It is a potent irritant, causing acantholysis and vesicle formation when applied topically.

T31046

298530-298718

Sentence

denotes

713, 715, 717 The chemical is thought to disrupt the oxidative metabolism in the mitochondria, causing mitochondrial swelling, plasma membrane damage, and changes in membrane permeability.

T12731

298719-298830

Sentence

denotes

713 The mucosa of the gastrointestinal tract is most commonly affected in horses because they ingest the toxin.

T3675

298831-298897

Sentence

denotes

Cell swelling and necrosis occur, resulting in mucosal ulceration.

T51929

298898-299027

Sentence

denotes

Oral, esophageal, gastric, and small and large intestinal ulceration have been observed in natural and experimental canthariasis.

T89256

299028-299154

Sentence

denotes

713, 715, 717 Severe fibrinous to pseudomembranous inflammation and submucosal edema of the intestine have also been reported.

T63243

299155-299347

Sentence

denotes

Diarrhea probably results from the severe ulceration and inflammation of the large intestine, causing increased secretion of water, electrolytes, and protein and decreased absorption of fluid.

T34025

299348-299502

Sentence

denotes

Large volumes of fluid and protein are lost in the gastrointestinal tract, causing hemoconcentration and profound hypoalbuminemia in some affected horses.

T99143

299503-299616

Sentence

denotes

713, 715, 717 Cystitis and myocarditis occur in natural and experimentally induced cases of cantharidin toxicity.

T95204

299617-299737

Sentence

denotes

713, 715, 717 The toxin is excreted by the kidneys, and high concentrations of cantharidin in the urine induce cystitis.

T28209

299738-299844

Sentence

denotes

Occasionally, hemorrhagic cystitis may occur, resulting in hematuria or frank hemorrhage into the bladder.

T97254

299845-299963

Sentence

denotes

713 The cause of myocarditis and myocardial necrosis is unknown but may be a direct effect of toxin on the myocardium.

T21690

299964-300085

Sentence

denotes

Increased plasma creatine kinase activity is often observed and has been postulated to arise from the damaged myocardium.

T23742

300086-300285

Sentence

denotes

713, 714 Affected horses have a characteristically stiff gait, but histopathologic evidence of skeletal muscle injury that explains the elevated plasma creatine kinase activity has not been observed.

T64251

300286-300363

Sentence

denotes

714 The kidneys are often pale, swollen, and moist, with occasional infarcts.

T82868

300364-300488

Sentence

denotes

715 Hypocalcemia and hypomagnesemia are biochemical features of cantharidin toxicity in horses that have not been explained.

T12794

300489-300679

Sentence

denotes

713, 714, 717 Hypocalcemia may result from hypoalbuminemia, but the ionized calcium concentration is often decreased, indicating that hypoalbuminemia is not responsible for the hypocalcemia.

T14437

300680-300683

Sentence

denotes

714

T92434

300684-300875

Sentence

denotes

Cantharidin toxicity can cause a range of clinical signs, from mild depression and abdominal discomfort to fulminant signs of toxemia and rapid death, depending on the ingested dose of toxin.

T35722

300876-301068

Sentence

denotes

713, 714, 717 Most commonly, clinical signs include depression, sweating, irritability, abdominal pain, elevated heart and respiratory rates, fever, polyuria, polydipsia, and profuse diarrhea.

T71127

301069-301117

Sentence

denotes

713, 714, 717 Blood is rarely seen in the feces.

T71588

301118-301156

Sentence

denotes

Stranguria and pollakiuria are common.

T69280

301157-301237

Sentence

denotes

713 Signs of hypocalcemia include synchronous diaphragmatic flutter and tremors.

T59268

301238-301278

Sentence

denotes

A stiff and stilted gait may be evident.

T84265

301279-301360

Sentence

denotes

Neurologic signs such as head pressing, swaying, and disorientation may be noted.

T1277

301361-301451

Sentence

denotes

717 Signs of systemic inflammation resulting from endotoxemia may be seen in severe cases.

T8748

301452-301580

Sentence

denotes

Some horses develop severe depression and toxemia and may die within hours of ingesting cantharidin without developing diarrhea.

T88585

301581-301672

Sentence

denotes

713, 717 Hematologic abnormalities include hemoconcentration and neutrophilic leukocytosis.

T96162

301673-301749

Sentence

denotes

713, 714 Occasionally, neutropenia and leukopenia may accompany endotoxemia.

T48133

301750-301863

Sentence

denotes

Serum biochemical analysis usually reveals increased creatine kinase activity, hypocalcemia, and hypoalbuminemia.

T95436

301864-301998

Sentence

denotes

713, 714 Biochemical abnormalities include hypocalcemia (both ionized and total calcium concentrations), hypomagnesemia, and azotemia.

T58069

301999-302085

Sentence

denotes

713, 714, 717 Urine specific gravity is characteristically in the hyposthenuric range.

T24865

302086-302153

Sentence

denotes

713, 714 Microscopic hematuria and mild proteinuria may be evident.

T69672

302154-302219

Sentence

denotes

Fecal occult blood is often present, but hematochezia is unusual.

T6207

302220-302334

Sentence

denotes

A tentative diagnosis can be made on the basis of clinical signs and identification of blister beetles in the hay.

T58127

302335-302438

Sentence

denotes

Determining the species of the insects may be necessary to estimate the amount of cantharidin ingested.

T64373

302439-302512

Sentence

denotes

All species of Epicauta contain cantharidin, but some have small amounts.

T90672

302513-302636

Sentence

denotes

Definitive diagnosis requires the measurement of the cantharidin concentration in gastric or intestinal contents and urine.

T4284

302637-302645

Sentence

denotes

713, 716

T79108

302647-302867

Sentence

denotes

Arsenic toxicosis is an unusual cause of diarrhea in horses, resulting from ingestion of arsenic-containing herbicides, insecticides, and other pest-control products contaminating water or roughage used as a food source.

T29517

302868-302934

Sentence

denotes

718 The toxicity of arsenic depends on the valence of the element.

T71189

302935-303001

Sentence

denotes

718, 719 Arsenate may be reduced to arsenite in mammalian systems.

T99932

303002-303086

Sentence

denotes

719 It is thought to be more toxic than arsenate and less rapidly excreted in urine.

T30834

303087-303224

Sentence

denotes

719 Arsenate and arsenite uncouple oxidative phosphorylation, leading to the breakdown of energy metabolism in the cells of many tissues.

T93137

303225-303311

Sentence

denotes

719 Widespread cellular injury and death occur rapidly during acute arsenic toxicosis.

T88357

303312-303353

Sentence

denotes

Multiorgan failure is usually the result.

T55157

303354-303428

Sentence

denotes

Cardiomyopathy and pulmonary disease are common causes of death in humans.

T56727

303429-303548

Sentence

denotes

720 Damage to the large intestine is probably caused in part by direct cellular toxicity and corrosion by the compound.

T85885

303549-303707

Sentence

denotes

However, vasculitis is a hallmark of the disease in humans and horses and is thought to be the most important mechanism of large intestinal disease in humans.

T97041

303708-303825

Sentence

denotes

718, 721 Acute hemorrhagic colitis is a feature of arsenic toxicosis, with severe mural edema and mucosal ulceration.

T19899

303826-303885

Sentence

denotes

718 Profuse hemorrhagic diarrhea and abdominal pain result.

T76312

303886-303954

Sentence

denotes

Chronic arsenic toxicity can occur but appears to be rare in horses.

T49593

303955-304081

Sentence

denotes

Depression, weakness, abdominal pain, hemorrhagic diarrhea, and shock are characteristic of acute arsenic toxicosis in horses.

T8377

304082-304129

Sentence

denotes

718 Death may occur before diarrhea is evident.

T23555

304130-304298

Sentence

denotes

Initial clinical signs may be difficult to distinguish from other peracute forms of colitis and are related to endotoxic shock, metabolic disturbances, and dehydration.

T24171

304299-304421

Sentence

denotes

Later, cardiac arrhythmias, pulmonary edema, acute renal failure, and neurologic deficits (ataxia and stupor) may develop.

T99729

304422-304461

Sentence

denotes

718 Anuria or polyuria may be observed.

T20578

304462-304594

Sentence

denotes

Hemolytic anemia caused by preferential binding of arsenic compounds to red blood cells is a feature of arsenic poisoning in humans.

T95567

304595-304727

Sentence

denotes

720 Hematologic abnormalities resulting from injury to bone marrow cells and ongoing hemolysis may be seen after the peracute stage.

T12945

304728-304798

Sentence

denotes

Leukopenia and thrombocytopenia have been described in human patients.

T31677

304799-304972

Sentence

denotes

720 Serum biochemical analysis may reveal azotemia, hepatocellular enzyme activities higher than generally attributed to endotoxemia, and increased creatine kinase activity.

T14217

304973-305101

Sentence

denotes

718 Urine specific gravity may be in the isosthenuric range, with hematuria, cylindruria, and proteinuria evident by urinalysis.

T92854

305102-305218

Sentence

denotes

Diagnosis may be possible by measuring blood and urine arsenic concentration, but these tests may not be diagnostic.

T56476

305219-305317

Sentence

denotes

Postmortem diagnosis is confirmed by measuring arsenic concentrations in liver and kidney samples.

T98262

305318-305399

Sentence

denotes

718 History of exposure and clinical signs remain the primary means of diagnosis.

T31580

305400-305503

Sentence

denotes

Severe intestinal anaphylaxis is a syndrome in horses characterized by peracute, rapidly fatal colitis.

T956

305504-305611

Sentence

denotes

722 The severe syndrome is clinically and pathologically similar to other known causes of peracute colitis.

T71398

305612-305700

Sentence

denotes

Some cases are less severe and manifest as mild to moderate diarrhea or colic (or both).

T19871

305701-305850

Sentence

denotes

The syndrome of intestinal anaphylaxis can be produced by either an IgE-mediated type I hypersensitivity or an IgEindependent anaphylactoid reaction.

T45455

305851-306541

Sentence

denotes

723, 724 Intestinal anaphylaxis is usually induced by local gastrointestinal exposure to a food, environmental, drug, or other allergen 723,725 but may also occur with systemic exposure to an allergen. [726] [727] [728] Massive mast cell degranulation, secretion of inflammatory mediators, and activation of enteric neural reflexes in the intestine cause profound alterations in blood flow, increased vascular permeability and interstitial edema, recruitment of neutrophils, altered motility, mucosal injury, absorption of microbial products, and mucosal hypersecretion. [729] [730] [731] [732] [733] Systemic signs may be caused by the anaphylactic reaction or may be associated with SIRS.

T67959

306542-306728

Sentence

denotes

The peracute form is characterized by severe intramural edema and hemorrhagic inflammation of the large intestine, often producing submucosal thickening on the order of many centimeters.

T35986

306729-306827

Sentence

denotes

162, 722 Vascular thrombosis may be widespread, with mucosal and serosal petechiae and ecchymoses.

T5517

306828-306936

Sentence

denotes

Less severe forms of intestinal anaphylaxis may manifest as patchy areas of intestinal edema and congestion.

T21420

306937-307037

Sentence

denotes

726 Diarrhea results from intestinal inflammation initiated by the type I hypersensitivity response.

T5870

307038-307274

Sentence

denotes

Many of the mediators of type I hypersensitivity, such as histamine and 5-HT, have well-documented stimulatory effects on mucosal secretory activity, vascular and epithelial permeability, and motility [729] [730] [731] in the intestine.

T18093

307275-307381

Sentence

denotes

Systemic inflammation resulting from endotoxemia may be overwhelming once the mucosal barrier breaks down.

T89514

307382-307475

Sentence

denotes

Infarction of intestinal segments and other organs may result from intravascular coagulation.

T70852

307476-307619

Sentence

denotes

Ileus, abdominal distention, and moderate to severe abdominal pain may result from motility disturbances and infarction of the large intestine.

T43452

307620-307706

Sentence

denotes

The clinical signs are similar to those described for other forms of peracute colitis.

T98625

307707-307783

Sentence

denotes

Severe diarrhea is possible, but death may occur before diarrhea is evident.

T56137

307784-307837

Sentence

denotes

Multiorgan failure resulting from DIC is not unusual.

T48097

307838-307917

Sentence

denotes

The rapid onset of weakness, staggering, and trembling commonly precedes death.

T93979

307918-307964

Sentence

denotes

The syndrome may cause death in 4 to 24 hours.

T4878

307965-308054

Sentence

denotes

Diagnosis is based on clinical signs, postmortem findings, and exclusion of other causes.

T5060

308055-308094

Sentence

denotes

Most diagnostic tests are inconclusive.

T94178

308095-308301

Sentence

denotes

If an antigen is suspected to be the trigger of the anaphylaxis, a Prausnitz-Kustner passive cutaneous anaphylaxis sensitization test can confirm the presence of antigen-specific IgE in the patient's serum.

T46359

308302-308305

Sentence

denotes

726

T67767

308306-308534

Sentence

denotes

Overeating of soluble carbohydrates, especially so-called hot grains such as corn, overwhelms the digestive capability of the small intestine, resulting in a high percentage of soluble carbohydrates entering the large intestine.

T71549

308535-308665

Sentence

denotes

The amount of soluble carbohydrates that will produce diarrhea varies according to the previous dietary history of the individual.

T16061

308666-308786

Sentence

denotes

Horses fed diets higher in soluble carbohydrates are more resistant to the deleterious effects of carbohydrate overload.

T44532

308787-308880

Sentence

denotes

Gradual accommodation to a diet high in carbohydrates can be accomplished over several weeks.

T32173

308881-309141

Sentence

denotes

Horses fed an unusually large amount of grains or other form of soluble carbohydrates often develop diarrhea and may, depending on the amount ingested, develop severe colitis, systemic inflammation resulting from endotoxemia, metabolic acidosis, and laminitis.

T631

309142-309307

Sentence

denotes

229, [734] [735] [736] The pathogenesis of colitis from carbohydrate overload is primarily caused by the toxic effects on the microbial flora in the large intestine.

T7223

309308-309501

Sentence

denotes

735 A sudden delivery of soluble carbohydrates to the large intestine causes rapid fermentation by gram-positive lactic acid-producing bacteria and a sudden increase in organic acid production.

T55799

309502-309596

Sentence

denotes

229 The cecal pH level rapidly decreases, and the lactic acid concentration rapidly increases.

T5871

309597-309810

Sentence

denotes

229 Rapid organic acid production overwhelms the buffering capacity of the large intestine, not only by directly depleting the buffers found in the contents but also by reducing the efficiency of buffer secretion.

T6188

309811-309957

Sentence

denotes

Bicarbonate secretion is linked to absorption of volatile fatty acids, which are produced in low amounts by fermentation of soluble carbohydrates.

T8416

309958-310080

Sentence

denotes

The contents of the large intestine become profoundly acidic, resulting in unfavorable conditions for the microbial flora.

T34745

310081-310233

Sentence

denotes

Lactic acid-producing bacteria flourish, whereas the gramnegative bacteria, especially the Enterobacteriaceae, are killed in large numbers by the acids.

T99698

310234-310301

Sentence

denotes

Large quantities of endotoxin are released from the dying bacteria.

T32751

310302-310488

Sentence

denotes

229 The osmotic load from lactic acid produced in the large intestine is an important factor in the development of diarrhea because organic acids such as lactic acid are poorly absorbed.

T23733

310489-310565

Sentence

denotes

Mild cases of carbohydrate overload may result purely from osmotic diarrhea.

T25215

310566-310736

Sentence

denotes

In more severe cases the acidic contents of the large intestine are toxic to the mucosa, causing necrosis of the mucosal tissues similar to that seen in ruminal acidosis.

T69792

310737-310968

Sentence

denotes

Mucosal ulceration allows absorption of large quantities of endotoxin and lactic acid produced by the massive die-off of acid-intolerant microbes and fermentation of soluble carbohydrates, normally poorly absorbed by intact mucosa.

T5160

310969-311127

Sentence

denotes

736 Systemic inflammation resulting from endotoxemia may be overwhelming; clinical and laboratory findings are consistent with that described for endotoxemia.

T19039

311128-311290

Sentence

denotes

Laminitis is a frequent complication; carbohydrate overload is used to induce laminitis as an experimental model because of the consistency of laminitis produced.

T20873

311291-311304

Sentence

denotes

229, 735, 736

T29264

311306-311476

Sentence

denotes

Clinical signs of colitis from carbohydrate overload can vary according to the amount of carbohydrate ingested and accommodation of the flora to a high-carbohydrate diet.

T37519

311477-311557

Sentence

denotes

Mild cases may result in a transient osmotic diarrhea, with no systemic effects.

T67626

311558-311724

Sentence

denotes

Severe cases are characterized by signs similar to those described for other forms of colitis, including abdominal pain, moderate to severe diarrhea, and dehydration.

T45171

311725-311796

Sentence

denotes

Signs of endotoxemia and sepsis are frequently present in severe cases.

T48987

311797-311864

Sentence

denotes

Nasogastric intubation may yield significant acidic gastric reflux.

T5830

311865-311994

Sentence

denotes

Particles of grain may be noted in the gastric reflux and the feces if grain overload is the source of the carbohydrate overload.

T46665

311995-312030

Sentence

denotes

Laminitis is a common complication.

T83641

312031-312165

Sentence

denotes

Sand enteropathy is often associated with acute intestinal obstruction due to abnormally large amounts of sand in the large intestine.

T46021

312166-312330

Sentence

denotes

737 However, chronic sand-induced diarrhea is a distinct syndrome that can occur at any age as a result of the abnormal accumulation of sand in the large intestine.

T43236

312331-312408

Sentence

denotes

738, 739 Chronic diarrhea and signs of colic may be seen without obstruction.

T21234

312409-312594

Sentence

denotes

Diagnosis is usually based on the presence of abnormal amounts of sand in the feces, although some horses with sand enteropathy may not be passing sand in the feces at any given moment.

T84782

312595-312665

Sentence

denotes

Occasionally, radiography may be required to detect sand in the colon.

T11092

312666-312669

Sentence

denotes

738

T79914

312671-312995

Sentence

denotes

The principles of therapy for acute diarrhea resulting from colitis are similar regardless of the cause and include replacement of fluid and electrolyte losses, control of colonic inflammation, reduction of fluid secretion, promotion of mucosal repair, control of endotoxemia and sepsis, and reestablishment of normal flora.

T92694

312996-313151

Sentence

denotes

The reader is referred elsewhere in this chapter for a discussion of general treatment of endotoxemia, for which many of the principles of therapy overlap.

T51348

313152-313256

Sentence

denotes

Replacement of fluid and electrolyte losses is of primary concern in treating horses with salmonellosis.

T29930

313257-313338

Sentence

denotes

Depending on the severity of the disease, fluid losses may be minimal or massive.

T81491

313339-313395

Sentence

denotes

Fluid and electrolytes can be administered orally or IV.

T65781

313396-313534

Sentence

denotes

Some horses with mild to moderate diarrhea may maintain hydration and electrolyte balance by consuming water and electrolytes voluntarily.

T60330

313535-313614

Sentence

denotes

Fresh water and water containing electrolytes should be available in all cases.

T83455

313615-313768

Sentence

denotes

In many instances, periodic nasogastric intubation and administration of water and electrolytes through the tube may be sufficient to maintain hydration.

T4457

313769-313923

Sentence

denotes

740 IV administration of fluids is preferred in cases requiring significant quantities of fluid to replace and maintain hydration and electrolyte balance.

T6494

313924-314055

Sentence

denotes

357 It is not unusual for patients with severe diarrhea to require large volumes (50-100 L/day) of IV fluids to maintain hydration.

T56691

314056-314313

Sentence

denotes

Monitoring of packed cell volume, serum electrolyte concentration, venous blood gases, blood urea nitrogen and creatinine, urine protein and cytology, and body weight is important to evaluate hydration, electrolyte and acid-base balance, and renal function.

T5510

314314-314442

Sentence

denotes

Isotonic sodium chloride or lactated Ringer's solution is frequently used to restore and maintain fluid and electrolyte balance.

T97224

314443-314542

Sentence

denotes

Potassium chloride can be added to the fluids and administered at a rate up to 0.5 to 1.0 mEq/kg/h.

T31706

314543-314595

Sentence

denotes

Generally, a rate of less than 0.5 mEq/kg/h is used.

T20680

314596-314775

Sentence

denotes

Hypertonic NaCl solutions (1-2 L of 5% or 7.5% NaCl) have been used in horses with acute, severe hyponatremia (<120 mEq/dL) and those with hemodynamic shock resulting from sepsis.

T87121

314776-314850

Sentence

denotes

The beneficial effects of hypertonic NaCl are short-lived (30-60 minutes).

T45380

314851-314971

Sentence

denotes

Isotonic solutions should be administered concurrently or immediately after administration of hypertonic NaCl solutions.

T91433

314972-315077

Sentence

denotes

Isotonic (1.3%) or hypertonic (5.0%) sodium bicarbonate solutions are used to correct metabolic acidosis.

T24157

315078-315284

Sentence

denotes

Prolonged administration of sodium-containing fluids may promote diuresis and renal water loss or accumulation of peripheral edema and should be used conservatively when a relative free water loss is noted.

T57146

315285-315439

Sentence

denotes

Administration of isotonic dextrose (5%) or 2.5% dextrose/0.45% NaCl solutions may be beneficial when free water loss (relative sodium excess) is evident.

T28660

315440-315621

Sentence

denotes

Many horses with acute colitis are concurrently hypoproteinemic because of gastrointestinal losses and are absorbing bacterial products that induce a systemic inflammatory response.

T36886

315622-315713

Sentence

denotes

Plasma oncotic pressures are abnormally low in the face of increased vascular permeability.

T2192

315714-315823

Sentence

denotes

Interstitial edema formation is a clinical problem in these patients, which contributes to organ dysfunction.

T30455

315824-316022

Sentence

denotes

Crystalloid fluids, although critical for replacing water and electrolyte losses resulting from diarrhea, may actually contribute to a decline in plasma oncotic pressure as a result of hemodilution.

T97036

316023-316144

Sentence

denotes

436, 439 Administration of colloid solutions is helpful for volume expansion and maintenance of plasma oncotic pressures.

T5682

316145-316218

Sentence

denotes

Discussion of colloid replacement is included in the section Endotoxemia.

T19724

316219-316330

Sentence

denotes

Control of colonic inflammation and secretion is a difficult and poorly studied aspect of equine acute colitis.

T42015

316331-316477

Sentence

denotes

The role of inflammation and mediators such as prostaglandins as a cause of fluid loss is well known during S. enterica and clostridial infection.

T77185

316478-316640

Sentence

denotes

103, 142, 198, 552, 571, 637, 638, 741 COX inhibitors (NSAIDs) have antisecretory effects on the inflamed intestinal tract, 91, 169 including in the equine colon.

T6023

316641-316755

Sentence

denotes

742, 743 NSAIDs are commonly administered to horses with colitis to reduce inflammationassociated fluid secretion.

T91464

316756-316900

Sentence

denotes

However, prostaglandins such as PGE 2 and PGI 2 also have cytoprotective effects on gastrointestinal mucosa and are critical for mucosal repair.

T50

316901-317061

Sentence

denotes

91, 701 NSAIDs used pharmacologically to inhibit colonic inflammation and secretion may be detrimental to mucosal integrity and healing if not used judiciously.

T41106

317062-317271

Sentence

denotes

NSAIDs exacerbate colonic inflammation in humans with inflammatory colitis, impede mucosal healing in several models of mucosal injury, and have well-documented detrimental effects on colonic mucosa in horses.

T83875

317272-317444

Sentence

denotes

91, 690, 698, 701 In addition to toxicity to the colonic mucosa, gastric ulceration is not unusual in horses with enterocolitis and may be related to treatment with NSAIDs.

T57177

317445-317714

Sentence

denotes

Although the use of COX-2-selective NSAIDs should, in theory, be less likely to harm or impede repair of the colonic mucosal in patients with colonic inflammation causing diarrhea, the safety and efficacy of these medications has not been evaluated in this application.

T79766

317715-317953

Sentence

denotes

The prothrombotic adverse effects of COX-2-selective drugs 744 suggest that very cautious use of highly COX-2-selective medications is warranted in patients with systemic inflammation at risk for thrombosis (e.g., endotoxemia and sepsis).

T98815

317954-318057

Sentence

denotes

In addition to NSAIDs, other drugs are occasionally used as antiinflammatory and antisecretory therapy.

T69683

318058-318131

Sentence

denotes

Bismuth subsalicylate is commonly used in adults and foals with diarrhea.

T78079

318132-318279

Sentence

denotes

The volume required for any effect in adults with colitis is quite high (1-4 L by nasogastric tube every 4-8 hours), which often precludes its use.

T31182

318280-318504

Sentence

denotes

Metronidazole has beneficial effects in experimental models of gastrointestinal inflammation, including NSAID toxicity, 706 and may be useful for treating horses with colitis; however, evidence supporting its use is lacking.

T84477

318505-318641

Sentence

denotes

Sucralfate (20 mg/kg by mouth every 6 hours) has been advocated to aid in healing of the colonic mucosa in patients with NSAID toxicity.

T10811

318642-318862

Sentence

denotes

There is evidence in experimental phenylbutazone toxicosis in foals suggesting that sucralfate administration lessens ulceration and other histopathologic lesions throughout the alimentary tract and lessens protein loss.

T2134

318863-318965

Sentence

denotes

745 There is no evidence supporting the use of sucralfate to treat colonic ulceration in adult horses.

T67629

318966-319176

Sentence

denotes

Misoprostol (5 μg/kg by mouth every 12 hours or 2 μg/kg by mouth every 6-8 hours) and other synthetic PGE analogs enhance mucosal healing in the intestine and promote recovery in experimental models of colitis.

T15289

319177-319285

Sentence

denotes

746 Misoprostol may be particularly useful for treating NSAID toxicity, either the generalized form or RDUC.

T96003

319286-319393

Sentence

denotes

However, the efficacy of misoprostol in hastening mucosal healing is clinically unproven in equine colitis.

T4644

319394-319579

Sentence

denotes

The primary drawbacks of prostaglandin analogs such as misoprostol are the adverse effects of the drug, including abdominal cramping, diarrhea, sweating, and abortion in pregnant mares.

T82058

319580-319707

Sentence

denotes

Psyllium mucilloid can be added to the diet (5 tablespoons every 12-24 hours) to increase the production of SCFAs in the colon.

T86422

319708-319876

Sentence

denotes

Amylase-resistant fermentable fiber such as psyllium is hydrolyzed by colonic bacteria to SCFAs such as butyrate, which represent a major energy source for colonocytes.

T77326

319877-320068

Sentence

denotes

Butyrate and other SCFAs hasten epithelial maturation and stimulate salt (and thus fluid) absorption in the colon, improve the clinical course of ulcerative colitis, and hasten colon healing.

T65647

320069-320249

Sentence

denotes

747 Psyllium is itself a source of butyrate in the colon and also promotes the movement of amylase-sensitive carbohydrates into the distal colon, which are then fermented to SCFAs.

T1283

320250-320335

Sentence

denotes

Psyllium is thought to be clinically useful for promoting mucosal healing in colitis.

T34102

320336-320405

Sentence

denotes

Many horses with colitis have mild to severe signs of abdominal pain.

T51628

320406-320622

Sentence

denotes

Analgesia can be accomplished with NSAIDs such as flunixin, but the potential for worsening mucosal injury or nephrotoxicity may prevent the use of analgesic doses, especially in horses with suspected NSAID toxicity.

T53238

320623-320697

Sentence

denotes

Relative COX-2-selective inhibitors may spare the gastrointestinal mucosa.

T45674

320698-320926

Sentence

denotes

For example, meloxicam and firocoxib have analgesic properties in horses in experimental models of ischemic colic and spare the intestinal mucosa from the detrimental effects associated with nonselective COX inhibitor treatment.

T77430

320927-321020

Sentence

denotes

695, 748 Xylazine, detomidine, or butorphanol (bolus dosing) may provide temporary analgesia.

T37415

321021-321243

Sentence

denotes

Constant rate infusions of butorphanol, lidocaine, and/or ketamine (alone or in combination) may provide more profound analgesia and can be useful if one is certain that an obstructive or infarctive process is not present.

T53660

321244-321299

Sentence

denotes

Pain management is discussed in Chapter 3 of this text.

T95129

321300-321410

Sentence

denotes

Broad-spectrum antibiotic treatment is often recommended in neutropenic horses or horses with signs of sepsis.

T34113

321411-321483

Sentence

denotes

Broadspectrum antibiotics lessen septic complications in human patients.

T79123

321484-321553

Sentence

denotes

Evidence supporting this principle in horses with colitis is lacking.

T50702

321554-321694

Sentence

denotes

Treatment with antibiotics is not thought to alter the course of the enterocolitis, but it may lessen dissemination and severity of disease.

T50505

321695-321798

Sentence

denotes

Treatment with antibiotics directly targeted at S. enterica is often reserved for patients with sepsis.

T17860

321799-321916

Sentence

denotes

Lipid-soluble antibiotics are ideally suited for S. enterica infections because the bacteria persist intracellularly.

T74512

321917-322027

Sentence

denotes

Enrofloxacin is often preferred, but antimicrobial sensitivity of the isolate should dictate directed therapy.

T11577

322028-322193

Sentence

denotes

In patients in which the likelihood of N. risticii infection is high, treatment with directed antimicrobial therapy is often indicated before a definitive diagnosis.

T37823

322194-322271

Sentence

denotes

Lipid-soluble drugs are preferred because the organism can live within cells.

T75095

322272-322492

Sentence

denotes

Oxytetracycline (6.6 mg/kg/day IV), often followed by doxycycline (10 mg/kg PO every 12 hours), appear to be the most effective antibiotics for treatment of Potomac horse fever and are considered the treatment of choice.

T88889

322493-322564

Sentence

denotes

Treatment is most successful if initiated before the onset of diarrhea.

T81380

322565-322683

Sentence

denotes

584, 749 If antibiotics are being administered at the onset of enterocolitis, they should be discontinued if possible.

T74561

322684-322810

Sentence

denotes

Specific treatment with metronidazole is effective for treating clostridiosis in humans and appears to be effective in horses.

T80836

322811-322970

Sentence

denotes

624, 750 Metronidazole resistance in clinical isolates of C. difficile has been reported in one outbreak but appears to be rare in most human and equine cases.

T80473

322971-323130

Sentence

denotes

751 Metronidazole-resistant isolates were sensitive to vancomycin, which may be effective for treating clinical cases if metronidazole resistance is suspected.

T6667

323131-323225

Sentence

denotes

Vancomycin use is not recommended in horses because of concerns for antimicrobial stewardship.

T10835

323226-323361

Sentence

denotes

C. perfringens type C antitoxin has been recommended for treatment of neonatal clostridiosis, but there is no evidence of its efficacy.

T516

323362-323450

Sentence

denotes

752 Antitoxin preparations are not advocated for use in adult horses with clostridiosis.

T15916

323451-323578

Sentence

denotes

Hypercoagulability is a common complication of enterocolitis, associated with systemic inflammation resulting from endotoxemia.

T24666

323579-323755

Sentence

denotes

Administration of heparin (20-80 IU/kg SC or IV every 6-12 hours) may prevent thrombosis in these patients, provided antithrombin III concentrations are adequate in the plasma.

T79915

323756-323883

Sentence

denotes

Concentrated sources of antithrombin III are not available for use in horses, but whole plasma may provide an important source.

T74584

323884-324023

Sentence

denotes

Treatment with heparin is thought to decrease thrombosis, especially of the jugular vein, which is a serious complication of salmonellosis.

T28311

324024-324192

Sentence

denotes

Low-dose aspirin treatment (10 mg/kg PO every 24-48 hours) in conjunction with heparin treatment may provide added benefit by irreversibly inhibiting platelet function.

T14693

324193-324267

Sentence

denotes

753 Heparin and aspirin may have protective effects on the digital lamina.

T10973

324268-324537

Sentence

denotes

753, 754 Heparin may enhance the phagocytic activity of the reticuloendothelial system by enhancing the efficiency of opsonins, such as fibronectin and immunoglobulin, stimulating phagocytosis of products of coagulation and possibly other particles, including bacteria.

T53667

324538-324705

Sentence

denotes

755, 756 Probiotics Maintenance of the bacterial flora in the gastrointestinal tract is an important defense mechanisms preventing colonization by pathogenic bacteria.

T16162

324706-324788

Sentence

denotes

Little work has been done to investigate the efficacy of these products in horses.

T26997

324789-324912

Sentence

denotes

Preparations of Saccharomyces boulardii were shown to decrease the duration and severity of disease in horses with colitis.

T48719

324913-325046

Sentence

denotes

757 In foals, probiotic use was associated with increased risk of diarrhea and, especially, diarrhea requiring clinical intervention.

T30823

325047-325183

Sentence

denotes

In humans, fecal transplantation (known to most veterinarians as transfaunation) has been proven effective for intestinal clostridiosis.

T59686

325184-325349

Sentence

denotes

As the intestinal microbiota are extremely diverse, 756 restoration of the overall flora is more likely to be effective than restoration of single bacterial species.

T6078

325350-325571

Sentence

denotes

Absorbent powders are often used to reduce the bioactivity and absorption of bacterial toxins produced by bacterial or toxic metabolites produced by bacteria and other microorganisms (e.g., lactic acid in grain overload).

T56050

325572-325755

Sentence

denotes

In a rat model of cantharidin toxicosis, mineral oil, which is often used in equine cantharidin toxicosis, increased cantharidin absorption and also increased morbidity and mortality.

T22509

325756-325840

Sentence

denotes

758 In that study, rats treated with charcoal or DTO smectite had improved survival.

T58711

325841-326075

Sentence

denotes

DTO smectite powder (Bio-Sponge, Platinum Performance, Buellton, California) binds C. difficile and C. perfringens exotoxins in vitro 343, 759 and may be useful for treating intestinal clostridiosis, or unspecified colitis, in horses.

T12015

326076-326211

Sentence

denotes

DTO smectite is available as a powder or paste and should be administered according to the manufacturer's instructions for 3 to 5 days.

T1409

326212-326303

Sentence

denotes

Good nursing care and adequate nutrition are vital to the treatment of horses with colitis.

T54558

326304-326480

Sentence

denotes

Normal intake of roughage to provide energy may be inadequate; however, feeding of grains should be avoided to prevent delivery of highly fermentable carbohydrate to the colon.

T35799

326481-326664

Sentence

denotes

Dietary management usually consists of restricting or eliminating long-stem roughage (hay) from the diet and feeding exclusively a complete pelleted diet (at least 30% dietary fiber).

T66147

326665-326768

Sentence

denotes

The rationale behind this recommendation is to reduce the mechanical and physiologic load on the colon.

T75322

326769-326818

Sentence

denotes

Frequent meals (4-6 times a day) are recommended.

T44572

326819-326946

Sentence

denotes

Corn oil (1 cup every 12-24 hours) can be added to the pellets to increase the caloric intake without adding roughage or grain.

T6559

326947-327072

Sentence

denotes

It is important to note that if a horse with colitis refuses to eat pelleted feed, then high-quality grass hay should be fed.

T18960

327073-327242

Sentence

denotes

In anorectic or severely catabolic patients, enteral and parenteral nutrition (total and partial) has been used successfully to provide calories and nutritional support.

T46338

327243-327371

Sentence

denotes

Treatment of S. vulgaris infection requires treatment of the migrating parasite larvae and the lesions produced by the parasite.

T43768

327372-327542

Sentence

denotes

Fenbendazole (10 mg/kg PO every 24 hours for 3 days or 10 mg/kg PO every 24 hours for 5 days) and ivermectin (200 mg/kg, PO) are effective in killing fourth-stage larvae.

T69824

327543-327656

Sentence

denotes

647 Other anthelmintics may also be effective when given at higher doses than those required to kill adult worms.

T40350

327657-327736

Sentence

denotes

The efficacy of these anthelmintics against larvae within thrombi is not known.

T97637

327737-327834

Sentence

denotes

Thrombolytic and antithrombotic therapy has been advocated in horses with suspected strongylosis.

T55154

327835-327929

Sentence

denotes

647, 654 Heparin (20-80 IU IV or SC every 6-12 hours) may be administered as an anticoagulant.

T84764

327930-328059

Sentence

denotes

High-molecular-weight heparin causes anemia by inducing aggregation of red blood cells, which is an undesirable effect in sepsis.

T75760

328060-328145

Sentence

denotes

Low-molecular-weight heparins appear to be less likely to have this effect in horses.

T87752

328146-328251

Sentence

denotes

Aspirin (10-30 mg/kg PO every 12-48 hours) is usually combined with heparin to inhibit platelet adhesion.

T85407

328252-328377

Sentence

denotes

Aspirin may also inhibit release of platelet products, such as thromboxane, which affect the motility of the large intestine.

T6811

328378-328503

Sentence

denotes

Low-molecularweight dextrans have been advocated as antithrombotics that act by inhibiting platelet function and coagulation.

T30747

328504-328622

Sentence

denotes

654 The clinical efficacy of dextran administration appears to be good, but no controlled studies have been performed.

T75667

328623-328808

Sentence

denotes

Anthelmintic administration is usually the only treatment necessary for mild to moderate cases of cyathostomiasis treated early in the course of the disease (within 1-3 weeks of onset).

T61235

328809-328906

Sentence

denotes

Fenbendazole is effective against many larval stages, but resistance is high in some populations.

T84294

328907-329038

Sentence

denotes

Although the reported efficacy of ivermectin is variable against certain stages, 760 one study reported an overall efficacy of 75%.

T87372

329039-329207

Sentence

denotes

761 Currently, fenbendazole (7.5-10 mg/kg PO every 24 hours for 5 days) followed on day 6 by ivermectin (200 mg/kg PO) is the most commonly advocated treatment regimen.

T87683

329208-329385

Sentence

denotes

659, 762 Moxidectin (400 μg/kg PO every 24 hours) may also be effective against adult organisms and L 3 and L 4 larval stages 763 and may be useful for treating cyathostomiasis.

T70694

329386-329519

Sentence

denotes

Antiinflammatory therapy may be beneficial, especially in severe or refractory cases or before treatment with larvicidal medications.

T40587

329520-329734

Sentence

denotes

Pretreatment with dexamethasone or prednisolone is indicated before anthelmintic administration if heavy larval loads are suspected to prevent an acute exacerbation of the disease by rapid death of encysted larvae.

T32979

329735-329877

Sentence

denotes

Larvicidal treatment with moxidectin appears to be less likely than fenbendazole to result in tissue inflammation resulting from larval death.

T14604

329878-330046

Sentence

denotes

764 NSAID administration may have limited value, but dexamethasone appears to be efficacious in refractory cases when used in conjunction with larvicidal anthelmintics.

T82219

330047-330150

Sentence

denotes

659, 662 Bismuth subsalicylate is often administered orally as an antisecretory agent in young animals.

T86959

330151-330243

Sentence

denotes

Supportive care may be necessary in severe cases, particularly if hypoproteinemia is severe.

T94871

330244-330338

Sentence

denotes

Administration of IV crystalloid fluids and plasma or other colloids is occasionally required.

T6454

330339-330384

Sentence

denotes

Proper nutritional support is also important.

T73421

330385-330508

Sentence

denotes

Reduction of arsenic absorption by administration of cathartics such as activated charcoal should be initiated immediately.

T32628

330509-330684

Sentence

denotes

718 Chelation therapy with sodium thiosulfate (20-30 g in 300 mL of water, administered orally) and dimercaprol (British anti-Lewisite; 3 mg/kg PO every 4 hours) is indicated.

T64365

330685-330793

Sentence

denotes

718 Dimercaprol is a specific antidote for trivalent arsenicals, but its efficacy in horses is questionable.

T61432

330794-330981

Sentence

denotes

Treatment of intestinal anaphylaxis is in principle similar to treatment of other forms of colitis, but it is often unsuccessful because of the rapidly progressive nature of the syndrome.

T41810

330982-331143

Sentence

denotes

162, 722, 727 Early treatment with prednisolone sodium succinate (10-20 mg/kg IV) or dexamethasone (0.1-0.2 mg/ kg IV) may be essential for successful treatment.

T72607

331144-331147

Sentence

denotes

722

T48378

331149-331212

Sentence

denotes

The peritoneum consists of a single layer of mesothelial cells.

T80296

331213-331323

Sentence

denotes

The mesothelial lining of the diaphragm, abdominal walls, and pelvic cavity is termed the parietal peritoneum.

T29700

331324-331404

Sentence

denotes

The visceral peritoneum forms the serosal surfaces of the intraabdominal organs.

T17381

331405-331606

Sentence

denotes

Caudally, the peritoneum reflects over the surfaces of the pelvic organs (portions of the urogenital tract and rectum), excluding them from the peritoneal space, and defining the retroperitoneal space.

T70109

331607-331741

Sentence

denotes

The peritoneal space communicates with the lumen of the uterus (and thus the external environment) via the fallopian tubes in females.

T61081

331742-331789

Sentence

denotes

In males the peritoneum forms a true blind sac.

T88296

331790-331944

Sentence

denotes

The vascular supply and nervous innervation of the visceral peritoneum are supplied by the splanchnic vessels and visceral autonomic nerves, respectively.

T69393

331945-332100

Sentence

denotes

Branches of the intercostal, lumbar, and iliac arteries supply the parietal peritoneum, and the phrenic and intercostal nerves provide nervous innervation.

T8665

332101-332262

Sentence

denotes

Inflammation of the parietal peritoneum is perceived as somatic pain, resulting in a splinted abdominal wall, pain on external palpation, and reluctance to move.

T58831

332263-332424

Sentence

denotes

The peritoneal lining functions as a semipermeable barrier to the diffusion of water and low-molecular-weight solutes between the blood and the abdominal cavity.

T60767

332425-332574

Sentence

denotes

765 The peritoneum secretes a serous fluid that lubricates the abdominal cavity, inhibits adhesion formation, and has minor antibacterial properties.

T88567

332575-332690

Sentence

denotes

765, 766 Macrophages, mast cells, mesothelial cells, and lymphocytes provide immune function within the peritoneum.

T91992

332691-332836

Sentence

denotes

767 The peritoneal surface maintains a high level of fibrinolytic activity through the production of plasminogen activators by mesothelial cells.

T35936

332837-332990

Sentence

denotes

This function, together with the lubricant properties of the PF, helps to maintain gliding surfaces within the peritoneum and prevent adhesion formation.

T57021

332991-333101

Sentence

denotes

PF produced by the mesothelium tends to move ventrally and cranially, aided largely by diaphragmatic movement.

T48370

333102-333318

Sentence

denotes

PF, waste products, and foreign material exit the peritoneal cavity to enter the lymphatic system through diffusely distributed subendothelial pores or via the large diaphragmatic stomata, depending on particle size.

T51220

333319-333483

Sentence

denotes

Large molecules and particles greater than approximately 40,000 MW (such as bacteria) exit through the diaphragmatic stomata and ultimately enter the thoracic duct.

T16672

333484-333579

Sentence

denotes

The term peritonitis refers to inflammation of the mesothelial lining of the peritoneal cavity.

T11859

333580-333820

Sentence

denotes

Peritonitis can occur in association with any insult-mechanical, chemical, or infectious-that results in disruption or irritation of the peritoneal lining, inflammation or infection of abdominal organs, or compromise of the intestinal wall.

T35687

333821-333965

Sentence

denotes

765 Common mechanical injuries include blunt or perforating trauma to the abdominal wall, breeding and foaling accidents, and abdominal surgery.

T48982

333966-334160

Sentence

denotes

A variety of iatrogenic insults can cause peritonitis, such as abdominocentesis, enterocentesis, splenic puncture, bowel trocarization, liver biopsy, uterine biopsy, castration, and rectal tear.

T71626

334161-334279

Sentence

denotes

Chemical insults of endogenous origin include blood, urine, pancreatic enzymes, bile, gastric juice, chyme, and chyle.

T94534

334280-334381

Sentence

denotes

Talc, contrast agents, antibiotics, and lavage solutions are additional examples of chemical insults.

T50807

334382-334529

Sentence

denotes

Traumatic events often involve bacterial contamination at the time of injury, and mechanical and chemical injuries can become infected secondarily.

T48117

334530-334763

Sentence

denotes

The most common manifestation of peritonitis is acute, diffuse, septic peritonitis following inflammation, vascular insult, perforation, or surgical manipulation (enterotomy, resection, and anastomosis) of the gastrointestinal tract.

T80665

334764-334848

Sentence

denotes

The septic process in such cases involves mixed bacteria of gastrointestinal origin.

T77657

334849-334910

Sentence

denotes

Penetrating abdominal wounds also result in mixed infections.

T82082

334911-335081

Sentence

denotes

Less commonly, singular bacterial forms gain access to the peritoneum through hematogenous spread, extension from a contiguous organ, or through the female genital tract.

T90769

335082-335275

Sentence

denotes

Primary monomicrobial infections have been reported involving Streptococcus equi subsp. equi, 768 S. equi subsp. zooepidemicus, 769 Rhodococcus equi, 770 and Corynebacterium pseudotuberculosis.

T17230

335276-335539

Sentence

denotes

771 Several case series involving peritonitis associated with Actinobacillus equuli have been reported. [772] [773] [774] [775] Sepsis, septic omphalitis, ascending urinary tract infections, and uterine infections are additional causes of monomicrobial infection.

T28085

335540-335674

Sentence

denotes

Most cases of trauma or intestinal perforation result in contamination of the peritoneum with large numbers of many types of bacteria.

T98656

335675-335834

Sentence

denotes

The intestinal tract contains a mixed population of bacteria, and the quantity of bacteria and prevalence of anaerobic species increase in the distal segments.

T65960

335835-335922

Sentence

denotes

Not surprisingly, mortality associated with contamination from the lower bowel is high.

T29616

335923-336042

Sentence

denotes

Hirsch and Jang 776 reported isolation of an infective agent from exudative equine PF in approximately 25% of attempts.

T94592

336043-336179

Sentence

denotes

Obligate anaerobic bacteria were cultured most frequently, followed by members of the Enterobacteriaceae family (predominantly E. coli).

T74606

336180-336260

Sentence

denotes

Penicillin-resistant Bacteroides fragilis was isolated from 10% to 20% of cases.

T61195

336261-336423

Sentence

denotes

In another study in which bacteria were identified in equine abdominal fluid by cytologic examination or culture, E. coli was the organism most commonly isolated.

T40454

336424-336689

Sentence

denotes

777 In human beings and laboratory animals, despite the variety of organisms initially introduced by polymicrobial contamination, established infections are characterized by only a few types of bacteria, which are often gram-negative aerobes and anaerobic bacteria.

T6967

336690-336808

Sentence

denotes

This selectivity occurs through the processes of selective reduction of bacterial populations and bacterial synergism.

T62356

336809-336921

Sentence

denotes

An example of synergism in human beings and laboratory animals is peritonitis involving E. coli and B. fragilis.

