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Enteritis, Proximal
Enteritis, Proximal BASIC INFORMATION DEFINITION Inflammatory disease of the duodenum and proximal jejunum resulting in excessive enteric fluid and electrolyte secretion and large-volume enterogastric reflux
SYNONYMS • Anterior enteritis • Duodenitis-proximal jejunitis (DPJ)
EPIDEMIOLOGY CONTAGION AND ZOONOSIS Although infectious or toxic agents may contribute to proximal enteritis, the disease typically occurs in an individual horse on a farm rather than as an outbreak.
CLINICAL PRESENTATION HISTORY, CHIEF COMPLAINT Depression, inappetence, fever, and variable signs of colic (mild to severe) PHYSICAL EXAM FINDINGS • Depression • Pyrexia is commonly observed. • Variable tachycardia and tachypnea • Variable signs of colic, which are almost always relieved by passage of a nasogastric tube and gastric decompression
A significant volume of gastric reflux (5–25 L) is usually obtained initially. Reflux volume may increase with therapy when the patient is rehydrated. ○ The reflux may be orange to dark brown in color and often has a fetid odor. Hemorrhagic gastric reflux is occasionally encountered. • Injected, hyperemic mucous membranes with a “toxic line” are usually encountered. • Moderate to severe dehydration, with prolonged capillary refill time, prolonged skin tent, and poor jugular refill. • Decreased to absent gastrointestinal borborygmi. • Mild abdominal distension may be present. • Rectal examination: ○ Mild to moderately distended or thickened small intestine is usually appreciated. ○ Concurrent large colonic gas distension is occasionally noted with severe, diffuse intestinal ileus. ETIOLOGY AND PATHOPHYSIOLOGY • The specific cause of proximal enteritis is unknown, although several infectious or toxic agents have been proposed. It is likely that a variety of causes result in a similar clinical syndrome. ○
Toxigenic Clostridium difficile is the pathogen most often isolated from horses with proximal enteritis, although C. difficile infection is not documented in all cases. ○ Clostridium perfringens and Salmonella spp. infection also occasionally manifest with signs consistent with proximal enteritis. ○ Cantharidin toxicity may result in small intestinal as well as colonic damage, and affected horses may present with clinical signs of proximal enteritis. ○ Lesions consistent with proximal enteritis have been produced exper imentally in horses exposed to toxins produced by Fusarium moniliforme. However, neurologic signs and central nervous system lesions typical of leukoencephalomalacia were also observed in those horses and are not described in most cases of proximal enteritis. • Regardless of the specific inciting cause, the gross pathologic findings in horses with proximal enteritis include duodenal and proximal jejunal serositis with mucosal and submucosal hyperemia and edema. Histopathologic findings include loss of intestinal villi and necrosis of epithelial cells with neutrophilic infiltration and sub○
170 Enteritis, Proximal
mucosal and serosal hemorrhages and fibrinopurulent exudates. • Several factors may contribute to the large-volume enterogastric reflux in proximal enteritis. ○ With severe intestinal mural inflammation and epithelial cell necrosis, fluid, electrolytes, and plasma protein are lost passively through the damaged mucosa. ○ In addition, an active secretory component may be induced by bacterial toxins and likely plays a role in most cases, resulting in further enteric fluid and electrolyte loss. ○ Intestinal mural edema and inflammation and villus loss also decrease the small intestinal absorptive capacity and inhibit normal peristalsis, resulting in enterogastric reflux. ○ Finally, in some cases of proximal enteritis, pancreatic secretions are increased because of concurrent pancreatitis. • Bacterial toxins enter the systemic circulation through the compromised enteric mucosal barrier or via the portal circulation, resulting in the clinical signs of endotoxemia and the systemic inflammatory response syndrome.
DIAGNOSIS DIFFERENTIAL DIAGNOSIS • Strangulating or nonstrangulating small intestinal obstruction • Ulcerative duodenitis or gastric outflow obstruction (see “Ulcerative Duodenitis” and “Pyloric Stenosis” in this section)
INITIAL DATABASE • Complete blood count ○ Leukopenia characterized by a neutropenia with increased band neutrophils and toxic changes in neutrophils is typically seen. ○ The hematocrit varies with hydration status but can be markedly increased in severe cases (>60%). ○ Thrombocytopenia is occasionally present in severe cases with con current disseminated intravascular coagulation (DIC). • Serum biochemistry profile ○ Variable electrolyte derangements are common, with hypokalemia, hyponatremia, hypochloremia, and hypocalcemia most common ○ Serum total protein (TP) concentration may be increased with dehydration or normal or low with enteric loss ○ Some degree of azotemia is common and may be caused by prerenal or renal causes (or both).