T19700

336922-337061

Sentence

denotes

The presence of each organism is beneficial to the survival of the other, and each is important in the overall pathogenesis of the disease.

T52951

337062-337228

Sentence

denotes

E. coli is associated with septicemia and early mortality, whereas B. fragilis infection tends to result in chronic abscessation with delayed morbidity and mortality.

T59645

337229-337404

Sentence

denotes

766 Other causes of equine peritonitis include parasites, viral disorders (influenza, equine viral arteritis, equine infectious anemia, African horse sickness), and neoplasia.

T82259

337405-337526

Sentence

denotes

Verminous arteritis caused by strongylosis can lead to vascular damage (thromboembolism and infarction) to the intestine.

T47742

337527-337657

Sentence

denotes

The activities of strongyles, ascarids, and tapeworms can result in perforation of the bowel and damage to other abdominal organs.

T61633

337658-337807

Sentence

denotes

There has been one report of septic peritonitis caused by colonic perforation associated with aberrant migration of Gasterophilus intestinalis larva.

T41780

337808-338290

Sentence

denotes

778 Biologic events resulting from contamination of the abdomen or injury to the mesothelial cells include release of catecholamines, histamine, and serotonin from peritoneal mast cells; vasodilation and hyperemia; an increase in peritoneal vascular permeability; secretion of protein-rich fluid into the peritoneum; transformation of mesothelial cells into macrophages; and influx of PMN cells, humoral opsonins, natural antibodies, and serum complement into the peritoneal cavity.

T28130

338291-338477

Sentence

denotes

765 Other possible events include depression of the peritoneal fibrinolytic activity, fibrin deposits on the peritoneal surface, and inflammatory-mediated and sympathetic-mediated ileus.

T17585

338478-338641

Sentence

denotes

These processes serve to confine contamination and infection and, with clean, minimally invasive procedures such as enterocentesis or trocarization, are effective.

T86062

338642-338769

Sentence

denotes

However, with greater severity of peritoneal contamination or irritation, these processes are magnified and become deleterious.

T83377

338770-338969

Sentence

denotes

Consequences include hypovolemia, hypoproteinemia, gastrointestinal ileus, ischemia of the bowel wall with subsequent absorption of bacteria and toxins, and ultimately adhesion and abscess formation.

T6760

338970-339126

Sentence

denotes

Equine peritoneal macrophages release a multitude of inflammatory mediators when exposed to bacterial LPS, and endotoxemia contributes the clinical picture.

T27887

339127-339188

Sentence

denotes

A complete review of endotoxemia is presented in Endotoxemia.

T50443

339189-339408

Sentence

denotes

A complete pathologic description of peritonitis includes origin (primary or secondary), onset (peracute, acute, and chronic), distribution (localized versus diffuse), and presence of bacteria (septic versus nonseptic).

T17292

339409-339493

Sentence

denotes

Clinically, viewing the pathogenesis of peritonitis as a series of stages is useful.

T18663

339494-339666

Sentence

denotes

The contamination stage, lasting 3 to 6 hours, involves introduction of bacteria into the peritoneum and initiation of the acute inflammatory response previously described.

T30476

339667-339890

Sentence

denotes

If the organisms are not eliminated, the process evolves to the stage of acute diffuse peritonitis as, regardless of the location of the initial contamination, bacteria spread throughout the peritoneum within several hours.

T33562

339891-339949

Sentence

denotes

The stage of acute diffuse peritonitis lasts up to 5 days.

T78800

339950-340080

Sentence

denotes

The inflammatory response persists and escalates with continued exudation of proteinaceous fluid and influx of inflammatory cells.

T23361

340081-340182

Sentence

denotes

Offending organisms are delivered to the lymphatic system and may be eliminated by the immune system.

T7463

340183-340318

Sentence

denotes

Alternatively, organisms can gain access to the systemic circulation in sufficient numbers to result in clinically relevant bacteremia.

T57974

340319-340461

Sentence

denotes

This stage of the disease process has the highest mortality because of the effects of severe peritoneal inflammation, endotoxemia, and sepsis.

T84207

340462-340712

Sentence

denotes

If the animal survives this stage but fails to eliminate infection from the peritoneal cavity, the disease enters a transitional phase referred to as the acute adhesive (or localizing) stage, typically occurring 4 to 10 days after the initial insult.

T41802

340713-340833

Sentence

denotes

Neutrophils are still active, macrophages are increasing in numbers, and fibrin aggregates are being organized or lysed.

T79112

340834-340956

Sentence

denotes

If infection persists beyond this point, organization of fibrin proceeds and organisms become isolated from host defenses.

T31507

340957-341033

Sentence

denotes

At this point, the disease process enters the stage of chronic abscessation.

T8786

341034-341117

Sentence

denotes

This stage can begin as early as 8 days after inoculation and persist indefinitely.

T84396

341118-341258

Sentence

denotes

Clinical signs of peritonitis depend on the primary disease process, the duration of the problem, and the extent of peritoneal inflammation.

T43968

341259-341433

Sentence

denotes

Localized peritonitis may have few or no systemic manifestations, whereas severe localized or generalized peritonitis often is accompanied by severe toxemia, sepsis, or both.

T67141

341434-341557

Sentence

denotes

Septic peritonitis usually causes more severe clinical signs because of the systemic inflammatory response and endotoxemia.

TextSentencer_T336

341558-341674

Sentence

denotes

Most clinical signs are nonspecific and include fever, lethargy, inappetence, decreased borborygmi, and dehydration.

TextSentencer_T337

341675-341740

Sentence

denotes

Additional signs include colic, ileus, weight loss, and diarrhea.

TextSentencer_T338

341741-341941

Sentence

denotes

768 Horses with peracute peritonitis, as occurs with rupture of the bowel or rectal tear, have clinical signs associated with severe endotoxemia, weakness, lethargy, colic, and/or circulatory failure.

TextSentencer_T339

341942-342000

Sentence

denotes

Fever may not be present depending on the degree of shock.

TextSentencer_T340

342001-342159

Sentence

denotes

Parietal pain, characterized by reluctance to move, splinting of the abdominal wall, and sensitivity to external abdominal pressure occur in some acute cases.

TextSentencer_T341

342160-342336

Sentence

denotes

With extensive abdominal fecal contamination, rectal examination may reveal a gritty feeling of the serosal and parietal surface of the peritoneum because of fibrin deposition.

TextSentencer_T342

342337-342571

Sentence

denotes

In horses with more chronic peritonitis, clinical signs include intermittent colic, lethargy, anorexia, weight loss, intermittent fever, ventral edema, exercise intolerance, decreased or absent intestinal sounds, and mild dehydration.

TextSentencer_T343

342572-342614

Sentence

denotes

Heart and respiratory rates may be normal.

TextSentencer_T344

342615-342716

Sentence

denotes

Fecal output may be normal; however, horses with chronic diarrhea and weight loss have been reported.

TextSentencer_T345

342717-342896

Sentence

denotes

Rectal examination findings can include pain on palpation of fibrinous or fibrous adhesions, intestinal distention, an abdominal mass, or an impression of bowel floating in fluid.

TextSentencer_T346

342897-342973

Sentence

denotes

In many cases, rectal examination does not reveal significant abnormalities.

TextSentencer_T347

342974-343146

Sentence

denotes

768 In cases of A. equuli peritonitis, clinical signs in most horses included lethargy, inappetence, and mild to moderate abdominal pain if acute or weight loss if chronic.

TextSentencer_T348

343147-343301

Sentence

denotes

773, 774 Postpartum mares with peritonitis secondary to a uterine perforation typically present with fever and depression, with or without abdominal pain.

TextSentencer_T349

343302-343431

Sentence

denotes

Septic tenosynovitis of the tarsal sheath secondary to bacterial peritonitis from gastrointestinal perforation has been reported.

TextSentencer_T350

343432-343552

Sentence

denotes

779 Foals with peritonitis usually exhibit signs of colic (acute or chronic) and are febrile, depressed, and inappetent.

TextSentencer_T351

343553-343706

Sentence

denotes

In young foals, peritonitis can cause rapid metabolic deterioration, and determination and correction of the primary problem require immediate attention.

TextSentencer_T352

343707-343819

Sentence

denotes

In older foals, peritonitis may occur insidiously in association with S. equi subsp. equi or R. equi infections.

TextSentencer_T353

343820-343901

Sentence

denotes

Clinicopathologic abnormalities vary depending on the time of onset and severity.

TextSentencer_T354

343902-343998

Sentence

denotes

In the acute stage, leukopenia, hemoconcentration, metabolic acidosis, and azotemia predominate.

TextSentencer_T355

343999-344073

Sentence

denotes

After several days, leukocytosis and hyperfibrinogenemia are more typical.

TextSentencer_T356

344074-344153

Sentence

denotes

In chronic peritonitis, hyperproteinemia with hyperglobulinemia may be present.

TextSentencer_T357

344154-344176

Sentence

denotes

SAA is also increased.

TextSentencer_T358

344177-344291

Sentence

denotes

254 Neonates with uroperitoneum tend to develop azotemia, hyponatremia, hypochloremia, hyperkalemia, and acidemia.

TextSentencer_T359

344292-344349

Sentence

denotes

PF analysis is principal to the diagnosis of peritonitis.

TextSentencer_T360

344350-344441

Sentence

denotes

Detailed description of PF analysis is provided in the Examination section of this chapter.

TextSentencer_T361

344442-344650

Sentence

denotes

PF WBC counts in acute peritonitis are reportedly higher than those in chronic peritonitis, 768 but this is not always the case, and the WBC count does not always correlate with disease severity or prognosis.

TextSentencer_T362

344651-344760

Sentence

denotes

The PF WBC count can be greater than 100,000/μL following enterocentesis, with no clinical signs or problems.

TextSentencer_T363

344761-344886

Sentence

denotes

780 Conversely, peritoneal WBC counts of fewer than 100,000/μL may be found in foals or horses with intraabdominal abscesses.

TextSentencer_T364

344887-345023

Sentence

denotes

781 The peritoneal WBC count can increase to greater than 150,000/μL following celiotomy 782 and can be higher if an enterotomy is done.

TextSentencer_T365

345024-345127

Sentence

denotes

Postoperatively, the WBC count normally continues to decline and returns to near normal by 5 to 7 days.

TextSentencer_T366

345128-345230

Sentence

denotes

Failure of the WBC count to decrease suggests peritonitis resulting from a postoperative complication.

TextSentencer_T367

345231-345333

Sentence

denotes

Finally, PF WBC counts greater than 500,000/μL indicate severe focal or generalized peritoneal sepsis.

TextSentencer_T368

345334-345461

Sentence

denotes

With acute peritonitis, PMN cells typically increase to a greater degree than mononuclear cells, but this depends on the cause.

TextSentencer_T369

345462-345632

Sentence

denotes

In horses with gastrointestinal disease and endotoxemia, the number of peritoneal mononuclear cells increases, as does transformation of mesothelial cells to macrophages.

TextSentencer_T370

345633-345762

Sentence

denotes

In chronic cases, one easily may mistake transforming mesothelial cells for neoplastic cells, which can make diagnosis difficult.

T29902

345763-345886

Sentence

denotes

The presence of free and phagocytosed bacteria in PF indicates generalized suppuration, abscessation, or compromised bowel.

T38782

345887-346039

Sentence

denotes

If one observes numerous microorganisms of mixed types free in the PF, especially in conjunction with plant material, bowel rupture likely has occurred.

T58325

346040-346182

Sentence

denotes

The presence of toxic or degenerate neutrophils and bacteria within PMN cells helps to distinguish PF from intestinal contents in such horses.

T56393

346183-346315

Sentence

denotes

Fluid obtained from enterocentesis is largely devoid of WBCs but is discolored and contains mixed microorganisms and plant material.

T98366

346316-346521

Sentence

denotes

Bacterial contamination of a sample can occur during collection of the sample, and iatrogenic contamination of a sample can result in free and intracellular bacteria, particularly if processing is delayed.

T10318

346522-346601

Sentence

denotes

In such cases the bacterial numbers are few and the neutrophils appear healthy.

T44848

346602-346781

Sentence

denotes

In some cases of gastrointestinal perforation the luminal material, inflammatory cells, and protein may be sequestered by the omentum and further contained by fibrinous adhesions.

T67995

346782-346948

Sentence

denotes

Abdominal fluid obtained via standard ventral paracentesis may have low cellularity and protein content but large numbers of mixed bacteria, indicating bowel rupture.

T44894

346949-347123

Sentence

denotes

768 Examples include gastric rupture along the greater curvature of the stomach between the omental layers (omental bursa) and perforated gastric or duodenal ulcers in foals.

T68552

347124-347274

Sentence

denotes

Correlating all cytologic findings with clinical and clinicopathologic findings is important for interpreting the results of PF cytologic examination.

T96466

347275-347413

Sentence

denotes

Biochemical analysis of PF may be useful in detecting sepsis when cytologic examination and culture are negative or otherwise unavailable.

T38264

347414-347569

Sentence

denotes

PF pH and glucose concentrations from horses with septic peritonitis were significantly lower than in horses with nonseptic peritonitis and healthy horses.

T86631

347570-347731

Sentence

denotes

783 PF pH less than 7.3, glucose less than 30 mg/dL, and fibrinogen concentration greater than 200 mg/dL were considered highly predictive of septic peritonitis.

T71368

347732-347899

Sentence

denotes

Serum to peritoneal glucose concentration differences of greater than 50 mg/dL were considered the most diagnostically useful test for septic peritonitis in the study.

T62044

347900-348066

Sentence

denotes

PF lactate concentration is also increased because of septic peritonitis, and a blood-to-peritoneal lactate concentration difference may have diagnostic significance.

T63606

348067-348226

Sentence

denotes

In a small study in dogs, a blood-to-fluid lactate difference of ≤2.0 mmol/L was shown to be 100% sensitive and specific for a diagnosis of septic peritonitis.

T35040

348227-348445

Sentence

denotes

784 PF samples should be submitted for aerobic and anaerobic cultures in appropriate media (i.e., BBL Port-A-Cul tubes, Becton, Dickinson & Co., Franklin Lakes, NJ, in an attempt to identify the pathogenic organism(s).

T58449

348446-348589

Sentence

denotes

To enhance recovery of bacteria, PF may be inoculated into blood culture medium (i.e., Septi-Chek Columbia, Hoffmann-LaRoche Inc., Nutley, NJ).

T58026

348590-348795

Sentence

denotes

If the horse has received prior antimicrobial treatment, the fluid sample should be passed through an antimicrobial removal device before culture (i.e., A.R.D., Becton Dickinson & Co., Franklin Lakes, NJ).

T95852

348796-348863

Sentence

denotes

Early and aggressive therapy is important for a successful outcome.

T59344

348864-348975

Sentence

denotes

Treatment goals are to resolve the primary problem, minimize inflammation, and prevent long-term complications.

T45985

348976-349061

Sentence

denotes

In the acute phase, analgesia and therapy as described for endotoxemia are important.

T45905

349062-349199

Sentence

denotes

Flunixin meglumine is advocated for its local and systemic antiinflammatory effects and may be effective in retarding adhesion formation.

T61544

349200-349318

Sentence

denotes

785 Initial antimicrobial selection should be broad spectrum based on the presumption that mixed infection is present.

T15126

349319-349503

Sentence

denotes

IV administration is preferred over oral or intramuscular routes in acute, diffuse, septic peritonitis because more reliable concentrations of drugs are achieved in the tissues and PF.

T4271

349504-349731

Sentence

denotes

786 The combination of a β-lactam antibiotic with an aminoglycoside, such as potassium penicillin (22,000-44,000 IU/kg IV every 6 hours) combined with gentamicin (6.6 mg/kg every 24 hours), is appropriate in most circumstances.

T90615

349732-349893

Sentence

denotes

Metronidazole (25 mg/ kg orally every 12 hours) can be added to the regimen given the strong possibility of infection involving penicillin-resistant B. fragilis.

T77610

349894-349991

Sentence

denotes

This regimen can be modified when culture and antimicrobial sensitivity results become available.

T67684

349992-350122

Sentence

denotes

Peritonitis caused by A. equuli generally responds well to therapy with penicillin either alone or in combination with gentamicin.

T29865

350123-350278

Sentence

denotes

Aminoglycosides and NSAIDs have the potential to induce acute renal tubular damage, particularly with concurrent dehydration and decreased renal perfusion.

T16993

350279-350386

Sentence

denotes

Therefore adequate restoration and maintenance of hydration and monitoring of renal function are important.

T37697

350387-350501

Sentence

denotes

Monitoring of the WBC count, plasma fibrinogen, SAA, and abdominal fluid analysis often guide duration of therapy.

T28389

350502-350703

Sentence

denotes

Horses with abdominal abscessation resulting from monomicrobial infections typically require weeks to months of therapy, whereas polymicrobial infection may require many months of antibiotic treatment.

T31626

350704-350814

Sentence

denotes

Further details regarding principles of antimicrobial therapy are provided elsewhere in this text (Chapter 2).

T34220

350815-350954

Sentence

denotes

Abdominal drainage and lavage can help remove excess fluid, foreign materials, fibrin, and bacterial products from horses with peritonitis.

T45040

350955-351046

Sentence

denotes

Postoperative lavage decreases the incidence of experimentally induced abdominal adhesions.

T71270

351047-351307

Sentence

denotes

787 Open surgical exploration provides the most effective and thorough examination of all peritoneal surfaces and is recommended if gastrointestinal perforation or ischemia is suspected or in any other case in which correction of a primary lesion is indicated.

T93443

351308-351438

Sentence

denotes

A ventral abdominal drain can either be placed at the time of surgery or in the standing horse with sedation and local anesthesia.

T69412

351439-351490

Sentence

denotes

Techniques have been described in detail elsewhere.

T35677

351491-351731

Sentence

denotes

788, 789 Peritoneal lavage is typically performed with 10 to 20 L of a balanced isotonic electrolyte solution twice a day for 3 to 5 days, until the lavage solution becomes clear or until the catheter becomes clogged with fibrin or omentum.

T38470

351732-351831

Sentence

denotes

Hypertonic solutions should be avoided because they can result in fluid shifts into the peritoneum.

T96350

351832-351976

Sentence

denotes

The addition of povidone iodine to a balanced solution should be avoided because concentrations as low as 3% can induce peritoneal inflammation.

T83337

351977-352153

Sentence

denotes

790 Other agents such as antibiotics or heparin have also been suggested as components of the lavage solution, but data demonstrating their benefit are not currently available.

T70493

352154-352291

Sentence

denotes

Active (or closed suction) abdominal drains have also been advocated, with similar benefits and potential complications to other methods.

T36284

352292-352409

Sentence

denotes

789 Lavage with a plain isotonic solution did not alter the pharmacokinetics of gentamicin administered systemically.

T48614

352410-352546

Sentence

denotes

791 Thus alteration of antimicrobial dosing does not appear necessary if lavage with plain solutions is part of the therapeutic regimen.

T96322

352547-352760

Sentence

denotes

Complications associated with the use of abdominal drains or repeated peritoneal drainage include retrograde infection, local irritation, pneumoperitoneum, and SC seepage around the drain and resultant cellulitis.

T77375

352761-352961

Sentence

denotes

If the patient is hypovolemic or hypoproteinemic, volume replacement and administration of plasma or synthetic colloids should be considered before removing large quantities of fluid from the abdomen.

T57574

352962-353108

Sentence

denotes

In horses with suspected parasitic involvement, one should give larvicidal doses of an anthelmintic once the condition of the horse is stabilized.

T4881

353109-353199

Sentence

denotes

Ivermectin, fenbendazole, and thiabendazole have been recommended as larvicidal therapies.

T15243

353200-353347

Sentence

denotes

The decision to perform surgical versus medical treatment is controversial in horses with peritonitis and needs to be made on a case-by-case basis.

T48575

353348-353609

Sentence

denotes

Although surgical exploration may allow diagnosis and resolution of the inciting cause and more thorough lavage of the abdomen, the risks of anesthesia, possible additional cost of surgery, and potential for a prolonged return to performance may be significant.

T73365

353610-353943

Sentence

denotes

In a recent study of horses and foals with peritonitis, survival to discharge without surgery was associated with lack of signs of abdominal pain, normal or improved rectal temperature, normal or improved borborygmi, normal fecal production, no abnormal findings on palpation per rectum, no nasogastric reflux, and yellow/ orange PF.

T29355

353944-354235

Sentence

denotes

792 A retrospective comparison of medical and surgical treatment of postpartum mares with peritonitis secondary to a uterine tear found no significant difference between admission variables, survival rate, hospital bill, duration of hospital stay, and likelihood to foal following discharge.

T78805

354236-354441

Sentence

denotes

793 A limitation of this study is the ability to definitively diagnose a uterine tear in those mares treated medically; if a tear was not palpable, the diagnosis was based on the exclusion of other causes.

T34182

354442-354522

Sentence

denotes

The prognosis is grave for peritonitis associated with gastrointestinal rupture.

T88724

354523-354606

Sentence

denotes

Reported survival rates for horses with peritonitis vary but can be as high as 78%.

T64656

354607-354762

Sentence

denotes

792, 794 In one study with a 78% overall survival rate, 68% of horses treated medically survived 792 ; in another, 93% of those treated medically survived.

T79297

354763-354935

Sentence

denotes

795 Some of the variability in reported survival percentages can be related to inclusion criteria, mainly whether or not horses with gastrointestinal rupture were included.

T26251

354936-355117

Sentence

denotes

Septic peritonitis following abdominal surgery was associated with high mortality (56%) in some reports, 777 although no difference in short-term survival was seen in another study.

T59075

355118-355270

Sentence

denotes

796 Peritonitis associated with A. equuli carries a very favorable prognosis, and all horses in these reports responded to medical therapy if attempted.

T41692

355271-355324

Sentence

denotes

773, 774 Pathophysiology of Mucosal Injury and Repair

T6606

355325-355516

Sentence

denotes

To gain an appreciation of the mechanisms in which the mucosa is injured and subsequently repaired, it is important to understand how the integrity of the mucosa is physiologically regulated.

T74732

355517-355724

Sentence

denotes

Regulation of mucosal integrity is referred to as mucosal barrier function, which is vital because it prevents bacteria and associated toxins from gaining access to subepithelial tissues and the circulation.

T42583

355725-355898

Sentence

denotes

However, the mucosa has two conflicting functions: it must serve as a protective barrier while continuing to absorb solutes necessary to maintain the well-being of the host.

T70075

355899-356092

Sentence

denotes

This conflict is most notable at the intercellular (paracellular) space, which allows passage of select solutes and water 797-800 but does not admit large molecules, including bacterial toxins.

T22026

356093-356269

Sentence

denotes

801 The paracellular space is almost exclusively regulated by the tight junction, 574 which is the interepithelial junction at the apical-most aspect of the paracellular space.

T29691

356270-356559

Sentence

denotes

Although these tight junctions were originally viewed as inert cellular adhesion sites, it has become clear in recent years that tight junction permeability is dependent on tissue-specific molecular structure and regulated by a complex array of intracellular proteins and the cytoskeleton.

T14112

356560-356660

Sentence

denotes

Tight junctions consist of a group of transmembrane proteins that interdigitate from adjacent cells.

T94891

356661-356853

Sentence

denotes

Although occludin was originally thought to be the predominant tight junction transmembrane protein, a group of proteins termed claudins appear to fine-tune the function of the tight junction.

T11769

356854-357015

Sentence

denotes

For example, select claudins are responsible for the relative porosity of the barrier to select electrolytes based on their charge within the paracellular space.

T29304

357016-357188

Sentence

denotes

802 These transmembrane proteins interact with the cytoskeleton via a series of intracellular proteins, including zonula occludens (ZO)-1, ZO-2, ZO-3, cingulin, and others.

T51596

357189-357301

Sentence

denotes

803 In addition, local regulatory proteins such as the small GTPase Rho are critical to tight junction function.

T36945

357302-357510

Sentence

denotes

Generally, the relative contractile state of the actin cytoskeleton determines the degree to which tight junctions are open or closed, but the complexities of regulation of this process are poorly understood.

T73914

357511-357790

Sentence

denotes

804 , 805 The most sensitive measure of mucosal barrier function is transepithelial electrical resistance, which is measured by mounting mucosa in an in vitro system called an Ussing chamber, because this measurement is largely a reflection of the permeability of mucosa to ions.

T7095

357791-357903

Sentence

denotes

806, 807 There are two routes ions it may follow when traversing the epithelium: transcellular and paracellular.

T71598

357904-358222

Sentence

denotes

801 Because cell membranes have a resistance to the passive flow of ions 1.5 to 3 log units greater than that of the epithelium as a whole, measurements of transepithelial resistance largely reflect the resistance of the paracellular space, particularly the tight junctions that regulate the paracellular flow of ions.

T54581

358223-358449

Sentence

denotes

807 Because tight junctions differ in structure from different portions of the mucosa, 808 measurements of transepithelial resistance reflect the net resistance of the epithelium of variable permeability within a given tissue.

T3887

358450-358640

Sentence

denotes

For example, tight junctions in the intestinal glandular structures called crypts are leakier than those in the surface epithelium because of fewer and less organized tight junction strands.

T85595

358641-358803

Sentence

denotes

806, 809 Conversely, surface epithelium has a greater number of well-organized tight junction strands that result in epithelium with a relatively high resistance.

T93740

358804-358950

Sentence

denotes

806 This correlates well with the absorptive function of epithelium located on the mucosal surface and the secretory function of crypt epithelium.

T25244

358951-359026

Sentence

denotes

The structure of tight junctions also varies with the segment of intestine.

T59792

359027-359176

Sentence

denotes

For example, tight junctions have more strands in the ileum than the jejunum, which is reflected by a higher transepithelial resistance in the ileum.

T28004

359177-359277

Sentence

denotes

810 In addition, cells are more closely apposed at the level of the tight junction within the colon.

T75381

359278-359416

Sentence

denotes

This is in keeping with the largely absorptive role of the colon and is advantageous given the hostile microbial environment of the colon.

T55530

359417-359628

Sentence

denotes

There are four regions of the stomach based on the type of mucosal lining (in an orad to aborad order): nonglandular stratified squamous epithelium, cardiac epithelium, proper gastric mucosa, and pyloric mucosa.

T43258

359629-359776

Sentence

denotes

811 Stratified squamous epithelium has distinct differences in terms of barrier function compared with the remainder of the gastrointestinal tract.

T21054

359777-359953

Sentence

denotes

This epithelium has baseline transepithelial resistance measurements of approximately 2 to 3000 Ω•cm 2 , which is an order of magnitude higher than the adjacent cardiac mucosa.

T14695

359954-360028

Sentence

denotes

812, 813 Thus the stratified squamous mucosa is exceptionally impermeable.

T67169

360029-360104

Sentence

denotes

This is the only mechanism this mucosa has to defend itself against injury.

T24608

360105-360268

Sentence

denotes

The stratified squamous epithelium consists of four layers: the outer stratum corneum, stratum transitionale, stratum spinosum, and the basal stratum germinativum.

T61425

360269-360469

Sentence

denotes

However, not all layers contribute equally to barrier function, which is largely composed of interepithelial tight junctions in the stratum corneum and mucosubstances secreted by the stratum spinosum.

T49639

360470-360683

Sentence

denotes

812, 814 The relative impermeability of stratified squamous mucosa can be demonstrated by the effects of HCl on this type of epithelium in vitro, which has very little effect until it reaches a pH of 2.5 or below.

T25348

360684-360911

Sentence

denotes

813 Although the majority of the literature on equine ulceration pertains to the effects of HCl and inhibitors of HCl secretion, [815] [816] [817] [818] other factors may be critical to the development of gastric ulcer disease.

T68930

360912-361188

Sentence

denotes

The site of HCl secretion (proper gastric mucosa) is protected from so-called back diffusion of H + ions by a relatively high transepithelial electrical resistance (compared with cardiac mucosa), but there are also a number of other critical mechanisms to prevent acid injury.

T15317

361189-361338

Sentence

denotes

The gastric mucosa secretes both mucus and bicarbonate, which together form an HCO 3 − containing gel that titrates acid before it reaches the lumen.

T24790

361339-361512

Sentence

denotes

819 , 820 The mucous layer is principally formed by glycoproteins (mucins) secreted by goblet cells but also includes other gastric secretions and sloughed epithelial cells.

T21636

361513-361678

Sentence

denotes

Mucins consist of core peptides with a series of densely packed O-linked polysaccharide side chains that, once secreted, become hydrated and form a viscoelastic gel.

T34890

361679-361766

Sentence

denotes

The mucous layer, however, does not form an absolute barrier to back diffusion of acid.

T52424

361767-361921

Sentence

denotes

For acid that does back diffuse into the gastric mucosa, epithelial Na + /H + exchangers are capable of expelling H + once the cell reaches a critical pH.

T7192

361922-362103

Sentence

denotes

820 Recent studies have renewed interest in the protective mechanisms of mucus because of the discovery of a group of compounds secreted by goblet cells called the trefoil peptides.

T68292

362104-362277

Sentence

denotes

The name of these peptides is derived from a highly conserved cloverleaf structural motif, which confers substantial resistance to degradation by proteases including pepsin.

T19611

362278-362457

Sentence

denotes

There are three known members of this group, pS2, SP, and intestinal trefoil factor (ITF), the latter of which is solely secreted by goblet cells in the small and large intestine.

T24275

362458-362638

Sentence

denotes

Both pS2 and SP are secreted by goblet cells within the stomach and are believed to intercalate with mucous glycoproteins, possibly contributing to the barrier properties of mucus.

T31766

362639-362712

Sentence

denotes

821 These peptides also play a critical role in repair of injured mucosa.

T30950

362713-362969

Sentence

denotes

An additional mucosal function that serves to reduce the level of injury is adaptive cytoprotection, in which application of topical irritants to gastric mucosa results in subsequent protection of mucosa in response to repeated exposure to damaging agents.

T4311

362970-363184

Sentence

denotes

For example, pretreatment with 10% ethanol protected against mucosal damage in response to subsequent application of absolute ethanol, and this effect was abolished by treatment with the COX inhibitor indomethacin.

T55176

363185-363430

Sentence

denotes

822 The cytoprotective effects of prostaglandins have been demonstrated directly in studies in which preadministration of prostaglandins protected gastric mucosa from damage by agents such as concentrated hydrochloric acid and hypertonic saline.

T87493

363431-363596

Sentence

denotes

823 Prostaglandins appear to be cytoprotective in the stomach at doses less than those used to inhibit gastric acid secretion, ruling out a simple antacid mechanism.

T39675

363597-363724

Sentence

denotes

824 Although not fully characterized, cytoprotection has been attributed in part to prostaglandin-stimulated mucous production.

T86181

363725-363882

Sentence

denotes

825 An associated beneficial effect of prostaglandins is the increased production of bicarbonate, which is trapped within mucus on the surface of the mucosa.

T65627

363883-364013

Sentence

denotes

826, 827 Interestingly, PGE 2 appears to lose its cytoprotective activity in the presence of the mucolytic agent N-acetylcysteine.

T71979

364014-364275

Sentence

denotes

Attention has also been directed at enhanced mucosal blood flow as a potential mechanism for prostaglandin-mediated cytoprotection-for example, pretreatment with PGI 2 protected against ethanol-induced mucosal damage as a result of increased mucosal blood flow.

T12927

364276-364520

Sentence

denotes

828 In addition PGE 2 , which is also cytoprotective despite the fact that it does not increase blood flow, 829 prevents vascular stasis associated with irritant-induced vascular damage by inhibiting neutrophil adherence to damaged endothelium.

T23979

364521-364642

Sentence

denotes

830 Sensory nerves distributed throughout gastrointestinal mucosa have also been implicated in cytoprotective mechanisms.

T37364

364643-364856

Sentence

denotes

As an example of their importance in mucosal cytoprotection, pretreatment of newborn rats with capsaicin (which dose dependently destroys sensory nerves) renders the mature rats more susceptible to gastric injury.

T90967

364857-365015

Sentence

denotes

831 Alternatively, the use of a low dose of capsaicin, which stimulates rather than destroys sensory nerves, protects gastric mucosa against injurious agents.

T62087

365016-365183

Sentence

denotes

832, 833 Sensory nerves contain neuropeptides such as calcitonin-gene-related peptide (CGRP) and substance P, which may play a protective role via vascular mechanisms.

T96992

365184-365308

Sentence

denotes

For instance, CGRP stimulates increased gastric blood flow, which is theorized to reduce injury similarly to prostaglandins.

T23150

365309-365427

Sentence

denotes

Recent studies suggest that the roles of prostaglandins and CGRP in gastric cytoprotection are intimately intertwined.

T77971

365428-365589

Sentence

denotes

In particular, PGI 2 is believed to sensitize sensory nerves following treatment with a mild irritant, with resultant increases in CGRP release and mucosal flow.

T49641

365590-365686

Sentence

denotes

Similar studies have shown that antagonists of CGRP inhibit the cytoprotective action of PGE 2 .

T42833

365687-365782

Sentence

denotes

834 Another neural mediator, nitric oxide, has also been implicated in adaptive cytoprotection.

T29464

365783-365924

Sentence

denotes

Interestingly, nitric oxide has a number of actions that are similar to those of prostaglandins, including maintenance of mucosal blood flow.

T20032

365925-365928

Sentence

denotes

835

T67897

365929-366165

Sentence

denotes

Regulation of barrier function in the intestine is not as well characterized as that of the stomach, although mechanisms of barrier function, including secretion of mucus and regulation of mucosal blood flow, are presumed to be similar.

T21347

366166-366343

Sentence

denotes

The proximal duodenum also has to protect itself from acid damage as it receives gastric contents, and this involves secretion of mucus and bicarbonate similarly to the stomach.

T84177

366344-366490

Sentence

denotes

One other mechanism that helps both the stomach and the intestine to maintain mucosal barrier function is the speed with which the mucosa repairs.

T23710

366491-366590

Sentence

denotes

For a defect to develop in the mucosal barrier, injurious factors have to outpace mucosal recovery.

T10037

366591-366703

Sentence

denotes

Such recovery initially involves epithelial migration across denuded regions of basement membrane (restitution).

T48826

366704-366790

Sentence

denotes

821 This process is so rapid that epithelial defects may be resurfaced within minutes.

T78203

366791-366930

Sentence

denotes

For example, in bile salt-injured equine colon, denuded surface mucosa was completely covered by restituting epithelium within 180 minutes.

T25976

366931-367140

Sentence

denotes

207 In the small intestine, intestinal villi greatly amplify the surface area of the mucosal luminal surface, which in turn takes far longer to resurface with restituting epithelium once it has become denuded.

T68544

367141-367244

Sentence

denotes

836 Intestinal villi, however, are able to dramatically reduce the denuded surface area by contracting.

T61392

367245-367248

Sentence

denotes

837

T14624

367250-367435

Sentence

denotes

Although the stratified squamous epithelium is relatively impermeable to HCl, there are a number of factors that can dramatically enhance the damaging effects of HCl in this epithelium.

T62135

367436-367619

Sentence

denotes

In particular, bile salts and SCFAs are capable of breaking down the squamous epithelial barrier at an acid pH, exposing deep layers to HCl, with subsequent development of ulceration.

T24113

367620-367747

Sentence

denotes

813, 838 Relatively high concentrations of SCFA normally exist within the equine stomach as a result of microbial fermentation.

T70006

367748-367888

Sentence

denotes

812 These weak acids penetrate squamous mucosa and appear to damage Na + transport activity principally located in the stratum germinativum.

T82500

367889-367984

Sentence

denotes

Bile salts may also be present in the proximal stomach as a result of reflux from the duodenum.

T9192

367985-368172

Sentence

denotes

Although such reflux has a relatively high pH, it appears that bile salts adhere to stratified squamous epithelium, becoming lipid soluble and triggering damage once the pH falls below 4.

T27123

368173-368313

Sentence

denotes

839 Diet and management (e.g., periods of fasting) also play crucial roles in the development of conditions conducive to gastric ulceration.

T46477

368314-368460

Sentence

denotes

Typically, there is a pH gradation in horses from proximal to distal compartments of the stomach, with the lowest pH values in the distal stomach.

T86187

368461-368589

Sentence

denotes

840 During periods of fasting, this stratification is disrupted such that low pH values may be recorded in the proximal stomach.

T70351

368590-368713

Sentence

denotes

841 Fasting conditions also increase the concentration of duodenal contents within the proximal stomach, particularly bile.

T63989

368714-368805

Sentence

denotes

839 Proper gastric mucosa is exposed to injurious agents, including pepsin, bile, and acid.

T42859

368806-369091

Sentence

denotes

The latter is constantly secreted by parietal cells in the horse as an adaptation to nearcontinuous intake of roughage, 811 but it is tightly regulated by enterochromaffin (ECL)-like cells within the proper gastric mucosa and G and D cells, which are present within the pyloric mucosa.

T79970

369092-369261

Sentence

denotes

Acid secretion is amplified by ECL-released histamine, which interacts with H 2 receptors on parietal cells, and G cells, which release the prosecretory hormone gastrin.

T30296

369262-369437

Sentence

denotes

A combination of histamine and gastrin can have a synergistic effect on parietal cell gastric secretion, because these mediators have distinct receptors and second messengers.

T51608

369438-369560

Sentence

denotes

On the other hand, D cells are sensitive to an acidic environment and release somatostatin, which inhibits acid secretion.

T64832

369561-369780

Sentence

denotes

842 Nonetheless, gastric mucosa may be exposed to acid for prolonged periods of time, particularly in horses that are extensively meal fed and do not have the benefit of roughage, which tends to buffer stomach contents.

T92678

369781-369977

Sentence

denotes

839, 842 Aside from peptic ulceration, induced by combinations of acid and pepsin, research in the human field has revealed the tremendous importance of Helicobacter pylori in inducing ulceration.

T28705

369978-370145

Sentence

denotes

Infection with this organism has the effect of raising gastric pH because of disruption of gastric glands but also induces an inflammatory reaction that causes damage.

T37733

370146-370248

Sentence

denotes

843 However, there is very little evidence that this organism is involved in gastric ulcers in horses.

T51843

370249-370466

Sentence

denotes

In the absence of a known role for infectious agents in gastric ulceration in animals, ulceration likely develops from injurious factors similar to those found in the proximal stomach, including gastric acid and bile.

T86573

370467-370627

Sentence

denotes

Some factors that are important to the induction of squamous epithelial ulceration may not be important in the development of proper gastric mucosal ulceration.

T15775

370628-370800

Sentence

denotes

For example, feed deprivation and intensive training reproducibly induce squamous epithelial ulceration in horses but have little effect on proper gastric mucosa in horses.

T75069

370801-370923

Sentence

denotes

844 Gastric acid likely plays a key role, whereas other factors such as NSAIDs serve to reduce gastric defense mechanisms.

T8582

370924-371066

Sentence

denotes

In particular, inhibition of prostaglandin production would reduce mucous and bicarbonate secretion while reducing gastric mucosal blood flow.

T53191

371067-371299

Sentence

denotes

845 Some of the NSAIDs also have a topical irritant effect, although this appears to be of minor significance, because the route of administration (oral or parenteral) seems to have little influence on the development of ulceration.

T78822

371300-371569

Sentence

denotes

846 The source of prostaglandins responsible for gastric protection was originally assumed to be COX-1, because this COX isoform is constitutively expressed in gastric mucosa, whereas COX-2 is not expressed in the stomach unless it is induced by inflammatory mediators.

T50842

371570-371758

Sentence

denotes

However, mice in which the COX-1 gene has been knocked out fail to develop spontaneous gastric lesions, 847 possibly because of compensatory increases in prostaglandin production by COX-2.

T91649

371759-371889

Sentence

denotes

848 This concept agrees with recent data indicating that inhibition of both COX isoforms is required to induce gastric ulceration.

T98577

371890-372121

Sentence

denotes

849 From a clinical perspective, these data indicate that drugs selective for either COX-1 or COX-2 may be less ulcerogenic in the horse because they allow the uninhibited COX isoforms to continue to produce protective prostanoids.

T8096

372122-372355

Sentence

denotes

Because COX-2 elaborates prostaglandins induced by inflammatory stimuli, preferential or selective inhibitors of COX-2 may be particularly useful because of their ability to serve as antiinflammatory agents that are less ulcerogenic.

T71297

372356-372359

Sentence

denotes

392

T25115

372360-372476

Sentence

denotes

The most notable cause of intestinal mucosal injury in horses, particularly those suffering from colic, is ischemia.

T73705

372477-372582

Sentence

denotes

Initially, it seems intuitive that by reducing gastrointestinal blood supply, the mucosa becomes injured.

T70218

372583-372770

Sentence

denotes

The anatomy of the gastrointestinal tract, and the differing structure of the intestinal mucosa at various anatomic locations, has a significant influence on the extent of mucosal injury.

T48032

372771-373007

Sentence

denotes

Ischemic injury may be induced by several different mechanisms, including occlusion of arterial supply by a thrombus, strangulation of intestinal vasculature, and generalized reduction in blood flow associated with various shock states.

T56183

373008-373157

Sentence

denotes

A number of seemingly distinct mechanisms of intestinal injury, such as intestinal distention, also trigger mucosal injury via an ischemic mechanism.

T27711

373158-373325

Sentence

denotes

Reperfusion injury may also influence the extent of mucosal injury following an ischemic episode and has been proposed as a potential site of therapeutic intervention.

T92249

373326-373598

Sentence

denotes

850, 851 It is critical that the mechanisms of ischemia/reperfusion injury be understood to develop an understanding of the severity of various clinical conditions, and begin to formulate a therapeutic approach to diseases characterized by this devastating form of injury.

T51795

373599-373720

Sentence

denotes

The intestinal circulation is capable of closely regulating blood flow during periods of low systemic perfusion pressure.

T54860

373721-373971

Sentence

denotes

852, 853 In particular, local regulation of resistance vessels within the microvasculature is particularly prominent; metabolic end products of ATP result in continued dilatation of resistance vessels despite reductions in systemic arterial pressure.

T30342

373972-374219

Sentence

denotes

This results in continued perfusion of gastrointestinal tissues during the early stages of shock, while other organs such as skeletal muscle undergo massive shunting of blood as a result of marked increases in the resistance of resistance vessels.

T58041

374220-374452

Sentence

denotes

The reasons for these differences in regulation are not entirely clear but may relate to the relatively high level of energy required to fuel the intestinal mucosa and the serious systemic effects of breaches in the mucosal barrier.

T80374

374453-374631

Sentence

denotes

When blood flow falls below a critical level, regulatory systems are no longer effective and oxygen uptake by the gastrointestinal tissue decreases, culminating in tissue damage.

T62397

374632-374836

Sentence

denotes

852 The villous tip is the most susceptible region affected by hypoxia in the equine small intestine, largely because of the countercurrent exchange mechanism of blood flow in the small intestinal villus.

T8522

374837-375087

Sentence

denotes

852 This countercurrent exchange mechanism is attributable to the vascular architecture, which consists of a central arteriole that courses up the core villus, arborizes at the tip, and is drained by venules coursing down the periphery of the villus.

T24678

375088-375246

Sentence

denotes

854 As oxygenated blood flows into the central arteriole, oxygen tends to diffuse across to the adjacent venules, which are flowing in the opposite direction.

T89253

375247-375396

Sentence

denotes

This series of events takes place along the length of the villus, resulting in a villous tip that is relatively hypoxic even under normal conditions.

T61062

375397-375570

Sentence

denotes

Furthermore, when blood flow is reduced, as occurs in hypovolemic or septic shock, the countercurrent exchange of oxygen is enhanced, and the tip becomes absolutely hypoxic.

T94947

375571-375720

Sentence

denotes

852 This mechanism might explain why the small intestinal mucosa is more susceptible to ischemic injury, compared with the colon, which has no villi.

T3404

375721-375865

Sentence

denotes

The duration of ischemia required to produce severe morphologic damage to the equine colon is approximately 25% longer than the small intestine.

T99697

375866-375869

Sentence

denotes

855

T7298

375870-376077

Sentence

denotes

Intestinal mucosal epithelium is very susceptible to hypoxia because of the relatively high level of energy required to fuel the Na + /K + -ATPase that directly or indirectly regulates ion and nutrient flux.

T30095

376078-376169

Sentence

denotes

The first biochemical event to occur during hypoxia is a loss of oxidative phosphorylation.

T51117

376170-376337

Sentence

denotes

The resulting diminished ATP concentration causes failure of the energydependent Na + /K + -ATPase and the accumulation of sodium and subsequently intracellular water.

T85229

376338-376443

Sentence

denotes

The pH of the cytosol drops as lactic acid and inorganic phosphates accumulate from anaerobic glycolysis.

T49203

376444-376629

Sentence

denotes

The falling pH damages cell membranes, including lysosomal membranes, resulting in the release and activation of lysosomal enzymes into the cytosol, further damaging cellular membranes.

T81152

376630-376786

Sentence

denotes

Damage to the cell membrane allows the accumulation of high concentrations of calcium in the cytosol, which activates calcium-dependent degradative enzymes.

T50792

376787-376932

Sentence

denotes

856 These events result in cytoplasmic blebbing of the basal membrane, with subsequent detachment of cells from the underlying basement membrane.

T46501

376933-377199

Sentence

denotes

Recent studies on epithelial injury during ischemia suggest that the majority of epithelial cells undergo programmed cell death (apoptosis) during ischemia and reperfusion rather than necrosis, allowing retention of reusable components of irreversibly injured cells.

T75655

377200-377310

Sentence

denotes

857 In one study, 80% of detached epithelium during small intestinal ischemia/reperfusion underwent apoptosis.

T98643

377311-377607

Sentence

denotes

858 Although the most obvious result of apoptosis is loss of surface epithelium, a number of cells on the lower portion of the villus (in the small intestine) and cells within the crypts may also undergo apoptosis that only becomes evident up to 24 hours following reperfusion of ischemic tissue.

T77633

377608-377808

Sentence

denotes

859 Morphologic changes observed in ischemic-injured small intestinal mucosa follow a similar sequence regardless of whether injury is induced by ischemia alone or ischemia/ reperfusion (Table 12.6 ).

T71107

377809-377952

Sentence

denotes

860 Initially, epithelium separates from the underlying basement membrane, forming a fluid-filled space termed Grüenhagen's space (Fig. 12.7 ).

T11939

377953-378163

Sentence

denotes

The mechanism of fluid accumulation in this space is not entirely understood but may result from continued epithelial absorption of NaCl and water before it has fully detached from neighboring epithelial cells.

T25153

378164-378256

Sentence

denotes

This fluid accumulation likely exacerbates epithelial separation from the basement membrane.

T53653

378257-378423

Sentence

denotes

Subsequently, epithelium progressively sloughs from the tip of the villus toward the crypts, which are the last components of the intestinal mucosa to become injured.

T9794

378424-378622

Sentence

denotes

163, 406, 861 This likely relates to the vascular architecture, because crypts receive a blood supply that is separate from the vasculature involved in the villous countercurrent exchange mechanism.

T92149

378623-378818

Sentence

denotes

The early morphologic changes observed in the equine large colon during ischemia are somewhat different from those described in the equine small intestine because of the lack of intestinal villi.

T48377

378819-378922

Sentence

denotes

As might be expected, the more superficially located surface cells are sloughed before those in crypts.

T73001

378923-379084

Sentence

denotes

855, 862 The orderly progression of tissue injury has been used by one group of investigators to accurately predict survival in horses with large colon volvulus.

T75500

379085-379325

Sentence

denotes

Biopsies were taken from the pelvic flexure, which has been previously shown to accurately reflect mucosal changes along the length of the colon, 863 and histologically examined for the width of the crypts and intercrypt interstitial space.

T51385

379326-379409

Sentence

denotes

The latter measurements were expressed as an interstitium: crypt width (I:C) ratio.

T52434

379410-379495

Sentence

denotes

Nonviable colon was defined as that which had >60% loss of crypt and an I:C ratio >3.

T74572

379496-379570

Sentence

denotes

Using this methodology, survival was correctly predicted in 94% of horses.

T95915

379571-379574

Sentence

denotes

864

T83672

379575-379805

Sentence

denotes

Since the dramatic decline in S. vulgaris-induced colic, which was frequently associated with infarction of intestinal arterial blood supply, 865 the vast majority of ischemic lesions are associated with strangulating obstruction.

T14411

379806-379931

Sentence

denotes

Therefore it is important to consider mechanisms of ischemic injury in horses with naturally occurring strangulating lesions.

T10613

379932-380113

Sentence

denotes

The majority of experimental work has either assessed complete ischemia (complete occlusion of the arterial blood supply) 855 or lowflow ischemia (reduction of arterial blood flow).

T36956

380114-380345

Sentence

denotes

866, 867 During intestinal strangulation, however, a disparity between the degree of occlusion of the veins and arteries occurs in which veins are occluded before arteries because of differences in the compliance of vascular walls.

T98235

380346-380531

Sentence

denotes

Strangulating lesions are typically hemorrhagic (hemorrhagic strangulating obstruction), because the arteries continue to supply blood to tissues that have little or no venous drainage.

T76824

380532-380638

Sentence

denotes

This results in ischemic injury, as previously outlined, but also in tremendous congestion of the tissues.

T50366

380639-380863

Sentence

denotes

Such hemorrhagic congestion has two opposing effects: it disrupts tissue architecture, including the mucosa and its epithelium, but it continues to provide oxygenated blood to the tissues during much of the ischemic episode.

T85056

380864-381088

Sentence

denotes

In contrast, when strangulation results in sudden cessation of arterial blood flow (ischemic strangulating obstruction), tissues appear pale, and the mucosa rapidly degenerates because of a complete lack of oxygenated blood.

T7043

381089-381358

Sentence

denotes

163 From a clinical standpoint, this makes it difficult to assess the degree of mucosal injury in horses with strangulating injuries, because intestine that may look nonviable (dark red) may in fact have less mucosal injury than that of ischemic strangulated intestine.

T78613

381359-381500

Sentence

denotes

868 An additional consideration in clinical strangulating obstruction is the degree of ischemia that may be induced by intestinal distention.

T37688

381501-381781

Sentence

denotes

For example, experimental distention (18 cm of H 2 O for 2 hours) and decompression (2 hours) of the jejunum resulted in a significant increase in microvascular permeability and a significant decrease in tissue oxygenation similar to what would be expected with low-flow ischemia.

T51804

381782-381913

Sentence

denotes

869, 870 In particular, microscopic evaluation of vasculature revealed capillary endothelial cell damage and local edema formation.

T1691

381914-382057

Sentence

denotes

871 These data suggest that distended intestine proximal to an obstruction may undergo mucosal injury despite its relatively normal appearance.

T32098

382058-382212

Sentence

denotes

Indeed, in one study, intraluminal pressures greater than 15 cm H 2 O in naturally occurring cases of colic correlated with a poor prognosis for survival.

T85592

382213-382216

Sentence

denotes

872

T60704

382217-382500

Sentence

denotes

Although it has recently been taken for granted that reperfusion of ischemic tissues results in exacerbation of mucosal injury, it should be remembered that mechanisms underlying intestinal reperfusion injury have been largely defined in laboratory animals under specific conditions.

T67681

382501-382622

Sentence

denotes

104, 410, [873] [874] [875] On the other hand, studies on reperfusion injury in horses have had some conflicting results.

T5733

382623-382712

Sentence

denotes

861, 867, 876 This may be attributed to the way in which the studies have been performed.

T14329

382713-383017

Sentence

denotes

In particular, the type of ischemia used in most laboratory animal studies has been "low-flow ischemia" (in which the blood flow is typically reduced to 20% of baseline flow), whereas studies in horses have used a number of different ischemic models, including various types of strangulating obstruction.

T27371

383018-383159

Sentence

denotes

Although strangulating obstruction is of great clinical relevance, this type of ischemic insult is less likely to develop reperfusion injury.

T34522

383160-383401

Sentence

denotes

861, 877, 878 Conversely, low-flow ischemia appears to prime tissues for subsequent injury once the tissue is reperfused, and there is considerable evidence to support the presence of reperfusion injury in horses following low-flow ischemia.

T14749

383402-383488

Sentence

denotes

866, 867, 871, 879 Nonetheless, low-flow ischemia may not be a common clinical entity.

T42129

383489-383692

Sentence

denotes

In addition to the type of ischemia, there are other factors involved in priming tissues for reperfusion injury, including species and anatomic-specific variation in oxidant enzyme and neutrophil levels.

T12203

383693-383976

Sentence

denotes

For example, the foal appears to have very low levels of small intestinal xanthine oxidase, an enzyme that plays a critical role in triggering reperfusion injury in laboratory animals, 410, 875, 880 whereas adult levels are much greater, particularly in the proximal small intestine.

T61427

383977-384242

Sentence

denotes

881 In addition, horses appear to have low numbers of resident neutrophils in the intestinal mucosa, 882 and it is this population of neutrophils (rather than those recruited from the circulation) that appear to be most critical for induction of reperfusion injury.

T4103

384243-384405

Sentence

denotes

104 Studies demonstrating reperfusion injury in the equine colon following low-flow ischemia have shown significant accumulation of neutrophils within the mucosa.

T67946

384406-384556

Sentence

denotes

866 A complete understanding of the mechanisms of neutrophilic infiltration and the mechanisms by which they damage tissue will require further study.

T10690

384557-384778

Sentence

denotes

Reperfusion injury is initiated during ischemia when the enzyme xanthine dehydrogenase is converted to xanthine oxidase, and its substrate, hypoxanthine, accumulates simultaneously because of ATP utilization (Fig. 12.8) .

T21408

384779-384898

Sentence

denotes

850, 883 There is little xanthine oxidase activity during ischemia, because oxygen is required as an electron acceptor.

T40413

384899-385041

Sentence

denotes

During reperfusion, xanthine oxidase rapidly degrades hypoxanthine in the presence of oxygen, producing the superoxide radical as a byproduct.

T8583

385042-385169

Sentence

denotes

850 The superoxide radical contributes to oxidative tissue damage and, most importantly, activates neutrophil chemoattractants.

T41287

385170-385337

Sentence

denotes

410, 875 Inhibition of xanthine oxidase in feline studies of intestinal ischemia/reperfusion injury prevents infiltration of neutrophils and subsequent mucosal injury.

T97887

385338-385917

Sentence

denotes

410, 874 Inhibition of xanthine oxidase has had no effect on ischemia/reperfusion injury in equine small intestine 876 and colon, 407 suggesting that either reperfusion injury is simply a continuation of injury initiated during ischemia, as suggested in some equine studies, 856 or that the classic reperfusion injury pathway is activated by alternate sources of ROMs. The latter has been suggested by studies in feline models of ischemia/reperfusion injury, in which the source of a significant proportion of ROMs is unknown, and independent of xanthine oxidase and neutrophils.

T44865

385918-386123

Sentence

denotes

874 In a veterinary review of the pathogenesis of intestinal reperfusion injury in the horse, the concept of a therapeutic window in which treatment of reperfusion injury would be beneficial was suggested.

T42109

386124-386287

Sentence

denotes

850 The basis of this concept is that there are certain conditions under which ischemic injury is minimal and that tissues are severely damaged during reperfusion.

T52150

386288-386457

Sentence

denotes

877 Thus under conditions of low-flow ischemia, very little injury is demonstrated during 3 hours of ischemia, but remarkable injury occurs during 1 hour of reperfusion.

T55555

386458-386644

Sentence

denotes

410, 874, 875 A therapeutic window may not exist under conditions of strangulating obstruction in which severe injury occurs during ischemia and minimal injury occurs during reperfusion.

T60042

386645-386806

Sentence

denotes

884 This in turn greatly reduces clinicians' abilities to ameliorate ischemia/reperfusion injury with treatments such as antioxidants at the time of reperfusion.

T39977

386807-386881

Sentence

denotes

Mechanisms of gastric repair are highly dependent on the extent of injury.

T93919

386882-387030

Sentence

denotes

For instance, superficial erosions can be rapidly covered by migration of epithelium adjacent to the wound, a process termed epithelial restitution.

T27888

387031-387181

Sentence

denotes

Ulceration (full-thickness disruption of mucosa and penetration of the muscularis mucosa), however, requires repair of submucosal vasculature and ECM.

T9128

387182-387340

Sentence

denotes

This is initiated by the formation of granulation tissue, which supplies connective tissue elements and microvasculature necessary for mucosal reconstruction.

T57234

387341-387485

Sentence

denotes

Connective tissue elements include proliferating fibroblasts that accompany newly produced capillaries that form from proliferating endothelium.

T60571

387486-387646

Sentence

denotes

Recent studies indicate that nitric oxide is critical to both of these processes, 835, 885 which likely explains the reparative properties of it in the stomach.

T79020

387647-387791

Sentence

denotes

886 Once an adequate granulation bed has been formed, newly proliferated epithelium at the edge of the wound begins to migrate across the wound.

T60979

387792-387905

Sentence

denotes

Gastric glands at the base of the ulcer begin to bud and migrate across the granulation bed in a tubular fashion.

T44997

387906-388019

Sentence

denotes

887 Epidermal growth factor (EGF) is expressed by repairing epithelium and appears to facilitate these processes.

T19572

388020-388139

Sentence

denotes

888 These events are facilitated by a mucoid cap, which retains reparative factors and serum adjacent to the wound bed.

T42475

388140-388326

Sentence

denotes

845 Once the ulcer crater has been filled with granulation tissue, and the wound has been reepithelialized, the subepithelial tissue remodels by altering the type and amount of collagen.

T26771

388327-388515

Sentence

denotes

Despite the remodeling process, ulcers tend to recur at sites of previous ulceration, and there is concern that this remodeling can result in excessive deposition of collagen and fibrosis.

T17505

388516-388519

Sentence

denotes

821

T24096

388520-388651

Sentence

denotes

Reparative mechanisms are similar in the intestine, except that in the small intestine, mucosal villi contribute to mucosal repair.

T52345

388652-388867

Sentence

denotes

Once intestinal epithelium is disrupted, there are two events that occur almost immediately to reduce the size of the denuded portion of the villus: contraction of the villus and epithelial restitution (Fig. 12.9 ).

T22982

388868-389066

Sentence

denotes

For example, in porcine ileum subjected to 2 hours of ischemia, villi were 60% of their former height, and 50% of the denuded villous surface area was covered in flattened epithelium within 6 hours.

T32722

389067-389226

Sentence

denotes

836 Villous contraction appears to be regulated by enteric nerves, because inhibition of enteric nerve conduction prevents villous shortening following injury.

T45869

389227-389384

Sentence

denotes

The contractile component of the villus is a network of myofibroblasts distributed throughout the lamina propria of the villus and along the central lacteal.

T92425

389385-389605

Sentence

denotes

Inhibition of villous contraction results in retarded epithelial repair because of the larger denuded surface that remains to be covered by migrating epithelium compared with similarly injured villi that have contracted.

T58035

389606-389776

Sentence

denotes

837 PGE 2 has also been implicated in regulating villous contraction, because application of PGE 2 resulted in villous contraction when perfused through normal rat ileum.

T39366

389777-389966

Sentence

denotes

889 As villi contract, assuming there is an intact basement membrane, epithelium from the margins of the wound migrates in a centripetal direction to resurface toward the tip of the villus.

T19838

389967-390105

Sentence

denotes

837 The process of restitution is similar in denuded colonic mucosa, except that it may proceed more rapidly because of the lack of villi.

T99041

390106-390231

Sentence

denotes

207 Epithelial restitution is solely a migratory event that does not depend on provision of new enterocytes by proliferation.

T16692

390232-390364

Sentence

denotes

Cellular migration is initiated by extension of cellular lamellipodia that receive signals from the basement membrane via integrins.

T67446

390365-390476

Sentence

denotes

Intracellular signaling converges on the actin cytoskeleton, which is responsible for movement of lamellipodia.

T87671

390477-390569

Sentence

denotes

Specific components of the basement membrane appear to be critical to the migratory process.

T92035

390570-390742

Sentence

denotes

For example, application of antibodies to collagen types III and IV, which are important components of intestinal mucosal basement membrane, impeded epithelial restitution.

T60921

390743-390932

Sentence

denotes

890, 891 Other elements of the basement membrane, including proteoglycans, hyaluronic acid, and noncollagenous proteins, such as fibronectin and laminin, may also provide important signals.

T94124

390933-391180

Sentence

denotes

892 The subepithelial matrix components that facilitate restitution may form the basis for clinical treatments designed to speed up the repair process, analogous to the administration of matrix components to horses with articular cartilage damage.

T21092

391181-391405

Sentence

denotes

Although epithelial restitution results in gross closure of previously denuded regions of gastrointestinal mucosa, the closure of interepithelial spaces is ultimately required to restore normal epithelial barrier resistance.

T75751

391406-391632

Sentence

denotes

893 Because the tight junction is principally responsible for regulating the permeability of the interepithelial space, it is likely that repair and closure of this structure is critical to restore intestinal barrier function.

T86800

391633-391916

Sentence

denotes

Recent research indicates that prostaglandins play a vital role in the recovery of tight junction resistance, 893 indicating that the administration of nonselective COX inhibitors to horses with colic, particularly those recovering from strangulating obstruction, may be deleterious.

T82708

391917-392076

Sentence

denotes

Judicious use of NSAIDs is appropriate until more selective drugs that allow continued production of reparative prostaglandins are available for use in horses.

T16006

392077-392230

Sentence

denotes

Recent studies have shown that NSAIDs preferential for COX-2 allow for optimal repair of injured intestine compared with traditional nonselective NSAIDs.

T69566

392231-392386

Sentence

denotes

392 Once the epithelial barrier has been restored, normal mucosal architecture must be reestablished to allow normal gut absorptive and digestive function.

T32679

392387-392570

Sentence

denotes

In porcine ileum subjected to 2 hours of ischemia, the epithelial barrier was restored within 18 hours, but villi were contracted and covered in epithelium with a squamous appearance.

T94150

392571-392640

Sentence

denotes

Restoration of normal villous architecture required a further 4 days.

T79304

392641-392760

Sentence

denotes

836 The flattened villous epithelium that characterizes restitution is replaced by newly proliferated crypt epithelium.

T80476

392761-392919

Sentence

denotes

Under normal circumstances, new enterocytes are formed by the division of stem cells, of which there are approximately four at the base of each mucosal crypt.

T81690

392920-392985

Sentence

denotes

Newly divided enterocytes migrate from the crypt onto the villus.

T33693

392986-393090

Sentence

denotes

894 During migration, enterocytes differentiate and acquire specific absorptive and digestive functions.

T45437

393091-393228

Sentence

denotes

Fully differentiated enterocytes reside on the upper third of the villus for 2 to 3 days and are then sloughed into the intestinal lumen.

T72756

393229-393329

Sentence

denotes

895 This process is accelerated during mucosal repair, which requires increased proliferative rates.

T31031

393330-393508

Sentence

denotes

Increased proliferation may be stimulated within 12 to 18 hours by a variety of locally available gutderived factors, including luminal nutrients, polyamines, and growth factors.

T13031

393509-393634

Sentence

denotes

836 The return of the normal leaf-like shape of the villus occurs subsequent to the appearance of normal columnar epithelium.

T52436

393635-393797

Sentence

denotes

Although prostaglandins have been strongly implicated in mucosal cytoprotective function, relatively few studies have assessed their importance in mucosal repair.

T14682

393798-393999

Sentence

denotes

One study implicated prostaglandins in growth factor-stimulated restitution, 896 but a more prominent role of prostaglandins in mucosal repair is their ability to close interepithelial tight junctions.

T79314

394000-394316

Sentence

denotes

893, 897, 898 For instance, ischemic-injured small intestine rapidly recovered barrier function (as measured in vitro as transepithelial resistance) in the presence of prostaglandins I 2 and E 2 , despite the fact that these prostanoids had relatively little effect on villous contraction and epithelial restitution.

T35874

394317-394548

Sentence

denotes

However, electron microscopic examination of tissues reveals dilation of tight junctions in tissues treated with NSAIDs, 898 whereas those additionally treated with prostaglandins have closely apposed tight junctions (Fig. 12.10) .

T81426

394549-394745

Sentence

denotes

Prostaglandins stimulate closure of tight junctions via the second messengers cAMP and Ca 2+ , 893 which interestingly were among the first mediators found to modulate tight junction permeability.

T16081

394746-394993

Sentence

denotes

899, 900 Such tight junction closure is of considerable importance to patients with intestinal injury that are treated with nonsteroidal antiinflammatory agents, because reduced prostaglandin levels may result in increased intestinal permeability.

T16277

394994-395261

Sentence

denotes

For example, in a study on ischemic-injured porcine ileum, treatment with the NSAID indomethacin resulted in a significant increase in intestinal permeability to inulin and lipopolysaccharide compared with tissues that were additionally treated with PGI 2 and PGE 2 .

T51693

395262-395265

Sentence

denotes

893

T5204

395266-395359

Sentence

denotes

The process of restitution is absolutely dependent on a group of compounds called polyamines.

T61863

395360-395499

Sentence

denotes

901, 902 The rate-limiting enzyme in the formation of the polyamines spermine, spermidine, and putrescine is ornithine decarboxylase (ODC).

T90191

395500-395707

Sentence

denotes

In rats with stress-induced duodenal ulcers, systemic administration of the ODC inhibitor dl-alpha-difluoromethyl ornithine significantly reduced polyamine levels and markedly reduced epithelial restitution.

T43234

395708-395873

Sentence

denotes

Intragastric treatment of these same rats with putrescine, spermidine, and spermine prevented the delayed mucosal repair induced by dl-alpha-difluoromethylornithine.

T93319

395874-396121

Sentence

denotes

901 Interestingly, gastric tissue levels of ODC were increased in rats with stress-induced gastric ulcers, suggesting that polyamine production is enhanced during tissue injury and may contribute to the normal rapid rate of epithelial restitution.

T91051

396122-396208

Sentence

denotes

903 The mechanisms by which polyamines stimulate epithelial restitution are not clear.

T1769

396209-396382

Sentence

denotes

McCormack et al. hypothesized that polyamines increased transglutaminase activity, an enzyme that catalyzes the cross-linking of cytoskeletal and basement membrane proteins.

T82899

396383-396589

Sentence

denotes

904 Further investigation of the role of polyamines in IEC-6 cell migration showed that depletion of polyamines resulted in disruption of the cytoskeleton and reduced the physical extension of lamellipodia.

T53218

396590-396642

Sentence

denotes

905 More recent studies have clarified this pathway.

T91673

396643-396776

Sentence

denotes

Polyamines regulate cytoskeletal cellular migration via activation of the small GTPase Rho-A by elevating intracellular Ca 2+ levels.

T30396

396777-396922

Sentence

denotes

These elevations in Ca 2+ result from polyamine regulation of expression of voltage-gated K + channels and altered membrane electrical potential.

T74036

396923-397040

Sentence

denotes

906 Polyamines also play a role in the normal physiologic regulation of crypt cell proliferation and differentiation.

T82238

397041-397222

Sentence

denotes

907, 908 They are produced by fully differentiated enterocytes at the villous tip and may reach the crypt either within sloughed luminal epithelium or via local villous circulation.

T49462

397223-397387

Sentence

denotes

909 Following intestinal injury, polyamines appear to stimulate enhanced proliferation by increasing the expression of protooncogenes, which control the cell cycle.

T80609

397388-397587

Sentence

denotes

910 The mechanism by which polyamines influence gene expression likely relates to the cationic nature of these compounds, which may influence the tertiary structure of negatively charged DNA and RNA.

T93197

397588-397591

Sentence

denotes

901

T62861

397592-397729

Sentence

denotes

Locally produced growth factors, including EGF, TGF-α, TGFβ, and hepatocyte growth factor, have the ability to modulate mucosal recovery.

T48323

397730-397892

Sentence

denotes

The most important of these growth factors in early mucosal repair events is TGF-β, which is a potent stimulus of epithelial restitution and modulator of the ECM.

T1459

397893-398123

Sentence

denotes

821 Neutralization of TGF-β retards epithelial migration in vitro, and it appears that TGF-β may serve as a point of convergence for mediators of restitution, because neutralizing TGF-β also inhibits the effects of other peptides.

T58297

398124-398246

Sentence

denotes

However, TGF-β paradoxically inhibits epithelial proliferation, reducing the supply of new enterocytes for mucosal repair.

T70662

398247-398442

Sentence

denotes

Conversely, EGF, produced by the salivary glands and duodenal Brunner's glands, and the related TGF-α, produced by small intestinal enterocytes, are potent stimulants of enterocyte proliferation.

T79664

398443-398617

Sentence

denotes

These growth factors share approximately 30% of their amino acid structure, bind to the same receptor on the basolateral surface of enterocytes, and are not related to TGF-β.

T21483

398618-398786

Sentence

denotes

911 The physiologic role of EGF is somewhat difficult to discern because it is present in the intestinal lumen, with no apparent access to its basally located receptor.

T43915

398787-398986

Sentence

denotes

912 It has been proposed that EGF acts as a "surveillance agent" that gains access to its receptor during epithelial injury (when the EGF receptor would likely be exposed) to stimulate proliferation.

T82178

398987-399156

Sentence

denotes

912 TGF-α presumably has a similar role, but it is present in greater concentrations in the small intestine because it is produced by differentiated villous enterocytes.

T81022

399157-399285

Sentence

denotes

The mature peptide is cleaved from the extracellular component of the transmembrane TGF-α precursor and released into the lumen.

T76567

399286-399289

Sentence

denotes

911

T62249

399290-399415

Sentence

denotes

Another group of proreparative peptides that are locally produced within the gastrointestinal tract are the trefoil peptides.

T18352

399416-399527

Sentence

denotes

Under physiologic conditions, trefoil peptides are secreted by mucusproducing cells at distinct anatomic sites.

T84672

399528-399661

Sentence

denotes

For example, the trefoil peptide pS2 is produced by gastric epithelium, whereas ITF is produced by small and large intestinal mucosa.

T6630

399662-399782

Sentence

denotes

701 However, any of the trefoil peptides may be upregulated within repairing epithelium regardless of the anatomic site.

T86341

399783-399947

Sentence

denotes

821, 913 In addition, trefoil peptides have the ability to induce their own expression, amplifying the level of these reparative factors at sites of mucosal repair.

T1729

399948-400103

Sentence

denotes

914 Trefoil peptides are the most potent stimulants of epithelial migration in vitro, and their effects are independent of growth factors, including TGF-β.

T57297

400104-400293

Sentence

denotes

915 Recent evidence suggests that EGF receptor activation is required for the induction of pS2 and another of the trefoil peptides called spasmolytic peptide in gastric epithelium in vitro.

T36115

400294-400504

Sentence

denotes

The importance of trefoil peptides to the mucosal repair response in vivo is illustrated by gene knockout studies, in which mice deficient in ITF have a dramatically reduced ability to repair intestinal injury.

T16848

400505-400664

Sentence

denotes

916 Detergent-induced mucosal injury was lethal because of a lack of restitution compared with wild-type mice that fully recovered from similar mucosal injury.

T50709

400665-400768

Sentence

denotes

The fact that restitution was restored by administration of ITF has important therapeutic implications.

T45956

400769-401019

Sentence

denotes

The mechanism by which trefoil peptides stimulate epithelial migration has yet to be fully characterized, but it appears to involve translocation of the adherens junction protein E-cadherin, allowing cells to become untethered from neighboring cells.

T19127

401020-401023

Sentence

denotes

821

T86225

401024-401117

Sentence

denotes

The principal metabolic fuel of enterocytes is glutamine, and for colonocytes it is butyrate.

T708

401118-401254

Sentence

denotes

However, recent studies suggest that glutamine and butyrate have more specific proliferative actions aside from their role as nutrients.

T44012

401255-401378

Sentence

denotes

For example, in the piglet IPEC-J2 enterocyte cell line, glutamine enhanced gene transcription by increasing MAPK activity.

T50913

401379-401472

Sentence

denotes

917, 918 Similarly, butyrate stimulated mucosal growth following colonic infusion in the rat.

T56090

401473-401673

Sentence

denotes

919 Because of such growth-promoting actions, glutamine was shown to prevent the intestinal mucosal atrophy and dysfunction that accompany starvation 920, 921 and long-term total parenteral nutrition.

T25624

401674-401853

Sentence

denotes

922, 923 Glutamine improves the function of transplanted small intestine 924, 925 and protects intestinal mucosa from injury if administered before chemotherapy 926 and radiation.

T78723

401854-401935

Sentence

denotes

927, 928 Intestinal nutrients may also synergize with other proliferative agents.

T70371

401936-402155

Sentence

denotes

For example, administration of glutamine and TGF-α to porcine ileum that had been subjected to 2 hours of ischemia resulted in a synergistic increase in MAPK activity, enterocyte proliferation, and villous surface area.

T78828

402156-402448

Sentence

denotes

836 Although there has been a concern that such early return to normal surface area may result in dysfunctional mucosal digestive and absorptive function because of resurfacing denuded mucosa with immature epithelium, nutrients and growth factors also appear to promote early differentiation.

T61895

402449-402585

Sentence

denotes

In the case of glutamine and TGF-α restoration of postischemic small intestine, rapid recovery of digestive enzymes was also documented.

T75865

402586-402589

Sentence

denotes

929

T75244

402591-402711

Sentence

denotes

Effective gastrointestinal motility involves a complex interaction between the ENS, muscular wall, and luminal contents.

T23914

402712-402936

Sentence

denotes

Additional factors that influence the net transit of digesta include gravity, the volume and viscosity of the contents, and pressure gradients created by simultaneous contraction and relaxation of adjacent segments of bowel.

T90664

402937-403103

Sentence

denotes

Casual use of the term intestinal motility in veterinary medicine often underestimates the complexity of the processes involved in the transit of intestinal contents.

T90567

403104-403231

Sentence

denotes

This is particularly true when the term is used to describe the frequency and or intensity of intestinal sounds, or borborygmi.

T64052

403232-403332

Sentence

denotes

The existence of borborygmi does not always equate with progressive movement of intestinal contents.

T59542

403333-403414

Sentence

denotes

Disruption to normal motility occurs commonly in horses for a variety of reasons.

T56955

403415-403710

Sentence

denotes

Examples of diseases in which altered motility may be present include grass sickness, gastroduodenal ulceration, intraluminal obstruction or impaction, excessive wall distention, strangulating obstruction, peritonitis, and inflammatory disorders such as duodenitis proximal jejunitis or colitis.

T61030

403711-403854

Sentence

denotes

Ineffective intestinal motility is also a feature of several neonatal diseases, including prematurity, systemic sepsis, and perinatal asphyxia.

T59614

403855-403976

Sentence

denotes

Certain parasitic infections, electrolyte derangements, and endotoxemia can modify digesta transit in horses of all ages.

T13081

403977-404087

Sentence

denotes

General anesthesia and specific sedatives, such as xylazine, romifidine, or detomidine, also disturb motility.

T30207

404088-404164

Sentence

denotes

The inhibition of propulsive bowel activity usually is referred to as ileus.

T37487

404165-404287

Sentence

denotes

Ileus is ascribed most frequently to the condition that occurs after laparotomy and is termed simple or uncomplicated POI.

T90213

404288-404401

Sentence

denotes

The term complicated or paralytic ileus describes intestinal motility disturbed for longer periods after surgery.

T82123

404402-404784

Sentence

denotes

POI in horses is associated most commonly with surgery of the small intestine, particularly after resection and anastomosis, 930, 931 and can have a negative effect on short-term postoperative survival. [932] [933] [934] [935] Motility dysfunction likely is present in all horses after laparotomy, but many are affected subclinically and require minimal or no specific intervention.

T80635

404785-404990

Sentence

denotes

In symptomatic animals, clinical signs are apparent shortly after recovery and include colic, tachycardia, dehydration, decreased borborygmi and fecal output, and sequestration of fluid within the stomach.

T29606

404991-405094

Sentence

denotes

Rectal examination and ultrasound reveal small intestinal distention with rare or absent wall movement.

T78293

405095-405179

Sentence

denotes

The severity and duration of intestinal stasis varies, lasting from minutes to days.

T44754

405180-405485

Sentence

denotes

A specific motility disorder involving the cecum or ileocecocolic region occurs sporadically in horses. [936] [937] [938] The condition most commonly occurs after general anesthesia and extraabdominal surgery, particularly orthopedic and upper airway procedures, and often is categorized as a form of POI.

T29842

405486-405608

Sentence

denotes

Other cases occur spontaneously, often in animals with painful primary conditions such as uveitis or septic tenosynovitis.

T35373

405609-405833

Sentence

denotes

In a study of 114 horses diagnosed with cecal impaction, 12 were hospitalized for a condition other than colic at the time of diagnosis, and 9 others were being treated with phenylbutazone, most for a musculoskeletal injury.

T22793

405834-405929

Sentence

denotes

939 Eight of the 114 horses had undergone general anesthesia in the 8 days preceding diagnosis.

T32388

405930-406036

Sentence

denotes

The syndrome is frustrating in that clinical signs are often subtle unless cecal perforation has occurred.

T12605

406037-406159

Sentence

denotes

In horses with a cecal emptying defect after anesthesia, overt signs are usually apparent 3 to 5 days after the procedure.

T96933

406160-406257

Sentence

denotes

The earliest detectable signs include depression and a reduction in feed intake and fecal output.

T93369

406258-406391

Sentence

denotes

Ineffective emptying results in overfilling of the cecum with moist contents, which is manifested by signs of mild to moderate colic.

T61639

406392-406496

Sentence

denotes

If the condition is recognized late or untreated, the cecum may rupture and result in fatal peritonitis.

T9856

406497-406670

Sentence

denotes

Current understanding of motility throughout the equine gastrointestinal tract is remarkably limited, and much of our presumptive knowledge comes from work in other species.

T98173

406671-406843

Sentence

denotes

The ENS is involved in all aspects of motility, either directly via neurotransmitters or indirectly via interstitial cells of Cajal (ICC) or immune or endocrine regulation.

T8465

406844-407020

Sentence

denotes

The inherent rhythmicity of electric activity in the intestine is controlled by the ICC, which is specialized cells that are electrically coupled to myocytes via gap junctions.

T79138

407021-407164

Sentence

denotes

940 These cells are responsible for generating and propagating slow-wave activity; hence, they are deemed the pacemaker cells of the intestine.

T63761

407165-407461

Sentence

denotes

A decrease in ICC density has been observed in horses with obstructive disorders of the large intestine 941 and in the ileum and pelvic flexure of horses diagnosed with equine grass sickness (dysautonomia), 942 although such a decrease was not evident in a horse with dysautonomia that recovered.

T29929

407462-407561

Sentence

denotes

943 This alteration in ICC infrastructure appears to result in reduced slow-wave activity in vitro.

T33324

407562-407632

Sentence

denotes

944 The ENS primarily controls and coordinates intestinal contraction.

T2939

407633-407758

Sentence

denotes

A combination of central and autonomic innervation influences events, but contraction does not require external neural input.

T67640

407759-407958

Sentence

denotes

The parasympathetic supply to the gastrointestinal tract is via the vagus and pelvic nerves, and the sympathetic supply is through postganglionic fibers of the cranial and caudal mesenteric plexuses.

T91407

407959-408191

Sentence

denotes

A complex network of interneurons within each plexus integrates and amplifies neural input; the intensity and frequency of resultant smooth muscle contractions are proportional to the amount of sympathetic and parasympathetic input.

T23761

408192-408353

Sentence

denotes

Additional binding sites for a number of other endogenous chemicals, including dopamine, motilin, and serotonin, exist within the ENS and on smooth muscle cells.

T97845

408354-408527

Sentence

denotes

945 Acetylcholine is the dominant excitatory neurotransmitter in the gastrointestinal tract and exerts its action through muscarinic type 2 receptors on smooth muscle cells.

T54166

408528-408677

Sentence

denotes

Sympathetic fibers innervating the gastrointestinal tract are adrenergic, postganglionic fibers with cell bodies located in the prevertebral ganglia.

T3075

408678-408931

Sentence

denotes

Activation of α 2 -adrenergic receptors on cholinergic neurons within enteric ganglia inhibits the release of acetylcholine, reducing intestinal contraction. β 1 -, β 2 -, and β-atypical receptors are directly inhibitory to the intestinal smooth muscle.

T76462

408932-409075

Sentence

denotes

946 Inhibitory nonadrenergic, noncholinergic neurotransmitters include adenosine triphosphate, vasoactive intestinal peptide, and nitric oxide.

T82120

409076-409202

Sentence

denotes

947, 948 These neurotransmitters are critical for mediating descending inhibition during peristalsis and receptive relaxation.

T58740

409203-409322

Sentence

denotes

Substance P is a nonadrenergic, noncholinergic neurotransmitter that may be involved in contraction of the large colon.

T90393

409323-409594

Sentence

denotes

949, 950 The rate and force of intestinal contractions along the small intestine and large colon of the horse are important determinants of intestinal motility; of even greater importance to the net propulsion of digesta are the cyclical patterns of contractile activity.

T61141

409595-409709

Sentence

denotes

These patterns are known as the small intestinal and colonic migrating motility (or myoelectric) complexes (MMCs).

T12108

409710-409844

Sentence

denotes

951, 952 The colonic complex usually originates in the right ventral colon and variably traverses the ascending and descending colons.

T89014

409845-409977

Sentence

denotes

Many of these complexes are related temporally to a specialized motility event of the ileum, the migrating action potential complex.

T19020

409978-409981

Sentence

denotes

953

T35600

409983-410109

Sentence

denotes

Local inflammation within the intestinal muscularis and inhibitory neural events are important initiators of intestinal ileus.

T14243

410110-410303

Sentence

denotes

954, 955 Intestinal inflammation not only is important in primary intestinal diseases in horses, such as DPJ and colitis, but also is induced after simple intestinal handling during laparotomy.

T4283

410304-410490

Sentence

denotes

In rodents, simple intestinal manipulation causes a cascade of inflammation within the muscularis, resulting in leukocyte infiltration and subsequent suppression of muscle contractility.

T2444

410491-410584

Sentence

denotes

Similar inflammatory effects were evident with mechanical manipulation of the equine jejunum.

T41963

410585-410770

Sentence

denotes

956 The inflammatory response to bowel manipulation is not limited to the affected tissue, but it can also result in global inflammation and ileus throughout the gastrointestinal tract.

T63450

410771-410913

Sentence

denotes

957 The associated inflammatory events are extremely complex, involving a milieu of proinflammatory cytokines, prostaglandins, and leukocytes.

T5264

410914-411078

Sentence

denotes

Depletion or inactivation of muscularis macrophage function can prevent inflammation associated with intestinal manipulation and associated decreased contractility.

T90001

411079-411168

Sentence

denotes

958 Mast cell activation is involved in intestinal manipulation-associated POI in humans.

T26123

411169-411266

Sentence

denotes

959 Inflammation associated with colonic manipulation may involve gut-derived bacterial products.

T40023

411267-411448

Sentence

denotes

960 Another factor in the development of intestinal stasis after inflammation is the local overproduction of nitric oxide caused by the upregulation of iNOS by resident macrophages.

T79623

411449-411560

Sentence

denotes

961 The iNOS upregulation was important for initiation of the inflammatory response and inhibition of motility.

T88805

411561-411655

Sentence

denotes

Nitric oxide is a key inhibitory neurotransmitter of the nonadrenergic, noncholinergic system.

T3335

411656-411871

Sentence

denotes

948 In the horse, significant neutrophilic inflammation is apparent in the jejunum from clinical cases necessitating resection and following a period of recovery in the jejunum subjected to 1 or 2 hours of ischemia.

T48199

411872-412022

Sentence

denotes

962 The ischemic tissue also had evidence of leukocyte activation, as demonstrated by calprotectin-positive cells in associated tissue histologically.

T28896

412023-412237

Sentence

denotes

The inhibitory effects of α 2 -adrenergic agonists such as xylazine and detomidine on duodenal, cecal, and large colon motility are well described, because these drugs activate presynaptic receptors within the ENS.

T19328

412238-412488

Sentence

denotes

4,963,964-968 IV-administered xylazine inhibits cecal and large colon motility for 20 to 30 minutes without seriously disrupting small intestinal myoelectric activity, and detomidine can reduce large intestinal myoelectric activity for up to 3 hours.

T91573

412489-412556

Sentence

denotes

Detomidine decreases duodenal motility in a dose-dependent fashion.

T12965

412557-412727

Sentence

denotes

969 The α 2antagonist yohimbine has a weak but positive effect on cecal emptying in normal ponies, suggesting that normal motility is under constant α 2 -adrenergic tone.

T70212

412728-412869

Sentence

denotes

4 Several opioid agonists also have documented inhibitory effects on equine gastrointestinal motility at both a central and peripheral level.

T15550

412870-413065

Sentence

denotes

Morphine administration decreased frequency of defecation and fecal moisture content while increasing gastrointestinal transit time in normal horses at a dose of 0.5 mg/kg twice daily for 6 days.

T68095

413066-413244

Sentence

denotes

970 Single doses of fentanyl or morphine decrease jejunal and colonic MMC activity in ponies, whereas the antagonist naloxone elicited increased propulsive activity in the colon.

T56918

413245-413368

Sentence

denotes

971 Fentanyl administered as an IV constant rate infusion did not have an apparent deleterious effect on duodenal motility.

T32241

413369-413486

Sentence

denotes

972 Butorphanol, an opioid agonistantagonist, decreases myoelectrical activity in the jejunum but not pelvic flexure.

T90341

413487-413768

Sentence

denotes

973 In another series of experiments, butorphanol alone did not decrease gastric or duodenal motility, 974 but administration in combination with xylazine resulted in a synergistic inhibitory effect, which was more pronounced than that obtained by administration of xylazine alone.

T68509

413769-413927

Sentence

denotes

968 Administration of butorphanol as a constant rate infusion appears to have a minimal to no effect on global gastrointestinal 470, 975 or duodenal motility.

T82143

413928-414203

Sentence

denotes

976 When lidocaine, ketamine, and butorphanol were administered alone or in combination as constant rate infusions to healthy horses, combinations containing butorphanol (butorphanol/lidocaine, or a combination of all three drugs) delayed total gastrointestinal transit time.

T73014

414204-414363

Sentence

denotes

977 N-Butylscopolammonium bromide has a profound but very short-lived negative effect on duodenal motility, but this effect was not significant between groups.

T15551

414364-414447

Sentence

denotes

976 Atropine is a postganglionic blocking agent that binds to muscarinic receptors.

T9267

414448-414664

Sentence

denotes

When administered at 0.04 mg/kg, atropine inhibits individual small intestinal, cecal, and colonic contractions for about 120 minutes but suppresses small intestinal and colonic migrating complexes for up to 8 hours.

T28313

414665-414668

Sentence

denotes

978

T43916

414669-414760

Sentence

denotes

Neural reflexes may mediate inhibition of motility associated with peritoneal inflammation.

T72901

414761-415018

Sentence

denotes

979, 980 The afferent segment is composed partly of capsaicin-sensitive visceral afferent C fibers that terminate in the dorsal horn of the spinal cord, in which they can activate inhibitory sympathetic fibers or synapse directly on the sympathetic ganglia.

T25642

415019-415276

Sentence

denotes

Consequently, the efferent limb of the reflex expresses increased sympathetic outflow, primarily mediated through stimulation of α 2 -adrenoreceptors, and inhibition of acetylcholine release, which provides the rationale for α 2 -blockade in treating ileus.

T90080

415277-415390

Sentence

denotes

Intraluminal infusion of capsaicin before abdominal surgery ameliorated the severity of POI in experimental rats.

T46965

415391-415484

Sentence

denotes

This finding highlights the importance of visceral afferent fibers in the development of POI.

T16926

415485-415488

Sentence

denotes

981

T30041

415489-415569

Sentence

denotes

Ileus also can occur in association with intestinal obstruction or displacement.

T40402

415570-415736

Sentence

denotes

Mild to moderate distention of the bowel, such as that occurring in the early stages of an intraluminal obstruction, evokes an increase in local contractile activity.

T96651

415737-415843

Sentence

denotes

982, 983 Excessive distention results in the inhibition of motility within the distended segment of bowel.

T73347

415844-415935

Sentence

denotes

Intestinal stasis is not always detrimental and under certain conditions may be protective.

T28958

415936-416098

Sentence

denotes

Repeated distention for determination of nociceptive threshold results in an overall decrease in duodenal motility over time, irrespective of other interventions.

T56083

416099-416299

Sentence

denotes

972, 976 Endotoxin Endotoxemia is a clinical feature of many diseases of the equine gastrointestinal tract, and endotoxins independently can exert a negative effect on intestinal motility and transit.

T1447

416300-416603

Sentence

denotes

214 A variety of mediators likely are involved, but the activation of α 2adrenoreceptors and production of prostanoids appear to be important, because pretreatment with yohimbine or NSAIDs (phenylbutazone or flunixin), respectively, ameliorates the inhibitory effects of experimental endotoxin infusion.

T77694

416604-416694

Sentence

denotes

201, [984] [985] [986] Pretreatment with metoclopramide or cisapride had a similar effect.

T59326

416695-416845

Sentence

denotes

71, 987 Endotoxin infusion induced an inflammatory response in the intestine of rats that mimicked the response induced by handling during laparotomy.

T36332

416846-417042

Sentence

denotes

988 The similarity of the responses was highlighted in a recent study that demonstrated that prior exposure of the muscularis to endotoxin protected the intestine from the effects of manipulation.

T17998

417043-417286

Sentence

denotes

989 In rats, colonic manipulation alone causes transference of intraluminal LPS to the muscularis, which likely contributes to the global gastrointestinal inflammatory response and decrease in contractility associated with tissue manipulation.

T20036

417287-417482

Sentence

denotes

960 In response to endotoxin alone, the inflammatory response within the jejunal muscularis is predominantly monocytic, whereas the response to polymicrobial sepsis is predominantly neutrophilic.

T77804

417483-417486

Sentence

denotes

990

T99886

417487-417563

Sentence

denotes

Temperature also appears to affect in vitro slow-wave activity in the horse.

T71846

417564-417759

Sentence

denotes

In a recent study, the slow-wave frequency was approximately linearly related to temperature in the range studied (27-41°C) and was highly temperature sensitive in isolated equine ileal segments.

T96535

417760-417822

Sentence

denotes

991 The pathophysiology of cecal emptying defect is not known.

T48531

417823-417931

Sentence

denotes

This syndrome may best mimic POI in human beings, which is generally considered a large intestinal disorder.

T61476

417932-418101

Sentence

denotes

An important difference in horses is that laparotomy is a rare predisposing factor, and most cases occur in horses undergoing routine extraabdominal surgical procedures.

T30375

418102-418195

Sentence

denotes

The disorder, therefore, is probably not appropriately considered as a form of POI in horses.

T12750

418196-418371

Sentence

denotes

General anesthesia itself is a potent inhibitor of gastrointestinal motility in horses, but these effects are short-lived and reversible within hours of anesthetic withdrawal.

T19865

418372-418533

Sentence

denotes

952 The return of normal motility in horses after experimental ileus was most delayed in the cecum, suggesting that this may be a common site of ileus in horses.

T92985

418534-418682

Sentence

denotes

992 A link between routine postoperative medications, such as phenylbutazone and aminoglycoside antibiotics, has been suspected but not established.

T86468

418683-418791

Sentence

denotes

An inhibitory effect of NSAIDs on large colon contractility has been demonstrated using in vitro techniques.

T15155

418792-418944

Sentence

denotes

993 Primary sympathetic overstimulation could be involved, because many of the affected animals are young, male horses or animals with painful diseases.

T9453

418945-419055

Sentence

denotes

The duration of surgery influences the development of small intestinal POI but not cecal emptying dysfunction.

T60396

419056-419149

Sentence

denotes

938, 994 Technique may have a weak influence on small intestinal POI after jejunojejunostomy.

T75082

419150-419308

Sentence

denotes

The duration of intestinal ileus was shorter in animals that received a side-to-side stapled anastomosis than those that had a hand-sewn end-to-end procedure.

T42866

419309-419423

Sentence

denotes

932 The duration of ileus after stapled end-to-end anastomosis was not different from that after either procedure.

T75772

419424-419614

Sentence

denotes

Jejunocecostomy more commonly results in POI than other types of small intestinal resection and anastomosis, whether related to diseases necessitating this procedure or the procedure itself.

T20247

419615-419822

Sentence

denotes

995 Other reported risk factors for the development of POI include age (>10 years), small intestinal resection and anastomosis, breed (Arabians had a greater risk than other breeds), and duration of surgery.

T88027

419823-420105

Sentence

denotes

994 A prospective study found small intestinal lesion, high packed cell volume, and duration of anesthesia to increase the risk of POI, whereas performance of a pelvic flexure enterotomy and intraoperative administration of lidocaine may have a modest protective effect against POI.

T6471

420106-420109

Sentence

denotes

996

T62230

420111-420188

Sentence

denotes

The diagnosis of ileus is based on history and physical examination findings.

T45937

420189-420856

Sentence

denotes

Case inclusion criteria for clinical studies of POI have varied. [994] [995] [996] [997] Recent surveys of the Diplomates of the European Colleges of Equine Internal Medicine and Veterinary Surgery and the American Colleges of Veterinary Surgery, Veterinary Internal Medicine, and Veterinary Emergency and Critical Care revealed that the presence of reflux on passage of a nasogastric tube, evidence of multiple fluid-distended loops of small intestine on ultrasonographic examination, and the presence of multiple fluid-distended loops of small intestine on rectal palpation were the features most commonly identified as "extremely important" for a diagnosis of POI.

T66506

420857-420954

Sentence

denotes

998, 999 One can palpate cecal distention with digesta in horses with advanced cecal dysfunction.