Metabolic acidosis and hyper lactatemia (>2 mmol/L) suggests impaired peripheral perfusion and tissue oxygenation caused by hypovolemia. • Transabdominal ultrasonography ○ Mild to severe small intestinal distension with increased small intestinal mural thickness (>5 mm) is usually appreciated. ○ The duodenum is typically dilated and hypomotile with increased mural thickness (>5 mm). • Peritoneal fluid analysis ○ Variable. In most cases, peritoneal fluid is grossly normal with a mildly increased nucleated cell count and TP concentration. ○ However, exudative fluid with a more substantially increased nucleated cell count may be seen if concurrent peritonitis has occurred because of bacterial translocation. ○ In severe cases, peritoneal fluid can be grossly serosanguineous, which may make it difficult to differentiate proximal enteritis from a strangulating intestinal obstruction. ○
ADVANCED OR CONFIRMATORY TESTING • Diagnostic testing for specific causes of proximal enteritis should include the following. ○ Polymerase chain reaction or culture for Salmonella spp. on gastric reflux and feces ○ Gram stain and toxin assays for C. perfringens and C. difficile toxins on gastric reflux and feces. ○ ±Urine analysis for cantharidin if historical exposure • Gastroduodenoscopy may be indicated to rule out ulcerative duodenitis and pyloric outflow obstruction, but visualization of the pylorus and duodenum may be difficult with largevolume gastric reflux.
TREATMENT THERAPEUTIC GOAL(S) Supportive care
ACUTE GENERAL TREATMENT • An indwelling nasogastric tube should be maintained and the patient monitored for gastric reflux q2–3h to maintain gastric decompression and prevent gastric rupture. A careful record of gastric reflux volume can direct fluid therapy to meet ongoing fluid losses. • IV fluid therapy ○ Fluid resuscitation with hypertonic saline (2–4 mL/kg IV bolus) or hydroxyethyl starch (5–10 mL/kg
IV bolus) or both is indicated in severely dehydrated patients. ○ This should be followed by isotonic balanced polyionic crystalloid fluids (eg, Normosol-R or Plasmalyte) at 50 to 150 mL/kg/day, depending on the degree of dehydration and ongoing losses in gastric reflux. ○ Supplementation with potassium chloride (10–40 mEq/L with the rate not to exceed 0.5 mEq/kg/h), 23% calcium gluconate (1–2 mL/kg/ day) or magnesium sulfate (20– 25 g/450 kg horse/day) is often necessary to correct electrolyte derangements. ○ Colloidal support with equine plasma (20–40 mL/kg IV) or hydroxyethyl starch (5–10 mL/kg IV bolus q24–48h or 1 mL/kg/h IV continuous rate infusion [CRI]) is indicated in hypoproteinemic patients. (Note: Patients with initially normal TP concentrations may have hypoproteinemia after rehydration.) ○ Horses with inflammatory intestinal diseases such as proximal enteritis are particularly prone to thrombophlebitis. Long-term polyethylene IV catheters should be used and removed at the first sign of a problem with the catheter or vein. • Antiinflammatory and analgesic therapy ○ Flunixin meglumine: 0.5 to 1.1 mg/ kg IV q12h for analgesic and antiinflammatory effects; may be decreased to 0.25 mg/kg IV q6–8h ○ Lidocaine: 1.3 mg/kg IV as a slow bolus; then 0.05 mg/kg/min IV CRI for analgesic and prokinetic effects ○ ± Dimethylsulfoxide (90% solution): 20 to 100 mg/kg diluted to less than 10% solution in IV fluids q12h for 1 to 3 days (may scavenge free radicals and limit oxidative injury) • Antiendotoxic therapy ○ Equine plasma (2–4 L IV or more if hypoproteinemic; regular equine plasma or hyperimmune plasma with antiendotoxin antibodies) or hyperimmune antiendotoxin serum (Endoserum, 1–2 mL/kg diluted in 3–5 L isotonic fluids IV) ○ Polymixin-B: 2000 to 6000 IU/kg (diluted in 500–1000 mL 0.9% saline) IV q12h for 1 to 3 days after the patient is hydrated and if renal function is adequate • Laminitis prophylaxis ○ Placement of frog supports and maintenance in deep bedding should be initiated immediately. ○ Periodic or continuous maintenance in ice boots during initial therapy may be helpful in preventing laminitis, although this is not universally accepted.