T66473

420955-421249

Sentence

denotes

Distinguishing functional ileus from mechanical obstruction is important and can be difficult, but horses with mechanical obstruction typically have sustained high volumes of gastric reflux that vary little over time and abdominal pain, which is typically not relieved by gastric decompression.

T88649

421250-421469

Sentence

denotes

Abdominal ultrasound in horses with ileus typically reveals mild to moderately fluid-filled hypomotile to immotile small intestine, without alteration in the amount or character of PF or small intestinal wall thickness.

T86971

421470-421602

Sentence

denotes

Horses with reflux from other causes (peritonitis and mechanical obstruction) will have changes reflective of their disease process.

T13627

421603-421791

Sentence

denotes

This differentiation is important for appropriate case management, because horses with a mechanical obstruction often need either primary or repeat laparotomy, which should not be delayed.

T29687

421792-421885

Sentence

denotes

The management of intestinal ileus depends on the segment of gastrointestinal tract involved.

T25329

421886-422052

Sentence

denotes

Therapy for ileus of the proximal gastrointestinal tract involves a combination of gastric decompression, fluid and electrolyte therapy, and antiinflammatory therapy.

T72892

422053-422190

Sentence

denotes

Electrolyte therapy is critical, particularly for maintaining adequate extracellular concentrations of potassium, calcium, and magnesium.

T51340

422191-422365

Sentence

denotes

Calculation of the volume of fluid to be administered should include maintenance requirements plus an estimate of losses, especially those lost through gastric decompression.

T84314

422366-422499

Sentence

denotes

Parenteral provision of calories should be considered when feed has been withheld for more than 96 hours, particularly after surgery.

T95521

422500-422625

Sentence

denotes

Hand walking also may provide some benefit to these animals but is not likely to have a direct effect on intestinal motility.

T26886

422626-422715

Sentence

denotes

Drugs that can have an inhibitory effect on motility should be avoided or used sparingly.

T61802

422716-422839

Sentence

denotes

Horses with primary cecal impaction or impaction caused by an emptying defect may require surgery to prevent fatal rupture.

T73385

422840-423042

Sentence

denotes

The surgical management of these cases is controversial and may include typhlotomy alone, typhlotomy with a bypass procedure such as ileocolic or jejunocolic anastomosis, or a bypass without typhlotomy.

T8413

423043-423119

Sentence

denotes

1000 Most horses that undergo simple typhlotomy have an uneventful recovery.

T21836

423120-423313

Sentence

denotes

1001 In a large retrospective study, 44/54 horses treated medically survived to discharge, whereas 37 of 49 horses treated surgically were allowed to recover, 35 of which survived to discharge.

T83166

423314-423487

Sentence

denotes

939 Ileocolostomy was only performed in two of the 37 horses treated surgically (one of which survived to discharge), with the remainder receiving typhlotomy without bypass.

T76581

423488-423657

Sentence

denotes

Survival to 1 year was not statistically different between horses treated medically (18/19) or surgically (25/28), although 6 horses had a recurrence of cecal impaction.

T3076

423658-423854

Sentence

denotes

939 Experimental and anecdotal evidence provides a strong rationale for using antiinflammatory drugs to prevent and treat gastrointestinal ileus, particularly in animals that may have endotoxemia.

T75478

423855-424075

Sentence

denotes

1002 Flunixin meglumine is used widely in equine practice as an analgesic and antiinflammatory agent, and it ameliorates many of the adverse systemic effects of endotoxin, particularly those on the cardiovascular system.

T21982

424076-424167

Sentence

denotes

A potential negative effect of NSAIDs on large intestinal contractility has been suggested.

T83231

424168-424278

Sentence

denotes

A differential effect on contractility between selective and nonselective COX inhibitors is currently unknown.

T10913

424279-424383

Sentence

denotes

Broadspectrum antimicrobials are indicated when one suspects sepsis or in cases of profound neutropenia.

T15387

424384-424591

Sentence

denotes

High concentrations of aminoglycoside antimicrobials inhibited intestinal contractions in exposed sections of intestine in vitro, but this inhibitory effect is unlikely to occur at clinically relevant doses.

T79822

424592-424674

Sentence

denotes

1003 Motility-enhancing drugs have been advocated to treat gastrointestinal ileus.

T65718

424675-424869

Sentence

denotes

Unfortunately, information directly pertinent to horses is limited and must be extrapolated cautiously from that of other species because of the differences in intestinal anatomy and physiology.

T22873

424870-425068

Sentence

denotes

Prokinetic drugs potentially can shorten the length of hospitalization, reducing the cost of treatment and the number of potential complications such as weight loss, thrombophlebitis, and laminitis.

T71879

425069-425189

Sentence

denotes

Experimental evidence indicates that prokinetic drugs can minimize the development of postoperative abdominal adhesions.

T97049

425190-425372

Sentence

denotes

1004 Most prokinetic drugs require a healthy gut wall to enhance intestinal contraction, and downregulation of motilin receptors has been demonstrated in the inflamed equine jejunum.

T91941

425373-425593

Sentence

denotes

473 Therefore one should not assume that many of these drugs would be effective in the presence of an inflammatory injury such as that which can occur after intestinal manipulation at surgery or that associated with DPJ.

T17277

425594-425753

Sentence

denotes

Bethanechol is a parasympathomimetic agent that acts at the level of the myenteric plexus and directly on intestinal smooth cells through muscarinic receptors.

T50609

425754-425867

Sentence

denotes

In the horse, this effect is mediated predominantly by the M3 receptor, but the M2 receptor may also play a role.

T5325

425868-425965

Sentence

denotes

1005 Bethanechol is a synthetic ester of acetylcholine and is not degraded by anticholinesterase.

T34578

425966-426161

Sentence

denotes

Bethanechol has cholinergic side effects, including abdominal discomfort, sweating, and salivation, although these are minimal when the drug is administered at 0.025 mg/kg body mass SC or orally.

T1507

426162-426404

Sentence

denotes

Bethanechol has efficacy in diseases that involve abnormal gastric emptying and delayed small intestinal transit and increases gastric contractility and hastens the emptying of liquid and solid phase markers from the stomach of normal horses.

T44110

426405-426562

Sentence

denotes

1006 Bethanechol also increases the strength and duration of wall contractions in the cecum and right ventral colon, consequently speeding up cecal emptying.

T92321

426563-426656

Sentence

denotes

4 Neostigmine increases receptor concentration of acetylcholine by inhibiting cholinesterase.

T11989

426657-426801

Sentence

denotes

The drug (0.022-0.025 mg/kg IV) promotes cecal and colonic contractile activity and hastens the emptying of radiolabeled markers from the cecum.

T58635

426802-426960

Sentence

denotes

4 Neostigmine has been used to manage small intestinal ileus, but it significantly delayed the emptying of 6-mm beads from the stomach of normal adult horses.

T81512

426961-426965

Sentence

denotes

1007

T97311

426966-427080

Sentence

denotes

Metoclopramide acts principally as a 5-hydroxytryptamine 4-receptor (5HT-4) agonist and 5HT-3-receptor antagonist.

T68498

427081-427213

Sentence

denotes

In contrast to newer generation benzamides, metoclopramide is also an antagonist at dopamine 1 (DA1) and dopamine 2 (DA2) receptors.

T54514

427214-427320

Sentence

denotes

Antagonism of prejunctional DA2 receptors facilitates acetylcholine release and smooth muscle contraction.

T97220

427321-427480

Sentence

denotes

Metoclopramide crosses the blood-brain barrier, where its antagonist properties on central DA2 receptors can result in extrapyramidal signs, including seizure.

T86346

427481-427603

Sentence

denotes

Metoclopramide increased contractility of muscle strips in vitro in the pyloric antrum, proximal duodenum, and midjejunum.

T40060

427604-427757

Sentence

denotes

1008 These in vitro data support previous work in which metoclopramide administration restored gastroduodenal coordination of motility in a model of POI.

T23377

427758-427862

Sentence

denotes

1009 In another study, metoclopramide had no effect on jejunal or pelvic flexure myoelectrical activity.

T37607

427863-428101

Sentence

denotes

973 Constant IV infusion (0.04 mg/kg/h) of metoclopramide was well tolerated in a population of postoperative horses and significantly decreased the volume and duration of gastric reflux over control and intermittent drug infusion groups.

T50580

428102-428248

Sentence

denotes

1010 Cisapride is a second-generation benzamide that acts as a 5HT-4 agonist and 5HT-3-receptor antagonist but is without antidopaminergic action.

T45358

428249-428355

Sentence

denotes

Stimulation of 5HT-4 receptors within the ENS enhances release of acetylcholine from the myenteric plexus.

T67122

428356-428866

Sentence

denotes

Several reports suggest the efficacy of cisapride in managing intestinal disease in horses, including the resolution of persistent large colon impaction, treatment of equine grass sickness, and as a preventative for POI in horses after small intestinal surgery (0.1 mg/kg body mass intramuscularly during the postoperative period). [1011] [1012] [1013] [1014] The horse erratically absorbs tablets administered rectally, but a method for preparing a parenteral form of the drug from tablets has been described.

T38406

428867-429145

Sentence

denotes

1015 Cisapride has the potential to cause adverse cardiac side effects mediated through blockage of the rapid component of the delayed rectifier potassium current that include lengthening of the QT interval and development of torsades de pointes, a potentially fatal arrhythmia.

T31181

429146-429274

Sentence

denotes

1016 These adverse effects have resulted in withdrawal of the drug in the United States but have not been reported in the horse.

T59171

429275-429453

Sentence

denotes

Tegaserod, a 5HT-4 agonist, increases pelvic flexure smooth muscle contractility (0.27 mg/kg PO) 1017 and hastens gastrointestinal transit time (0.02 mg/kg IV) in healthy horses.

T17179

429454-429569

Sentence

denotes

1018 It has not, to the author's knowledge, been objectively evaluated in abnormal horses, but it may prove useful.

T11461

429570-429898

Sentence

denotes

In humans, this drug was marketed for women with constipation-predominant or mixed symptom irritable bowel syndrome and demonstrated clear benefits in quality of life and gastrointestinal symptoms but is currently only available in a restricted fashion because of an association with ischemic colitis and cardiovascular disease.

T51075

429899-429977

Sentence

denotes

1019 Domperidone acts as a competitive antagonist at peripheral DA2 receptors.

T28198

429978-430132

Sentence

denotes

The drug is a therapeutic agent (1.1 mg/kg/ day) for mares grazing endophyte-infected tall fescue, principally because of drug-enhanced prolactin release.

T12640

430133-430233

Sentence

denotes

Modest efficacy of domperidone (0.2 mg/kg IV) has been demonstrated in experimental ileus in ponies.

T53563

430234-430421

Sentence

denotes

1011 In another study, a much higher oral dosage (5 mg/kg) was required to increase gastric emptying; 1.1 mg/kg orally had limited effects on the gastrointestinal tract in healthy horses.

T45410

430422-430426

Sentence

denotes

1020

T25474

430427-430607

Sentence

denotes

Erythromycin, a macrolide antibiotic, is a direct motilin receptor agonist on smooth muscle cells and may act within the ENS to facilitate the release of acetylcholine and motilin.

T8647

430608-430716

Sentence

denotes

Erythromycin displaces motilin from its receptor in the equine duodenum, jejunum, cecum, and pelvic flexure.

T41606

430717-430825

Sentence

denotes

476 Erythromycin enhances gastric emptying in normal horses but has a more pronounced effect on the hindgut.

T87990

430826-430974

Sentence

denotes

1006, 1021 Erythromycin lactobionate (1.0 mg/kg IV) hastens cecal emptying in normal animals and induces colonic MMC-like activity across the colon.

T28684

430975-431051

Sentence

denotes

Administration often is associated with defecation and abdominal discomfort.

T81797

431052-431217

Sentence

denotes

The prokinetic effect of erythromycin apparent in the ileum, cecum, and pelvic flexure documented in normal horses was reduced in the immediate postoperative period.

T44689

431218-431325

Sentence

denotes

686 Luminal distention and decompression resulted in inflammation and a decreased response to erythromycin.

T97596

431326-431538

Sentence

denotes

1022 A decrease in motilin receptors in response to luminal distention has been documented in the equine jejunum, 473 and this may explain the difference in response between normal and clinically affected horses.

T39406

431539-431618

Sentence

denotes

Repeated dosing can cause downregulation of motilin receptors in other species.

T37224

431619-431718

Sentence

denotes

1023 Erythromycin can induce diarrhea in adults; therefore, one should avoid dosing over many days.

T37775

431719-431975

Sentence

denotes

Potassium penicillin (20 million IU IV to adult horses) can stimulate defecation and increase myoelectrical activity in the cecum and pelvic flexure, and these effects are not produced by an equimolar amount of potassium ion given IV as potassium chloride.

T13506

431976-431980

Sentence

denotes

1024

T34379

431981-432063

Sentence

denotes

Naloxone (0.05 mg/kg IV) induces contractile activity in the cecum and left colon.

T69726

432064-432147

Sentence

denotes

971 Defecation commonly follows administration of naloxone within 15 to 20 minutes.

T68315

432148-432353

Sentence

denotes

N-methylnaltrexone increases jejunal and pelvic flexure contractility in vitro 1025 and prevents the negative effects of morphine on fecal output and intestinal transit time when administered concurrently.

T64734

432354-432503

Sentence

denotes

1026 α 2 -Adrenoreceptor antagonists such as yohimbine or tolazoline counteract increased sympathetic outflow in response to nociceptive stimulation.

T24868

432504-432599

Sentence

denotes

Yohimbine infusion (75 μg/kg) also may attenuate the negative effects of endotoxin on motility.

T90374

432600-432608

Sentence

denotes

201, 985

T33279

432610-432775

Sentence

denotes

The use of IV lidocaine as a prokinetic has gained tremendous popularity and was reported to be the agent most commonly used by equine surgeons for treatment of POI.

T98947

432776-432932

Sentence

denotes

1027 In more recent surveys, flunixin meglumine and lidocaine were used most frequently for the treatment of POI by specialists in Europe and North America.

T86908

432933-433070

Sentence

denotes

998, 999 Lidocaine may exert prokinetic effects by suppressing primary afferent neurons, limiting reflex efferent inhibition of motility.

T85264

433071-433218

Sentence

denotes

1028 Other proposed mechanisms of action include antiinflammatory properties, potentially through NF-κB signaling 1029 or improving mucosal repair.

T45439

433219-433377

Sentence

denotes

413 IV lidocaine also has analgesic effects, although it was shown to alter somatic but not visceral antinociception in clinically normal horses in one study.

T75040

433378-433473

Sentence

denotes

1030 Lidocaine increased contractile activity in isolated strips of proximal duodenum in vitro.

T30104

433474-433611

Sentence

denotes

1008 The most commonly cited dosage is a 1.3-mg/kg bolus, typically over 15 minutes, followed by a 0.05-mg/kg/min constant rate infusion.

T22480

433612-433808

Sentence

denotes

This dosage did not alter MMC duration or spiking activity, reset the MMC in the jejunum in clinically normal horses 1031 or significantly alter a variety of indicators of POI after colic surgery.

T84536

433809-433960

Sentence

denotes

1032 Significantly more horses with POI stopped refluxing within 30 hours following the institution of lidocaine infusion, relative to saline infusion.

T21439

433961-434138

Sentence

denotes

475 Lidocaine administration did not affect the prevalence of POI, duration or volume of reflux, or survival in horses requiring surgery for treatment of small intestinal colic.

T41794

434139-434266

Sentence

denotes

1033 Lidocaine infusion can be associated with reversible side effects that include muscle fasciculations, ataxia, and seizure.

T9221

434267-434328

Sentence

denotes

Consequently, the rate of infusion requires close monitoring.

T67107

434329-434451

Sentence

denotes

Prolonged infusion of lidocaine in the horse appears safe, although accumulation of the GX metabolite has been documented.

T12240

434452-434531

Sentence

denotes

1034 Ischemic Disorders of the Intestinal Tract g Y PATHOPHYSIOLOGY OF STRANGU-

T22770

434532-434663

Sentence

denotes

Strangulating obstruction of the intestine is characterized by simultaneous occlusion of the intestinal lumen and its blood supply.

T89279

434664-434743

Sentence

denotes

Although strangulation of the intestinal lumen g Previous version by Anthony T.

T94579

434744-434946

Sentence

denotes

Blikslager. results in clinical signs similar to those of simple obstruction, occlusion of the blood supply results in a more rapid deterioration of the intestinal mucosa and subsequent onset of sepsis.

T70754

434947-435204

Sentence

denotes

Although there has been a great deal of interest in the relevance and treatment of intestinal reperfusion injury, 851, 861, 882 the lesion that develops during strangulation is often severe, leaving little viable bowel for further injury during reperfusion.

T46435

435205-435447

Sentence

denotes

882 Although extensive lengths of strangulated small intestine may be resected, strangulation of the large colon presents a much greater treatment dilemma because strangulated intestine usually extends beyond the limits of surgical resection.

T50294

435448-435573

Sentence

denotes

1035 Therefore horses with large intestinal strangulation are often recovered with extensive intestinal injury left in place.

T11240

435574-435753

Sentence

denotes

As a result, subtle degrees of reperfusion injury may be very important in horses with large colon disease, warranting further work in this area in an attempt to reduce mortality.

T51078

435754-435835

Sentence

denotes

851 Strangulating obstruction may be divided into hemorrhagic and ischemic forms.

T89024

435836-436001

Sentence

denotes

163 In hemorrhagic strangulating obstruction, which is most common, the veins become occluded before the arteries because of the greater stiffness of arterial walls.

T18432

436002-436125

Sentence

denotes

This lesion is noted by a darkened appearance in affected bowel and increased thickness as blood is pumped into the lesion.

T94354

436126-436261

Sentence

denotes

Ischemic strangulating obstruction occurs if the intestine is twisted tightly enough to simultaneously occlude both arteries and veins.

T38539

436262-436454

Sentence

denotes

In the case of the colon, some researchers suggest that this may be determined by how much ingesta is in the colon, because intestinal contents may prevent the intestine from twisting tightly.

T48734

436455-436618

Sentence

denotes

1036 Tissue involved in ischemic strangulating obstruction appears pale and of normal or reduced thickness because of a complete lack of blood flow ( Fig. 12.11 ).

T27636

436619-436775

Sentence

denotes

Bowel peripheral to strangulating lesions may also become injured as a result of distention, which reduces mural blood flow once it reaches critical levels.

T16139

436776-436850

Sentence

denotes

As this intestine is decompressed, it may also undergo reperfusion injury.

T21837

436851-436866

Sentence

denotes

879, 1037, 1038

T29974

436868-437045

Sentence

denotes

Horses with small intestinal strangulating obstruction typically have moderate to severe signs of abdominal pain that is only intermittently responsive to analgesic medications.

T302

437046-437211

Sentence

denotes

During the latter stages of the disease process, horses may not experience much pain but rather become profoundly depressed as affected intestine undergoes necrosis.

T5512

437212-437388

Sentence

denotes

Affected horses have progressive signs of sepsis, including congested mucous membranes, delayed capillary refill time, and an elevated heart rate (>60 beats/min in most cases).

T52527

437389-437546

Sentence

denotes

Reflux is typically obtained after passage of a stomach tube, and loops of distended small intestine are usually detected on rectal palpation of the abdomen.

T16016

437547-437641

Sentence

denotes

These latter findings are variable, depending on the duration and location of the obstruction.

T1351

437642-437782

Sentence

denotes

For example, horses with ileal obstructions tend to reflux later in the course of the disease process than horses with jejunal obstructions.

T97575

437783-438009

Sentence

denotes

A horse that has an entrapment of small intestine in the epiploic foramen or a rent in the proximal small intestinal mesentery may not have palpable loops of small intestine because of the cranial location of these structures.

T230

438010-438178

Sentence

denotes

1039 Abdominocentesis can provide critical information on the integrity of the intestine and is indicated in horses with suspected strangulation of the small intestine.

T15058

438179-438400

Sentence

denotes

Affected horses typically have serosanguineous abdominal fluid with an elevated protein concentration (>2.5 mg/dL) and an increase in PF:plasma lactate, although these cases must be differentiated from proximal enteritis.

T46465

438401-438561

Sentence

denotes

11, 22, 783 When an initial sample is inconclusive, repeated measurement of PF lactate may provide additional support for a diagnosis of a strangulating lesion.

T31306

438562-438837

Sentence

denotes

27 Generally, horses with small intestinal strangulation show continued signs of abdominal pain, whereas horses with proximal enteritis (discussed in Duodenitis-Proximal Jejunitis previously in this chapter) tend to be depressed after initial episodes of mild abdominal pain.

T91247

438838-439093

Sentence

denotes

1040 In addition, horses with small intestinal strangulation continue to deteriorate clinically despite appropriate medical therapy and begin to show elevated WBC counts (>10,000 cells/μL) in the abdominal fluid as the duration of strangulation increases.

T62055

439094-439367

Sentence

denotes

There are horses in which small intestinal strangulation and proximal enteritis cannot be not readily distinguished, at which point surgery may be elected rather than prolonging the decision to perform abdominal exploration on a horse with a potential strangulating lesion.

T90968

439368-439372

Sentence

denotes

1040

T7562

439373-439650

Sentence

denotes

The prognosis for survival in horses with small intestinal strangulating lesions is generally lower than for most forms of colic, 995 but some reports indicate that more than 80% of horses with small intestinal strangulating lesions will survive to discharge from the hospital.

T50722

439651-439795

Sentence

denotes

1041 Owners should be warned that long-term survival rates are less than 70%, 1042 in part because of long-term complications such as adhesions.

T50043

439796-439941

Sentence

denotes

1043 , 1044 The prognosis is particularly poor for some forms of strangulation, including entrapment of small intestine within a mesenteric rent.

T52853

439942-440085

Sentence

denotes

1045 Some horses with small intestinal strangulation can be managed surgically without resection, with favorable short-and long-term prognosis.

T56586

440086-440256

Sentence

denotes

1046 Geriatric horses have a higher likelihood of small intestinal strangulation, relative to mature counterparts undergoing colic surgery, but carry a similar prognosis.

T86824

440257-440556

Sentence

denotes

1047 In one hospital, horses with gastrosplenic ligament entrapment (GLE) had higher short-term survival (72.7%), relative to horses with other small intestinal strangulating lesions (50%), 1048 whereas short-term survival was similar between horses with GLE (88%) and EFE (85%) at another hospital.

T52378

440557-440692

Sentence

denotes

1049 Short-term survival in horses with EFE was higher (95%) than for other causes of small intestinal strangulation in another report.

T85040

440693-440697

Sentence

denotes

1050

T22492

440698-440878

Sentence

denotes

The epiploic foramen is a potential opening (because the walls of the foramen are usually in contact) to the omental bursa located within the right cranial quadrant of the abdomen.

T55574

440879-441039

Sentence

denotes

It is bounded dorsally by the caudate process of the liver and caudal vena cava and ventrally by the pancreas, the hepatoduodenal ligament, and the portal vein.

T59877

441040-441169

Sentence

denotes

1039 Intestine may enter the foramen from the visceral surface of the liver toward the right body wall or the opposite direction.

T47609

441170-441221

Sentence

denotes

Studies differ as to which is the most common form.

T11610

441222-441473

Sentence

denotes

In the case of entrapments that enter the foramen in a left-to-right direction, the omental bursa is ruptured as the intestine migrates through the epiploic foramen, which may contribute to the intraabdominal hemorrhage often seen with this condition.

T30418

441474-441596

Sentence

denotes

Clinical signs include acute onset of severe colic with examination findings compatible with small intestinal obstruction.

T81500

441597-441780

Sentence

denotes

The stereotypic behavior of crib biting is a significant risk factor for EFE, 1051 possibly because of changes in abdominal pressure as the horse prepares the esophagus to ingest air.

T32471

441781-441865

Sentence

denotes

Other risk factors include increased height of the horse and previous colic surgery.

T70441

441866-441972

Sentence

denotes

1051 The condition was once believed to be more prevalent in older horses, 1039 but this has been refuted.

T55000

441973-442053

Sentence

denotes

1051 The disorder has also been recognized in foals as young as 4 months of age.

T87228

442054-442250

Sentence

denotes

1052 The diagnosis is definitively made at surgery, although ultrasonographic findings of distended loops of edematous small intestine adjacent to the right middle body wall are suggestive of EFE.

T96868

442251-442397

Sentence

denotes

1039 Generally, thickened, immotile intestine on ultrasonographic examination is highly predictive for small intestinal strangulating obstruction.

T26959

442398-442603

Sentence

denotes

1053, 1054 Small intestine entrapped in the epiploic foramen may be limited to a portion of the intestinal wall (parietal hernia), 1055 and the large colon may become entrapped within the epiploic foramen.

T8464

442604-442797

Sentence

denotes

1051 In treating EFE, the epiploic foramen must not be enlarged either by blunt force or with a sharp instrument, because rupture of the vena cava or portal vein and fatal hemorrhage may occur.

T66519

442798-442950

Sentence

denotes

Prognosis has substantially improved over the past decade, with current short-term survival rates (discharge from the hospital) ranging from 74% to 95%.

T62400

442951-443124

Sentence

denotes

1039, [1049] [1050] [1051] 1056 Survival to 1 year (50.6%) and 2 years (34.3%) postoperatively declines substantially, with a median survival time of 397 days in one report.

T54310

443125-443165

Sentence

denotes

1051 Preoperative abdominocentesis, 1039

T2362

443167-443311

Sentence

denotes

As horses age, lipomas form between the leaves of the mesentery and develop mesenteric stalks as the weight of the lipoma tugs on the mesentery.

T58462

443312-443429

Sentence

denotes

The stalk of the lipoma may subsequently wrap around a loop of small intestine or small colon, causing strangulation.

T75526

443430-443754

Sentence

denotes

Strangulating lipomas should be suspected in aged (>15 years) geldings with acute colic referable to the small intestinal tract. [1057] [1058] [1059] Ponies also appear to be at risk for developing disease, 1059 suggesting alterations in fat metabolism may predispose certain horses to the development of mesenteric lipomas.

T88930

443755-443858

Sentence

denotes

The diagnosis is usually made at surgery, although on rare occasions a lipoma can be palpated rectally.

T67098

443859-443991

Sentence

denotes

Treatment involves surgical resection of the lipoma and strangulated bowel, although strangulated intestine is not always nonviable.

T76093

443992-444122

Sentence

denotes

1059 Studies indicate that approximately 50% 1058 to 78% 1059 of horses are discharged from the hospital after surgical treatment.

T36499

444123-444250

Sentence

denotes

A volvulus is a twist along the axis of the mesentery, whereas torsion is a twist along the longitudinal axis of the intestine.

T23346

444251-444451

Sentence

denotes

Small intestinal volvulus is theoretically initiated by a change in local peristalsis or the occurrence of a lesion around which the intestine and its mesentery may twist (e.g., an ascarid impaction).

T61097

444452-444557

Sentence

denotes

1060 It is reportedly one of the most commonly diagnosed causes of small intestinal obstruction in foals.

T63055

444558-444724

Sentence

denotes

1061, 1062 It has been theorized that young foals may be at risk for small intestinal volvulus because of changing feed habits and adaptation to a bulkier adult diet.

T42398

444725-444913

Sentence

denotes

Onset of acute, severe colic; a distended abdomen; and radiographic evidence of multiple loops of distended small intestine in a young foal would be suggestive of small intestine volvulus.

T94285

444914-445033

Sentence

denotes

However, it is not possible to differentiate volvulus from other causes of small intestinal obstruction preoperatively.

T99080

445034-445267

Sentence

denotes

In adult horses volvulus frequently occurs in association with another disease process, during which small intestinal obstruction results in distention and subsequent rotation of the small intestinal around the root of the mesentery.

T11696

445268-445434

Sentence

denotes

Although any segment of the small intestine may be involved, the distal jejunum and ileum are most frequently affected because of their relatively longer mesenteries.

T70378

445435-445541

Sentence

denotes

1060 The diagnosis is made at surgery by palpating a twist at the origin of the cranial mesenteric artery.

T12420

445542-445708

Sentence

denotes

Treatment includes resection of devitalized bowel, which may not be an option because of the extent of small intestinal involvement (similar to large colon volvulus).

T66140

445709-445829

Sentence

denotes

Prognosis is based on the extent of small intestine involved and its appearance after surgical correction of the lesion.

T62311

445830-445950

Sentence

denotes

Generally, horses in which more than 50% of the small intestine is devitalized are considered to have a grave prognosis.

T61851

445951-445955

Sentence

denotes

1063

T28374

445956-446210

Sentence

denotes

There are a number of structures that, when torn, may incarcerate a segment of intestine (typically the small intestine), including intestinal mesentery, 1045 the gastrosplenic ligament, 1048,1049,1064 the broad ligament, 1065 and the cecocolic ligament.

T86490

446211-446316

Sentence

denotes

1066 Horses with such incarcerations present signs typical of a horse with strangulating small intestine.

T30595

446317-446443

Sentence

denotes

The prognosis for many of these cases appears to be worse than for horses with other types of small intestinal strangulations.

T78731

446444-446662

Sentence

denotes

Of horses with small intestine entrapped in a mesenteric rent, only 7 of 15 horses were discharged from the hospital, and only 2 of 5 horses for which follow-up information was available survived long term (>5 months).

T45494

446663-446816

Sentence

denotes

1045 Poor outcome may result from the difficulty in releasing the incarcerated intestine, the degree of hemorrhage, and the length of intestine affected.

T96250

446817-446948

Sentence

denotes

Inguinal hernias are more common in Standardbred and Tennessee Walking Horses that tend to have congenitally large inguinal canals.

T48743

446949-447089

Sentence

denotes

1060 Inguinal hernias may also occur in neonatal foals but differ from hernias in mature horses in that they are typically nonstrangulating.

T6292

447090-447214

Sentence

denotes

The nature of the hernia (direct versus indirect) is determined on the basis of the integrity of the parietal vaginal tunic.

T36270

447215-447400

Sentence

denotes

In horses in which the bowel remains within the parietal vaginal tunic, the hernia is referred to as indirect because, strictly speaking, the bowel remains within the peritoneal cavity.

T6390

447401-447526

Sentence

denotes

Direct hernias are those in which strangulated bowel ruptures through the parietal vaginal tunic and occupies an SC location.

T53778

447527-447762

Sentence

denotes

These direct hernias most commonly occur in foals and should be suspected when a congenital inguinal hernia is associated with colic, swelling that extends from the inguinal region of the prepuce, and intestine that may be palpated SC.

T16218

447763-447959

Sentence

denotes

1067, 1068 Although most congenital indirect inguinal hernias resolve with repeated manual reduction or application of a diaper, surgical intervention is recommended for congenital direct hernias.

T83168

447960-448115

Sentence

denotes

1068 Historical findings in horses with strangulating inguinal hernias include acute onset of colic in a stallion that had recently been used for breeding.

T55598

448116-448326

Sentence

denotes

A cardinal sign of inguinal herniation is a cool, enlarged testicle on one side of the scrotum. [1069] [1070] [1071] However, inguinal hernias, including of the large colon, have also been reported in geldings.

T17961

448327-448547

Sentence

denotes

1072, 1073 Inguinal hernias can be detected on rectal palpation, and manipulation of herniated bowel per rectum has been used to reduce a hernia, but this procedure is not recommended because of the risk of rectal tears.

T54146

448548-448705

Sentence

denotes

In many horses the short segment of herniated intestine will markedly improve in appearance once it has been reduced and does not always have to be resected.

T31638

448706-448892

Sentence

denotes

1074 The affected testicle will be congested because of vascular compromise within the spermatic cord, and although it may remain viable, it is generally recommended that it be resected.

T46555

448893-449089

Sentence

denotes

1074 The prognosis in adult horses is good, with up to 75% of horses surviving to 6 months of age. [1069] [1070] [1071] Horses that have been treated for inguinal hernias may be used for breeding.

T4724

449090-449307

Sentence

denotes

In these horses the remaining testicle will have increased sperm production, although an increased number of sperm abnormalities will be noticed after surgery because of edema and increased temperature of the scrotum.

T39017

449308-449397

Sentence

denotes

Although umbilical hernias are common in foals, strangulation of herniated bowel is rare.

T73305

449398-449483

Sentence

denotes

In one study, 6 of 147 (4%) horses with umbilical hernias had incarcerated intestine.

T86927

449484-449589

Sentence

denotes

1075 Clinical signs include a warm, swollen, firm, and painful hernia sac associated with signs of colic.

T27338

449590-449710

Sentence

denotes

The affected segment of bowel is usually small intestine, but herniation of cecum or large colon has also been reported.

T43306

449711-449834

Sentence

denotes

1076 In rare cases a hernia that involves only part of the intestinal wall may be found; this is termed a Richter's hernia.

T11969

449835-449913

Sentence

denotes

In foals that have a Richter's hernia, an enterocutaneous fistula may develop.

T56075

449914-450065

Sentence

denotes

1076 In one study, 13 of 13 foals with strangulating umbilical hernias survived to discharge, although at least 3 were lost to long-term complications.

T40456

450066-450070

Sentence

denotes

1076

T31757

450071-450211

Sentence

denotes

An intussusception involves a segment of bowel (intussusceptum) that invaginates into an adjacent aboral segment of bowel (intussuscipiens).

T24218

450212-450391

Sentence

denotes

The reason for such invagination is not always clear, but it may involve a lesion at the leading edge of the intussusception, including small masses, foreign bodies, or parasites.

T34390

450392-450465

Sentence

denotes

In particular, tapeworms (Anoplocephala perfoliata) have been implicated.

T96181

450466-450594

Sentence

denotes

1077 Ileocecal intussusceptions are the most common intestinal intussusceptions in the horse and typically affect young animals.

T8500

450595-450703

Sentence

denotes

In one study evaluating 26 cases of ileocecal intussusception, the median age of affected horses was 1 year.

T56866

450704-450918

Sentence

denotes

1078 Acute ileocecal intussusceptions are those in which the horses have a duration of colic of less than 24 hours and involve variable lengths of intestine, which ranged in one study from 6 cm to 457 cm in length.

T95914

450919-451005

Sentence

denotes

In acute cases the involved segment of ileum typically has a compromised blood supply.

T66129

451006-451156

Sentence

denotes

Chronic ileocecal intussusceptions typically involve short segments of ileum (up to 10 cm in length), and the ileal blood supply is frequently intact.

T30556

451157-451266

Sentence

denotes

1078 Abdominocentesis results are variable because strangulated bowel is contained within the adjacent bowel.

T71153

451267-451427

Sentence

denotes

There is often evidence of obstruction of the small intestine, including nasogastric reflux and multiple distended loops of small intestine on rectal palpation.

T92838

451428-451561

Sentence

denotes

Horses with chronic ileocecal intussusceptions have mild, intermittent colic, often without evidence of small intestinal obstruction.

T86564

451562-451667

Sentence

denotes

In one study a mass was palpated in the region of the cecal base in approximately 50% of affected horses.

T32268

451668-451751

Sentence

denotes

1078 Transabdominal ultrasound may be helpful in discerning the nature of the mass.

T25118

451752-451926

Sentence

denotes

The intussusception has a characteristic target appearance on cross section [1079] [1080] [1081] and has been reported as a frequent incidental finding in Standardbred foals.

T22422

451927-452034

Sentence

denotes

1082 Other segments of the small intestine may also be intussuscepted, including the jejunum (Fig. 12.12) .

T29179

452035-452144

Sentence

denotes

In one study of 11 jejunojejunal intussusceptions, the length of bowel involved ranged between 0.4 and 9.1 m.

T94156

452145-452267

Sentence

denotes

1083 Attempts at reducing intussusceptions at surgery are usually futile because of intramural swelling of affected bowel.

T79351

452268-452318

Sentence

denotes

Jejunojejunal intussusceptions should be resected.

T74797

452319-452476

Sentence

denotes

For acute ileocecal intussusceptions the small intestine should be transected as far distally as possible, and a jejunocecal anastomosis should be performed.

T67967

452477-452599

Sentence

denotes

In cases with particularly long intussusceptions (up to 10 m has been reported), an intracecal resection may be attempted.

T20869

452600-452735

Sentence

denotes

1084 For horses with chronic ileocecal intussusceptions, a jejunocecal bypass without small intestinal transection should be performed.

T93575

452736-452921

Sentence

denotes

The prognosis is good for horses with chronic ileocecal intussusceptions and guarded to poor for horses with acute ileocecal intussusceptions, depending on the length of bowel involved.

T26291

452922-452926

Sentence

denotes

1078

T4675

452927-453004

Sentence

denotes

Herniation of intestine through a rent in the diaphragm is rare in the horse.

T81448

453005-453097

Sentence

denotes

Any segment of bowel may be involved, although small intestine is most frequently herniated.

T44370

453098-453191

Sentence

denotes

1085 Diaphragmatic rents may be congenital or acquired, but acquired hernias are more common.

T79456

453192-453389

Sentence

denotes

1085 Congenital rents may result from incomplete fusion of any of the four embryonic components of the diaphragm: pleuroperitoneal membranes, transverse septum, body wall, and esophageal mesentery.

T36374

453390-453478

Sentence

denotes

1085 Abdominal compression of the foal at parturition may result in a congenital hernia.

T57906

453479-453703

Sentence

denotes

1085 Acquired hernias are presumed to result from trauma to the chest or a sudden increase in intraabdominal pressure, such as might occur during parturition, distention of the abdomen, a sudden fall, and strenuous exercise.

T10379

453704-453974

Sentence

denotes

1086 Hernias have been described in a number of different locations; large congenital hernias are typically present at the ventralmost aspect of the diaphragm, and most acquired hernias are located at the junction of the muscular and tendinous portions of the diaphragm.

T97710

453975-454052

Sentence

denotes

1085 A peritoneopericardial hernia has been documented in at least one horse.

T62903

454053-454161

Sentence

denotes

1087 The clinical signs are usually associated with intestinal obstruction rather than respiratory distress.

T20523

454162-454313

Sentence

denotes

1086 Careful auscultation may reveal an area of decreased lung sounds associated with obstructed intestine and increased fluid within the chest cavity.

T41070

454314-454423

Sentence

denotes

1088 Such signs may prompt thoracic radiography or ultrasound, both of which can be used to make a diagnosis.

T37781

454424-454575

Sentence

denotes

Auscultation may also reveal thoracic intestinal sounds, but it is typically not possible to differentiate these from sounds referred from the abdomen.

T87274

454576-454745

Sentence

denotes

In one report, two of three horses diagnosed with small intestinal strangulation by diaphragmatic hernia had respiratory acidemia, attributable to decreased ventilation.

T59495

454746-455224

Sentence

denotes

1089 Treatment of horses with diaphragmatic hernia is fraught with complications because of the need to reduce and resect strangulated bowel and the need to repair the defect in the diaphragm; prognosis has not appeared to improve over time. [1089] [1090] [1091] [1092] Because dorsal defects in the diaphragm are among the most common forms of diaphragmatic defect, it may not be possible to close the diaphragmatic hernia by way of the approach used for abdominal exploratory.

T51035

455225-455377

Sentence

denotes

Because herniation is likely to recur, it is appropriate to schedule a second surgery using an appropriate approach to resolve the diaphragmatic defect.

T2646

455378-455466

Sentence

denotes

Horses with large colon volvulus have rapid onset of severe, unrelenting abdominal pain.

T77416

455467-455533

Sentence

denotes

Postpartum broodmares appear to be at risk for this form of colic.

T58583

455534-455819

Sentence

denotes

1035 Once the large colon is strangulated (>270-degree volvulus), gas distention is marked, leading to gross distention of the abdomen, compromised respiration as the distended bowel presses up against the diaphragm, and visceral pooling of blood as the caudal vena cava is compressed.

T72021

455820-455911

Sentence

denotes

Horses with this condition are frequently refractory to even the most potent of analgesics.

T53551

455912-456018

Sentence

denotes

These horses may prefer to lie in dorsal recumbency, presumably to take weight off the strangulated colon.

T54679

456019-456167

Sentence

denotes

An abbreviated physical examination is warranted in these cases because the time from the onset of strangulation to surgical correction is critical.

T57176

456168-456297

Sentence

denotes

Under experimental conditions the colon is irreversibly damaged within 3 to 4 hours of a 360-degree volvulus of the entire colon.

T74438

456298-456428

Sentence

denotes

855 Despite severe pain and hypovolemia, horses may have a paradoxically low heart rate, possibly related to increased vagal tone.

T35025

456429-456633

Sentence

denotes

Results of abdominocentesis often do not indicate the degree of colonic compromise, 1035, 1093 and in many cases it is not worth attempting to obtain abdominal fluid because of extreme colonic distention.

T74792

456634-456770

Sentence

denotes

1093 Rectal palpation reveals severe gas distention of the large colon, frequently associated with colonic bands traversing the abdomen.

T34977

456771-456855

Sentence

denotes

Severe colonic distention may restrict access to the abdomen beyond the pelvic brim.

T3578

456856-457029

Sentence

denotes

One study has shown that plasma lactate levels below 6.0 mmol/L had a sensitivity of 84% and a specificity of 83% in predicting survival in horses with large colon volvulus.

T38494

457030-457034

Sentence

denotes

1094

T77369

457035-457263

Sentence

denotes

At surgery the volvulus is typically located at the mesenteric attachment of the colon to the dorsal body wall, and the most common direction of the twist is dorsomedial when the right ventral colon is used as a reference point.

T71277

457264-457459

Sentence

denotes

1035 However, the colon may twist in the opposite direction, twist greater than 360 degrees (up to 720 degrees has been reported), or twist at the level of the diaphragmatic and sternal flexures.

T44892

457460-457653

Sentence

denotes

1035 In all cases the colon should be decompressed as much as possible, and in many cases a colonic evacuation by way of a pelvic flexure enterotomy will greatly aid correction of the volvulus.

T6807

457654-457771

Sentence

denotes

After correction of the volvulus, a determination must be made as to whether the colon has been irreversibly injured.

T58910

457772-457958

Sentence

denotes

This should be based on mucosal color and bleeding (if an enterotomy has been performed), palpation of a pulse in the colonic arteries, serosal color, and appearance of colonic motility.

T16379

457959-458076

Sentence

denotes

1036 If the colon is judged to be irreversibly damaged, the feasibility of a large colon resection can be considered.

T93359

458077-458250

Sentence

denotes

Although 95% of the colon can be resected (that part of the colon distal to the level of the cecocolic fold), damage from the volvulus may exceed that which can be resected.

T445

458251-458350

Sentence

denotes

In these cases surgeons may elect to resect as much damaged bowel as possible or advise euthanasia.

T58649

458351-458355

Sentence

denotes

1036

T81077

458356-458465

Sentence

denotes

Although early reports of short-term survival were low (35%), 1093 survival can vary with degree of volvulus.

T12852

458466-458595

Sentence

denotes

Shortterm survival was reported as 36% for horses with 360-degree volvulus compared with 71% for horses with 270-degree volvulus.

T41882

458596-458730

Sentence

denotes

1035 More recent studies report higher short-term survival (88%), with duration of disease as a major factor associated with survival.

T88143

458731-458942

Sentence

denotes

1095 Impression of improved prognosis was echoed in a recent survey of the American Colleges of Veterinary Surgery Diplomates, who also note time to surgery as the most important factor associated with survival.

T6162

458943-459141

Sentence

denotes

1096 Another study reports much higher short-term survival (74%) with large colon resection, along with positive survival rates at 1 year (67.8%), 2 years (66%), and 3 years (63.5%) postoperatively.

T42902

459142-459286

Sentence

denotes

1097 Postoperative complications include hypovolemic and endotoxemic shock, extensive loss of circulating protein, DIC, diarrhea, and laminitis.

T89588

459287-459339

Sentence

denotes

Large colon volvulus may have a propensity to recur.

T29088

459340-459464

Sentence

denotes

Although one study documented a recurrence rate of less than 5%, 1093 some authors believe recurrence may be as high as 50%.

T7072

459465-459653

Sentence

denotes

1036 Methods to prevent recurrence may be considered in patients at risk for recurrence, particularly broodmares that tend to suffer from the disease recurrently during the foaling season.

T37050

459654-459658

Sentence

denotes

1098

T13156

459659-459743

Sentence

denotes

The most common intussusceptions of the large intestine are cecocecal and cecocolic.

T44644

459744-459844

Sentence

denotes

1099 Both are likely attributable to the same disease process, with variable inversion of the cecum.

T95324

459845-459989

Sentence

denotes

These conditions tend to occur in young horses (63% were younger than 3 years old in one study) and may be associated with intestinal tapeworms.

T51038

459990-460120

Sentence

denotes

1099 Clinical signs are variable, including acute, severe colic, intermittent pain over a number of days, and chronic weight loss.

T16597

460121-460221

Sentence

denotes

1099 These variable presentations likely relate to the degree to which the cecum has intussuscepted.

T57896

460222-460338

Sentence

denotes

Initially, the cecal tip inverts, creating a cecocecal intussusception, which does not obstruct the flow of ingesta.

T35287

460339-460531

Sentence

denotes

As the intussusception progresses, the cecum inverts into the right ventral colon (cecocolic intussusception), which obstructs the flow of ingesta and often causes severe colic (Fig. 12.13 ).

T74939

460532-460749

Sentence

denotes

The cause of abdominal pain is often difficult to differentiate in these cases, although it is sometimes possible to detect a mass on the right side of the abdomen by either rectal palpation or ultrasound examination.

T44348

460750-460896

Sentence

denotes

1099 Treatment involves manual surgical reduction by retracting the intussusceptum directly or by way of an enterotomy in the right ventral colon.

T74161

460897-461053

Sentence

denotes

1099, 1100 Sometimes the cecum cannot be readily reduced because of severe thickening, and in other cases surgical procedures result in fatal contamination.

T47131

461054-461244

Sentence

denotes

In one report 8 of 11 horses were euthanized in the perioperative period because of complications, 1101 and in another report 12 of 30 horses were euthanized either before or during surgery.

T84116

461245-461334

Sentence

denotes

The latter included all of the horses with chronic disease because of irreversible FIG.

T50000

461335-461338

Sentence

denotes

12.

T63018

461339-461390

Sentence

denotes

13 Cecocolic intussusception in a horse with colic.

T78483

461391-461504

Sentence

denotes

An enterotomy has been made in the right ventral colon (short arrows) to reveal an intussuscepted cecum (arrows).

T84990

461505-461677

Sentence

denotes

Although this picture was taken at necropsy, an enterotomy such as the one shown in this figure can be used to exteriorize and resect the majority of the compromised cecum.

T70073

461678-461730

Sentence

denotes

Note the ileum adjacent to the colon (double arrow).

T11978

461731-461752

Sentence

denotes

changes to the cecum.

T99175

461753-462007

Sentence

denotes

1099 One report on cecocolic intussusceptions indicated that 7 of 8 horses that underwent right ventral colon enterotomy and cecal resection survived long term, 1100 suggesting that continued improvements in surgical techniques may improve the prognosis.

T86340

462008-462252

Sentence

denotes

Colocolic intussusceptions are exceptionally rare but have reportedly affected the pelvic flexure and the left colon. [1102] [1103] [1104] Although the condition is reportedly more common in young horses, 1102,1104 older horses may be affected.

T12530

462253-462336

Sentence

denotes

1103 Clinical findings may include a palpable mass on the left side of the abdomen.

T88105

462337-462377

Sentence

denotes

1102 Ultrasonography may also be useful.

T6344

462378-462479

Sentence

denotes

Treatment requires manual reduction of the intussusception at surgery or resection of affected bowel.

T63002

462480-462868

Sentence

denotes

Because the left colons can be extensively exteriorized and manipulated at surgery, the prognosis is fair. [1102] [1103] [1104] Y RECTAL PROLAPSE Rectal prolapse may occur secondary to any disease that causes tenesmus, including diarrhea, rectal neoplasia, and parasitism, 1105 or it can occur secondary to elevations in intraabdominal pressure during parturition or episodes of coughing.

T93871

462869-463009

Sentence

denotes

1106 Rectal prolapse is classified into four categories (Table 12 .7) depending on the extent of prolapsed tissue and the level of severity.

T94901

463010-463149

Sentence

denotes

1107 Type I rectal prolapse is most common and is characterized by a doughnut-shaped prolapse of rectal mucosa and submucosa (Fig. 12.14) .

T46606

463150-463289

Sentence

denotes

Type II prolapse involves full-thickness rectal tissue, and type III prolapse additionally has invagination of small colon into the rectum.

T42873

463290-463462

Sentence

denotes

Type IV prolapse involves intussusception of proximal rectum or small colon through the anus in the absence of prolapse of tissue at the mucocutaneous junction at the anus.

T22053

463463-463605

Sentence

denotes

1107 These can be differentiated from other forms of prolapse by their appearance and a palpable trench between prolapsed tissue and the anus.

T74815

463606-463770

Sentence

denotes

Type I prolapses are most frequently seen in horses with diarrhea, and the rectal mucosa becomes irritated and protrudes intermittently during episodes of tenesmus.

T80854

463771-463828

Sentence

denotes

If tenesmus persists, rectal mucosa can remain prolapsed.

T98282

463829-464029

Sentence

denotes

Rectal mucosa rapidly becomes congested and edematous under these conditions and should be treated with osmotic agents such as glycerin or magnesium sulfate and by massaging and reducing the prolapse.

T69727

464030-464111

Sentence

denotes

1108 A purse-string suture may be necessary to keep the mucosa inside the rectum.

T94368

464112-464268

Sentence

denotes

Topical application of lidocaine solution or jelly, epidural anesthesia, and sedation may help reduce tenesmus that incites and exacerbates rectal prolapse.

T99551

464269-464333

Sentence

denotes

Similar treatments can be applied with type II rectal prolapses.

T49364

464334-464468

Sentence

denotes

However, these more severe prolapses may not be reducible without surgical resection of mucosa and submucosa from the prolapsed bowel.

T60036

464469-464576

Sentence

denotes

1105, 1106 Types III and IV rectal prolapses are more serious injuries because the small colon is involved.

T55559

464577-464735

Sentence

denotes

1109 In horses with type III prolapse, an abdominocentesis should be performed to determine whether the injury to the small colon has resulted in peritonitis.

T12412

464736-464885

Sentence

denotes

The small colon component should be reduced manually if possible, whereas prolapsed rectal tissue typically requires mucosal or submucosal resection.

T89410

464886-465094

Sentence

denotes

Surgical exploration of the abdomen should be performed to determine the status of the small colon, although serial abdominocenteses can be used in lieu of surgery to detect progressive necrosis of the bowel.

T44902

465095-465160

Sentence

denotes

Type IV prolapses are seen most commonly in horses with dystocia.

T43481

465161-465317

Sentence

denotes

1106 This type of prolapse is almost always fatal because of stretching and tearing of mesenteric vasculature, with subsequent infarction of affected bowel.

T26367

465318-465394

Sentence

denotes

Euthanasia is often warranted on the basis of physical examination findings.

T12127

465395-465515

Sentence

denotes

Confirmation of severe small colon injury requires abdominal exploration using either a midline approach or laparoscopy.

T71405

465516-465762

Sentence

denotes

1110 It is conceivable that a horse with a compromised small colon could undergo a colostomy of the proximal small colon, but the compromised small colon will typically necrose beyond that which can be resected using a midline abdominal approach.

T85778

465763-465767

Sentence

denotes

1108

T12383

465768-465975

Sentence

denotes

Nonstrangulating infarction occurs secondary to cranial mesenteric arteritis caused by migration of S. vulgaris 1111 and has become a relatively rare disorder since the advent of broadspectrum anthelmintics.

T92393

465976-466200

Sentence

denotes

Although thromboemboli have been implicated in the pathogenesis of this disease, careful dissection of naturally occurring lesions has not revealed the presence of thrombi at the site of intestinal infarctions in most cases.

T36690

466201-466284

Sentence

denotes

1111 These findings suggest that vasospasm plays an important role in this disease.

T32839

466285-466422

Sentence

denotes

1060 Clinical signs are highly variable, depending on the extent to which arterial flow is reduced and the segment of intestine affected.

T94332

466423-466610

Sentence

denotes

Any segment of intestine supplied by the cranial mesenteric artery or one of its major branches may be affected, but the distal small intestine and large colon are more commonly involved.

T8973

466611-466735

Sentence

denotes

1111 There are no clinical variables that can be used to reliably differentiate this disease from strangulating obstruction.

T37024

466736-466785

Sentence

denotes

1099 In some cases massive infarction results 12.

T84190

466786-466823

Sentence

denotes

14 Type I rectal prolapse in a horse.

T25020

466824-466977

Sentence

denotes

Note circumferential protrusion of partial-thickness rectal tissue (arrows) that is becoming congested as a result of pressure from the surrounding anus.

T3775

466978-467001

Sentence

denotes

in acute, severe colic.

T78156

467002-467132

Sentence

denotes

1111 Occasionally, an abnormal mass and fremitus may be detected on rectal palpation of the root of the cranial mesenteric artery.

T6980

467133-467323

Sentence

denotes

This disease should be considered a differential diagnosis in horses with a history of inadequate anthelmintic treatment and the presence of intermittent colic that is difficult to localize.

T42279

467324-467443

Sentence

denotes

Although fecal parasite egg counts should be performed, they are not indicative of the degree of parasitic infestation.

T19790

467444-467594

Sentence

denotes

In addition to routine treatment of colic, dehydration, and endotoxemia, medical treatment may include aspirin (20 mg/ kg/day) to decrease thrombosis.

T53587

467595-467649

Sentence

denotes

11 Definitive diagnosis requires surgical exploration.

T32638

467650-467823

Sentence

denotes

Affected horses can be difficult to treat because of the patchy distribution of the lesions and the possibility of lesions extending beyond the limits of surgical resection.

T41309

467824-467867

Sentence

denotes

Further infarction may occur after surgery.

T70079

467868-468036

Sentence

denotes

The prognosis is fair for horses with intermittent mild episodes of colic that may be amenable to medical therapy but poor in horses that require surgical intervention.

T27429

468037-468041

Sentence

denotes

1111

T96266

468042-468161

Sentence

denotes

Examination and approach to the horse with colic are discussed in Chapter 7; pain management is discussed in Chapter 3.

T4502

468162-468256

Sentence

denotes

These are critical factors in the diagnosis and treatment of a horse with obstructive disease.

T63957

468257-468358

Sentence

denotes

Simple obstruction involves intestinal obstruction of the lumen without obstruction of vascular flow.

T70872

468359-468563

Sentence

denotes

Because there is a tremendous volume of fluid that enters the small intestinal lumen on a daily basis, the obstructed intestine tends to become distended, which in turn may cause reduced mural blood flow.

T38434

468564-468689

Sentence

denotes

879 Ultimately, such distention can result in necrosis of tissues, particularly in the immediate vicinity of the obstruction.

T73976

468690-468905

Sentence

denotes

1112 There are relatively few causes of simple obstruction in the small intestine, and the incidence of these types of obstructions is low (approximately 3% of all referred horses in one large hospital-based study).

T66222

468906-468987

Sentence

denotes

1041 In some geographic regions this type of obstruction has a higher prevalence.

T55038

468988-469075

Sentence

denotes

For example, in the southeastern United States, ileal impactions are relatively common.

T21707

469077-469247

Sentence

denotes

Impactions caused by Parascaris equorum typically occur in foals younger than 6 months of age that have been on a poor deworming program and have a heavy parasite burden.

T76202

469248-469436

Sentence

denotes

Products that cause sudden ascarid death, including organophosphates, ivermectin, and pyrantel pamoate, have been incriminated in triggering acute intestinal obstruction by dead parasites.

T68723

469437-469544

Sentence

denotes

1116 This is a particular problem with ascarids because of the relatively large size of the adult parasite.

T23948

469545-469714

Sentence

denotes

Clinical signs include acute onset of colic after administration of an anthelmintic and signs compatible with small intestinal obstruction, including nasogastric reflux.

T11756

469715-469770

Sentence

denotes

Occasionally, dead parasites are present in the reflux.

T72612

469771-469842

Sentence

denotes

The onset of the disease varies according to the degree of obstruction.

T94646

469843-469962

Sentence

denotes

1116 A tentative diagnosis may be made on the basis of the history and signs referable to small intestinal obstruction.

T46683

469963-470127

Sentence

denotes

Abdominal ultrasound may indicate the presence of multiple loops of distended small intestine and can be used to estimate ascarid burden within the small intestine.

T60543

470128-470210

Sentence

denotes

1117 Initial medical treatment should include pain management and supportive care.

T93758

470211-470374

Sentence

denotes

Surgical treatment may involve an enterotomy removal of ascarids, although manual reduction without enterotomy was associated with improved survival in one report.

T29712

470375-470502

Sentence

denotes

1118 The prognosis is fair in cases that are rapidly addressed but poor in foals with evidence of hypovolemia and septic shock.

T32941

470503-470566

Sentence

denotes

In one study, long-term survival of 25 affected horses was 33%.

T61350

470567-470640

Sentence

denotes

1116 Another reported 80% short-term survival and 60% survival to 1 year.

T15346

470641-470645

Sentence

denotes

1118

T71847

470646-470733

Sentence

denotes

Ileal impactions occur most commonly in adult horses in the southeastern United States.

T83352

470734-470926

Sentence

denotes

Although feeding of coastal Bermuda hay has been implicated in this regional distribution, 1115 it has been difficult to separate geographic location from regional hay sources as risk factors.

T34214

470927-471170

Sentence

denotes

1119 Nonetheless, it is likely that feeding suboptimal quality coastal Bermuda hay puts horses at risk for ileal impaction, possibly because this type of hay may have a high fiber content and thin strands that can lead to premature swallowing.

T15966

471171-471270

Sentence

denotes

The relationship between fiber content and eating patterns is theoretical and remains to be proved.

T21554

471271-471396

Sentence

denotes

Sudden changes in feed from an alternative type of hay to coastal Bermuda hay likely put a horse at risk for ileal impaction.

T37219

471397-471513

Sentence

denotes

1119 Studies in the United Kingdom have revealed tapeworm infection as an important risk factor for ileal impaction.

T56836

471514-471684

Sentence

denotes

Based on risk analysis, the data suggested that more than 80% of the ileal impaction cases studied were associated with serologic or fecal evidence of tapeworm infection.

T11042

471685-471883

Sentence

denotes

1120 Because of the poor sensitivity of fecal analysis for tapeworms, a serologic test (ELISA) has been developed by Proudman et al. with a sensitivity of approximately 70% and a specificity of 95%.

T10238

471884-472129

Sentence

denotes

1121, 1122 Clinical signs of horses with ileal impaction are typical for a horse with small intestinal obstruction, including onset of moderate to severe colic and rectally palpable loops of distended small intestine as the condition progresses.

T91068

472130-472451

Sentence

denotes

Because the ileum is the distal-most aspect of the small intestinal tract, nasogastric reflux may take a considerable time to develop and is found in only approximately 50% to 60% of horses requiring surgical correction of impacted ileum 1113, 1123 ; reflux is more likely in horses with ileal impaction taken to surgery.

T93745

472452-472572

Sentence

denotes

1113 A definitive diagnosis is usually made at surgery, although an impacted ileum may on occasion be palpated rectally.

T14047

472573-472662

Sentence

denotes

1114 Multiple loops of distended small intestine make the impaction difficult to palpate.

T80236

472663-472732

Sentence

denotes

More than 50% of ileal impactions may resolve with medical treatment.

T85763

472733-472908

Sentence

denotes

1113 Most reports indicate a good to excellent prognosis for short-term survival 1113, 1115, 1123 with 1-year survival of 91% to 92% in horses treated surgically or medically.

T18021

472909-472913

Sentence

denotes

1113

T45289

472914-473118

Sentence

denotes

Ileal hypertrophy is a disorder in which the muscular layers (both circular and longitudinal) of the ileum thicken for unknown reasons (idiopathic) or secondary to an incomplete or functional obstruction.

T28984

473119-473326

Sentence

denotes

A proposed mechanism for idiopathic ileal hypertrophy is parasympathetic neural dysfunction resulting in chronically increased muscle tone and subsequent hypertrophy of the muscular layers of the ileal wall.

T39755

473327-473392

Sentence

denotes

Such neural dysfunction possibly results from parasite migration.

T65096

473393-473598

Sentence

denotes

1124 Alternative hypotheses include chronic increases in the muscular tone of the ileocecal valve, leading to muscular hypertrophy of the ileum as it contracts against a partially occluded ileocecal valve.

T67068

473599-473684

Sentence

denotes

The jejunum may also be hypertrophied, either alone or in combination with the ileum.

T78926

473685-473800

Sentence

denotes

1124 Clinical signs include chronic intermittent colic as the ileum hypertrophies and gradually occludes the lumen.

T87357

473801-473961

Sentence

denotes

Partial anorexia and chronic weight loss (1-6 months) were documented in 45% of affected horses, most likely because of intermittent colic and reduced appetite.

T49332

473962-474113

Sentence

denotes

1124 Because the ileal mucosa is not affected by this condition, there is no reason to believe that these horses experience malabsorption of nutrients.

T7614

474114-474228

Sentence

denotes

The diagnosis is usually made at surgery, although the hypertrophied ileum may be palpated rectally in some cases.

T37622

474229-474348

Sentence

denotes

1124 An ileocecal or jejunocecal anastomosis to bypass the hypertrophied ileum is usually performed in affected horses.

T32147

474349-474449

Sentence

denotes

Without surgical bypass intermittent colic persists, and the thickened ileum may ultimately rupture.

T58120

474450-474501

Sentence

denotes

1124 The prognosis is fair with surgical treatment.

T12032

474502-474684

Sentence

denotes

1125 Secondary ileal hypertrophy is most commonly noted in horses that have previously had colic surgery and that may have a partial or functional obstruction at an anastomotic site.

T3235

474685-474811

Sentence

denotes

For example, in one case report a horse developed ileal hypertrophy after surgical correction of an ileocecal intussusception.

T60634

474812-474970

Sentence

denotes

1126 Ileal hypertrophy was also observed in a horse in which an ileocolic anastomosis was incorrectly oriented during surgical treatment of a cecal impaction.

T72749

474971-475047

Sentence

denotes

1000 Horses are typically reexamined for recurrence of colic in these cases.

T42855

475048-475171

Sentence

denotes

Surgical therapy is directed at addressing the cause of small intestinal obstruction and resecting hypertrophied intestine.

T45929

475172-475363

Sentence

denotes

Meckel's diverticulum is an embryonic remnant of the vitelloumbilical duct, which fails to completely atrophy and becomes a blind pouch projecting from the antimesenteric border of the ileum.

T33976

475364-475431

Sentence

denotes

1127, 1128 Similar diverticula have also been noted in the jejunum.

T98039

475432-475593

Sentence

denotes

1129 These diverticula may become impacted, resulting in partial luminal obstruction, or may wrap around an adjacent segment of intestine, causing strangulation.

T30524

475594-475781

Sentence

denotes

1128 Occasionally, an associated mesodiverticular band may course from the diverticulum to the umbilical remnant and serve as a point around which small intestine may become strangulated.

T20130

475782-475986

Sentence

denotes

Mesodiverticular bands may also originate from the embryonic ventral mesentery and attach to the antimesenteric surface of the bowel, forming a potential space within which intestine may become entrapped.

T22986

475987-476145

Sentence

denotes

1038 Clinical signs range from chronic colic, for an impacted Meckel's diverticulum, to acute, severe colic if a mesodiverticular band strangulates intestine.

T91602

476146-476258

Sentence

denotes

The diagnosis is made at surgery, and treatment requires resection of the diverticulum and any associated bands.

T97624

476259-476419

Sentence

denotes

1038 The prognosis is good for horses with simple impaction of a Meckel's diverticulum and guarded for horses with an associated small intestinal strangulation.

T42379

476420-476424

Sentence

denotes

1038

T62740

476425-476691

Sentence

denotes

Adhesions of one segment of bowel to another or of a segment of intestine to other organs and the body wall typically occur after abdominal surgery and may be clinically silent, cause chronic colic attributable to partial obstruction, or result in acute obstruction.

T12622

476692-476782

Sentence

denotes

These differing clinical syndromes are attributable to the type of adhesions that develop.

T18958

476783-477052

Sentence

denotes

For example, a fibrous adhesion that does not by itself obstruct the intestinal lumen might serve as the pivot point for a volvulus, whereas an adhesion between adjacent segments of the intestinal tract may create a hairpin turn that causes chronic partial obstruction.

T20960

477053-477142

Sentence

denotes

1130 The number of adhesions that develop may also vary dramatically from horse to horse.

T66693

477143-477440

Sentence

denotes

Some horses may develop a single adhesion adjacent to an anastomotic site or a discrete segment of injured intestine, whereas other horses may develop diffuse adhesions involving multiple segments of intestine, likely because of widespread inflammatory disease at the time of the original surgery.

T91784

477441-477612

Sentence

denotes

The mechanisms by which adhesions develop are complex but likely involve injury to the serosa initiated by intestinal ischemia, reperfusion injury, and luminal distention.

T38265

477613-477725

Sentence

denotes

1037 Such injury involves infiltration of neutrophils into the serosa, accompanied by loss of mesothelial cells.

T7790

477726-477980

Sentence

denotes

In one study assessing the margins of resected small intestine, extensive neutrophil infiltration was documented in the serosa, particularly in the proximal resection margin that had been distended before correction of a variety of strangulating lesions.

T53756

477981-478254

Sentence

denotes

868 Regions of serosal injury and inflammation subsequently undergo reparative events similar to those of any wound, including local production of fibrin, de novo synthesis of collagen by infiltrating fibroblasts, and ultimately maturation and remodeling of fibrous tissue.

T46689

478255-478395

Sentence

denotes

Unfortunately, during this process fibrin may result in injured intestinal surfaces adhering to adjacent injured bowel or an adjacent organ.

T1626

478396-478503

Sentence

denotes

Once a fibrinous adhesion has developed, new collagen synthesis may result in a permanent fibrous adhesion.

T48337

478504-478624

Sentence

denotes

Alternatively, fibrinous exudate may be lysed by proteases released by local phagocytes, reversing the adhesive process.

T96233

478625-478716

Sentence

denotes

Formation of adhesions may be viewed as an imbalance of fibrin deposition and fibrinolysis.

T67028

478717-479182

Sentence

denotes

1131 Prevention of adhesions relies on inhibition of the mechanisms involved in adhesion formation, including reduction of serosal injury with early intervention and good surgical technique, reduction of inflammation by administration of antiinflammatory medications, physical separation of inflamed serosal surfaces (e.g., carboxymethylcellulose, hyaluronan), [1132] [1133] [1134] and pharmacologic modulation of fibrinous adhesion formation (e.g., heparin 1135 ).

T64982

479183-479352

Sentence

denotes

Early return of motility in the small intestine after surgery may reduce contact time between inflamed surfaces of intestine, reducing the chances of adhesion formation.

T37915

479353-479480

Sentence

denotes

1131 Horses at greatest risk of developing adhesions after colic surgery appear to be those that have small intestinal disease.

T31328

479481-479631

Sentence

denotes

1130 In one study of horses undergoing surgical correction of small intestinal obstruction, 22% developed a surgical lesion associated with adhesions.

T36609

479632-479768

Sentence

denotes

Foals appear to have an increased incidence of adhesions compared with mature horses, regardless of the nature of the abdominal surgery.

T9159

479769-479902

Sentence

denotes

1130 One study indicated that 17% of foals developed lesions attributable to adhesions regardless of the type of the initial surgery.

T38888

479903-480134

Sentence

denotes

1136 Studies conflict as to whether the degree of surgical intervention influences adhesion formation, 1130 but horses that require enterotomy or resection and anastomosis were at greatest risk of developing adhesions in one study.

T91531

480135-480241

Sentence

denotes

1137 Adhesions are among the most important reasons for repeat laparotomy in postoperative colic patients.

T29360

480242-480451

Sentence

denotes

1137, 1138 Clinical signs in horses with adhesions are highly variable, depending on whether the adhesion is causing partial obstruction, complete luminal obstruction, or involvement of intestinal vasculature.

T7462

480452-480632

Sentence

denotes

Adhesions are an important differential for intermittent colic in the postoperative period, particularly if such colic was not relieved by nasogastric decompression of the stomach.

T7348

480633-480798

Sentence

denotes

Continued intermittent colic should prompt abdominocentesis to determine whether there is evidence of septic peritonitis, which may contribute to adhesion formation.

T80778

480799-480880

Sentence

denotes

If postoperative colic persists, repeat laparotomy or laparoscopy may be elected.

T50758

480881-481089

Sentence

denotes

In one study on adhesions, 70% of repeat laparotomies were performed within 60 days, suggesting that surgical colic attributable to adhesions typically occurs within 2 months of an initial surgical procedure.

T94632

481090-481246

Sentence

denotes

Unfortunately, the prognosis for horses with colic attributable to adhesions is poor, with only 16% of horses surviving adhesion-induced colic in one study.

T23605

481247-481513

Sentence

denotes

1130 Y LARGE INTESTINAL SIMPLE OBSTRUCTION Simple obstructions of the large intestine, such as impaction, tend to have a more gradual onset than those of the small intestine, although horses may experience acute and severe pain with some forms of colon displacement.

T56650

481514-481594

Sentence

denotes

In fact, some of these cases mimic and may progress toward large colon volvulus.

T59841

481595-481673

Sentence

denotes

Medical therapy is frequently successful in correcting large colon impactions.

T70942

481674-481968

Sentence

denotes

However, cecal impactions present much more of a dilemma because of the greater propensity of this organ to rupture, the relative difficulty of surgically manipulating the cecum, and the onset of cecal dysfunction that may prevent the cecum from emptying after surgical resolution of impaction.

T19052

481969-482207

Sentence

denotes

Cecal impaction may be divided into two syndromes: primary cecal impactions that result from excessive accumulation of ingesta in the cecum and secondary cecal impactions that develop while a horse is being treated for a separate problem.

T26689

482208-482428

Sentence

denotes

936, 1139 Although primary impactions typically consist of impacted, relatively dry fecal material and secondary cecal impactions tend to have very fluid contents, there is considerable overlap between the two syndromes.

T80948

482429-482593

Sentence

denotes

In horses with primary cecal impactions, there is a gradual onset of abdominal pain over a number of days reminiscent of the development of a large colon impaction.

T19331

482594-482706

Sentence

denotes

Cecal impactions should be differentiated from large colon impactions on the basis of rectal palpation findings.

T68591

482707-482867

Sentence

denotes

These impactions have a propensity to rupture before the development of severe abdominal pain or systemic deterioration and therefore must be closely monitored.

T83934

482868-483024

Sentence

denotes

1139 Secondary cecal impactions typically develop after unrelated surgical procedures that result in postoperative pain (particularly orthopedic surgeries).

T13695

483025-483217

Sentence

denotes

1140 Secondary cecal impactions may be even more difficult to detect because postoperative depression and decreased fecal output may be attributed to the operative procedure rather than colic.

T16182

483218-483335

Sentence

denotes

By the time horses with secondary cecal impactions show noticeable signs of colic, the cecum may be close to rupture.

T26092

483336-483394

Sentence

denotes

In many cases there will be no signs of impending rupture.

T90979

483395-483564

Sentence

denotes

1140 Therefore the feed intake and manure production of all horses that undergo surgery in which considerable postoperative pain may develop should be closely monitored.

T83079

483565-483733

Sentence

denotes

A recent study indicated that horses producing less than three piles of manure daily in the postoperative period are at risk of developing a large intestinal impaction.

T21051

483734-483914

Sentence

denotes

Horses that underwent prolonged (>1 hour) orthopedic surgery that received inadequate treatment with phenylbutazone were at considerable risk of reduced postoperative fecal output.

T60091

483915-484022

Sentence

denotes

1141 A diagnosis of cecal impaction is based on rectal palpation of a firm, impacted or fluid-filled cecum.

T79790

484023-484117

Sentence

denotes

In some cases, cecal impactions may be difficult to differentiate from large colon impactions.

T80023

484118-484288

Sentence

denotes

Careful palpation, however, will reveal the inability to move the hand completely dorsal to the impacted viscus because of the cecum's attachment to the dorsal body wall.

T96204

484289-484440

Sentence

denotes

Treatment may include initial medical therapy with IV or oral fluids and analgesics, or surgical intervention with typhlotomy alone or jejunocecostomy.

T96857

484441-484557

Sentence

denotes

In two recent larger scale retrospective studies, the prognosis appeared to vary significantly by geographic region.

T41071

484558-484680

Sentence

denotes

1139, 939 In one, a very favorable short-term outcome was achieved with either medical (81%) or surgical (95%) management.

T92906

484681-484751

Sentence

denotes

939 In the majority of surgical cases, typhlotomy alone was performed.

T99040

484752-484856

Sentence

denotes

In another, shortterm outcome was less favorable with either medical (61%) or surgical (82%) management.

T55529

484857-485020

Sentence

denotes

1139 Many (68%) cases in the latter report appeared to have secondary cecal impactions as they had recent illness or surgery unrelated to gastrointestinal disease.

T90895

485021-485136

Sentence

denotes

This report underscores the importance of prompt diagnosis and supports the benefit of early surgical intervention.

T98591

485137-485293

Sentence

denotes

Ingesta impactions of the large colon occur at sites of anatomic reductions in luminal diameter, particularly the pelvic flexure and the right dorsal colon.

T81287

485294-485379

Sentence

denotes

1142 Although there are a number of reported risk factors, most have not been proved.

T343

485380-485512

Sentence

denotes

A sudden restriction in exercise associated with musculoskeletal injury appears to be frequently associated with onset of impaction.

T27357

485513-485735

Sentence

denotes

1143 Twice-daily feeding of concentrate results in large fluxes of fluid into and out of the colon, associated with readily fermentable carbohydrate in the colon and subsequent increases in serum aldosterone, respectively.

T5807

485736-485908

Sentence

denotes

1144 These fluid fluxes, which may cause dehydration of ingesta during aldosteronestimulated net fluid flux out of the colon, may be prevented with frequent small feedings.

T45539

485909-486122

Sentence

denotes

Impaction of the ascending colon can be induced by the drug amitraz, an acaricide associated with clinical cases of colon impaction, 1145, 1146 providing some clues as to the pathogenesis of large colon impaction.

T89401

486123-486310

Sentence

denotes

Amitraz appears to alter pelvic flexure pacemaker activity, resulting in uncoordinated motility patterns between the left ventral and left dorsal colon and excessive retention of ingesta.

T78983

486311-486444

Sentence

denotes

Absorption of water from the ingesta increases with retention time, dehydrating the contents of the colon and resulting in impaction.

T86591

486445-486542

Sentence

denotes

It is conceivable that parasite migration in the region of a pacemaker may have a similar action.

T85283

486543-486672

Sentence

denotes

653 Other factors implicated in large colon impaction include limited exercise, poor dentition, coarse roughage, and dehydration.

T383

486673-486746

Sentence

denotes

Clinical signs of large colon impaction include slow onset of mild colic.

T94273

486747-486866

Sentence

denotes

Fecal production is reduced, and the feces are often hard, dry, and covered with mucus because of delayed transit time.

T43351

486867-486949

Sentence

denotes

The heart rate may be mildly elevated during episodes of pain but is often normal.

T35899

486950-487123

Sentence

denotes

Signs of abdominal pain are typically well controlled with administration of analgesics but become increasingly more severe and refractory if the impaction does not resolve.

T84099

487124-487201

Sentence

denotes

The diagnosis is based on rectal palpation of a firm mass in the large colon.

T78670

487202-487325

Sentence

denotes

The extent of the impaction may be underestimated by rectal palpation alone because much of the colon remains out of reach.

T94278

487326-487417

Sentence

denotes

1142 Adjacent colon may be distended if the impaction has resulted in complete obstruction.

T25262

487418-487553

Sentence

denotes

Initial medical treatment should include pain management and enteral fluid therapy if reflux is not obtained on nasogastric intubation.

T62513

487554-487654

Sentence

denotes

Hydration of colonic contents is superior with enteral fluid therapy compared with IV fluid therapy.

T56307

487655-487770

Sentence

denotes

1147, 1148 Saline cathartics such as magnesium sulfate (0.1 mg/kg in 2-4 L by nasogastric tube) may also be useful.

T58944

487771-487810

Sentence

denotes

Access to feed should not be permitted.

T81817

487811-487959

Sentence

denotes

If the impaction remains unresolved, the horse's pain becomes uncontrollable, or extensive gas distention of the colon occurs, surgery is indicated.

T2748

487960-488049

Sentence

denotes

At surgery the contents of the colon are evacuated by way of a pelvic flexure enterotomy.

T58071

488050-488167

Sentence

denotes

Long-term survival is good with medical management (95%) and fair (58%) in horses that require surgical intervention.

T38156

488168-488172

Sentence

denotes

1143

T99420

488173-488270

Sentence

denotes

Enteroliths are mineralized masses typically composed of ammonium magnesium phosphate (struvite).

T20158

488271-488395

Sentence

denotes

37 However, magnesium vivianite has also been identified in enteroliths, along with variable quantities of Na, S, K, and Ca.

T52189

488396-488582

Sentence

denotes

The formation of Mg-based minerals is puzzling because of the relative abundance of Ca in colonic fluids, which would favor the formation of Ca phosphates (apatite) rather than struvite.

T5261

488583-488648

Sentence

denotes

Elevated dietary intake of magnesium and protein may play a role.

T19111

488649-488945

Sentence

denotes

Feeding of alfalfa hay and decreased dietary proportions of grass hay and pasture grass have been consistently identified as risk factors in horses with enterolithiasis. [1149] [1150] [1151] Alfalfa hay has a concentration of magnesium approximately six times the daily requirements of the horse.

T22129

488946-489097

Sentence

denotes

1152 The high protein concentration in alfalfa hay may contribute to calculus formation by increasing the ammonia nitrogen load in the large intestine.

T66611

489098-489255

Sentence

denotes

Enteroliths most commonly form around a nucleus of silicon dioxide (a flintlike stone), but nidi have included nails, rope, and hair that have been ingested.

T96194

489256-489333

Sentence

denotes

1153 Enteroliths are usually found in the right dorsal and transverse colons.

T56394

489334-489448

Sentence

denotes

1152 Although enterolithiasis has a wide geographic distribution, horses in California have the highest incidence.

T31549

489449-489647

Sentence

denotes

In one California study, horses with enterolithiasis represented 28% of the surgical colic population, and Arabians, Morgans, American Saddlebreds, and donkeys were at greatest risk of this disease.

T93216

489648-489763

Sentence

denotes

37 In a study of enterolithiasis in Texas, risk factors also included feeding of alfalfa hay and the Arabian breed.

T60686

489764-489826

Sentence

denotes

In that study, Miniature Horses were also found to be at risk.

T68634

489827-490003

Sentence

denotes

1149 Horses with enteroliths are rarely younger than 4 years old, with a median age of 11 in one report 37 ; an enterolith has been reported in an 11-month-old Miniature Horse.

T31793

490004-490094

Sentence

denotes

1154 The most common reported clinical signs are episodic mild to moderate abdominal pain.

T21672

490095-490172

Sentence

denotes

37, 1152 Enteroliths may be diagnosed by abdominal radiography or at surgery.

T50128

490173-490296

Sentence

denotes

40, 1155 On rare occasions an enterolith may be palpated rectally, particularly if it is present in the distal small colon.

T59009

490297-490396

Sentence

denotes

Generally, surgery is required, although there are reports of enteroliths being retrieved rectally.

T91055

490397-490519

Sentence

denotes

In one study 14% of horses that required treatment of enterolithiasis had a history of passing an enterolith in the feces.

T7916

490520-490617

Sentence

denotes

37 Enteroliths are typically located in the right dorsal colon, transverse colon, or small colon.

T93636

490618-490739

Sentence

denotes

After removal of an enterolith, further exploration must be conducted to determine whether other enteroliths are present.

T1639

490740-490825

Sentence

denotes

Solitary enteroliths are usually round, whereas multiple enteroliths have flat sides.

T10781

490826-490982

Sentence

denotes

The prognosis is good (92% 1-year survival in 900 horses), unless the colon is ruptured during removal of an enterolith, which was reported in 15% of cases.

T1776

490983-490985

Sentence

denotes

37

T24918

490986-491106

Sentence

denotes

Sand impactions are common in horses with access to sandy soils, particularly horses whose feed is placed on the ground.

T61907

491107-491160

Sentence

denotes

Some horses, especially foals, deliberately eat sand.

T21399

491161-491268

Sentence

denotes

Fine sand tends to accumulate in the ventral colon, whereas coarse sand may accumulate in the dorsal colon.

T65079

491269-491428

Sentence

denotes

737, 1156 Individual differences in colonic function may contribute to accumulation of sand because some horses can clear consumed sand, whereas others cannot.

T7242

491429-491533

Sentence

denotes

Distention resulting from the impaction itself, or gas proximal to the impaction, causes abdominal pain.

T74471

491534-491625

Sentence

denotes

Sand may also trigger diarrhea, presumably as a result of irritation of the colonic mucosa.

T12055

491626-491736

Sentence

denotes

738 In horses with sand impactions, clinical signs are similar to those of horses with large colon impactions.

T53519

491737-491865

Sentence

denotes

Sand may be found in the feces, and auscultation of the ventral abdomen may reveal sounds of sand moving within the large colon.

T79833

491866-492041

Sentence

denotes

1157 The diagnosis is made via radiography or surgery but may be tentatively based on clinical signs compatible with a large colon impaction and evidence of sand in the feces.

T87719

492042-492149

Sentence

denotes

Sand sedimentation is performed by mixing feces with water in a rectal palpation sleeve or other container.

T33059

492150-492235

Sentence

denotes

Abdominal radiographs can be used to detect mineral opacity within the ventral colon.

T83545

492236-492341

Sentence

denotes

38, 1158 Ultrasonography can also be used to support the diagnosis but is not as accurate as radiography.

T20070

492342-492517

Sentence

denotes

1159 Abdominal paracentesis is not recommended in suspected cases, because large quantities of sand in the ventral colon make inadvertent perforation of the colon more likely.

T75513

492518-492575

Sentence

denotes

737 Medical management typically offers a good prognosis.

T31199

492576-492717

Sentence

denotes

1160 Administration of psyllium hydrophilic mucilloid (0.25-0.5 kg/500 kg in 2 L mineral oil by stomach tube) may facilitate passage of sand.

T2977

492718-492811

Sentence

denotes

If mixed with water, it should be administered rapidly because of formation of a viscous gel.

T71302

492812-492905

Sentence

denotes

The psyllium leaves the oil phase and mixes with the water, forming a gel within the stomach.

T80962

492906-492983

Sentence

denotes

Psyllium is thought to act by stimulating motility or agglutinating the sand.

T3175

492984-493059

Sentence

denotes

However, one experimental study failed to show a benefit of this treatment.

T82588

493060-493220

Sentence

denotes

1161 If a severe impaction is present, then psyllium should not be given until the impaction is softened by administering IV or oral fluids and other laxatives.

T49265

493221-493377

Sentence

denotes

Perforation is a potential complication in horses with sand impactions because the sand stretches and irritates the intestinal wall and causes inflammation.

T30908

493378-493467

Sentence

denotes

If colic becomes intractable, surgical evacuation of the large colon should be performed.

T24367

493468-493512

Sentence

denotes

The prognosis is generally regarded as good.

T13992

493513-493634

Sentence

denotes

737, 1156 Large Colon Displacement Displacement of the ascending colon is a common cause of large intestinal obstruction.

T18450

493635-493720

Sentence

denotes

The ascending colon is freely movable except for the right dorsal and ventral colons.

T62440

493721-493929

Sentence

denotes

Contact with adjacent viscera and the abdominal wall tends to inhibit movement of the ascending colon from a normal position; accumulation of gas and fluid or ingesta, however, may cause the colon to migrate.

T30162

493930-494065

Sentence

denotes

1162 Feeding behavior, including feeding of large concentrate meals, likely plays a role in initiating displacement of the large colon.

T90783

494066-494215

Sentence

denotes

Large concentrate meals increase the rate of passage of ingesta, allowing a greater percentage of soluble carbohydrates to reach the large intestine.

T80007

494216-494334

Sentence

denotes

1163 This in turn increases the rate of fermentation and the amount of gas and volatile fatty acids that are produced.

T34227

494335-494457

Sentence

denotes

The production of large amounts of volatile fatty acids stimulates the secretion of large volumes of fluid into the colon.

T70740

494458-494697

Sentence

denotes

2 The association between feeding concentrate and development of displacements of the large colon is illustrated by studies indicating that ascending colon displacement is more prevalent in horses fed a high-concentrate, low-roughage diet.

T64708

494698-494816

Sentence

denotes

1164 Abnormal motility patterns of the ascending colon may also contribute to the development of colonic displacement.

T23168

494817-495025

Sentence

denotes

Feeding stimulates colonic motility by way of the gastrocolic reflex, but large meals may alter normal motility patterns and concurrently allow rapid accumulation of gas and fluid resulting from fermentation.

T88496

495026-495145

Sentence

denotes

1163, 1165 Migration of parasite larvae (strongyles) through the intestinal wall also alters colonic motility patterns.

T29927

495146-495276

Sentence

denotes

650 S. vulgaris infection results in reduced blood flow to segments of the large intestine without necessarily causing infarction.

T54904

495277-495515

Sentence

denotes

Electrical activity of the colon and cecocolic junction increases after infection with S. vulgaris and cyathostome larvae, probably reflecting a direct effect of migration through the intestine and an early response to reduced blood flow.

T5692

495516-495667

Sentence

denotes

650 Displacements of the ascending colon are generally divided into three types: left dorsal displacement, right dorsal displacement, and retroflexion.

T31599

495668-495783

Sentence

denotes

1162, 1166 Left dorsal displacement is characterized by entrapment of the ascending colon in the renosplenic space.

T77724

495784-495924

Sentence

denotes

The colon is often twisted 180 degrees, such that the left ventral colon is situated in a dorsal position relative to the left dorsal colon.

T10916

495925-496085

Sentence

denotes

The entrapped portion may be only the pelvic flexure or may involve a large portion of the ascending colon, with the pelvic flexure situated near the diaphragm.

T27239

496086-496260

Sentence

denotes

The colon may become entrapped by migrating dorsally between the left abdominal wall and the spleen or may migrate in a caudodorsal direction over the nephrosplenic ligament.

T57954

496261-496410

Sentence

denotes

1166 Occasionally, the ascending colon can be palpated between the spleen and abdominal wall, lending support to the first mechanism of displacement.

T22665

496411-496608

Sentence

denotes

Gastric distention is thought to predispose horses to left dorsal displacement of the ascending colon by displacing the spleen medially, allowing the colon room to migrate along the abdominal wall.

T71655

496609-496756

Sentence

denotes

1166 Right dorsal displacement begins by movement of the colon cranially, either medial (medial flexion) or lateral (lateral flexion) to the cecum.

T38529

496757-496884

Sentence

denotes

According to one author, the proportion of right dorsal displacements with medial versus lateral flexion is approximately 1:15.

T69753

496885-496958

Sentence

denotes

1166 In either case the pelvic flexure ends up adjacent to the diaphragm.

T86048

496959-497104

Sentence

denotes

Retroflexion of the ascending colon occurs by movement of the pelvic flexure cranially without movement of the sternal or diaphragmatic flexures.

T14497

497105-497239

Sentence

denotes

Displacement of the ascending colon partially obstructs the lumen, resulting in accumulation of gas or ingesta and causing distention.

T78170

497240-497330

Sentence

denotes

The distention may be exacerbated by the secretion of fluid in response to the distention.

T51231

497331-497443

Sentence

denotes

Tension and stretch of the visceral wall are important sources of the pain associated with colonic displacement.

T61023

497444-497550

Sentence

denotes

Tension on mesenteric attachments and the root of the mesentery by the enlarged colon may also cause pain.

T73494

497551-497634

Sentence

denotes

1162 Ischemia is rarely associated with nonstrangulating displacement of the colon.

T7527

497635-497786

Sentence

denotes

Congestion and edema, however, are often seen in the displaced segments of colon because of increased hydrostatic pressure from reduced venous outflow.

T95428

497787-497834

Sentence

denotes

Morphologic damage to tissues is usually minor.

T6318

497835-498020

Sentence

denotes

Clinically, displacement of the ascending colon is often characterized by intermittent signs of mild to moderate abdominal pain of acute onset, but an insidious onset may also be noted.

T91940

498021-498097

Sentence

denotes

1166 Dehydration may occur if the duration of the displacement is prolonged.

T94330

498098-498185

Sentence

denotes

The heart rate may be increased in conjunction with abdominal pain but is often normal.

T49391

498186-498255

Sentence

denotes

Abdominal distention may be present, and fecal production is reduced.

T54104

498256-498434

Sentence

denotes

Left dorsal displacements are often diagnosed by rectal palpation, because the ascending colon can be traced to the nephrosplenic space, and the spleen may be displaced medially.

T77420

498435-498519

Sentence

denotes

Alternatively, a tentative diagnosis can be reached using abdominal ultrasonography.

T92858

498520-498643

Sentence

denotes

1167 The spleen can be imaged on the left side of the abdomen, but the left kidney will be obscured by gas-distended bowel.

T35458

498644-498799

Sentence

denotes

Evaluation of this technique indicates that there are very few instances of false-positive results, although false-negative results may occasionally occur.

T11001

498800-498848

Sentence

denotes

1167 A definitive diagnosis may require surgery.

T64863

498849-499057

Sentence

denotes

Right dorsal displacements are characterized by the presence of the distended ventral colon running across the pelvic inlet and may be felt between the cecum and the body wall if a lateral flexion is present.

T24594

499058-499101

Sentence

denotes

The pelvic flexure is usually not palpable.

T1193

499102-499179

Sentence

denotes

Retroflexion of the ascending colon may produce a palpable kink in the colon.

T32112

499180-499389

Sentence

denotes

If the displaced colons are not distended by gas in the instance of right dorsal displacement and retroflexion, the ascending colon may not be palpable and is conspicuous by its absence from a normal position.

T58369

499390-499608

Sentence

denotes

Horses with right dorsal displacement often have an increased GGT, relative to horses with left dorsal displacement, which is presumptively caused by compression of the bile duct and temporary extrahepatic obstruction.

T36702

499609-499915

Sentence

denotes

17 For nephrosplenic entrapment of the large colon, medical management is often effective. [1167] [1168] [1169] Medical therapy with phenylephrine and rolling under anesthesia (84%) was significantly more effective than phenylephrine (3-6 μg/kg/min over 15 minutes) and exercise (63.2%) in a recent report.

T58881

499916-500141

Sentence

denotes

1169 There are reports of fatal internal hemorrhage caused by rupture of large blood vessels after treatment of older horses with phenylephrine, and the drug should probably be used with caution in horses older than 15 years.

T92498

500142-500342

Sentence

denotes

1170 Medical therapy has also been reported effective (64%) in horses with right dorsal displacement, 1171 although definitive diagnosis of that condition is challenging without surgical confirmation.

T42829

500343-500423

Sentence

denotes

If medical management is not successful, horses should undergo surgery promptly.

T29862

500424-500492

Sentence

denotes

Surgical prognosis for horses with large colon displacement is good.

T80480

500493-500576

Sentence

denotes

A number of horses will suffer recurrence of nephrosplenic entrapment of the colon.

T22892

500577-500697

Sentence

denotes

Currently, the least invasive method of preventing this complication is laparoscopic closure of the nephrosplenic space.

T60346

500698-500712

Sentence

denotes

78, 1172, 1173

T96307

500714-500864

Sentence

denotes

Foreign material such as bedding, rope, plastic, fence material, and feedbags can cause obstruction and may be ingested, particularly by young horses.

T46728

500865-501004

Sentence

denotes

These foreign bodies may result in impaction with ingesta and distention of the intestine, typically in the transverse or descending colon.

T7850

501005-501039

Sentence

denotes

Young horses are usually affected.

T5382

501040-501124

Sentence

denotes

In one study the obstructing mass could be rectally palpated in three of six horses.

T82510

501125-501190

Sentence

denotes

1174 Fecaliths are common in ponies, miniature horses, and foals.

T60304

501191-501332

Sentence

denotes

1175 Older horses with poor dentition may also be predisposed to fecaliths because of the inability to fully masticate fibrous feed material.

T23575

501333-501417

Sentence

denotes

Fecaliths commonly cause obstruction in the descending colon and may cause tenesmus.

T80756

501418-501484

Sentence

denotes

1174 Other clinical signs are similar to those of enterolithiasis.

T27022

501485-501653

Sentence

denotes

Abdominal radiography may be useful in smaller patients to identify the obstruction, especially if gas distention around the foreign body or fecalith provides contrast.

T21998

501654-501693

Sentence

denotes

Surgical treatment is usually required.

T34676

501694-501866

Sentence

denotes

Mural masses such as abscesses, tumors (adenocarcinoma and lymphosarcoma), granulomas, and hematomas can cause luminal obstruction and impaction, typically in older horses.

T5699

501867-501981

Sentence

denotes

Impaction may result from obstruction of the lumen or impaired motility in the segment of intestine with the mass.

T1090

501982-502097

Sentence

denotes

Abscesses may originate from the lumen of the intestine or may extend from the mesentery or mesenteric lymph nodes.

T10791

502098-502193

Sentence

denotes

Intramural hematomas form most commonly in the descending colon and cause acute abdominal pain.

T14704

502194-502371

Sentence

denotes

1176 Once the acute pain caused by the hematoma subsides, impaction proximal to the hematoma develops as a result of impaired motility through the affected portion of the colon.