Enteritis, Proximal If signs of laminitis occur, treatment should be rapid and aggressive (see “Laminitis, Acute” in this section). • Oral medications and intestinal absorbants should be avoided because of likely poor absorption and the risk of gastric rupture. • Nutritional support ○ Addition of 1% to 2.5% dextrose to IV fluids during early therapy may help meet some of the patient’s initial energy requirements. ○ Parenteral nutrition should be considered in protracted cases with persistent gastric reflux for several days or more. • Antimicrobial therapy ○ Controversial because a specific infectious cause is often difficult to determine, and most horses recover without specific antimicrobial therapy. ○ Metronidazole (15–25 mg/kg by rectum) is indicated if clostridial toxin assay results are positive. ○ Broad-spectrum antimicrobial ther apy is indicated in patients with peritonitis or in profoundly neutropenic patients (which are at greater risk of development of secondary infections such as pneumonia or septic thrombophlebitis). May include potassium penicillin 22,000 to 44,000 IU/kg IV q6h and genta○
Enterolithiasis 171 micin (6.6 mg/kg IV q24h) or enrofloxacin (5 mg/kg IV q24h) • Other ○ Some evidence suggests that some horses with proximal enteritis may be hypercoagulable because of subclinical DIC and thus are at greater risk for thrombotic complications. Heparin (20–40 IU/kg IV or SC q8h) may be beneficial in these cases. ○ Some horses show signs of persistent abdominal pain despite gas tric decompression and analgesic therapy. Exploratory celiotomy is warranted in these cases to rule out a small intestinal obstructive lesion.
POSSIBLE COMPLICATIONS • Thrombophlebitis • Laminitis • Intestinal infarction • Gastroduodenal ulcers with prolonged anorexia • Increased risk of intraabdominal adhesions if laparotomy is necessary
portive care, and avoidance of laminitis • Guarded with concurrent peritonitis or serosanguineous peritoneal fluid, concurrent laminitis, or if laparotomy is necessary
PEARLS & CONSIDERATIONS It can be difficult to differentiate between proximal enteritis and a strangulating small intestinal obstruction in some cases. Peritoneal fluid analysis should be performed in these cases and exploratory celiotomy considered if signs of colic persist after gastric decompression.
SUGGESTED READING Davis JL: Medical disorders of the small intestine: duodenitis-proximal jejunitis. In Smith BP, editor: Large animal internal medicine. St Louis, 2009, Mosby Elsevier, pp 725–728. AUTHOR: KELSEY A. HART EDITORS: TIM MAIR and CERI SHERLOCK
PROGNOSIS AND OUTCOME • Fair with normal peritoneal fluid, good response to sup-
SYNONYMS • Anterior enteritis • Duodenitis-proximal jejunitis (DPJ)
EPIDEMIOLOGY CONTAGION AND ZOONOSIS Although infectious or toxic agents may contribute to proximal enteritis, the disease typically occurs in an individual horse on a farm rather than as an outbreak.
CLINICAL PRESENTATION HISTORY, CHIEF COMPLAINT Depression, inappetence, fever, and variable signs of colic (mild to severe) PHYSICAL EXAM FINDINGS • Depression • Pyrexia is commonly observed. • Variable tachycardia and tachypnea • Variable signs of colic, which are almost always relieved by passage of a nasogastric tube and gastric decompression
A significant volume of gastric reflux (5–25 L) is usually obtained initially. Reflux volume may increase with therapy when the patient is rehydrated. ○ The reflux may be orange to dark brown in color and often has a fetid odor. Hemorrhagic gastric reflux is occasionally encountered. • Injected, hyperemic mucous membranes with a “toxic line” are usually encountered. • Moderate to severe dehydration, with prolonged capillary refill time, prolonged skin tent, and poor jugular refill. • Decreased to absent gastrointestinal borborygmi. • Mild abdominal distension may be present. • Rectal examination: ○ Mild to moderately distended or thickened small intestine is usually appreciated. ○ Concurrent large colonic gas distension is occasionally noted with severe, diffuse intestinal ileus. ETIOLOGY AND PATHOPHYSIOLOGY • The specific cause of proximal enteritis is unknown, although several infectious or toxic agents have been proposed. It is likely that a variety of causes result in a similar clinical syndrome. ○
Toxigenic Clostridium difficile is the pathogen most often isolated from horses with proximal enteritis, although C. difficile infection is not documented in all cases. ○ Clostridium perfringens and Salmonella spp. infection also occasionally manifest with signs consistent with proximal enteritis. ○ Cantharidin toxicity may result in small intestinal as well as colonic damage, and affected horses may present with clinical signs of proximal enteritis. ○ Lesions consistent with proximal enteritis have been produced exper imentally in horses exposed to toxins produced by Fusarium moniliforme. However, neurologic signs and central nervous system lesions typical of leukoencephalomalacia were also observed in those horses and are not described in most cases of proximal enteritis. • Regardless of the specific inciting cause, the gross pathologic findings in horses with proximal enteritis include duodenal and proximal jejunal serositis with mucosal and submucosal hyperemia and edema. Histopathologic findings include loss of intestinal villi and necrosis of epithelial cells with neutrophilic infiltration and sub○
170 Enteritis, Proximal
mucosal and serosal hemorrhages and fibrinopurulent exudates. • Several factors may contribute to the large-volume enterogastric reflux in proximal enteritis. ○ With severe intestinal mural inflammation and epithelial cell necrosis, fluid, electrolytes, and plasma protein are lost passively through the damaged mucosa. ○ In addition, an active secretory component may be induced by bacterial toxins and likely plays a role in most cases, resulting in further enteric fluid and electrolyte loss. ○ Intestinal mural edema and inflammation and villus loss also decrease the small intestinal absorptive capacity and inhibit normal peristalsis, resulting in enterogastric reflux. ○ Finally, in some cases of proximal enteritis, pancreatic secretions are increased because of concurrent pancreatitis. • Bacterial toxins enter the systemic circulation through the compromised enteric mucosal barrier or via the portal circulation, resulting in the clinical signs of endotoxemia and the systemic inflammatory response syndrome.