T65661

502372-502473

Sentence

denotes

Trauma, ulceration of the mucosa, and parasitic damage are speculated causes of intramural hematomas.

T85966

502474-502674

Sentence

denotes

1176, 1177 Stricture of the large intestine occurs when fibrous tissue forms in a circular pattern around or within the intestine, reducing the luminal diameter and the ability of the wall to stretch.

T51662

502675-502791

Sentence

denotes

Strictures may be congenital or secondary to peritonitis, previous abdominal surgery, or inflammatory bowel disease.

T18525

502792-502953

Sentence

denotes

In a report of 11 horses with inflammatory bowel disease, 6 horses had strictures, 4 of which were in the small intestine and 2 of which were in the large colon.

T24846

502954-503025

Sentence

denotes

517 Clinical signs vary according to the degree of luminal obstruction.

T46298

503026-503127

Sentence

denotes

Partial obstruction and impaction tend to produce mild to moderate abdominal pain of insidious onset.

T90435

503128-503190

Sentence

denotes

Mural hematomas tend to produce signs of acute abdominal pain.

T600

503191-503335

Sentence

denotes

1176, 1177 Rectal palpation of the abdomen may reveal the presence of a mass or simply the impacted segment, without the mass itself being felt.

T87461

503336-503418

Sentence

denotes

Fever, weight loss, and anorexia may be noted if an abscess or tumor is the cause.

T97889

503419-503554

Sentence

denotes

An elevated WBC count; hyperfibrinogenemia; hyperglobulinemia; or normocytic, normochromic anemia may be seen with abscesses or tumors.

T65783

503555-503592

Sentence

denotes

PF may reflect the cause of the mass.

T56008

503593-503630

Sentence

denotes

Tumor cells may infrequently be seen.

T3582

503631-503776

Sentence

denotes

Evidence of inflammation with bacteria may be noted if the cause of colic is an abscess or granuloma, in which case the fluid should be cultured.

T29984

503777-503820

Sentence

denotes

Hematomas may cause hemorrhage into the PF.

T18664

503821-503879

Sentence

denotes

Treatment usually requires surgical resection of the mass.

T25108

503880-504018

Sentence

denotes

Abscesses may be treated with appropriate antibiotics if the impaction can be resolved medically with oral or IV analgesics and laxatives.

T21058

504019-504184

Sentence

denotes

Streptococcus spp., Actinomyces pyogenes, C. pseudotuberculosis, R. equi, anaerobic bacteria, and gram-negative enteric organisms are commonly involved in abscesses.

T60149

504185-504296

Sentence

denotes

Small colon impaction is distinct from other forms of impaction in its predispositions and clinical appearance.

T50183

504297-504390

Sentence

denotes

In one study the key risk factor for impaction of this segment of the intestine was diarrhea.

T18463

504391-504624

Sentence

denotes

1178 This paradoxic finding may be explained by edema of the colonic mucosa associated with proinflammatory causes of diarrheal disease that is usually noted in the ascending colon but may extend into the transverse and small colons.

T46741

504625-504819

Sentence

denotes

Once diarrheal disease is initiated, large volumes of ingesta are rapidly expelled from the ascending colon into the small colon, which has a far smaller diameter, especially if it is edematous.

T93801

504820-504953

Sentence

denotes

This may result in the initial appearance of diarrhea, followed by intermittent episodes of colic that may be explained by impaction.

T56086

504954-505051

Sentence

denotes

Diagnosis is by rectal examination, during which the rectum typically feels edematous and gritty.

T60837

505052-505182

Sentence

denotes

The most important point to remember is that horses should be closely assessed for impaction even if diarrheal disease is present.

T31972

505183-505355

Sentence

denotes

Other parameters that are typically helpful for assessing the severity of colic, such as heart rate, are not predictive of obstruction in horses with small colon impaction.

T93434

505356-505456

Sentence

denotes

1178 Horses may be treated medically during the early stages with fluids, laxatives, and analgesics.

T2211

505457-505597

Sentence

denotes

The key clinical sign that indicates the need for surgery appears to be abdominal distention, associated with distention of the large colon.

T46757

505598-505711

Sentence

denotes

Other clinical signs, such as elevations in heart rate and refractory colic, are less pronounced in this disease.

T5037

505712-505780

Sentence

denotes

Postdiarrheal disease is not the only form of small colon impaction.

T53180

505781-505881

Sentence

denotes

These impactions can be formed as simple collections of ingesta or in response to luminal narrowing.

T30166

505882-505959

Sentence

denotes

Atresia of a segment of the colon is a rare congenital abnormality in horses.

T11326

505960-506022

Sentence

denotes

1179 The heritability and causes of the condition are unknown.

T10437

506023-506183

Sentence

denotes

One potential mechanism for development of the lesion is intestinal ischemia during fetal life, which secondarily results in necrosis of a segment of intestine.

T32281

506184-506289

Sentence

denotes

1179 Clinical signs include a failure to pass meconium and colic within the first 12 to 24 hours of life.

T61548

506290-506426

Sentence

denotes

Secondary abdominal distention results from complete intestinal obstruction, and abdominal radiographs may reveal a gas-distended colon.

T717

506427-506460

Sentence

denotes

The diagnosis is made at surgery.

T82286

506461-506615

Sentence

denotes

Any portion of the colon may be absent, but the distal segment of the large colon or the proximal small colon (or both) is usually most severely affected.

T39900

506616-506717

Sentence

denotes

If sufficient tissue is present, anastomosis to the proximal blind end of the colon may be attempted.

T85409

506718-506846

Sentence

denotes

1179 The prognosis depends on the segment of the colon that is absent but is usually poor because of an absence of distal colon.

T12457

506847-506976

Sentence

denotes

Ileocolonic aganglionosis, commonly known as lethal white foal syndrome (LWFS), occurs in white foals with overo-spotted parents.

T31836

506977-507102

Sentence

denotes

Affected foals are either completely white or have very little pigmented hair around the muzzle, base of the tail, or hooves.

T83837

507103-507309

Sentence

denotes

They are homozygous for an abnormal endothelin receptor B (EDNRB) gene that results in altered neural crest cell migration or survival, which affects progenitor cells for melanocytes and intestinal ganglia.

T50851

507310-507490

Sentence

denotes

1180, 1181 The EDNRB genotype is highly correlated with white patterning; frame overo, highly white calico overo, and frame blend overo have the highest incidence of heterozygotes.

T57806

507491-507562

Sentence

denotes

1182 Rarely, an LWFS-affected foal may be born to a solid-colored mare.

T63197

507563-507773

Sentence

denotes

Homozygous foals have aganglionosis of the submucosal and myenteric ganglia of the distal portion of the ileum and large intestine, and extrinsic innervation of the ileum and pelvic flexure has been identified.

T80604

507774-507908

Sentence

denotes

1183, 1184 This results in a foal that appears normal at birth but develops signs of intestinal ileus and colic within 12 to 24 hours.

T47980

507909-507949

Sentence

denotes

The eyes are blue, and the skin is pink.

T31578

507950-508048

Sentence

denotes

A genetic test is available to identify horses that are heterozygous for the defective EDNRB gene.

T18409

508049-508193

Sentence

denotes

The mouth is bounded laterally by the cheeks, dorsally by the palate, and ventrally by the body of the mandible and by the mylohyoideus muscles.

T88107

508194-508231

Sentence

denotes

The caudal margin is the soft palate.

T29459

508232-508356

Sentence

denotes

The mouth of the horse is long and cylindric, and when the lips are closed, the contained structures almost fill the cavity.

T10166

508357-508458

Sentence

denotes

A small space remains between the root of the tongue and the epiglottis and is termed the oropharynx.

T18272

508459-508524

Sentence

denotes

The cavity of the mouth is subdivided into sections by the teeth.

T18095

508525-508749

Sentence

denotes

The space external to the teeth and enclosed by the lips is termed the vesicle of the mouth, and in the resting state the lateral margins of the vesicle, that is, the buccal mucosa, are in close contact with the cheek teeth.

T68133

508750-508838

Sentence

denotes

Caudally, the external space communicates with the pharynx through the aditus pharyngis.

T21244

508839-509040

Sentence

denotes

The mucous membrane of the mouth is continuous at the margin of the lips with the skin and during life is chiefly pink but can be more or less pigmented, depending on the skin color and the breed type.

T68674

509041-509136

Sentence

denotes

The lips are two muscular membranous folds that unite at angles close to the first cheek teeth.

T75875

509137-509185

Sentence

denotes

Each lip presents an outer and an inner surface.

T58549

509186-509296

Sentence

denotes

The upper lip has a shallow median furrow (philtrum); the lower lip has a rounded prominence or chin (mentum).

T57973

509297-509451

Sentence

denotes

The internal surface is covered with a thick mucous membrane that contains small, pitted surfaces that are the openings of the ducts of the labial glands.

T97333

509452-509543

Sentence

denotes

Small folds of the mucous membrane called the frenulum labii pass from the lips to the gum.

T25602

509544-509609

Sentence

denotes

The free border of the lip is dense and bears short, stiff hairs.

T3443

509610-509745

Sentence

denotes

The arteries of the mouth are derived from the maxillary, mandibular, labial, and sphenopalatine arteries of the major palatine artery.

T4253

509746-509797

Sentence

denotes

The veins drain chiefly to the lingual facial vein.

T92439

509798-509930

Sentence

denotes

Sensory nerves originate from the trigeminal nerve (cranial nerve V) and the motor nerves from the facial nerve (cranial nerve VII).

T77275

509931-510067

Sentence

denotes

The cheeks spread back from the lips and form both sides of the mouth and are attached to the alveolar borders of the bones of the jaws.

T81032

510068-510172

Sentence

denotes

The cheeks are composed of skin and muscular and glandular layers and then the internal mucous membrane.

T16510

510173-510202

Sentence

denotes

The skin is thin and pliable.

T51829

510203-510440

Sentence

denotes

In contrast, the oral mucous membrane is dense and in many areas of the oral cavity is attached firmly to the periosteum so that construction of oral mucosal flaps can be achieved only by horizontal division of the periosteal attachment.

T68469

510441-510525

Sentence

denotes

Such a feature is important in reconstructive techniques applied to the oral cavity.

T3928

510526-510681

Sentence

denotes

The blood supply to the cheeks comes from the facial and buccal arteries and the sensory nerves from the trigeminal and motor nerves from the facial nerve.

T24525

510682-510820

Sentence

denotes

The hard palate (palatum durum) is bounded rostrally and laterally by the alveolar arches and is continuous with the soft palate caudally.

T23017

510821-510906

Sentence

denotes

The hard palate has a central raphe that divides the surface into two equal portions.

T99085

510907-511014

Sentence

denotes

From the line of the rostral cheek tooth, the hard palate is concave to the line of the caudal cheek tooth.

T31358

511015-511118

Sentence

denotes

Paired transverse ridges (about 18) traverse the concavity and have their free edges directed caudally.

T20100

511119-511224

Sentence

denotes

The incisive duct is a small tube of mucous membrane that extends obliquely through the palatine fissure.

T12139

511225-511403

Sentence

denotes

The dorsal component communicates by a slitlike opening in the rostral portion of the ventral nasal meatus, and its palatine end is blind and lies in the submucosa of the palate.

T88261

511404-511524

Sentence

denotes

When stallions display their flehmen response, watery secretions enter the nose from the glands of the vomeronasal duct.

T77439

511525-511597

Sentence

denotes

To what extent these secretions aid in pheromone reception is not known.

T37588

511598-511746

Sentence

denotes

1185 That portion of the palatine mucosa immediately behind the incisor teeth frequently is swollen (lampas) during eruption of the permanent teeth.

T42075

511747-511792

Sentence

denotes

This swelling is physiologic, not pathologic.

T55711

511793-511942

Sentence

denotes

The tongue is situated on the floor of the mouth between the bodies of the mandible and is supported by the sling formed by the mylohyoideus muscles.

T2001

511943-512022

Sentence

denotes

The root of the tongue is attached to the hyoid bone, soft palate, and pharynx.

T46650

512023-512131

Sentence

denotes

The upper surface and the rostral portion of the tongue are free; the body of the tongue has three surfaces.

T48832

512132-512193

Sentence

denotes

The apex of the tongue is spatulate and has a rounded border.

T51530

512194-512296

Sentence

denotes

The mucous membrane adheres intimately to the adjacent structure and on the dorsum is dense and thick.

T94200

512297-512441

Sentence

denotes

From the lower surface of the free part of the tongue, a fold of mucous membrane passes to the floor of the mouth, forming the lingual frenulum.

T60129

512442-512549

Sentence

denotes

Caudally, a fold passes on each side of the dorsum to join the soft palate, forming the palatoglossal arch.

T61628

512550-512695

Sentence

denotes

Dorsally from the soft palate the palatopharyngeal arch attaches and circumvents the aditus laryngis and attaches to the roof of the nasopharynx.

T10589

512697-512790

Sentence

denotes

The formula for the deciduous teeth of the horse is 2 times I3-3 C0-0 P3-3 for a total of 24.

T64208

512791-512883

Sentence

denotes

The permanent dental formula is 2 times I3-3 C1-1 P3-3 or P4-3 M3-3 for a total of 40 or 42.

T32079

512884-512980

Sentence

denotes

In the mare the canine teeth are usually small or do not erupt, reducing the number to 36 or 38.

T3687

512981-513128

Sentence

denotes

The first premolar tooth (wolf tooth) is often absent and has been reported as occurring in only 20% of the upper dentition of Thoroughbred horses.

T76757

513129-513251

Sentence

denotes

1186 The teeth of the horse are complex in shape and are compounded of different materials (dentin, cementum, and enamel).

T66220

513252-513380

Sentence

denotes

They function as grinding blades to masticate and macerate cellulose food in the important first stage of the digestive process.

T29928

513381-513474

Sentence

denotes

The cheek teeth in the horse are a welldocumented feature of the evolution of Equus caballus.

T16174

513475-513549

Sentence

denotes

The first deciduous incisor is present at birth or the first week of life.

T37426

513550-513747

Sentence

denotes

The second incisor erupts at 4 to 6 weeks of age; the third incisor, at 6 to 9 months of age; the first and second premolars, at birth to 2 weeks of age; and the third premolar, at 3 months of age.

T79485

513748-514226

Sentence

denotes

The eruption times for the permanent teeth are as follows: first incisor, 2½ years of age; second incisor, 3½ years of age; third incisor, 4½ years of age; the canine tooth, 4 to 5 years of age; the first premolar (wolf tooth), 5 to 6 months of age; the second premolar, 2½ years of age; the third premolar, 3 years of age; the fourth premolar, 4 years of age; the first molar, 10 to 12 months of age; the second molar, 2 years of age; and the third molar, 3½ to 4 years of age.

T12190

514227-514375

Sentence

denotes

This eruption sequence clearly indicates that the eruption of the second and third permanent premolar teeth have the potential for dental impaction.

T38234

514376-514501

Sentence

denotes

The modern horse has six incisor teeth in each jaw that are placed close together so that the labile edges form a semicircle.

T69379

514502-514605

Sentence

denotes

The occlusal surface has a deep enamel invagination (infundibulum) filled only partially with cementum.

T13714

514606-514783

Sentence

denotes

As the incisor teeth wear, a characteristic pattern forms in which the infundibulum is surrounded by rings of enamel, dentin, enamel, and crown cementum in a concentric pattern.

T26287

514784-515073

Sentence

denotes

Each incisor tooth tapers from a broad crown to a narrow root so as the midportion of the incisor is exposed to wear, the cross-sectional diameters are about equal; that is, at 14 years of age, the central incisor tooth of the horse has an occlusal surface that is an equilateral triangle.

T43755

515074-515243

Sentence

denotes

Observations on the state of eruption, the angles of incidence of the incisor teeth, and the pattern of the occlusal surfaces are used as guides for the aging of horses.

T18377

515244-515316

Sentence

denotes

The canine teeth are simple teeth without complex crowns and are curved.

T46812

515317-515421

Sentence

denotes

The crown is compressed and is smooth on its labial aspect but carries two ridges on its lingual aspect.

T77301

515422-515490

Sentence

denotes

No occlusal contact occurs between the upper and lower canine teeth.

T2034

515491-515591

Sentence

denotes

When erupted, the six cheek teeth of the horse function as a single unit in the mastication of food.

T93574

515592-515653

Sentence

denotes

Each arcade consists of three premolar and three molar teeth.

T53940

515654-515740

Sentence

denotes

The maxillary arcade is slightly curved, and the teeth have a square occlusal surface.

T6044

515741-515834

Sentence

denotes

The occlusal surfaces of the mandibular teeth are more oblong, and each arcade is straighter.

T73830

515835-515984

Sentence

denotes

The horse is anisognathic-that is, the distance between the mandibular teeth is narrower (one-third) than the distance between the upper cheek teeth.

T578

515985-516124

Sentence

denotes

This anatomic arrangement affects the inclination of the dental arcade as the jaws slide across each other in the food preparation process.

T49271

516125-516257

Sentence

denotes

The unworn upper cheek tooth presents a surface with two undulating and narrow ridges, one of which is lateral and the other medial.

T22945

516258-516330

Sentence

denotes

On the rostral and lingual side of the medial style is an extra hillock.

T33191

516331-516485

Sentence

denotes

The central portion of these surfaces is indented by two depressions that are comparable with, but much deeper than, the infundibula of the incisor teeth.

T80303

516486-516629

Sentence

denotes

When the teeth have been subjected to wear, the enamel that closed the ridges is worn through and the underlying dentin appears on the surface.

T11020

516630-516809

Sentence

denotes

After a time the chewing surface displays a complicated pattern that may be likened to the outline of an ornate letter B, and the upright stroke of the B is on the lingual aspect.

T91263

516810-517030

Sentence

denotes

Dentin supports the enamel internally, cementum supports the enamel lakes, and the peripheral cementum fills in the spaces between the teeth so that all six teeth may function as a single unit-that is, the dental arcade.

T5529

517031-517130

Sentence

denotes

Transverse ridges cross each tooth so that the entire maxillary arcade consists of a serrated edge.

T89355

517131-517228

Sentence

denotes

The serrations are formed so that a valley is present at the area of contact with adjacent teeth.

T15979

517229-517296

Sentence

denotes

These serrations match fitting serrations on the mandibular arcade.

T4532

517297-517442

Sentence

denotes

One should note that the mediolateral mandibular motion while chewing pellets does not provide full occlusal contact as it does when chewing hay.

T96665

517443-517536

Sentence

denotes

1187 The true roots of the cheek teeth are short compared with the total length of the tooth.

T85570

517537-517617

Sentence

denotes

Cheek teeth have three roots: two small lateral roots and one large medial root.

T10605

517618-517817

Sentence

denotes

That portion of the crown embedded within the dental alveolus is referred to as the reserve crown, and the term root is confined to that area of the tooth that is comparatively short and enamel free.

T5620

517818-517896

Sentence

denotes

Wear on the tooth gradually exposes the reserve crown, and the roots lengthen.

T8923

517897-517986

Sentence

denotes

In an adult 1000-lb horse the maxillary cheek teeth are between 8.0 and 8.5 cm in length.

T92651

517987-518071

Sentence

denotes

Dental wear accounts for erosion and loss of tooth substance at a rate of 2 mm/year.

T41176

518072-518120

Sentence

denotes

The pulp chambers of the teeth are also complex.

T72829

518121-518173

Sentence

denotes

The incisors and canines have a single pulp chamber.

T2835

518174-518247

Sentence

denotes

The mandibular cheek teeth have two roots and two separate pulp chambers.

T24838

518248-518331

Sentence

denotes

The maxillary cheek teeth, although they have three roots, have five pulp chambers.

T16445

518332-518510

Sentence

denotes

As occlusal wear proceeds, deposition of secondary dentin within the pulp chambers protects the chambers (e.g., the dental star, medial to the infundibulum on the incisor teeth).

T77977

518511-518726

Sentence

denotes

In the mandibular cheek teeth the transverse folding of the enamel anlage (during morphogenesis of the tooth) does not take place, and the occlusal surface is a simple surface of central dentin surrounded by enamel.

T78387

518727-518820

Sentence

denotes

Each tooth then is conformed to a single arcade by the presence of peripheral crown cementum.

T56805

518821-518963

Sentence

denotes

The oral cavity and oropharynx are subject to a variety of diseases, many of which produce the same clinical signs, regardless of their cause.

T55345

518964-519126

Sentence

denotes

The classic signs of dental disease in the horse include difficulty and slowness in feeding, together with a progressive unthriftiness and loss of body condition.

T50577

519127-519221

Sentence

denotes

In some instances, the horse may quid (drop food while chewing), and halitosis may be obvious.

T23547

519222-519329

Sentence

denotes

Additional problems reported by owners include bitting and riding problems and headshaking or head shyness.

T50678

519330-519507

Sentence

denotes

Facial or mandibular swelling, nasal discharge (dental disease associated with maxillary sinus), and mandibular fistulae (lower cheek tooth apical infections) are also possible.

T78513

519508-519581

Sentence

denotes

Some correlation exists between the age of the animal and clinical signs.

T66427

519582-519723

Sentence

denotes

One can examine a considerable portion of the mouth and teeth from the outside by palpation of the structures through the folds of the cheek.

T17110

519724-519817

Sentence

denotes

Most horses allow a cursory oral examination without sedation or the use of an oral speculum.

T65618

519818-519959

Sentence

denotes

In many horses, however, a detailed oral examination is best achieved after sedation and with the use of an oral speculum and a light source.

T75801

519960-520097

Sentence

denotes

The mouth should be irrigated to remove retained food material so as to be able to inspect and palpate the lips, cheeks, teeth, and gums.

T6986

520098-520252

Sentence

denotes

Ancillary aids for a complete examination of the oral cavity of the horse may include radiology, endoscopic examination, fluoroscopy, biopsy, and culture.

T91931

520253-520410

Sentence

denotes

Oral endoscopy should be performed with either sedation and an oral speculum or under general anesthesia to prevent inadvertent mastication of the endoscope.

T86523

520411-520469

Sentence

denotes

CT allows detailed imaging of the oral cavity and sinuses.

T23437

520470-520518

Sentence

denotes

The lips of the horse are mobile and prehensile.

T93008

520519-520625

Sentence

denotes

Consequently, loss of motor function (e.g., facial palsy) affects the efficiency of the prehensile system.

T64974

520626-520709

Sentence

denotes

The lips grasp food in grazing or browsing, and the incisor teeth section the food.

T45106

520710-520901

Sentence

denotes

With mastication and lubrication with saliva, the bolus of food forms and is manipulated from side to side across the mouth, assisted by the tight cheeks of the horse and the palatine ridges.

T93471

520902-520995

Sentence

denotes

Swallowing begins as the food bolus contacts the base of the tongue and the pharyngeal walls.

T62435

520996-521191

Sentence

denotes

During swallowing, the soft palate elevates to close the nasopharynx, the base of the tongue elevates, and the hyoid bone and the larynx move rostrally following contraction of the hyoid muscles.

T24921

521192-521417

Sentence

denotes

During this process, the rima glottidis closes and the epiglottis tilts dorsally and caudally to protect the airway so that food is swept through lateral food channels around the sides of the larynx into the laryngoesophagus.

T74479

521418-521616

Sentence

denotes

Fluoroscopic studies in nursing foals in the dorsoventral view showed that contact occurs between the lateral food channels in the midline so that in outline the food bolus achieves a bow-tie shape.

T3323

521617-521683

Sentence

denotes

1188 Dysphagia is defined as a difficulty or inability to swallow.

T56242

521684-521801

Sentence

denotes

Anatomic classifications for dysphagia include prepharyngeal, pharyngeal, and esophageal (postpharyngeal) dysphagias.

T94739

521802-521868

Sentence

denotes

The site of the cause for dysphagia influences the clinical signs.

T70391

521869-522031

Sentence

denotes

Prepharyngeal dysphagia is characterized by dropping food (quidding) or water from the mouth, reluctance to chew, hypersalivation, or abnormalities in prehension.

T21578

522032-522228

Sentence

denotes

Pharyngeal and esophageal dysphagias are characterized by coughing; nasal discharge containing saliva, water, or food material; gagging; anxiousness; and neck extension during attempts to swallow.

T92418

522229-522297

Sentence

denotes

The following section describes esophageal dysphagia in more detail.

T51913

522298-522410

Sentence

denotes

Causes of dysphagia can be divided into four types: painful, muscular, neurologic, or obstructive (Table 12.8) .

T21024

522411-522558

Sentence

denotes

Pain and obstruction cause dysphagia by interfering with the mechanics of prehension, bolus formation and transfer to the pharynx, and deglutition.

T11145

522559-522801

Sentence

denotes

Muscular and neurologic causes of dysphagia impede prehension and swallowing by affecting the motor function of the lingual or buccal musculature, muscles of mastication (temporal and masseters), and pharyngeal and cranial esophageal muscles.

T2300

522802-522897

Sentence

denotes

Sensory loss to the lips, buccal mucous membranes, pharynx, or tongue also may cause dysphagia.

T74168

522898-523162

Sentence

denotes

Neurologic causes of dysphagia may affect the forebrain, brainstem, or peripheral nerves that control prehension (cranial nerves Vm, Vs, VII, and XII), transfer of the food bolus to the pharynx (cranial nerves Vs and XII), and swallowing (cranial nerves IX and X).

T21166

523163-523403

Sentence

denotes

The latter point was classical thinking, but recent evidence suggests that, while stimulation of cranial nerve IX stimulates swallowing, bilateral blockade of that nerve does not prevent normal swallowing of either liquid or solid material.

T4472

523404-523618

Sentence

denotes

1189 Diagnosis of the cause of dysphagia is based on physical examination including a careful oral examination; neurologic examination; clinical signs; and endoscopy of the pharynx, esophagus, and guttural pouches.

T74712

523619-523696

Sentence

denotes

Radiology may be useful to assess the bony structures of the head and throat.

T70558

523697-523809

Sentence

denotes

Ultrasonography is valuable for examining the retropharyngeal space and esophagus to detect and evaluate masses.

T91424

523810-523936

Sentence

denotes

Pharyngeal or esophageal causes of dysphagia may be detected with routine endoscopic examination or with contrast radiography.

T58674

523937-524056

Sentence

denotes

Endoscopy may also be used to assess deglutition, but this function may be adversely affected by sedation of the horse.

T57276

524057-524183

Sentence

denotes

Deglutition may also be assessed using fluoroscopy 1190 or manometry, 1191 but these techniques require specialized equipment.

T4461

524184-524304

Sentence

denotes

Specific diagnostic procedures for nonalimentary causes of dysphagia are covered elsewhere in this text (see Chapter 7).

T44555

524305-524420

Sentence

denotes

Specific treatments aimed at resolving the underlying disorder causing dysphagia are discussed in detail elsewhere.

T96613

524421-524513

Sentence

denotes

Most horses with dysphagia should not be fed roughage with long fiber length (hay or grass).

T67892

524514-524681

Sentence

denotes

Dietary modifications that promote swallowing, such as feeding slurries made from complete pelleted feeds, may be sufficient to manage some cases of partial dysphagia.

T98296

524682-524781

Sentence

denotes

Aspiration pneumonia is a potential complication in horses with pharyngeal or esophageal dysphagia.

T7247

524782-524872

Sentence

denotes

Foals may be managed by feeding mare's milk or a suitable substitute via nasogastric tube.

T67835

524873-524964

Sentence

denotes

Pellet slurries or formulated liquid diets may be fed via nasogastric tube to older horses.

T26508

524965-525093

Sentence

denotes

Prolonged nutritional management of dysphagic horses may require extraoral feeding using a tube placed through an esophagostomy.

T88173

525094-525252

Sentence

denotes

1192 Formulated pelleted diets are often easy to administer through a tube as slurry and are balanced to meet the nutritional requirements for healthy horses.

T49705

525253-525356

Sentence

denotes

Sufficient quantities must be fed to deliver adequate calories (16) (17) Mcal/ day for a 500-kg horse).

T26339

525357-525467

Sentence

denotes

Adjustments may be necessary for horses that are cachectic or have extra metabolic demand (such as pregnancy).

T37520

525468-525573

Sentence

denotes

Adding corn oil to the ration (1 cup every 12 or 24 hours) is a common method of increasing fed calories.

T85563

525574-525688

Sentence

denotes

Equine-specific enteral formulations are also available (Well-Gel, Land O'Lakes Purina Feed LLC, Arden Hills, MN).

T58316

525689-525848

Sentence

denotes

Regardless of the method of nutritional management, salivary losses of electrolytes should be monitored and electrolyte replacement therapy provided as needed.

T81441

525849-525902

Sentence

denotes

Saliva contains high concentrations of Na, K, and Cl.

T90406

525903-526183

Sentence

denotes

A group of ponies with experimental esophagostomies 1193 and a horse with esophageal squamous cell carcinoma 1194 were fed a complete pelleted diet through esophagostomy tubes but developed metabolic acidosis, hyponatremia, and hypochloremia apparently because of salivary losses.

T93347

526184-526319

Sentence

denotes

Surprisingly, salivary losses of potassium did not result in hypokalemia in these cases, presumably because of replacement in the diet.

T97486

526320-526399

Sentence

denotes

Electrolyte replacement may be accomplished by adding NaCl and KCl to the diet.

T8129

526400-526489

Sentence

denotes

Horses can be maintained for months with frequent feedings through an esophagostomy tube.

T76323

526490-526618

Sentence

denotes

1194 Parenteral nutrition (total or partial) may be useful in the short term but is not often feasible for long-term management.

T90814

526619-526778

Sentence

denotes

Tooth eruption is a complex phenomenon involving the interplay of dental morphogenesis and those vascular forces responsible for creating the eruption pathway.

T74372

526779-526874

Sentence

denotes

These changes are responsible for osteitis and bone remodeling within the maxilla and mandible.

T3587

526875-526964

Sentence

denotes

Young horses frequently show symmetric bony swelling resulting from these eruption cysts.

T5131

526965-527088

Sentence

denotes

In some cases, additional clinical signs of nasal obstruction with respiratory stridor or nasal discharges may be apparent.

T81974

527089-527174

Sentence

denotes

Pathologic problems associated with maleruption include a variety of dental diseases.

T54451

527175-527258

Sentence

denotes

1195 Oral trauma can displace or damage erupting teeth or the permanent tooth buds.

T83271

527259-527355

Sentence

denotes

As a result, teeth may be displaced and erupt in abnormal positions or may have abnormal shapes.

T87724

527356-527500

Sentence

denotes

Supernumerary teeth, incisors and molars, can develop, as well as palatal displacement of impacted teeth (maxillary P3-3, or third cheek tooth).

T48203

527501-527662

Sentence

denotes

In almost all of these conditions some form of surgical treatment is necessary, but depending on the number and location, conservative therapy can be successful.

T43681

527663-527733

Sentence

denotes

1196 Dental impaction is a major cause of dental disease in the horse.

T24342

527734-527826

Sentence

denotes

In a series of 142 extracted teeth, 63 were P3-3 or P4-4 (cheek tooth 2 or 3, respectively).

T46216

527827-528020

Sentence

denotes

1197 Early observations had indicated that the first molar (M1, or cheek tooth 4) was the most commonly diseased tooth, and an "open infundibulum" in this tooth has been suggested as the cause.

T94620

528021-528237

Sentence

denotes

1198 In a later study, the mandibular cheek teeth 2 and 3 were the most commonly affected, whereas cheek teeth 2 and 4 were most commonly affected in the maxillary arcade, which was the more commonly affected arcade.

T31708

528238-528485

Sentence

denotes

1199 Studies on cementogenesis of the maxillary cheek teeth have shown, however, that most maxillary cheek teeth have a greater or lesser degree of hypoplasia of cementum within the enamel lakes and that this "lesion" rarely expands into the pulp.

T36623

528486-528580

Sentence

denotes

The central infundibular hole is the site of its vascular supply to the unerupted cement lake.

T46869

528581-528737

Sentence

denotes

On those occasions in which caries of cementum occurs-that is, secondary inflammatory disease and acid necrosis of the cementum-apical osteitis may develop.

T30221

528738-528803

Sentence

denotes

Pulpitis is key to the pathogenesis of dental decay in the horse.

T93877

528804-528941

Sentence

denotes

The initiation of inflammatory pulp changes may be a sequela to dental impaction or dental caries or may result from fracture of a tooth.

T89067

528942-529087

Sentence

denotes

If the onset of the inflammatory process is slow, then formation of secondary dentin within the pulp chambers may protect the pulp and the tooth.

T73253

529088-529179

Sentence

denotes

Secondary dentin formation occurs from stimulation of odontoblasts within the pulp chamber.

T61508

529180-529331

Sentence

denotes

Such changes are the normal process of protection during dental wear and attrition as crown substances wear away and the reserve crown comes into wear.

T25085

529332-529503

Sentence

denotes

In acute disease, however, this defense mechanism is ineffective, and the changes that occur and that are sequelae to pulpitis reflect the location of each affected tooth.

T58099

529504-529654

Sentence

denotes

For example, pulpitis and apical osteitis of the third mandibular cheek tooth most commonly results in the development of a mandibular dental fistula.

T21205

529655-529833

Sentence

denotes

Pulpitis of the third maxillary cheek tooth, however, results in an inflammatory disease within the rostral maxillary sinus and in development of chronic maxillary sinus empyema.

T10391

529834-530064

Sentence

denotes

Oblique radiographs greatly assist the diagnosis of dental decay by demonstrating sinus tract formation, sequestration of bone, mandibular osteitis, hyperplasia of cementum, and new bone formation (so-called alveolar periostitis).

T43983

530065-530130

Sentence

denotes

1200 Nuclear scintigraphy and CT can aid in an accurate diagosis.

T97122

530131-530242

Sentence

denotes

49 , 53 The management of dental decay in the horse usually involves surgical extraction of the diseased tooth.

T51521

530243-530347

Sentence

denotes

In some horses, apicoectomy and retrograde endodontic techniques may be used to save the diseased tooth.

T83816

530348-530402

Sentence

denotes

Care must be taken, however, in selection of patients.

T56404

530403-530569

Sentence

denotes

In most cases of apical osteitis in the horse that result from dental impaction, immature root structures make achieving an apical seal of the exposed pulp difficult.

T95825

530570-530768

Sentence

denotes

Gingival hyperemia and inflammation occur during the eruption of the permanent teeth and are common causes of a sore mouth in young horses (particularly 3-year-olds as the first dental caps loosen).

T77707

530769-530856

Sentence

denotes

Such periodontal changes usually resolve as the permanent dental arcade is established.

T24540

530857-531049

Sentence

denotes

During normal mastication, the shearing forces generated by the occlusal contact of the cheek teeth essentially clean the teeth of plaque and effectively inhibit deposition of dental calculus.

T11524

531050-531243

Sentence

denotes

Wherever occlusal contact is ineffective, periodontal changes and calculus buildup occur; for example, the deposition of calculus on the canine teeth of mature geldings and stallions is common.

T83077

531244-531541

Sentence

denotes

Routine dental prophylaxis forms an important component of maintaining normal occlusal contact, and for this reason arcade irregularities that result in enamel point formation on the buccal edges of the maxillary cheek teeth and the lingual edges of the mandibular cheek teeth should be corrected.

T79767

531542-531673

Sentence

denotes

These edges may be smoothed annually in horses that are at grass and twice yearly in young horses, aged horses, and stabled horses.

T17493

531674-531792

Sentence

denotes

Horses at grass have a greater range of occlusal contact and therefore better periodontal hygiene than stabled horses.

T39718

531793-532043

Sentence

denotes

In stabled horses the range of occlusal contact is narrower, and the formation of enamel points occurs more frequently with subsequent buccal ulceration and the initiation of a cycle of altered occlusal contact and, hence, irregular arcade formation.

T96320

532044-532127

Sentence

denotes

This process leads to severe forms of periodontal disease and wave mouth formation.

T35209

532128-532253

Sentence

denotes

Periodontal disease occurs with abnormal occlusal contact and initiation of the cycle of irregular wear and abnormal contact.

T83551

532254-532354

Sentence

denotes

Such changes progress to loss of alveolar bone, gross periodontal sepsis, and loss of tooth support.

T54922

532355-532456

Sentence

denotes

In this sense periodontal disease truly is the scourge of the equine mouth and results in tooth loss.

T45298

532457-532492

Sentence

denotes

1201 Y CONGENITAL AND DEVELOPMENTAL

T20370

532493-532630

Sentence

denotes

Palatine clefts may result from an inherited defect and are caused by failure of the transverse palatal folds to fuse in the oral cavity.

T80861

532631-532684

Sentence

denotes

Harelip accompanies few palatine clefts in the horse.

T93532

532685-532808

Sentence

denotes

The degree of palatine clefting depends on the stage at which interruption in the fusion of the palatopalatal folds occurs.

T42964

532809-532911

Sentence

denotes

Toxic or teratogenic effects are documented in other species, but few data are available in the horse.

T763

532912-533115

Sentence

denotes

Treatment for repair of uncomplicated palatine defects has been recommended, but prognosis is generally poor because of the considerable nursing care required and the high incidence of surgical failures.

T80371

533116-533222

Sentence

denotes

Early surgery and the use of mandibular symphysiotomy in affording surgical exposure should be emphasized.

T35064

533223-533430

Sentence

denotes

The combination of mandibular symphysiotomy and trans-hyoid pharyngotomy to approach the caudal margins of the soft palate affords surgical access, and mucosal flaps can be constructed to repair the defects.

T82335

533431-533559

Sentence

denotes

The incidence of breakdown in the surgical repair is high, and healing by first intention is the exception rather than the rule.

T34186

533560-533672

Sentence

denotes

A surgical report documented the successful closure of a median cleft of the lower lip and mandible in a donkey.

T86521

533673-533677

Sentence

denotes

1202

T95906

533678-533752

Sentence

denotes

Foals born with a severely deviated premaxilla and palate have a wry nose.

T24406

533753-533833

Sentence

denotes

One can achieve a good functional and cosmetic outcome with surgical correction.

T39436

533834-533972

Sentence

denotes

1203 Circumstantial evidence indicates that such a defect has a genetic cause, and the defect occurs most frequently in the Arabian breed.

T56983

533973-534138

Sentence

denotes

Subepiglottic cysts are congenital abnormalities resulting from cystic distortion of remnants of the thyroglossal duct, which may cause dyspnea and choking in foals.

T16628

534139-534198

Sentence

denotes

Surgical removal of these cysts results in normal function.

T9030

534199-534319

Sentence

denotes

The most significant developmental defect of dental origin is a maxilla that is longer than the mandible (parrot mouth).

T34665

534320-534468

Sentence

denotes

An overbite of 2 cm in the incisor arcade may be present in a horse with a mismatch of less than 1 cm between the first upper and lower cheek teeth.

T36368

534469-534545

Sentence

denotes

Parrot mouth and monkey or sow mouth are thought to be inherited conditions.

T99627

534546-534620

Sentence

denotes

Some correction of minor incisor malocclusion occurs up to 5 years of age.

T17104

534621-534724

Sentence

denotes

Recognition and detection of parrot mouth are important in the examination of potential breeding stock.

T25951

534725-534868

Sentence

denotes

Surgical attempts to inhibit overgrowth of the premaxilla by wiring or by the application of dental bite plate procedures have been documented.

T63799

534869-534873

Sentence

denotes

1204

T78008

534874-535158

Sentence

denotes

Wounds of the lips, incisive bone, and the mandibular incisor area occur commonly in the horse and usually result from the horse getting the lips, jaw, or teeth caught in feeding buckets, in fence posts, or in halters or having a segment of tongue encircled with hair in tail chewing.

T70946

535159-535279

Sentence

denotes

As the horse panics and pulls away from its oral entrapment, considerable trauma can occur to the lips, teeth, and gums.

T49214

535280-535466

Sentence

denotes

Most wounds repair satisfactorily, provided they are identified early after the injury and basic principles of wound hygiene, excision of necrotic tissue, and wound closure are observed.

T83209

535467-535569

Sentence

denotes

Oral mucosal defects should be closed and effective oral seals made before external wounds are closed.

T84830

535570-535727

Sentence

denotes

In some horses, offering specially constructed diets or feeding the horse by nasogastric tube or esophagostomy during the healing processes may be necessary.

T55874

535728-535952

Sentence

denotes

Foreign body penetration of the tongue, cheek, or palate has been reported in grazing and browsing horses and in particular in horses that have certain hay sources that contain desiccated barley awns or yellow bristle grass.

T25884

535953-536086

Sentence

denotes

1205 Other plant material and grass awns occasionally may penetrate the tongue, gingiva, or cheek, causing inflammation or abscesses.

T90954

536087-536257

Sentence

denotes

Metallic foreign bodies have been reported in the tongue, and a history of feeding hay or the use of cable-framed tractor tires was often reported as part of the history.

T25703

536258-536336

Sentence

denotes

1206 Ulcerative stomatitis may occur as the result of phenylbutazone toxicity.

T43989

536337-536439

Sentence

denotes

1207 Vesicular stomatitis is a highly contagious viral blistering disease of horses and other animals.

T42187

536440-536524

Sentence

denotes

Treatment of glossitis and stomatitis primarily aims at removing the inciting cause.

T27858

536525-536700

Sentence

denotes

A. lignieresii, the causative agent of actinobacillosis, has been isolated and identified from ulcers on the free border of the soft palate and oral and laryngeal granulomata.

T32823

536701-536799

Sentence

denotes

The bacterium also was reported in a sublingual caruncle in a horse with a greatly swollen tongue.

T78632

536800-536913

Sentence

denotes

1208 Therapy with 150 mL of 20% sodium iodide and 5 g of ampicillin every 8 to 12 hours effected a clinical cure.

T11924

536914-536978

Sentence

denotes

Saliva is important for lubricating and softening food material.

T84581

536979-537065

Sentence

denotes

The horse has paired parotid, mandibular, and polystomatic sublingual salivary glands.

T51759

537066-537224

Sentence

denotes

The parotid gland is the largest of the salivary glands in the horse and is situated in the space between the ramus of the mandible and the wing of the atlas.

T11444

537225-537351

Sentence

denotes

The parotid duct is formed at the ventral part of the gland near the facial crest by the union of three or four smaller ducts.

TextSentencer_T371

537352-537539

Sentence

denotes

The duct leaves the gland above the linguofacial vein, crosses the tendon of the sternocephalicus muscle, and enters the mouth obliquely in the cheek opposite the third upper cheek tooth.

TextSentencer_T372

537540-537675

Sentence

denotes

The parotic duct orifice is small, but some dilation of the duct and a circular mucous fold (the parotid papillae) exist at this point.

TextSentencer_T373

537676-537789

Sentence

denotes

The mandibular gland is smaller than the parotid gland and extends from the atlantal fossa to the basihyoid bone.

TextSentencer_T374

537790-537883

Sentence

denotes

For the most part, the mandibular gland is covered by the parotid gland and by the lower jaw.

TextSentencer_T375

537884-538079

Sentence

denotes

The mandibular duct is formed by the union of a number of small duct radicles that emerge along the concave edge of the gland and run rostral to the border of the mouth opposite the canine tooth.

TextSentencer_T376

538080-538131

Sentence

denotes

The orifice is at the end of a sublingual caruncle.

TextSentencer_T377

538132-538219

Sentence

denotes

The mandibular gland possesses serous, mucous, and mixed alveolar glandular components.

TextSentencer_T378

538220-538274

Sentence

denotes

The parotid gland is a compound alveolar serous gland.

TextSentencer_T379

538275-538427

Sentence

denotes

The parotid salivary gland can secrete saliva to yield rates of 50 mL/min, and a total daily parotid secretion can be as much as 12 L in a 500-kg horse.

TextSentencer_T380

538428-538562

Sentence

denotes

Parotid secretion only occurs during mastication, and administration of atropine or anesthesia of the oral mucosa can block secretion.

TextSentencer_T381

538563-538706

Sentence

denotes

Parotid saliva is hypotonic compared with plasma, but at high rates of flow, concentrations of sodium, chloride, and bicarbonate ions increase.

TextSentencer_T382

538707-538870

Sentence

denotes

Parotid saliva of the horse has a high concentration of calcium, and occasionally calculi (sialoliths) form within the duct radicles of the parotid salivary gland.

TextSentencer_T383

538871-539038

Sentence

denotes

1209 Congenital parotid duct atresia, acquired stricture from trauma to the duct, or obstruction by plant material (sticks or foxtails and other seeds) also may occur.

TextSentencer_T384

539039-539238

Sentence

denotes

The clinical signs of sialolithiasis or other forms of ductule obstruction include a fluid swelling in the form of a mucocele proximal to the stone and occasionally inflammation of the parotid gland.

TextSentencer_T385

539239-539339

Sentence

denotes

Ultrasonography is useful to diagnose salivary mucoceles and to detect foreign bodies or sialoliths.

TextSentencer_T386

539340-539472

Sentence

denotes

Measurement of electrolyte concentrations in aspirates from suspected mucoceles might be helpful to distinguish them from hematomas.

TextSentencer_T387

539473-539542

Sentence

denotes

Salivary potassium and calcium concentrations are higher than plasma.

TextSentencer_T388

539543-539672

Sentence

denotes

Treatment may require surgical removal of the stone or plant material in the case of sialolithiasis or foreign body obstructions.

TextSentencer_T389

539673-539793

Sentence

denotes

Other causes of obstruction may require resection of the affected portion of the duct or chemical ablation of the gland.

TextSentencer_T390

539794-539867

Sentence

denotes

1210 Primary sialadenitis is unusual but can occur in one or both glands.

TextSentencer_T391

539868-539941

Sentence

denotes

The condition is painful and may be associated with a fever and anorexia.

TextSentencer_T392

539942-540018

Sentence

denotes

Secondary sialadenitis is more common and usually is associated with trauma.

TextSentencer_T393

540019-540119

Sentence

denotes

Infectious sialadenitis from C. pseudotuberculosis 1211 or other bacterial pathogens also may occur.

TextSentencer_T394

540120-540247

Sentence

denotes

Diagnosis is by physical examination and by finding an enlarged edematous parotid gland tissue on ultrasonographic examination.

TextSentencer_T395

540248-540333

Sentence

denotes

Culture and cytologic examination of aspirates may be useful for diagnostic purposes.

TextSentencer_T396

540334-540388

Sentence

denotes

Treatment in usually palliative, consisting of NSAIDs.

TextSentencer_T397

540389-540480

Sentence

denotes

Appropriate antibiotic therapy is indicated as directed by culture and sensitivity results.

T2536

540481-540617

Sentence

denotes

Chemical irritation, glossitis, stomatitis, or other causes of prepharyngeal dysphagia cause ptyalism or excessive salivation in horses.

T94186

540618-540774

Sentence

denotes

Specific therapy for the ptyalism usually is not required as long as salivary losses are not excessive, resulting in dehydration and electrolyte imbalances.

T33810

540775-540854

Sentence

denotes

Ingestion of the fungal toxin slaframine also causes hypersalivation in horses.

T80662

540855-540965

Sentence

denotes

1212 The fungus Rhizoctonia leguminicola, which produces slaframine, causes black patch disease in red clover.

T44168

540966-541067

Sentence

denotes

Slaframine is a parasympathomimetic compound that stimulates exocrine secretion in the parotid gland.

T35394

541068-541206

Sentence

denotes

Slaframine toxicosis most commonly occurs in the spring or early summer and rarely requires treatment other than removal from the pasture.

T4556

541207-541312

Sentence

denotes

Mowing removes the source in most cases because regrowth in pastures often has less fungal contamination.

T6405

541313-541317

Sentence

denotes

1213

T51463

541319-541459

Sentence

denotes

The esophagus is a musculomembranous tube that originates from the pharynx dorsal to the larynx and terminates at the cardia of the stomach.

T62794

541460-541537

Sentence

denotes

1214 In adult Thoroughbred horses the esophagus is approximately 120 cm long.

T99157

541538-541698

Sentence

denotes

The cervical portion is approximately 70 cm long; the thoracic portion, approximately 50 cm long; and the short abdominal portion, only approximately 2 cm long.

T25902

541699-541798

Sentence

denotes

The cervical esophagus generally lies dorsal and to the left of the trachea in the cervical region.

T79835

541799-541956

Sentence

denotes

In the thorax the esophagus courses through the mediastinum lying dorsal to the trachea and crosses to the right of the aortic arch dorsal to the heart base.

T88325

541957-542092

Sentence

denotes

The esophagus has no digestive or absorptive functions and serves as a conduit to the stomach for food, water, and salivary secretions.

T3745

542093-542163

Sentence

denotes

The esophageal mucosa is a keratinized stratified squamous epithelium.

T22023

542164-542311

Sentence

denotes

1214 The submucosa contains elastic fibers that contribute to the longitudinal folds of the esophagus and confer elasticity to the esophageal wall.

T4913

542312-542494

Sentence

denotes

A transition occurs in the muscle type composing the tunica muscularis from striated skeletal muscle in the proximal two thirds of the esophagus to smooth muscle in the distal third.

T1417

542495-542584

Sentence

denotes

In the proximal esophagus the skeletal muscle layers spiral across one another at angles.

T93023

542585-542738

Sentence

denotes

Within the smooth muscle layers of the distal esophagus the outer layer becomes more longitudinal, whereas the inner layer thickens and becomes circular.

T20921

542739-542797

Sentence

denotes

The wall of the terminal esophagus can be 1 to 2 cm thick.

T97976

542798-542909

Sentence

denotes

Deep cervical fascia, pleura, and peritoneum contribute to the thin fibrous tunica adventitia of the esophagus.

T96455

542910-543110

Sentence

denotes

Motor innervation to the striated skeletal muscle of the esophagus includes the pharyngeal and esophageal branches of the vagus nerve, which originate in the nucleus ambiguus of the medulla oblongata.

T70345

543111-543202

Sentence

denotes

Parasympathetic fibers of the vagus nerve supply the smooth muscle of the distal esophagus.

T57056

543203-543255

Sentence

denotes

Sympathetic innervation of the esophagus is minimal.

T54292

543256-543405

Sentence

denotes

Passage of ingesta through the esophagus can be considered part of the swallowing process, which consists of oral, pharyngeal, and esophageal stages.

T84862

543406-543510

Sentence

denotes

The oral stage is voluntary and involves transport of the food bolus from the mouth into the oropharynx.

T83436

543511-543690

Sentence

denotes

During the involuntary pharyngeal stage the food bolus is forced through the momentarily relaxed upper esophageal sphincter by simultaneous contractions of the pharyngeal muscles.

T65077

543691-543880

Sentence

denotes

In the esophageal phase of swallowing the upper esophageal sphincter closes immediately, the lower esophageal sphincter opens, and esophageal peristalsis propels the bolus into the stomach.

T3331

543881-544031

Sentence

denotes

1215 Unlike a food bolus, liquids do not require peristalsis to reach the lower esophageal sphincter and may precede the food bolus during swallowing.

T4928

544032-544171

Sentence

denotes

The upper esophageal sphincter prevents esophagopharyngeal reflux during swallowing and air distention of the esophagus during inspiration.

T9834

544172-544333

Sentence

denotes

Upper esophageal pressure increases in response to pressure from a food bolus and to increased intraluminal acidity, as would occur with gastroesophageal reflux.

T59552

544334-544503

Sentence

denotes

The lower esophageal sphincter is a smooth muscle located at the gastroesophageal junction that is morphologically ill defined but forms an effective functional barrier.

T86072

544504-544629

Sentence

denotes

1215 Normally the lower esophageal sphincter is closed in response to gastric distention to restrict gastroesophageal reflux.

T21332

544630-544746

Sentence

denotes

Relaxation of the lower esophageal sphincter permits passage of ingested material from the esophagus to the stomach.

T48841

544747-544841

Sentence

denotes

Distention of the stomach with ingesta mechanically constricts the lower esophageal sphincter.

T91027

544842-544998

Sentence

denotes

Gastric distention also triggers a vagal reflex that increases lower esophageal sphincter tone, which is a safety mechanism against gastroesophageal reflux.

T88961

544999-545264

Sentence

denotes

The mechanical and vagal mechanisms that promote lower esophageal sphincter tone prevent spontaneous decompression of the stomach, which along with a lack of a vomiting reflex in the horse, increases the risk of gastric rupture during episodes of severe distention.

T25308

545265-545364

Sentence

denotes

A wide variety of congenital and acquired disorders of the esophagus have been described in horses.

T37824

545365-545450

Sentence

denotes

These are summarized in Table 12 .9 and discussed in detail in the following section.

T42972

545451-545500

Sentence

denotes

Esophageal obstruction has many causes (Table 12.

T10633

545501-545610

Sentence

denotes

10) and most often is manifested clinically by impaction of food material and resulting esophageal dysphagia.

T81878

545611-545772

Sentence

denotes

Esophageal obstruction may be caused by primary impactions (simple choke) of roughage, particularly leafy alfalfa hay; coarse grass hay; bedding; and even grass.

T76014

545773-545907

Sentence

denotes

1216 Prior esophageal trauma or poor mastication caused by dental abnormalities may predispose horses to primary esophageal impaction.

T25531

545908-546094

Sentence

denotes

1217 "Wolfing" or gulping food may precipitate primary impactions, particularly if the horse is exhausted or mildly dehydrated after a long ride or is weakened from chronic debilitation.

T8273

546095-546393

Sentence

denotes

Impactions also may result from disorders that physically impede the passage of food material and fluid by narrowing the luminal diameter, reduce the compliance of the esophageal wall, or alter the conformation of the esophageal wall such that food material accumulates in a pocket or diverticulum.

T64924

546394-546522

Sentence

denotes

Foreign bodies, intramural or extramural masses, or acquired or congenital anomalies cause these so-called secondary impactions.

T97447

546523-546801

Sentence

denotes

Intramural causes of esophageal obstruction include tumors (squamous cell carcinoma [SCC]), strictures, diverticula, and cysts. [1218] [1219] [1220] [1221] [1222] [1223] [1224] [1225] [1226] Mediastinal or cervical masses (tumors or abscesses) may cause extramural obstructions.

T93679

546802-546851

Sentence

denotes

Congenital anomalies are covered in detail later.

T14040

546852-547029

Sentence

denotes

A thorough physical examination, including complete oral and neurologic examination, can help rule out causes of dysphagia and nasal discharge other than esophageal obstruction.

T86320

547030-547199

Sentence

denotes

Clinical signs associated with esophageal obstructions are related primarily to regurgitation of food, water, and saliva caused by esophageal (postpharyngeal) dysphagia.

T84353

547200-547293

Sentence

denotes

1227 Horses with esophageal obstruction are often anxious and stand with their neck extended.

T17672

547294-547377

Sentence

denotes

Gagging or retching may be observed, particularly with acute proximal obstructions.

T42502

547378-547604

Sentence

denotes

Bilateral frothy nasal discharge containing saliva, water, and food material; coughing; odynophagia; and ptyalism are characteristic clinical signs, the severity of which varies with the degree and location of the obstruction.

T58920

547605-547680

Sentence

denotes

Distention in the jugular furrow may be evident at the site of obstruction.

T13566

547681-547877

Sentence

denotes

Other clinical signs related to regurgitation of saliva, water, and food material, such as dehydration, electrolyte, or acid-base imbalances; weight loss; and aspiration pneumonia may be observed.

T31997

547878-547989

Sentence

denotes

In extreme cases, pressure necrosis from the impaction or trauma to the esophagus may cause esophageal rupture.

T64804

547990-548115

Sentence

denotes

If the rupture is in the cervical esophagus, crepitus or cellulitis may be evident along with signs of systemic inflammation.

T60903

548116-548204

Sentence

denotes

Thoracic auscultation is important to determine whether aspiration pneumonia is present.

T53961

548205-548296

Sentence

denotes

Intrathoracic esophageal rupture may result in pleuritis and its associated clinical signs.

T25343

548297-548487

Sentence

denotes

Passage of a nasogastric tube is an effective way to detect and localize an obstruction but provides little information about the nature of the obstruction or the condition of the esophagus.

T4054

548488-548578

Sentence

denotes

The most direct method for diagnosis of esophageal obstructions is endoscopic examination.

T26987

548579-548853

Sentence

denotes

Esophageal obstruction occurs most commonly at sites of natural narrowing of the esophageal lumen, such as the cervical esophagus, the thoracic inlet, base of the heart, or the terminal esophagus; an endoscope greater than 1 m in length is necessary for complete evaluation.

T2568

548854-549022

Sentence

denotes

Endoscopic evaluation is useful before relief of an impaction to localize the obstruction and to investigate the nature of the impaction if one suspects a foreign body.

T67315

549023-549087

Sentence

denotes

Foreign bodies may be retrievable via transendoscopic tethering.

T71312

549088-549205

Sentence

denotes

1228 Critical diagnostic and prognostic information is also obtained via endoscopy after resolution of the impaction.

T82210

549206-549362

Sentence

denotes

Assessing the affected esophagus for mucosal ulceration, rupture, masses, strictures, diverticula, and signs of functional abnormalities is important (Figs.

T38277

549363-549381

Sentence

denotes

12.15 and 12.16) .

T7812

549382-549615

Sentence

denotes

Ultrasonography of the cervical region is useful not only to confirm a cervical esophageal impaction but also to provide critical information about the location and extent of the impaction and esophageal wall thickness and integrity.

T77813

549616-549672

Sentence

denotes

Ultrasonography may provide information about the cause.

T98040

549673-549849

Sentence

denotes

1194 Radiographic assessment of the esophagus can confirm the presence of esophageal obstruction in cases in which one cannot view the affected area adequately using endoscopy.

T49540

549850-549988

Sentence

denotes

Impacted food material in the esophagus may be visualized as a typical granular pattern with gas accumulation proximal to the obstruction.

T88825

549989-550140

Sentence

denotes

Air or barium contrast radiographic studies are most useful for evaluating the esophagus following relief of the impaction if one suspects a stricture.

T67437

550141-550605

Sentence

denotes

Esophageal dilation, diverticula, rupture, functional disorder (megaesophagus), or luminal narrowing caused by extraluminal compression are detected more easily using contrast radiographic studies than endoscopy (Fig. 12.17 ). [1229] [1230] [1231] Radiographic studies of the esophagus should be interpreted cautiously in sedated horses, particularly after passage of a nasogastric tube or other esophageal manipulations that may contribute to esophageal dilation.

T13459

550606-550608

Sentence

denotes

36

T91686

550609-550694

Sentence

denotes

The primary goal of treatment for esophageal impaction is to relieve the obstruction.

T88333

550695-550838

Sentence

denotes

A variety of approaches have been described, ranging from minimal conservative therapy to aggressive intervention to relieving the obstruction.

T69967

550839-551154

Sentence

denotes

Parenteral administration of acepromazine (0.05 mg/kg IV), xylazine (0.25-0.5 mg/kg IV) or detomidine (0.01-0.02 mg/kg IV), oxytocin (0.11-0.22 IU/kg intramuscularly), and/or esophageal instillation of lidocaine (30-60 mL of 1% lidocaine) may reduce esophageal spasms caused by pain or may decrease esophageal tone.

T10748

551155-551282

Sentence

denotes

36, 1232, 1233 N-Butylscopolammonium bromide may reduce smooth muscle tone and has been used to help resolve some obstructions.

T64739

551283-551414

Sentence

denotes

In many horses with esophageal obstruction secondary to a feed impaction, the problem may be resolved with conservative management.

T94172

551415-551523

Sentence

denotes

To facilitate examination, relieve anxiety, and relax the esophagus, one should begin by sedating the horse.

T86494

551524-551583

Sentence

denotes

A nasogastric tube is then passed to confirm the diagnosis.

T68522

551584-551719

Sentence

denotes

When an obstruction is encountered, gentle pressure is applied in an attempt to dislodge and move distally the offending feed material.

T99392

551720-551799

Sentence

denotes

If the choke is not easily dislodged with gentle pressure, the tube is removed.

T58175

551800-551900

Sentence

denotes

Appropriate sedative, antiinflammatory/analgesic, and smooth muscle-relaxing drugs are administered.

T78397

551901-552012

Sentence

denotes

The horse is moved to an unbedded stall with absolutely no food or water within reach and muzzled if necessary.

T44086

552013-552068

Sentence

denotes

The horse is left alone in the stall for several hours.

T98895

552069-552147

Sentence

denotes

If there is evidence of dehydration, appropriate IV fluid therapy is provided.

T79200

552148-552243

Sentence

denotes

If there is evidence of aspiration pneumonia, appropriate IV antimicrobial therapy is provided.

T39066

552244-552351

Sentence

denotes

On reexamination, a stomach tube is passed and gentle pressure is again applied to the area of obstruction.

T36784

552352-552506

Sentence

denotes

In many horses, the impaction will have softened and can be easily dislodged, if it has not resolved already, with minimal pressure from the stomach tube.

T23558

552507-552680

Sentence

denotes

Some clinicians prefer a more interventional approach to the resolution of an impaction, and some impactions are severe enough to require physical dispersal of the material.

T62571

552681-552824

Sentence

denotes

1232 A nasogastric tube can be used to displace the impacted material along with external massage if the obstruction is in the cervical region.

T444

552825-552988

Sentence

denotes

Careful lavage of the esophagus with water via an uncuffed or a cuffed nasogastric tube while the head is lowered may be a useful aid in breaking up the impaction.

T72027

552989-553148

Sentence

denotes

Some clinicians advocate a dual tube method in which a tube is placed through each nasal passage into the esophagus for ingress and egress of the lavage fluid.

T20602

553149-553304

Sentence

denotes

Because of the risk of aspiration of water and food material, esophageal lavage sometimes is done under general anesthesia with a cuffed nasotracheal tube.

T12158

553305-553504

Sentence

denotes

In refractory cases, IV administration of polyionic fluids provides hydration and alleviates any electrolyte or acid-base imbalances resulting from salivary losses of chloride, sodium, and potassium.

T11854

553505-553606

Sentence

denotes

1193 Oxytocin may or may not provide a direct effect for the resolution of an esophageal obstruction.

T16586

553607-553750

Sentence

denotes

Oxytocin reduced the area under the curve for esophageal smooth muscle strip contractions but had no effect on skeletal muscle strips in vitro.

T82604

553751-553909

Sentence

denotes

1234 In one in vivo report, oxytocin administration resulted in decreased esophageal tone in the proximal esophagus (aborad to the larynx and thoracic inlet).

T61224

553910-554008

Sentence

denotes

1233 In a separate study, oxytocin administration did not affect esophageal manometric recordings.

T27059

554009-554106

Sentence

denotes

1235 Rarely, esophageal obstruction ultimately may require esophagotomy to relieve the impaction.

T98611

554107-554274

Sentence

denotes

Strict restriction of food and water, including access to bedding material, must be enforced until the obstruction is resolved and the esophagus has regained function.

T79773

554275-554463

Sentence

denotes

Surgical removal of esophageal foreign bodies can be considered if the size and/or orientation of the object is such that transendoscopic retrieval is considered unlikely to be successful.

T98110

554464-554614

Sentence

denotes

1226, 1236 In one report, an intraluminal mass comprised of exuberant granulation tissue was removed via serial transendoscopic Nd:YAG laser ablation.

T52206

554615-554821

Sentence

denotes

1237 Systemic effects of dysphagia associated with esophageal impaction include dehydration, hyponatremia, hypochloremia, and metabolic alkalosis from prolonged loss of salivary free water and electrolytes.

T21122

554822-555021

Sentence

denotes

1193 Esophageal endoscopy should be performed after relief of the impaction to determine whether any complications of the impaction have developed or if a primary cause of the obstruction is present.

T25396

555022-555156

Sentence

denotes

Endoscopic examination is critical to determine the postobstruction treatment plan and for follow-up evaluation of esophageal healing.

T73192

555157-555299

Sentence

denotes

The horse should be reevaluated every 2 to 4 weeks following resolution of the impaction if esophageal dilation or mucosal injury is observed.

T86761

555300-555455

Sentence

denotes

In one report, male sex, age >15 years, and need for general anesthesia to relieve the obstruction were associated with an increased risk of complications.

T86137

555456-555697

Sentence

denotes

1238 Dilation proximal to the site of obstruction, mucosal injury from trauma, stricture formation, formation of a diverticulum, megaesophagus, and esophagitis are sequelae to esophageal obstruction that predispose patients to reobstruction.

T17178

555698-555855

Sentence

denotes

Underlying functional or morphologic abnormalities were much more likely in cases of recurrent, relative to first time, obstruction in a retrospective study.

T12629

555856-555909

Sentence

denotes

1216 The rate of reobstruction may be as high as 37%.

T91532

555910-556056

Sentence

denotes

Depending on the duration of the obstruction and the degree of trauma or dilation, the risk of reobstruction is high for 24 to 48 hours or longer.

T74763

556057-556145

Sentence

denotes

Food should be withheld for at least 24 to 48 hours after resolution of the obstruction.

T43072

556146-556312

Sentence

denotes

Sucralfate (20 mg/kg orally every 6 hours) may hasten healing if esophageal ulceration is evident, but the efficacy of sucralfate for this purpose is not established.

T89578

556313-556509

Sentence

denotes

Some clinicians suggest that administration of an NSAID may reduce the development of strictures, although judicious use of NSAIDs is recommended to prevent worsening of esophageal mucosal injury.

T18169

556510-556581

Sentence

denotes

Orally administered NSAIDs should be avoided if esophagitis is present.

T80726

556582-556930

Sentence

denotes

After 48 to 72 hours or when the esophageal mucosa has recovered as assessed by endoscopy, the horse may be fed soft food (moistened pellets and bran mashes) then transitioned gradually to a high-quality roughage diet over 7 to 21 days, depending on the degree of esophageal damage induced by the impaction and the nature of any underlying disease.

T4002

556931-557082

Sentence

denotes

The prognosis for survival is good (78-88%), but some horses may require permanent dietary modification if persistent chronic obstruction is a problem.

T83783

557083-557255

Sentence

denotes

1216, 1220, 1238 Aspiration pneumonia is a potential complication in every case of esophageal obstruction, and perforation is possible with severe or prolonged obstruction.

T52832

557256-557417

Sentence

denotes

In one report, duration of obstruction before presentation was a good predictor of pneumonia, whereas endoscopic evidence of tracheal food contamination was not.

T49736

557418-557690

Sentence

denotes

1216 Administration of broad-spectrum antibiotics that are effective against grampositive and gram-negative organisms, including metronidazole for anaerobes, is highly recommended if the duration of obstruction is either unknown or prolonged or if aspiration is suspected.

T57341

557691-557794

Sentence

denotes

Esophagitis refers to a clinical syndrome of esophageal inflammation that may or may not be ulcerative.

T96209

557795-557982

Sentence

denotes

The major protective mechanisms of the esophageal mucosa include salivary and food material buffers, normal peristaltic motility, and the barrier formed by the gastroesophageal sphincter.

T77261

557983-558135

Sentence

denotes

Reflux esophagitis is caused by repeated episodes of gastric fluid regurgitation into the distal esophagus and subsequent chemical injury to the mucosa.

T96952

558136-558300

Sentence

denotes

1239 Esophageal mucosal ulceration also can occur if the clearance of gastric fluid from the esophagus is delayed, such as in functional disorders of the esophagus.

T62849

558301-558476

Sentence

denotes

Like ulceration of the squamous portion of the stomach in horses, gastric acid and bile salt chemical injury is a major mechanism of esophageal squamous epithelial ulceration.

T72835

558477-558713

Sentence

denotes

838, 1239 Reflux esophagitis may occur along with gastric ulcer disease, motility disorders, increased gastric volume from gastric outflow obstructions, gastric paresis, intestinal ileus, or impaired lower esophageal sphincter function.

T78686

558714-558931

Sentence

denotes

1222, 1239 Other causes of esophagitis in horses include trauma (foreign bodies, food impactions, and nasogastric tubes), infection (mural abscesses), or chemical injury (pharmaceuticals and cantharidin; Fig. 12.18) .

T70766

558932-558948

Sentence

denotes

1236, 1240, 1241

T8478

558950-559061

Sentence

denotes

The clinical signs of esophagitis are nonspecific and similar to esophageal obstruction and gastric ulceration.

T31519

559062-559155

Sentence

denotes

Gagging or discomfort when swallowing may be evident, along with hypersalivation and bruxism.

T33706

559156-559209

Sentence

denotes

Esophageal (postpharyngeal) dysphagia may be evident.

T47584

559210-559301

Sentence

denotes

Partial or complete anorexia with resultant weight loss may be observed in affected horses.

T61037

559302-559408

Sentence

denotes

Esophageal hypomotility dysfunction caused by the inflammatory process may result in esophageal impaction.

T76079

559409-559527

Sentence

denotes

Clinical signs of underlying diseases that predispose to esophagitis may predominate or mask the signs of esophagitis.

T26972

559528-559761

Sentence

denotes

Horses with gastrointestinal motility disorders such as proximal enteritis or gastric outflow obstruction are at a high risk of developing reflux esophagitis because of the presence of gastric acid and bile salts in the fluid reflux.

T90893

559762-559854

Sentence

denotes

Foals with obstructive gastroduodenal ulcer disease (GDUD) commonly have reflux esophagitis.

T63471

559855-559999

Sentence

denotes

Diagnosis requires endoscopic examination, with diffuse, patchy, linear, or coalescing erosion or ulcerations or significant edema or hyperemia.

T24831

560000-560136

Sentence

denotes

Determining whether an underlying disease, such as infection, neoplasia, esophageal strictures, or diverticula, is present is important.

T7511

560137-560216

Sentence

denotes

Evaluation of the stomach is important to rule out gastric outflow obstruction.

T69992

560217-560300

Sentence

denotes

Contrast radiography may be helpful to assess esophageal motility and transit time.

T41162

560301-560310

Sentence

denotes

1230 FIG.

T58225

560311-560425

Sentence

denotes

12.18 Endoscopic view of the cervical esophagus of a horse that had repeated passages of a stiff nasogastric tube.

T28805

560426-560490

Sentence

denotes

The deep, linear ulceration of the esophageal mucosa is notable.

T33762

560491-560678

Sentence

denotes

The principles of therapy for reflux esophagitis include control of gastric acidity, mucosal protection, and correction of any underlying disorder contributing to gastroesophageal reflux.

T74727

560679-560800

Sentence

denotes

Reduction of gastric acid production with proton pump antagonists or H 2 receptor antagonists is critical for resolution.

T16500

560801-560893

Sentence

denotes

Some clinicians advocate using sucralfate to promote healing of ulcerated esophageal mucosa.

T45771

560894-561017

Sentence

denotes

The ability of sucralfate to bind ulcerated esophageal mucosa or hasten ulcer healing, however, is not proven in the horse.

T13153

561018-561106

Sentence

denotes

If a primary gastric outflow obstruction is present, surgical intervention is warranted.

T33824

561107-561307

Sentence

denotes

Horses with delayed gastric outflow without obstruction may benefit from prokinetics such as metoclopramide (0.02-0.1 mg/kg SC every 4-12 hours) or bethanechol (0.025-0.035 mg/kg SC every 4-24 hours).

T66083

561308-561456

Sentence

denotes

For esophagitis from trauma or pressure injury after esophageal impaction, judicious use of NSAIDs may be warranted to reduce inflammation and pain.

T77921

561457-561591

Sentence

denotes

Dietary modification may be necessary for patients with esophagitis, depending on the degree of ulceration or if motility is impaired.

T32525

561592-561693

Sentence

denotes

Horses with mild esophagitis should be fed frequent small meals of moistened pellets and fresh grass.

T42304

561694-561792

Sentence

denotes

Severe esophagitis may necessitate withholding food and complete esophageal rest for several days.

T94705

561793-561982

Sentence

denotes

Although the prognosis for esophagitis is good in the absence of underlying disease, the risk of stricture formation is high if severe circumferential or coalescing ulcerations are present.

T16845

561983-562063

Sentence

denotes

Esophagitis from severe trauma or infection may be prone to stricture formation.

T79551

562064-562208

Sentence

denotes

Motility dysfunction of the equine esophagus is most often manifest as hypomotility resulting in esophageal dilation (ectasia) or megaesophagus.

T76718

562209-562345

Sentence

denotes

Although megaesophagus in horses most commonly is acquired, reports indicate idiopathic megaesophagus in young horses may be congenital.

T17370

562346-562481

Sentence

denotes

1191, [1242] [1243] [1244] [1245] Acquired megaesophagus in horses may be a consequence of chronic or recurrent esophageal obstruction.

T36266

562482-562607

Sentence

denotes

1220, 1222 Esophageal impactions of a short duration cause a proximal dilation of the esophagus that is generally reversible.

T16158

562608-562758

Sentence

denotes

1230 If the duration of the obstruction is long enough, the motility of the esophagus proximal to the site of obstruction may be impaired permanently.

T71307

562759-562903

Sentence

denotes

Other causes of acquired megaesophagus include extraesophageal obstruction by tumors or abscesses, pleuropneumonia, and vascular ring anomalies.

T83659

562904-563118

Sentence

denotes

1220,1223 A retrospective report of horses with megaesophagus reveals an overrepresentation of Friesian horses (14 of 18 cases) suggesting the possibility of a predisposition for esophageal disorders in this breed.

T49611

563119-563239

Sentence

denotes

1214 The authors state that preliminary pedigree analyses suggest the possibility of a recessive pattern of inheritance.

T50115

563240-563330

Sentence

denotes

1214 Megaesophagus also may result from neurologic, neuromuscular, and muscular disorders.

T36749

563331-563545

Sentence

denotes

Neurologic diseases that cause vagal neuropathy, such as equine protozoal myeloencephalitis, equine herpesvirus myeloencephalitis, and idiopathic vagal neuropathy, have been associated with megaesophagus in horses.

T182

563546-563631

Sentence

denotes

Pleuropneumonia may be associated with a vagal neuropathy resulting in megaesophagus.

T42271

563632-563739

Sentence

denotes

Megaesophagus is an early sign of equine dysautonomia 1246 and may be observable in patients with botulism.

T33568

563740-563854

Sentence

denotes

Myasthenia gravis is a well-known cause of megaesophagus in nonequine species but has not been reported in horses.

T60730

563855-564052

Sentence

denotes

Also in other species, electrolyte disorders, cachexia, primary myopathies, myositis, and Addison's disease may affect esophageal motility but have not been associated with megaesophagus in horses.

T15741

564053-564167

Sentence

denotes

Iatrogenic megaesophagus can be induced by the α 2 -adrenergic agonist detomidine but is transient and reversible.

T89527

564168-564443

Sentence

denotes

36, 1247 Acepromazine, detomidine, and a combination of xylazine and butorphanol can alter proximal esophageal motility by disrupting coordinated peristalsis and decreasing spontaneous swallowing, but only acepromazine affected the manometric profile of the distal esophagus.

T57128

564444-564556

Sentence

denotes

1235 None of these drugs altered contractility of isolated esophageal smooth or striated muscle strips in vitro.

T44345

564557-564656

Sentence

denotes

1234 Nonetheless, the use of these drugs may complicate clinical evaluation of esophageal motility.

T60141

564657-564871

Sentence

denotes

Esophageal disorders including megaesophagus, esophageal diverticulum, and esophageal rupture appear to be more common in young Friesian horses, suggesting the possibility of a genetic predisposition in this breed.

T98778

564872-564974

Sentence

denotes

Esophageal inflammation, particularly reflux esophagitis, may affect motility and cause megaesophagus.

T35471

564975-565151

Sentence

denotes

Because esophageal hypomotility affects the tone and function of the lower esophageal sphincter, reflux esophagitis also may be a complication of a primary functional disorder.

T24633

565152-565272

Sentence

denotes

Assessing esophageal motility in horses with esophagitis that is not responding appropriately to treatment is important.

T3877

565273-565378

Sentence

denotes

Thorough neurologic examination is important to help rule out primary neurologic causes of megaesophagus.

T92732

565379-565540

Sentence

denotes

Because esophageal hypomotility is a functional obstruction, the clinical signs are similar to esophageal obstruction, although the onset is typically insidious.

T14926

565541-565611

Sentence

denotes

The clinical signs include those associated with esophageal dysphagia.

T54193

565612-565748

Sentence

denotes

1191, 1222, 1223, [1243] [1244] [1245] The cervical esophagus may be dilated enough to be evident externally, and weight loss is common.

T6412

565749-565857

Sentence

denotes

Diagnosis of esophageal hypomotility requires evaluation of transit via fluoroscopy or contrast radiography.

T50745

565858-566034

Sentence

denotes

1230, 1246 Endoscopy may reveal a dilated esophagus and an absence of peristaltic waves 1191, 1222 or evidence of underlying disease causing obstruction or esophageal dilation.

T16253

566035-566241

Sentence

denotes

1220, 1222 Esophageal manometry may be useful to document abnormal postdeglutition contraction pressures, contraction time, and propagation times but is not often available for routine clinical application.

T62981

566242-566366

Sentence

denotes

1248 If neurologic or neuromuscular disease is suspected, cerebrospinal fluid analysis or electromyography may be indicated.

T20836

566367-566435

Sentence

denotes

Treatment of an underlying cause should be initiated, if applicable.

T14214

566436-566564

Sentence

denotes

Dietary modification should include a soft/slurry diet and feeding from an elevated position to promote transit by gravity flow.

T99531

566565-566670

Sentence

denotes

Metoclopramide or bethanechol may benefit patients with reflux esophagitis associated with megaesophagus.

T65229

566671-566744

Sentence

denotes

The prognosis depends on the underlying cause and the degree of dilation.

T20599

566745-566935

Sentence

denotes

Although many cases of megaesophagus associated with reflux esophagitis respond well to treatment, many other forms of megaesophagus including congenital megaesophagus have a poor prognosis.

T53558

566936-567245

Sentence

denotes

Strictures most commonly are caused by pressure necrosis from esophageal impactions that induce circumferential erosion or ulceration of the esophageal mucosa, although esophageal injury caused by oral administration of corrosive medicinal agents and trauma to the neck may also result in stricture formation.

T12177

567246-567297

Sentence

denotes

1249 Congenital strictures also have been reported.

T19191

567298-567390

Sentence

denotes

1250 Strictures caused by mucosal and submucosal trauma are termed esophageal webs or rings.

T82930

567391-567555

Sentence

denotes

Strictures may also originate in the muscular layers and adventitia of the esophagus (mural strictures) or in all of the layers of the esophagus (annular stenosis).

T48863

567556-567749

Sentence

denotes

1217, 1250 Horses with these lesions have a presentation similar to those with simple obstructions, because strictures result in partial obstruction and impaction of food material in the lumen.

T13505

567750-567816

Sentence

denotes

Esophageal webs or rings may be detected with endoscopy (see Figs.

T8876

567817-567957

Sentence

denotes

12.15 and 12.16), whereas identification of mural strictures or annular stenosis may require a double-contrast esophagram (see Fig. 12.17) .

T74635

567958-568150

Sentence

denotes

In a retrospective study of horses with esophageal stricture following simple obstruction, maximal reduction in esophageal lumen diameter occurred within 30 days of the esophageal obstruction.

T7448

568151-568386

Sentence

denotes

Although surgery has been used to relieve such strictures, initial medical management is warranted because strictures may resolve with conservative therapy, and the esophagus continues to remodel for up to 60 days following ulceration.

T39808

568387-568636

Sentence

denotes

In one report, seven horses with esophageal obstruction-induced stricture were treated conservatively by feeding a slurry diet and administering antiinflammatory and antimicrobial medications, and five of seven were clinically normal within 60 days.

T34602

568637-568849

Sentence

denotes

1249 One of the five successfully treated horses had a 10-cm area of circumferential ulceration, suggesting that the potential exists for extensive mucosal injury to resolve without permanent stricture formation.

T1630

568850-568979

Sentence

denotes

If resolution of strictures within 60 days is insufficient, other methods to increase esophageal diameter should be investigated.

T24120

568980-569223

Sentence

denotes

Balloon dilation has been used successfully in several reports. [1251] [1252] [1253] [1254] [1255] [1256] Commercial balloon dilators have been adapted for use in the horse, although it is important to note that repeated dilation is necessary.

T83078

569224-569332

Sentence

denotes

1251, 1252, 1257 Corticosteroid injection was used successfully in conjunction with this procedure in foals.

T81643

569333-569652

Sentence

denotes

1251 Alternatively, a number of surgical techniques have been used to resolve strictures, including resection and anastomosis, 1258,1259 temporary esophagostomy with fenestration of the stricture, 1217 esophagomyotomy for strictures of the muscularis and adventitia, 1260, 1261 or patch grafting with local musculature.

T20080

569653-569793

Sentence

denotes

1262 Such surgeries, however, are fraught with complications, largely because of the propensity of the traumatized esophagus to restricture.

T52106

569794-569956

Sentence

denotes

1220, 1249 The esophagus lacks a serosal layer and does not rapidly form a fibrin seal as does the remainder of the intestinal tract, so anastomoses tend to leak.

T34969

569957-570074

Sentence

denotes

1259 In addition, tension on the esophagus during swallowing and movement of the neck impairs healing of anastomoses.

T71455

570075-570254

Sentence

denotes

1217, 1258 In spite of these difficulties, the long-term prognosis for horses with chronic esophageal strictures treated surgically is better than for those treated nonsurgically.

T30920

570255-570335

Sentence

denotes

1220 Two recent reviews describe surgical approaches to the esophagus in detail.

T88814

570336-570346

Sentence

denotes

1263, 1264

T47207

570348-570452

Sentence

denotes

Esophageal diverticula may be classified as traction (true) diverticula and pulsion (false) diverticula.

T33038

570453-570601

Sentence

denotes

Traction diverticula result from wounding and subsequent contraction of periesophageal tissues, with resultant tenting of the wall of the esophagus.

T41716

570602-570792

Sentence

denotes

Pulsion diverticula arise from protrusion of esophageal mucosa through defects in the muscular wall of the esophagus and usually result from trauma or acute changes in intraluminal pressure.

T1014

570793-570996

Sentence

denotes

1250 Traction diverticula appear as a dilation with a broad neck on contrast esophagography, whereas pulsion diverticula typically have a flask shape with a small neck on an esophagram (see Fig. 12.17) .

T76037

570997-571324

Sentence

denotes

1225, 1265 Although traction diverticula are usually asymptomatic and of little clinical significance, pulsion diverticula may fill with feed material, ultimately leading to esophageal obstruction and rupture. [1265] [1266] [1267] A movable mass in the midcervical region may be noticeable before onset of complete obstruction.

T72951

571325-571473

Sentence

denotes

1250 Pulsion diverticula may be corrected surgically by inverting or resecting prolapsed mucosa and closing the defect in the wall of the esophagus.

T32684

571474-571673

Sentence

denotes

1225, 1265, 1266 Inversion of excessive mucosa may reduce the diameter of the esophageal lumen and predispose horses to esophageal obstruction; therefore, it should be reserved for small diverticula.

T30517

571674-571678

Sentence

denotes

1225

T77440

571679-571726

Sentence

denotes

Congenital disorders of the esophagus are rare.

T98957

571727-572234

Sentence

denotes

Reported congenital abnormalities include congenital stenosis, 1268 persistent right aortic arch, 1223, [1269] [1270] [1271] [1272] [1273] other vascular anomalies, 1274 esophageal duplication cysts, [1275] [1276] [1277] intramural inclusion cysts, 1224, 1278 and idiopathic megaesophagus. [1243] [1244] [1245] In the one report of congenital stenosis, double-contrast radiography revealed concentric narrowing of the thoracic esophagus in the absence of any vascular abnormalities at the base of the heart.

T45000

572235-572353

Sentence

denotes

Successful treatment included having the foal stand with the forelimbs elevated off the ground following each feeding.

T37298

572354-572666

Sentence

denotes

1268 Persistent right aortic arch is a congenital anomaly in which the right fourth aortic arch becomes the definitive aorta instead of the left aortic arch, which results in constriction of the esophagus by the ligamentum arteriosum as it extends between the anomalous right aorta and the left pulmonary artery.

T39239

572667-572872

Sentence

denotes

1279 Clinical signs may include those associated with esophageal (postpharyngeal) dysphagia, drooling, and distention of the cervical esophagus resulting from partial obstruction of the thoracic esophagus.

T63588

572873-573015

Sentence

denotes

1223, 1269 Endoscopic examination typically reveals dilation of the esophagus cranial to the obstruction with evidence of diffuse esophagitis.

T48986

573016-573127

Sentence

denotes

Surgical treatment of persistent right aortic arch has been reported in foals, with varying degrees of success.

T89927

573128-573281

Sentence

denotes

1269, 1271, 1273 In one report, preoperative CT was used to identify the exact anatomic location of the offending lesion and guide the surgical approach.

T28269

573282-573498

Sentence

denotes

1273 Esophageal duplication cysts and intramural inclusion cysts cause typical signs of esophageal obstruction, including salivation, esophageal dysphagia, and swelling of the cervical esophagus as the cysts enlarge.

T72825

573499-573611

Sentence

denotes

1275, 1277, 1278 Such signs can make them difficult to differentiate from other forms of esophageal obstruction.

T66285

573612-573739

Sentence

denotes

Endoscopic examination may reveal compression of the esophageal lumen and communication with the esophageal lumen if it exists.

T92505

573740-573864

Sentence

denotes

Ultrasonographic examination may be the most useful method of antemortem diagnosis if the cyst is in the cervical esophagus.

T66965

573865-573985

Sentence

denotes

Examination of an aspirate of the mass may aid in the diagnosis by revealing the presence of keratinized squamous cells.

T93755

573986-574089

Sentence

denotes

1275, 1278 Surgical treatments have included complete surgical resection and surgical marsupialization.

T86098

574090-574183

Sentence

denotes

1275, 1277, 1278 The latter appears to be more successful and results in fewer complications.

T76364

574184-574392

Sentence

denotes

1277, 1280 Possible complications of surgical resection include laryngeal hemiplegia following surgical trauma to the recurrent laryngeal nerve in the region of the esophagus and esophageal fistula formation.

T16754

574393-574397

Sentence

denotes

1278

T74221

574398-574621

Sentence

denotes

Esophageal perforation typically occurs in the cervical region in response to external trauma, necrosis of the esophageal wall caused by a food impaction, or rupture of an esophageal lesion such as an impacted diverticulum.

T5320

574622-574774

Sentence

denotes

The esophagus is particularly vulnerable to external trauma in the distal third of the neck because only a thin layer of muscle covers it at this point.

T59543

574775-574928

Sentence

denotes

1281 Iatrogenic perforation may occur in response to excessive force with a stomach tube against an obstruction or a compromised region of the esophagus.

T65779

574929-575135

Sentence

denotes

1240 Esophageal perforations may be open or closed and tend to cause extensive cellulitis and necrosis of tissues surrounding the wound because of drainage of saliva and feed material within fascial planes.

T19664

575136-575191

Sentence

denotes

Systemic inflammation from septic cellulitis may occur.

T72546

575192-575372

Sentence

denotes

Closed perforations of the esophagus are particularly troublesome because food material, water, saliva, and air may migrate to the mediastinum and pleural space via fascial planes.

T79154

575373-575573

Sentence

denotes

1240, 1281 Because of the leakage of air into the tissues surrounding the rupture, extensive SC and fascial emphysema frequently develops and is usually evident clinically and on cervical radiographs.

T73291

575574-575668

Sentence

denotes

Pneumomediastinum and pneumothorax are potentially fatal complications of esophageal ruptures.

T92588

575669-575802

Sentence

denotes

If the esophagus ruptures into the mediastinum, horses most commonly present with signs of acute SIRS that may be mistaken for colic.

T13699

575803-576021

Sentence

denotes

Treatment should include converting closed perforations to open perforations if possible, 1282 extensive debridement and lavage of affected tissues, broad-spectrum antibiotics, tetanus prophylaxis, and esophageal rest.

T15804

576022-576118

Sentence

denotes

The clinician may achieve the latter by placing a feeding tube into the esophagus via the wound.

T66297

576119-576190

Sentence

denotes

Alternatively, a small nasogastric tube (12-Fr diameter) may be placed.

T97035

576191-576311

Sentence

denotes

1240 For open perforations, once the wound has granulated and contracted to a small size, oral feeding may be attempted.

T60501

576312-576407

Sentence

denotes

1281 Extensive loss of saliva via esophageal wounds may lead to hyponatremia and hypochloremia.

T46481

576408-576529

Sentence

denotes

Transient metabolic acidosis may occur because of salivary bicarbonate loss, followed by progressive metabolic alkalosis.

T48679

576530-576644

Sentence

denotes

1193 Although reports of esophageal wounds healing well by second intention exist, healing takes a prolonged time.

T45291

576645-576786

Sentence

denotes

1283 In addition, some perforations never completely heal and form permanent esophagocutaneous fistulae that may require surgical correction.

T18299

576787-576900

Sentence

denotes

The development of esophageal strictures is not common because wounds are usually linear and not circumferential.

T89797

576901-576943

Sentence

denotes

However, traction diverticula may develop.

T73380

576944-577051

Sentence

denotes

Other potential complications of esophageal wounds include Horner's syndrome and left laryngeal hemiplegia.

T40027

577052-577282

Sentence

denotes

1281 In a retrospective study on esophageal disorders, only 2 of 11 horses with esophageal perforations survived long term, 1220 and in a report of esophageal trauma following nasogastric intubation, 4 of 5 horses were euthanized.

T36354

577283-577449

Sentence

denotes

1240 The prognosis is poor in horses with esophageal perforations, largely because of the extent of cellulitis, tissue necrosis, shock, and local wound complications.

T30117

577450-577563

Sentence

denotes

Pathophysiology of mucosal injury and repair is detailed previously in this chapter in Mucosal Injury and Repair.

T91255

577564-577735

Sentence

denotes

Of importance, ulceration can occur in either the stratified squamous or glandular epithelium, although different clinical syndromes and pathophysiologic mechanisms apply.

T32793

577736-578019

Sentence

denotes

As a result, the broad term "equine gastric ulcer syndrome" (EGUS) has been used to encompass the wide array of associated clinical syndromes, 1284 although separation into equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD) has recently been proposed.

T99230

578020-578119

Sentence

denotes

1285 GDUD primarily affects weanling/ suckling foals and is typically considered a separate entity.

T26033

578120-578275

Sentence

denotes

1286 Regardless of terminology, EGUS in its various forms is arguably the most clinically and economically important clinical entity of the equine stomach.

T37544

578276-578366

Sentence

denotes

The prevalence of gastric ulceration has been reported for a variety of breeds and usages.

T47799

578367-578585

Sentence

denotes

The prevalence of squamous ulceration in horses in race training varies from 70% to 95% [1287] [1288] [1289] [1290] [1291] [1292] [1293] [1294] [1295] and can be as high as 100% when limited to animals actively racing.

T18732

578586-578978

Sentence

denotes

1291 Horses performing in other disciplines have also been evaluated, including active show horses (58% prevalence), 1296 endurance horses (67% overall 1297 ; 48% interseason and 93% during competition season 1298 ), Western performance horse (40%), 1299 Thoroughbred broodmares (67% pregnant; 77% nonpregnant), 1300 and nonracing performance horses (17% precompetition; 56% postcompetition).

T73884

578979-579270

Sentence

denotes

1301 In one large retrospective study (3715 adult horses from the years 1924-1996) evaluating incidences of gastric ulceration identified at necropsy, an overall prevalence of 10.3% was found, with the highest prevalence in Thoroughbreds (including Arabians) and Standardbred trotters (19%).

T11994

579271-579370

Sentence

denotes

1302 Horses in a university riding program demonstrated a low squamous ulceration prevalence (11%).

T35795

579371-579482

Sentence

denotes

1303 Approximately 49% of horses presented to a referral hospital for colic had evidence of gastric ulceration.

T88209

579483-579811

Sentence

denotes

1304 The reported prevalence of gastric ulceration in foals varies from 25% to 57%. [1305] [1306] [1307] Many earlier studies investigating prevalence of gastric ulceration do not differentiate between nonglandular and glandular lesions, and many evaluate only the nonglandular region of the stomach, but this trend is changing.

T53922

579812-579987

Sentence

denotes

In 1 of 162 horses in a hospital setting, 58% had antral or pyloric erosions or ulcerations, 58% had squamous mucosal lesions, and 8% had lesions involving the glandular body.

T33555

579988-580110

Sentence

denotes

1308 In other studies, 56% of Thoroughbreds had EGGD, 1293 and 47% of racehorses (Thoroughbred and Standardbred) had EGGD.

T30397

580111-580258

Sentence

denotes

1295 In the former, 1293 all horses with glandular lesions also had squamous disease, whereas such an association was not seen in the latter study.

T21571

580259-580349

Sentence

denotes

1295 In one report of endurance horses with a 67% overall lesion prevalence, 27% had EGGD.

T2278

580350-580474

Sentence

denotes

1297 In another, prevalence varied by season, with 16% EGGD prevalence out of competition and 33% during competition season.

T77339

580475-580553

Sentence

denotes

1298 In Danish horses, the prevalence of EGGD was 57% in two separate reports.

T30585

580554-580746

Sentence

denotes

1309, 1310 In a postmortem evaluation, lesions were most commonly located in the squamous mucosa along the margo plicatus, followed by the glandular body, proximal squamous mucosa, and antrum.

T44545

580747-580810

Sentence

denotes

1302 Overall, glandular lesions tend to occur near the pylorus.

T63449

580811-580921

Sentence

denotes

Because the pathophysiology of mucosal injury and repair was documented earlier, it will not be reviewed here.

T70125

580922-581047

Sentence

denotes

Acid secretion clearly plays a role in squamous mucosal ulceration, and key components of acid regulation will be summarized.