DIAGNOSIS DIFFERENTIAL DIAGNOSIS • Strangulating or nonstrangulating small intestinal obstruction • Ulcerative duodenitis or gastric outflow obstruction (see “Ulcerative Duodenitis” and “Pyloric Stenosis” in this section)
INITIAL DATABASE • Complete blood count ○ Leukopenia characterized by a neutropenia with increased band neutrophils and toxic changes in neutrophils is typically seen. ○ The hematocrit varies with hydration status but can be markedly increased in severe cases (>60%). ○ Thrombocytopenia is occasionally present in severe cases with con current disseminated intravascular coagulation (DIC). • Serum biochemistry profile ○ Variable electrolyte derangements are common, with hypokalemia, hyponatremia, hypochloremia, and hypocalcemia most common ○ Serum total protein (TP) concentration may be increased with dehydration or normal or low with enteric loss ○ Some degree of azotemia is common and may be caused by prerenal or renal causes (or both).
Metabolic acidosis and hyper lactatemia (>2 mmol/L) suggests impaired peripheral perfusion and tissue oxygenation caused by hypovolemia. • Transabdominal ultrasonography ○ Mild to severe small intestinal distension with increased small intestinal mural thickness (>5 mm) is usually appreciated. ○ The duodenum is typically dilated and hypomotile with increased mural thickness (>5 mm). • Peritoneal fluid analysis ○ Variable. In most cases, peritoneal fluid is grossly normal with a mildly increased nucleated cell count and TP concentration. ○ However, exudative fluid with a more substantially increased nucleated cell count may be seen if concurrent peritonitis has occurred because of bacterial translocation. ○ In severe cases, peritoneal fluid can be grossly serosanguineous, which may make it difficult to differentiate proximal enteritis from a strangulating intestinal obstruction. ○
ADVANCED OR CONFIRMATORY TESTING • Diagnostic testing for specific causes of proximal enteritis should include the following. ○ Polymerase chain reaction or culture for Salmonella spp. on gastric reflux and feces ○ Gram stain and toxin assays for C. perfringens and C. difficile toxins on gastric reflux and feces. ○ ±Urine analysis for cantharidin if historical exposure • Gastroduodenoscopy may be indicated to rule out ulcerative duodenitis and pyloric outflow obstruction, but visualization of the pylorus and duodenum may be difficult with largevolume gastric reflux.