T54324

581048-581224

Sentence

denotes

Horses secrete acid continuously, and measured pH of equine gastric contents is variable from less than 2 to greater than 6 depending on the horse's dietary state (fed/fasted).

T27950

581225-581354

Sentence

denotes

818, 1311 A protocol of repeated 24-hour periods of fasting and feeding has been shown to induce squamous erosion and ulceration.

T84854

581355-581620

Sentence

denotes

841 Because this protocol results in periods of prolonged gastric acidity (pH <2.0) and concurrent administration of the H 2 receptor antagonist ranitidine reduces lesion severity, it supports the role of acid exposure in the pathogenesis of squamous ulcer disease.

T28829

581621-581779

Sentence

denotes

This effect was also noted as pH of the proximal, but not ventral, stomach decreased in early morning hours, corresponding to periods of decreased hay intake.

T55409

581780-581870

Sentence

denotes

1312 Several peptides can stimulate or inhibit the secretion of acid by the parietal cell.

T87148

581871-581988

Sentence

denotes

The predominant stimuli to hydrochloric acid secretion are gastrin, histamine, and acetylcholine via the vagus nerve.

T65058

581989-582135

Sentence

denotes

1313 Gastrin is released by G cells within the antral mucosa, whereas histamine is released by mast cells and ECL-like cells in the gastric gland.

T10056

582136-582328

Sentence

denotes

Histamine binds to type 2 receptors on the parietal cell membrane, causing an increase in adenosine monophosphate (cAMP), resulting in phosphorylation of enzymes that activate the proton pump.

T22837

582329-582453

Sentence

denotes

Gastrin and acetylcholine can act via calcium-mediated intracellular pathways and also stimulate histamine release directly.

T26114

582454-582582

Sentence

denotes

1314 Isolated equine parietal cells respond maximally to histamine stimulation and only minimally to carbachol and pentagastrin.

T98578

582583-582674

Sentence

denotes

1315 In vivo, histamine or pentagastrin infusion can stimulate similar maximal acid output.

T5167

582675-582858

Sentence

denotes

1316 Interestingly, pentagastrin stimulation also induces a marked duodenal secretion of a sodium chloride-rich fluid, which can reflux back into the stomach under fasting conditions.

T30441

582859-583094

Sentence

denotes

1316 Gastrin release is primarily controlled by gastrinreleasing peptide, which is stimulated by gastric distention and increased luminal pH, but the interaction between gastrin and histamine has not been fully elucidated in the horse.

T19165

583095-583223

Sentence

denotes

Gastric acid secretion by parietal cells is primarily inhibited by somatostatin, which is released by fundic and antral D cells.

T69938

583224-583370

Sentence

denotes

The inhibitory effect of somatostatin is primarily paracrine, but plasma levels of somatostatin negatively correlate with gastric luminal acidity.

T35029

583371-583454

Sentence

denotes

1317 Gastric acid secretion also is inhibited by EGF, a peptide produced in saliva.

T42564

583455-583615

Sentence

denotes

1318 Foals can produce significant amounts of gastric acid by the second day of life, with consistent periods of acidity (pH <2.0) in clinically normal animals.

T29248

583616-583818

Sentence

denotes

1319, 1320 In one study, foals tended to have a high gastric pH at day 1 of age, 1319 but in a study of critically ill foals, some foals demonstrated periods of gastric acidity on the first day of life.

T55354

583819-584013

Sentence

denotes

1321 Suckling was associated with an immediate rise in gastric pH, whereas periods of rest in which foals did not suck for more than 20 minutes were associated with prolonged periods of acidity.

T71485

584014-584107

Sentence

denotes

1320 Premature human infants are capable of gastric acid production at 28 weeks of gestation.

T17022

584108-584235

Sentence

denotes

1322 Only 1 of 7 premature foals demonstrated an acidic pH recording in a study of gastric pH profiles in critically ill foals.

T68810

584236-584379

Sentence

denotes

1321 Although multiple factors were likely involved in those foals, the true ontogeny of gastric acid production in foals is currently unknown.

T97454

584380-584495

Sentence

denotes

Equine squamous mucosa is very thin at birth but becomes hyperplastic and parakeratotic within days (Fig. 12.19 ).

T8082

584496-584619

Sentence

denotes

814 The parallel between decreasing pH and proliferation of squamous epithelium correlates with that seen in other species.

T48576

584620-584781

Sentence

denotes

1323 The combination of a relatively thin gastric epithelium with a high acid output may leave neonatal foals susceptible to ulcer formation at a very young age.

T3655

584782-584927

Sentence

denotes

The difference in the normal appearance of the squamous mucosa should be considered when interpreting gastric endoscopy in a neonatal population.

T6971

584928-585153

Sentence

denotes

Overall, acid remains the major contributing factor to nonglandular mucosal damage, although other factors such as pepsin and bile salts may play an important role as well, either in the initiation or perpetuation of disease.

T96152

585154-585305

Sentence

denotes

Many aspects of diet and management are associated with the development of nonglandular ulceration in adult horses, although some data are conflicting.

T74428

585306-585388

Sentence

denotes

Risk factors associated with ESGD are clearer than are those associated with EGGD.

T28788

585389-585503

Sentence

denotes

Horses in race training have a high incidence of ESGD and are frequently fed high-concentrate, low-roughage diets.

T61618

585504-585647

Sentence

denotes

A diet high in concentrate and either high or low in forage, in conjunction with stall confinement but no exercise, induce ESGD within 2 weeks.

T76999

585648-585865

Sentence

denotes

1324 In one study, higher volatile fatty acid concentrations, higher gastric juice pH, and lower number and severity of ESGD were documented after feeding an alfalfa hay-grain diet compared with a bromegrass hay diet.

T50397

585866-586010

Sentence

denotes

1325 Many factors differed between the diets, however, such as digestible energy, bulk, crude protein, and mineral content (especially calcium).

T49051

586011-586283

Sentence

denotes

These findings were supported by a study in which an alfalfa hay/pelleted concentrate diet significantly reduced ESGD severity scores and/or prevented ulcer development relative to a coastal hay/concentrate diet in horses managed with dry lot housing and regular exercise.

T10909

586284-586393

Sentence

denotes

1326 Intermittent feeding has clearly been shown to induce ESGD and is a consistent model of ulcer induction.

T37421

586394-586565

Sentence

denotes

841, 1311, 1327 Similarly, quality of forage (straw versus other types) and increased time between forage meals was associated with higher incidence of ESGD in one report.

T10383

586566-586716

Sentence

denotes

1328 The pathophysiologic correlation between exercise and ESGD has not yet been defined despite the high prevalence of disease in performance horses.

T50038

586717-586935

Sentence

denotes

In one large epidemiologic study, there was a significant association between ESGD and individual trainer, urban versus rural area, lack of direct contact with other horses, solid barriers, and talk versus music radio.

T3625

586936-587120

Sentence

denotes

1329 ESGD can develop within 8 days of exercise varying from light halter to active race training, 1330 and time in work was found to be a risk factor for ESGD in racing Thoroughbreds.

T34840

587121-587333

Sentence

denotes

1331 During treadmill exercise at gaits faster than a walk, proximal gastric size decreases in conjunction with an increase in intraabdominal pressure, resulting in a simultaneous decrease in proximal gastric pH.

T53079

587334-587605

Sentence

denotes

1333 Both proximal gastric size and pH return to baseline levels as soon as the horse returned to a walk, and the resultant theory was that gastric contracture could result in increased acid exposure to the squamous mucosa by raising the level of liquid gastric contents.

T78869

587606-587759

Sentence

denotes

Stall confinement 1327 and transport 1334 are associated with ESGD, but a distinct mechanism for these associations has not been definitively determined.

T99713

587760-588052

Sentence

denotes

A recent study did not detect a difference in pH in the proximal or ventral stomach in response to three different environmental situations (stall confinement alone in a barn, stall confinement with a horse in an adjacent stall, and paddock turnout with a companion horse), each for 24 hours.

T82866

588053-588153

Sentence

denotes

1312 This work suggests that increased acid exposure to the proximal stomach alone is not causative.

T12860

588154-588275

Sentence

denotes

Several studies have failed to document a correlation between NSAID administration and naturally occurring ulcer disease.

T65354

588276-588410

Sentence

denotes

1287, 1288, 1290, 1291, 1302 NSAID administration, however, is a well-known cause of gastric ulceration under experimental conditions.

T16497

588411-588628

Sentence

denotes

393, 691, 692, 1335, 1336 NSAID-related ulceration is typically described as predominantly glandular in nature, although nonglandular ulceration can also occur by a mechanism that has not yet been fully characterized.

T32657

588629-588712

Sentence

denotes

NSAIDs cause a decrease in PGE 2 synthesis caused by inhibition of the COX pathway.

T82946

588713-588875

Sentence

denotes

A resultant decrease in glandular mucosal protection, most notably via decreased mucosal blood flow and mucous production, is the most likely mechanism of action.

T18295

588876-589058

Sentence

denotes

In one study, however, phenylbutazone administration resulted in ulceration of the glandular mucosa at the pyloric antrum but did not significantly alter mucosal PGE 2 concentration.

T5096

589059-589212

Sentence

denotes

1335 Other risk factors associated with gastric ulceration include gender and age, and the reported prevalence of gastric ulcers has increased over time.

T97870

589213-589326

Sentence

denotes

In one study, the frequency of gastric ulceration increased from <6% before 1945 to approximately 18% after 1975.

T15404

589327-589420

Sentence

denotes

1302 The association between sex or age and ulceration has not been consistent among studies.

T83384

589421-589506

Sentence

denotes

1291, 1293, 1302, 1337 Crib biting has also been discussed as a risk factor for ESGD.

T86976

589507-589639

Sentence

denotes

1331, 1338 In foals, risk factors are less clearly defined and will be discussed along with the clinical syndrome in each age group.

T76651

589640-589694

Sentence

denotes

Limited access to water has been associated with ESGD.

T49938

589695-589699

Sentence

denotes

1328

T48508

589700-589812

Sentence

denotes

Clinical signs typically associated with gastric ulceration in foals include poor appetite, diarrhea, and colic.

T22978

589813-589963

Sentence

denotes

Many foals probably never exhibit clinical signs, and some do not exhibit clinical signs until ulceration is severe or fatal perforation has occurred.

T52462

589964-590076

Sentence

denotes

Glandular ulceration is typically considered the most clinically significant type of disease in this population.

T16050

590077-590177

Sentence

denotes

The physiologic stress of a concurrent illness has been associated with gastric ulceration in foals.

T53954

590178-590421

Sentence

denotes

Retrospectively, 14 (23%) of 61 foals up to 85 days of age with a clinical disorder had lesions in the gastric glandular mucosa, 1307 and prospectively 8 (40%) of 20 foals up to 30 days of age with a clinical disorder had glandular ulceration.

T73392

590422-590556

Sentence

denotes

1339 In contrast, only 4% to 9% of clinically normal foals examined in endoscopic surveys had lesions in the gastric glandular mucosa.

T65213

590557-590764

Sentence

denotes

1306, 1340 Critically ill neonatal foals can have a markedly different pH profile compared with that seen in clinically normal foals, potentially caused by alterations in gastric motility and acid secretion.

T38974

590765-590914

Sentence

denotes

1321 Gastric ulceration was not identified in any animals at necropsy in that study; however, ulceration has been documented in a similar population.

T69311

590915-591070

Sentence

denotes

1305 Thus factors other than acid exposure, most notably mucosal perfusion, may play an important role in the "stress"-related ulceration seen in neonates.

T18780

591071-591269

Sentence

denotes

Gastric ulceration and rupture in the hospitalized neonatal population appears to occur less commonly now than in previous reports, despite a decline in the use of ulcer prophylaxis in one hospital.

T22139

591270-591378

Sentence

denotes

1341 Advances in overall neonatal care, especially supportive care, have likely contributed to this decline.

T18625

591379-591447

Sentence

denotes

GDUD occurs almost exclusively in suckling and early weanling foals.

T94301

591448-591625

Sentence

denotes

Clinical signs of duodenal ulceration are similar to those described for gastric ulceration (bruxism, colic, ptyalism, and diarrhea), but the consequences are often more severe.

T73602

591626-591832

Sentence

denotes

Lesions occur primarily in the proximal duodenum, ranging from diffuse inflammation to severe ulceration, but affected foals typically have severe squamous and/or glandular ulceration as well (Fig. 12.20) .

T72976

591833-591937

Sentence

denotes

Foals with duodenal ulceration often have delayed gastric emptying and may have gastroesophageal reflux.

T78272

591938-592064

Sentence

denotes

Complications can include gastric or duodenal rupture, pyloric or duodenal stricture (Fig. 12.21) , and ascending cholangitis.

T78739

592065-592179

Sentence

denotes

Severe squamous and esophageal ulceration and aspiration pneumonia can occur secondary to gastroesophageal reflux.

T69529

592180-592316

Sentence

denotes

1222, [1342] [1343] [1344] [1345] GDUD syndrome can occur in outbreaks and is most commonly identified in intensive breeding operations.

T93476

592317-592369

Sentence

denotes

The cause of duodenal lesions in foals is not known.

T50503

592370-592501

Sentence

denotes

One theory is that the problem begins with diffuse duodenal inflammation that can coalesce down to a focal area of ulceration (G.D.

T93046

592502-592517

Sentence

denotes

Lester and A.M.

T84766

592518-592551

Sentence

denotes

Merritt, personal communication).

T50440

592552-592676

Sentence

denotes

A temporal relationship between GDUD and rotaviral diarrhea has been suggested, but an infectious etiology remains unproven.

T14619

592677-592815

Sentence

denotes

Although lesion location and severity associated with rotaviral infection varies among species, duodenal ulceration has not been reported.

T97289

592816-592820

Sentence

denotes

1346

T49082

592822-592998

Sentence

denotes

Reported clinical signs attributable to EGUS in adult horses are variable and classically include anorexia and intermittent or recurrent postprandial colic of varying severity.

T51635

592999-593092

Sentence

denotes

1347 Overall, clinical signs are nonspecific and poorly associated with the presence of EGUS.

T54468

593093-593181

Sentence

denotes

1285 Many horses with endoscopic evidence of disease may appear to be clinically normal.

T35508

593182-593421

Sentence

denotes

Vague signs including decreased consumption of concentrates, postprandial episodes of colic, poor performance or failure to train up to expectations, poor quality hair coat, and diminished condition or failure to thrive have been reported.

T4399

593422-593573

Sentence

denotes

Diarrhea is not typically associated with gastric ulceration in adult horses, although ulceration can occur concurrently with other causes of diarrhea.

T82743

593574-593685

Sentence

denotes

Bleeding from ulcers in the gastric squamous mucosa is typically not associated with anemia or hypoproteinemia.

T70440

593686-593767

Sentence

denotes

Gastroscopy is the only reliable method for diagnosis of EGUS in the live animal.

T73150

593768-593960

Sentence

denotes

1285 Evaluation of the entire stomach and, preferably, proximal duodenum is critical to a diagnosis, because there is no relationship between the presence of squamous and glandular ulceration.

T43897

593961-594081

Sentence

denotes

1295, 1308, 1309 Urine 1348 and blood 1349 sucrose absorption testing or fecal albumin or hemoglobin 31 is not reliable.

T20017

594082-594278

Sentence

denotes

Various ulcer scoring systems have been promoted, but the system proposed by the Equine Gastric Ulcer Council 1284 (Table 12 .11) has been recommended because of its repeatability and ease of use.

T6727

594279-594455

Sentence

denotes

1285, 1350 Duodenal ulceration can be difficult to confirm, and duodenoscopy is the most specific means of diagnosis, although the procedure is more difficult than gastroscopy.

T83113

594456-594563

Sentence

denotes

Diffuse reddening or inflammation may be the only recognizable lesion in foals with early duodenal disease.

T54976

594564-594693

Sentence

denotes

In older foals with GDUD, detection of gastric outflow obstruction is critical to the therapeutic plan and appropriate prognosis.

T46472

594694-594751

Sentence

denotes

A distended stomach is typically evident with ultrasound.

T22517

594752-594885

Sentence

denotes

Abdominal radiography without contrast in foals with outflow obstruction typically reveals a distinctly enlarged, gas-filled stomach.

T34760

594886-595010

Sentence

denotes

Liquid barium contrast will either have markedly delayed (with incomplete obstruction) or no (complete obstruction) outflow.

T68410

595011-595202

Sentence

denotes

Clinically, foals with outflow obstruction will develop reflux after suckling, or marked reflux even with limited to no suckling if the duodenal obstruction is distal to the common bile duct.

T52753

595203-595328

Sentence

denotes

Multiple pharmacologic treatments have been suggested for the treatment of EGUS, and these can vary for ESGD, EGGD, and GDUD.

T22975

595329-595449

Sentence

denotes

Because acid has been implicated as the most important pathophysiologic component of ESGD, acid suppression is critical.

T50179

595450-595716

Sentence

denotes

The principal therapeutic options for ulcer treatment include H 2 antagonists (cimetidine, ranitidine, famotidine, and nizatidine), proton pump inhibitors (PPIs; omeprazole, pantoprazole, rabeprazole, and esomeprazole), the mucosal adherent sucralfate, and antacids.

T58102

595717-595904

Sentence

denotes

The H 2 antagonists suppress hydrochloric acid secretion through competitive inhibition of the parietal cell histamine receptor that can be partially overcome with exogenous pentagastrin.

T83690

595905-596036

Sentence

denotes

1351 Use of H 2 antagonists has been successful in raising gastric pH and resolving gastric lesions in both foals and adult horses.

T12651

596037-596175

Sentence

denotes

1320, 1344, 1352 Clinical and experimental evidence has demonstrated greater individual variability with lower dosages of H 2 antagonists.

T2277

596176-596312

Sentence

denotes

1339 Thus dosage recommendations are based on levels necessary to increase gastric pH and promote ulcer healing in a majority of horses.

T30270

596313-596423

Sentence

denotes

Commonly recommended ranitidine dosages are 6.6 mg/kg orally every 8 hours or 1.5 to 2 mg/kg IV every 6 hours.

T57729

596424-596649

Sentence

denotes

Although clinically normal foals respond predictably to ranitidine, 1320 sick neonates have shown variability in pH response to IV ranitidine, with a much shorter duration of action and, in some cases, no noticeable response.

T9540

596650-596774

Sentence

denotes

1321 PPIs block secretion of H + at the parietal cell membrane by irreversibly binding to the H + , K + -ATPase proton pump.

T70518

596775-596997

Sentence

denotes

The powder form of omeprazole is rapidly degraded in an acidic environment; an enteric-coated capsule or a specially formulated paste must be used to allow delivery of the active drug to the small intestine for absorption.

T6406

596998-597117

Sentence

denotes

An increase in gastric pH and a decrease in acid output are evident 5 to 8 hours after omeprazole paste administration.

T7806

597118-597720

Sentence

denotes

1353 Omeprazole (GastroGard, Merial, Ltd., Duluth, GA) is the only currently FDA-approved agent for the treatment of EGUS in the United States; other preparations, including enteric-coated granules and buffered formulations, are available elsewhere. [1354] [1355] [1356] In the United States, compounded preparations have shown limited to no efficacy in pharmacodynamic and clinical trials, 1357, 1358 and GastroGard was the only product (including buffers, H 2 -receptor antagonists, sucralfate, and compounded preparations) that decreased the odds of gastric ulceration in a population of racehorses.

T64470

597721-597814

Sentence

denotes

1359 Several studies have documented the safety of oral omeprazole in foals and adult horses.

T73794

597815-597915

Sentence

denotes

1360, 1361 Omeprazole appears more effective for ulcer healing than either ranitidine or cimetidine.

T76973

597916-598080

Sentence

denotes

1362, 1363 Omeprazole (4 mg/kg PO q 24 h) has consistently demonstrated efficacy of (70%-80% healing) for ESGD, including Thoroughbreds maintained in race training.

T85792

598081-598276

Sentence

denotes

816, 815, 1362, [1364] [1365] [1366] Treatment with 1 mg/kg, 2 mg/kg, or 4 mg/kg orally every 24 hours decreases or prevents disease or the recurrence of disease in horses maintained in training.

T84090

598277-598501

Sentence

denotes

815, 1330, 1367, 1368 Other preparations have shown efficacy for ESGD healing at lower dosages (1 mg/kg or 2 mg/kg PO q 24 h) in clinical trials, 1354, 1369, 1370 although a lower dosage is not yet recommended for treatment.

T50914

598502-598628

Sentence

denotes

Preexercise versus postexercise administration did not have a significant effect on healing of ESGD or EGGD in a recent trial.

T40308

598629-598748

Sentence

denotes

1371 Duration of therapy for ESGD has been recommended for 28 days, although most healing likely occurs within 21 days.

T1161

598749-598874

Sentence

denotes

1364 In summary, the primary current recommendation for treatment of ESGD is omeprazole, 4 mg/kg PO q 24 h for 21 to 28 days.

T65308

598875-598975

Sentence

denotes

In locations in which the enteric-coated granule formation is available, 1 mg/kg may be substituted.

T73434

598976-599052

Sentence

denotes

Alternate recommendations include ranitidine or lower dosages of omeprazole.

T4841

599053-599152

Sentence

denotes

1285 Lower healing rates (25%) have recently been reported following omeprazole treatment for EGGD.

T4347

599153-599336

Sentence

denotes

1354, 1370, 1371 Omeprazole (4 mg/kg) also has demonstrated efficacy for raising intragastric pH in clinically normal 1372 or critically ill 1373 foals and for ulcer healing in foals.

T28166

599337-599445

Sentence

denotes

1366 The definitive reason for this is unknown but may be related to timing or duration of acid suppression.

T18768

599446-599606

Sentence

denotes

A bacterial role in EGGD has not been established, despite solid efforts, and the addition of trimethoprim-sulfa did not have apparent benefit in ulcer healing.

T56735

599607-599784

Sentence

denotes

1374 Because these factors and basic principles of responsible antimicrobial use, antimicrobial therapy is not recommended for treatment of EGUS in general or EGGD specifically.

T58359

599785-600059

Sentence

denotes

1285 Sucralfate is effective in the treatment of peptic ulcers and prevention of stress-induced ulcers in humans, likely via adherence to ulcerated mucosa, stimulation of mucous secretion, enhanced PGE synthesis, and concentration of growth factor at the site of ulceration.

T66667

600060-600170

Sentence

denotes

1375 These are all factors relevant to glandular mucosa; thus, its use seems reasonable for treatment of EGGD.

T57094

600171-600271

Sentence

denotes

In one study, sucralfate did not promote subclinical ulcer healing in foals, relative to corn syrup.

T743

600272-600411

Sentence

denotes

1376 In a recent study, sucralfate (12 mg/kg PO q 12 h) combined with omeprazole (4 mg/kg PO q 24 h) resulted in a 67.5% EGGD healing rate.

T51855

600412-600578

Sentence

denotes

1377 Current recommendations for EGGD include omeprazole plus sucralfate at the previously mentioned dosages for a minimum of 4 weeks, followed by repeat gastroscopy.

T84035

600579-600673

Sentence

denotes

1285 Therapy for at least 8 weeks should be pursued before the addition of adjunctive therapy.

T69696

600674-600924

Sentence

denotes

The use of synthetic PGE 1 analogs, such as misoprostol, has been effective in the treatment of gastric and duodenal ulcers in humans, and the proposed mechanism of action involves both inhibition of gastric acid secretion and mucosal cytoprotection.

T12589

600925-601162

Sentence

denotes

1378 In horses, misoprostol (5 μg/kg) increases gastric pH 1379 and ameliorates deleterious effects of flunixin on mucosal recovery after ischemic injury in vitro, 391 but data supporting its use in clinical trials are currently lacking.

T87380

601163-601212

Sentence

denotes

Misoprostol is contraindicated in pregnant mares.

T58435

601213-601386

Sentence

denotes

Prokinetic drugs should be considered in foals with duodenal disease, gastroesophageal reflux, and when delayed gastric emptying without a physical obstruction is suspected.

T29518

601387-601483

Sentence

denotes

Bethanechol and erythromycin have been shown to increase the rate of gastric emptying in horses.

T41087

601484-601727

Sentence

denotes

1006 In foals with acute gastric atony, bethanechol 0.025 to 0.030 mg/kg SC every 3 to 4 hours has been effective in promoting gastric motility and emptying, followed by oral maintenance dosages of 0.35 to 0.45 mg/kg three to four times daily.

T82541

601728-601875

Sentence

denotes

Adverse effects can include diarrhea, inappetence, salivation, and colic, but at the dosages stated, adverse effects have been infrequent and mild.

T64989

601876-601973

Sentence

denotes

For foals with severe GDUD that have developed duodenal stricture, surgical therapy is necessary.

T11168

601974-602123

Sentence

denotes

1343, 1380 These animals require a serious financial commitment because intensive perioperative medical therapy is critical for a successful outcome.

T98278

602124-602201

Sentence

denotes

Prognosis in two recent abstracts has improved over that previously reported.

T33149

602202-602348

Sentence

denotes

In one, 98% of surgically treated foals survived to discharge from the hospital, with 68% survival 8 months following discharge from the hospital.

T89100

602349-602438

Sentence

denotes

1381 In that study, of the surviving Thoroughbreds of racing age, 71% had started a race.

T16004

602439-602562

Sentence

denotes

In another, short-term survival was reported as 80% for those foals treated surgically and 50% for those treated medically.

T95059

602563-602706

Sentence

denotes

976 A compounded IV preparation of omeprazole (0.5 mg/kg) increases gastric juice pH and decrease the number of nonglandular lesions in horses.

T89295

602707-602857

Sentence

denotes

1382 From a regulatory standpoint, omeprazole (4 mg/kg PO q 24 h) does not appear to affect quantitative measurements of performance in Standardbreds.

T52358

602858-602862

Sentence

denotes

1383

T90540

602863-603049

Sentence

denotes

Because gastric perforation caused by glandular ulcer disease has been reported in hospitalized neonates, many clinicians routinely use prophylactic antiulcer therapy in this population.

T99907

603050-603282

Sentence

denotes

Because some critically ill foals have a predominantly alkaline gastric pH profile, and because gastric acidity may be protective against bacterial translocation in neonates, the need for prophylactic ulcer therapy is controversial.

T24167

603283-603445

Sentence

denotes

In critically ill human neonates, although IV ranitidine therapy increases gastric pH and gastric bacterial colonization, it does not increase the risk of sepsis.

T9885

603446-603740

Sentence

denotes

1384 In a retrospective study of 85 hospitalized foals <30 days of age, no difference in the frequency of gastric ulceration at necropsy was found between those foals that received prophylactic treatment for gastric ulcers and those that did not; none died as a result of gastric ulcer disease.

T63413

603741-603900

Sentence

denotes

1341 In a multicenter retrospective study, acid prophylaxis was associated with an increased incidence of diarrhea but not with alteration in clinical outcome.

T83465

603901-603988

Sentence

denotes

1385 Many clinicians no longer recommend routine ulcer prophylaxis in all ill neonates.

T79650

603989-604109

Sentence

denotes

Exceptions could potentially include those foals requiring significant doses of NSAIDs for painful orthopedic disorders.

T36051

604110-604194

Sentence

denotes

In adults, dietary and environmental management can help prevent gastric ulceration.

T82425

604195-604303

Sentence

denotes

Pasture turnout and continuous access to good quality forage, especially alfalfa, are currently recommended.

T12146

604304-604455

Sentence

denotes

For horses at high risk, the best proven pharmacologic approach to prevention involves administration of omeprazole 1 to 2 mg/kg orally every 24 hours.

T4363

604456-604543

Sentence

denotes

815, 1363, 1367, 1368 Further work on these recommendations will likely be forthcoming.

T29148

604544-604627

Sentence

denotes

Although appealing, most agents have not yet been shown to promote healing of EGUS.

T76366

604628-604845

Sentence

denotes

Some products-including those containing sea buckthorn berries 1386 ; organic acids and B vitamins 1387 ; and a combination of yeast, magnesium hydroxide, and Apolectol 1388 -have shown promise for prevention of EGUS.

T10214

604846-604962

Sentence

denotes

Various other products, including a pectin-lecithin complex, have not demonstrated efficacy despite initial promise.

T32562

604963-605069

Sentence

denotes

1389 The use of antacids in the treatment of gastric ulcers has not been critically examined in the horse.

T27502

605070-605228

Sentence

denotes

Research in horses has shown that 30 g aluminum hydroxide/15 g magnesium hydroxide will result in an increase in gastric pH above 4 for approximately 2 hours.

T17937

605229-605459

Sentence

denotes

1390 Although antacids may be useful for the treatment of ulcers in horses, a dose of approximately 180 to 200 mL every 2 to 4 hours is necessary for a standard adult horse, and the use of antacids is not justified or recommended.

T3124

605460-605523

Sentence

denotes

Pyloric stenosis is a structural resistance to gastric outflow.

T66148

605524-605652

Sentence

denotes

Congenital pyloric stenosis has been reported in foals and one yearling and results from hypertrophy of the pyloric musculature.

T99985

605653-605891

Sentence

denotes

1061, 1391, 1392 Acquired pyloric stenosis can result from neoplasia or duodenal ulceration. [1393] [1394] [1395] [1396] Clinical signs are dependent on the degree of obstruction but include abdominal pain, salivation, and teeth grinding.

T75511

605892-605982

Sentence

denotes

Complete or near complete obstruction can result in gastric reflux and reflux esophagitis.

T52390

605983-606089

Sentence

denotes

In foals with congenital pyloric hypertrophy, clinical signs may begin with the consumption of solid feed.

T46080

606090-606203

Sentence

denotes

In foals, a presumptive diagnosis can be made via gastric endoscopy and radiography (plain and contrast studies).

T19571

606204-606325

Sentence

denotes

Depending on the cause and severity of disease, gastric endoscopy may provide a presumptive diagnosis in the adult horse.

T3319

606326-606380

Sentence

denotes

Measurement of gastric emptying can aid the diagnosis.

T84196

606381-606560

Sentence

denotes

Several methods of measurement are currently available, including nuclear scintigraphy, acetaminophen absorption, and postconsumption [ 13 C]octanoic acid blood or breath testing.

T79749

606561-606708

Sentence

denotes

986, 1006, 1397 During an exploratory laparotomy, a distended stomach and thickened pylorus are accompanied by a relatively empty intestinal tract.

T88581

606709-606845

Sentence

denotes

If complete obstruction is not present, medical therapy with a prokinetic such as bethanechol can increase the rate of gastric emptying.

T89975

606846-606979

Sentence

denotes

1006 Phenylbutazone and cisapride have also been shown to attenuate the delay in gastric emptying caused by endotoxin administration.

T27057

606980-607141

Sentence

denotes

986, 987 Surgical repair is necessary for definitive treatment of complete or near-complete obstruction and consists of either gastroenterostomy or pyloroplasty.

T40205

607142-607243

Sentence

denotes

1075, 1380 Pyloric-duodenal intussusception has been reported in an adult horse presenting for colic.

T58405

607244-607248

Sentence

denotes

1398

T63883

607249-607323

Sentence

denotes

Gastric dilatation can be classified as primary, secondary, or idiopathic.

T704

607324-607473

Sentence

denotes

Causes of primary gastric dilatation include gastric impaction, grain engorgement, excessive water intake after exercise, aerophagia, and parasitism.

T2268

607474-607621

Sentence

denotes

1396, 1399 Secondary gastric dilatation occurs more commonly and can result from primary intestinal ileus or small or large intestinal obstruction.

T45046

607622-607789

Sentence

denotes

Time to development of gastric reflux is proportional to the distance to the intestinal segment involved, with duodenal obstruction resulting in reflux within 4 hours.

T75145

607790-607927

Sentence

denotes

1400 Clinical signs of gastric dilatation include those associated with acute colic and, in severe cases, ingesta appearing at the nares.

T24716

607928-608022

Sentence

denotes

Associated laboratory abnormalities include hemoconcentration, hypokalemia, and hypochloremia.

T21049

608023-608100

Sentence

denotes

1396 The most common cause of gastric rupture in horses varies among reports.

T19456

608101-608368

Sentence

denotes

In a retrospective study of 54 horses, gastric rupture occurred most commonly as a secondary phenomenon (65%), usually caused by small intestinal obstruction, with primary gastric dilatation and idiopathic rupture occurring almost equally (15% and 17%, respectively).

T95074

608369-608553

Sentence

denotes

1399 In another retrospective study of 50 horses in combination with a search of the Veterinary Medical Database (VMDB), 60% of the gastric rupture cases were classified as idiopathic.

T12353

608554-608679

Sentence

denotes

1401 Risk factors for gastric rupture include feeding grass hay, not feeding grain, gelding, and a nonautomatic water source.

T85903

608680-608836

Sentence

denotes

1399, 1401 Nasogastric intubation does not preclude the possibility of gastric rupture, and the amount of reflux obtained before rupture is highly variable.

T78482

608837-608951

Sentence

denotes

1399 Because of the retrospective nature of these reports, one cannot rule out confounding factors with certainty.

T25969

608952-609047

Sentence

denotes

Regardless of the initiating cause, gastric rupture usually occurs along the greater curvature.

T40845

609048-609284

Sentence

denotes

In horses with rupture caused by gastric dilatation, tears in the seromuscular layer are frequently larger than the corresponding tears in the mucosal layer, indicating that the seromuscularis likely weakens and tears before the mucosa.

T67364

609285-609438

Sentence

denotes

1399, 1401 In contrast, horses with gastric rupture secondary to gastric ulceration usually demonstrate full-thickness tears of equal size in all layers.

T54972

609439-609571

Sentence

denotes

Gastric rupture is usually fatal because of widespread contamination of the peritoneal cavity, septic peritonitis, and septic shock.

T50471

609572-609713

Sentence

denotes

Initial clinical signs vary with the primary disease; however, when rupture occurs, an animal previously in pain can exhibit signs of relief.

T47550

609714-609844

Sentence

denotes

Subsequent signs are consistent with peritonitis and shock, including tachypnea, tachycardia, sweating, and muscle fasciculations.

T33922

609845-610090

Sentence

denotes

Surgical repair is difficult but has been reported for partial-thickness tears, 1402 and, in one case of a combined tear of the mucosa and muscularis with only a focal serosal tear, a full-thickness repair was performed with a favorable outcome.

T16904

610091-610095

Sentence

denotes

1403

T6134

610096-610180

Sentence

denotes

Gastric impaction can result in either acute or chronic signs of colic in the horse.

T43358

610181-610667

Sentence

denotes

Although a specific cause is not always evident, ingestion of coarse roughage (straw bedding and poor-quality forage), foreign objects (rubber fencing material), and feed that may swell after ingestion or improper mastication (persimmon seeds, mesquite beans, wheat, barley, and sugar beet pulp) has been implicated. [1404] [1405] [1406] [1407] Possible predisposing factors include poor dentition, poor mastication and rapid consumption of feedstuffs, and inadequate water consumption.

T19070

610668-610769

Sentence

denotes

Clinical signs can vary from anorexia and weight loss to those consistent with severe abdominal pain.

T54001

610770-610860

Sentence

denotes

In severe cases, spontaneous reflux may occur, with gastric contents visible at the nares.

T52526

610861-610970

Sentence

denotes

In cases presenting with acute severe abdominal pain, a diagnosis is often made during exploratory celiotomy.

T37449

610971-611163

Sentence

denotes

In animals not exhibiting signs of colic warranting surgical intervention, an endoscopic finding of a full stomach after a normally adequate fast (18-24 hours) can often confirm the diagnosis.

T53245

611164-611229

Sentence

denotes

Abdominal radiographs are reserved for smaller horses and ponies.

T52432

611230-611432

Sentence

denotes

In addition to pain management, specific treatment consists of gastric lavage via nasogastric intubation or massage and injection of fluid to soften the impaction during laparotomy. [1404] [1405] [1406]

T99510

611434-611580

Sentence

denotes

Nonulcerative gastritis rarely appears to be a clinical problem in the horse, but it has been reported at necropsy in a large retrospective study.

T1154

611581-611679

Sentence

denotes

1302 Emphysematous gastritis caused by C. perfringens 1408 and C. septicum 1409 has been reported.

T32718

611680-611739

Sentence

denotes

Neoplasia in the alimentary tract of the horse is uncommon.

T54459

611740-611910

Sentence

denotes

1410 Primary and metastatic neoplasia can affect multiple locations within the oral cavity and gastrointestinal tract, and occurrence is not isolated to geriatric horses.

T80522

611911-611994

Sentence

denotes

The alimentary form of lymphoma occurs commonly in horses less than 5 years of age.

T76103

611995-612110

Sentence

denotes

1411 In one study, Arabian horses were 4.5 times more likely to have intestinal neoplasia relative to other breeds.

T17139

612111-612207

Sentence

denotes

1412 Identification of tumor type is important for formulating a prognosis and therapeutic plan.

T47744

612208-612298

Sentence

denotes

The clinical signs associated with alimentary neoplasia are related to the tumor location.

T89137

612299-612656

Sentence

denotes

For example, oral tumors can cause cutaneous enlargement; tumors of the tongue can cause quidding, dysphagia, and halitosis 1413 ; tumors of the esophagus cause dysphagia, ptyalism, intermittent colic, weight loss, and halitosis 1219, 1414, 1415 ; and gastric neoplasia is associated with anorexia, weight loss, abdominal distention, and intermittent fever.

T50866

612657-612753

Sentence

denotes

1416 Abdominal neoplasia has been implicated in 4% of horses with intermittent or chronic colic.

T7199

612754-612846

Sentence

denotes

1417, 1418 Weight loss is the most common clinical sign of horses with intestinal neoplasia.

T37306

612847-612944

Sentence

denotes

1412 Acute signs of colic can occur with intestinal obstructions from malignant or benign tumors.

T40100

612945-612993

Sentence

denotes

Paraneoplastic syndromes can occur in the horse.

T95920

612994-613199

Sentence

denotes

These include weight loss despite adequate caloric intake (cancer cachexia), ectopic hormone production, anemia, leukocytosis, thrombocytopenia, hypergammaglobulinemia, fever, and neurologic abnormalities.

T68617

613200-613204

Sentence

denotes

1419

T38347

613205-613258

Sentence

denotes

Diagnosis of alimentary neoplasia can be challenging.

T66228

613259-613361

Sentence

denotes

Data collected from a complete blood count, biochemistry panel and urinalysis are rarely confirmatory.

T97746

613362-613543

Sentence

denotes

Normocytic normochromic anemia of chronic disease is the most common red cell abnormality associated with abdominal neoplasia; blood loss and hemolytic anemia occur less frequently.

T69221

613544-613615

Sentence

denotes

1420 Peripheral eosinophilia and MEED have been reported with lymphoma.

T65740

613616-613669

Sentence

denotes

1421 Leukocytosis and hyperfibrinogenemia are common.

T44480

613670-613774

Sentence

denotes

The most common biochemical abnormalities include hypoalbuminemia, hyperglobulinemia, and hypercalcemia.

T4765

613775-613846

Sentence

denotes

1422, 1423 Hypoglycemia can occur with pancreatic or hepatic neoplasia.

T61679

613847-613962

Sentence

denotes

1423 Rectal examination may detect an abdominal mass, thickening of the intestinal wall, or lymph node enlargement.

T82964

613963-614019

Sentence

denotes

Rectal biopsy can detect diffuse lymphoma in some cases.

T57845

614020-614118

Sentence

denotes

489 Some tumors can exfoliate into the peritoneal cavity, allowing diagnosis via abdominocentesis.

T88811

614119-614390

Sentence

denotes

1414, [1424] [1425] [1426] Collecting a large volume of fluid followed by Cytospin and subsequent cytologic evaluation may improve the diagnostic potential; characterization as an inflammatory exudate or modified transudate without any neoplastic cells present is common.

T8945

614391-614484

Sentence

denotes

Neoplasia was the apparent cause of hemoperitoneum in 13% of cases in one report of 54 cases.

T12930

614485-614573

Sentence

denotes

1427 Abdominocentesis accurately predicted neoplasia in 11 of 25 cases in another study.

T40547

614574-614666

Sentence

denotes

769 Specific immunoglobulin testing for IgM deficiency may aid in the diagnosis of lymphoma.

T41272

614667-614803

Sentence

denotes

1428 DNA cell cycle analysis of suspect neoplastic cells has been used to detect lymphoma in equine patients confirmed with the disease.

T5056

614804-614921

Sentence

denotes

This method of evaluating fluid or tissue aspirates may increase the accuracy for diagnosing neoplasia in the future.

T57514

614922-615073

Sentence

denotes

1429 Previously mentioned diagnostics, such as endoscopy, contrast radiography, and cross-sectional imaging may be helpful depending on tumor location.

T92296

615074-615151

Sentence

denotes

For abdominal neoplasia, transcutaneous ultrasonography is often most useful.

T92068

615152-615243

Sentence

denotes

An experienced sonographer and thorough examination are likely to improve diagnostic yield.

T17586

615244-615329

Sentence

denotes

46 Laparoscopy or exploratory laparotomy may be required to obtain a final diagnosis.

T33996

615330-615484

Sentence

denotes

Lymphoma is the most common neoplasia in the horse and has been divided into four categories 1412 ; only the intestinal/alimentary form will be discussed.

T98575

615485-615583

Sentence

denotes

The term lymphoma is preferred over lymphosarcoma because there is no benign form of this disease.

T12385

615584-615679

Sentence

denotes

1423 Lymphoma originates from lymphoid tissue and predominantly affects intestinal lymph nodes.

T84949

615680-615850

Sentence

denotes

Chronic weight loss, intermittent colic, and fever are the most common clinical findings 502,1430 ; chronic diarrhea, 1431 pruritus, and alopecia 1432 have been reported.

T35286

615851-615974

Sentence

denotes

Peripheral lymphadenopathy is not generally noted, but enlargement of mesenteric lym phadenopathy may be palpable rectally.

T49087

615975-616055

Sentence

denotes

Therapeutic large colon resection has been reported in two horses with lymphoma.

T23069

616056-616182

Sentence

denotes

1433 SCC is the second most common neoplasia in the horse and is the most common tumor of the proximal gastrointestinal tract.

T5504

616183-616278

Sentence

denotes

1434 In the oral cavity SCC may affect the lips, tongue, hard palate, pharynx, and oral mucosa.

T96515

616279-616396

Sentence

denotes

1435, 1436 Metastasis beyond the regional lymph nodes is rare for oral, esophageal, and SCC, although it is possible.

T69941

616397-616467

Sentence

denotes

Abnormal masses were palpable rectally in 4 of 5 cases of gastric SCC.

T41843

616468-616590

Sentence

denotes

1416 Most discussions of SCC treatment about the head are based on dermal, ocular, and adnexal SCC, which are more common.

T87704

616591-616877

Sentence

denotes

Available treatment includes surgical resection, iridium-192 brachytherapy, 5-fluorouracil, and intralesional cisplatin or carboplatin. [1437] [1438] [1439] [1440] [1441] The prognosis for survival is good if complete resection is possible, although it typically is not for gastric SCC.

T49997

616878-616912

Sentence

denotes

1423 Local recurrence is possible.

T25811

616913-617042

Sentence

denotes

One report of recurring SCC on the lip with metastasis to the lymph nodes was successfully treated with piroxicam over 58 months.

T10161

617043-617130

Sentence

denotes

1442 Hypertrophic osteopathy secondary to gastric SCC has been documented in one horse.

T20225

617131-617216

Sentence

denotes

1443 Adenocarcinoma has been reported in the small intestine, cecum, and large colon.

T66813

617217-617361

Sentence

denotes

1412, 1434, 1444 The tumor arises from the glandular crypts of the gastrointestinal tract and has been reported in middle-aged and older horses.

T4405

617362-617465

Sentence

denotes

Metastasis to the lymph nodes, liver, and lungs is possible; osseous metaplasia has also been reported.

T99474

617466-617604

Sentence

denotes

1445 In a retrospective study of intestinal neoplasia, adenocarcinoma represented 32% of cases, 82% of which involved the small intestine.

T85446

617605-617707

Sentence

denotes

1412 The short-term prognosis for resectable adenocarcinoma is fair; long-term prognosis remains poor.

T30262

617708-617850

Sentence

denotes

1412, 1446 Leiomyosarcoma and leiomyoma are malignant and benign, respectively, tumors of the smooth muscle lining the gastrointestinal tract.

T31837

617851-617980

Sentence

denotes

Both have been reported in the stomach, small intestine, and small colon/rectum; leiomyoma has also been reported in the omentum.

T73715

617981-618172

Sentence

denotes

1434, [1447] [1448] [1449] [1450] [1451] [1452] [1453] Clinical signs are consistent with intestinal obstruction, and prognosis is favorable with resection of the affected intestinal segment.

T14673

618173-618261

Sentence

denotes

Lipoma is a benign tumor that occurs in older horses arising from mesenteric adipocytes.

T93308

618262-618357

Sentence

denotes

Clinical signs do not typically occur unless the tumor stalk results in intestinal obstruction.

T57795

618358-618474

Sentence

denotes

Oral cavity neoplasia may involve the dental tissue (odontogenic tumors), bone (osteogenic tumors), or soft tissues.

T91230

618475-618556

Sentence

denotes

Ameloblastoma occurs in horses >10 years old, and it mainly affects the mandible.

T28009

618557-618635

Sentence

denotes

Ameloblastic odontoma affects younger horses and usually involves the maxilla.

T82927

618636-618673

Sentence

denotes

Both are benign but locally invasive.

T84297

618674-618830

Sentence

denotes

Radiographs may distinguish between an ameloblastoma (radiolucent lesion) and ameloblastic odontoma (radiolucent lesion with partially mineralized density).

T18643

618831-618927

Sentence

denotes

The best treatment option is surgical resection and/or radiation therapy regardless of the type.

T60664

618928-619058

Sentence

denotes

1454 Juvenile mandibular ossifying fibroma occurs in the rostral mandible of young horses between the age of 2 months and 2 years.

T99680

619059-619107

Sentence

denotes

It may cause significant distortion of the bone.

T38421

619108-619178

Sentence

denotes

Surgical excision of the mass has a good prognosis if diagnosed early.

T62497

619179-619256

Sentence

denotes

1455 Melanomas, sarcoids, SCC, and papilloma can occur on the mouth and lips.

T60432

619257-619388

Sentence

denotes

Melanomas are commonly found in the commissure of the lips and parotid salivary glands and can metastasize to regional lymph nodes.

T95834

619389-619477

Sentence

denotes

Sarcoids can cause local ulcerations of the buccal mucosa, which are difficult to treat.

T68105

619478-619583

Sentence

denotes

Intralesional cisplatin, cryosurgery, radiation, and laser excision have been tried with limited success.

T47556

619584-619700

Sentence

denotes

Equine papilloma virus is responsible for the common skin wart that is found on the lips and muzzle of young horses.

T80287

619701-619808

Sentence

denotes

These lesions are typically self-limiting, but cryosurgery or excision can be used for removal, if desired.

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