TREATMENT THERAPEUTIC GOAL(S) Supportive care
ACUTE GENERAL TREATMENT • An indwelling nasogastric tube should be maintained and the patient monitored for gastric reflux q2–3h to maintain gastric decompression and prevent gastric rupture. A careful record of gastric reflux volume can direct fluid therapy to meet ongoing fluid losses. • IV fluid therapy ○ Fluid resuscitation with hypertonic saline (2–4 mL/kg IV bolus) or hydroxyethyl starch (5–10 mL/kg
IV bolus) or both is indicated in severely dehydrated patients. ○ This should be followed by isotonic balanced polyionic crystalloid fluids (eg, Normosol-R or Plasmalyte) at 50 to 150 mL/kg/day, depending on the degree of dehydration and ongoing losses in gastric reflux. ○ Supplementation with potassium chloride (10–40 mEq/L with the rate not to exceed 0.5 mEq/kg/h), 23% calcium gluconate (1–2 mL/kg/ day) or magnesium sulfate (20– 25 g/450 kg horse/day) is often necessary to correct electrolyte derangements. ○ Colloidal support with equine plasma (20–40 mL/kg IV) or hydroxyethyl starch (5–10 mL/kg IV bolus q24–48h or 1 mL/kg/h IV continuous rate infusion [CRI]) is indicated in hypoproteinemic patients. (Note: Patients with initially normal TP concentrations may have hypoproteinemia after rehydration.) ○ Horses with inflammatory intestinal diseases such as proximal enteritis are particularly prone to thrombophlebitis. Long-term polyethylene IV catheters should be used and removed at the first sign of a problem with the catheter or vein. • Antiinflammatory and analgesic therapy ○ Flunixin meglumine: 0.5 to 1.1 mg/ kg IV q12h for analgesic and antiinflammatory effects; may be decreased to 0.25 mg/kg IV q6–8h ○ Lidocaine: 1.3 mg/kg IV as a slow bolus; then 0.05 mg/kg/min IV CRI for analgesic and prokinetic effects ○ ± Dimethylsulfoxide (90% solution): 20 to 100 mg/kg diluted to less than 10% solution in IV fluids q12h for 1 to 3 days (may scavenge free radicals and limit oxidative injury) • Antiendotoxic therapy ○ Equine plasma (2–4 L IV or more if hypoproteinemic; regular equine plasma or hyperimmune plasma with antiendotoxin antibodies) or hyperimmune antiendotoxin serum (Endoserum, 1–2 mL/kg diluted in 3–5 L isotonic fluids IV) ○ Polymixin-B: 2000 to 6000 IU/kg (diluted in 500–1000 mL 0.9% saline) IV q12h for 1 to 3 days after the patient is hydrated and if renal function is adequate • Laminitis prophylaxis ○ Placement of frog supports and maintenance in deep bedding should be initiated immediately. ○ Periodic or continuous maintenance in ice boots during initial therapy may be helpful in preventing laminitis, although this is not universally accepted.
Enteritis, Proximal If signs of laminitis occur, treatment should be rapid and aggressive (see “Laminitis, Acute” in this section). • Oral medications and intestinal absorbants should be avoided because of likely poor absorption and the risk of gastric rupture. • Nutritional support ○ Addition of 1% to 2.5% dextrose to IV fluids during early therapy may help meet some of the patient’s initial energy requirements. ○ Parenteral nutrition should be considered in protracted cases with persistent gastric reflux for several days or more. • Antimicrobial therapy ○ Controversial because a specific infectious cause is often difficult to determine, and most horses recover without specific antimicrobial therapy. ○ Metronidazole (15–25 mg/kg by rectum) is indicated if clostridial toxin assay results are positive. ○ Broad-spectrum antimicrobial ther apy is indicated in patients with peritonitis or in profoundly neutropenic patients (which are at greater risk of development of secondary infections such as pneumonia or septic thrombophlebitis). May include potassium penicillin 22,000 to 44,000 IU/kg IV q6h and genta○
Enterolithiasis 171 micin (6.6 mg/kg IV q24h) or enrofloxacin (5 mg/kg IV q24h) • Other ○ Some evidence suggests that some horses with proximal enteritis may be hypercoagulable because of subclinical DIC and thus are at greater risk for thrombotic complications. Heparin (20–40 IU/kg IV or SC q8h) may be beneficial in these cases. ○ Some horses show signs of persistent abdominal pain despite gas tric decompression and analgesic therapy. Exploratory celiotomy is warranted in these cases to rule out a small intestinal obstructive lesion.
POSSIBLE COMPLICATIONS • Thrombophlebitis • Laminitis • Intestinal infarction • Gastroduodenal ulcers with prolonged anorexia • Increased risk of intraabdominal adhesions if laparotomy is necessary
portive care, and avoidance of laminitis • Guarded with concurrent peritonitis or serosanguineous peritoneal fluid, concurrent laminitis, or if laparotomy is necessary
PEARLS & CONSIDERATIONS It can be difficult to differentiate between proximal enteritis and a strangulating small intestinal obstruction in some cases. Peritoneal fluid analysis should be performed in these cases and exploratory celiotomy considered if signs of colic persist after gastric decompression.
SUGGESTED READING Davis JL: Medical disorders of the small intestine: duodenitis-proximal jejunitis. In Smith BP, editor: Large animal internal medicine. St Louis, 2009, Mosby Elsevier, pp 725–728. AUTHOR: KELSEY A. HART EDITORS: TIM MAIR and CERI SHERLOCK
PROGNOSIS AND OUTCOME • Fair with normal peritoneal fluid, good response to sup-