Diarrhea

K. Gary Magdesian • Bradford P. Smith

Diarrhea is an increase in the frequency, fluidity, or volume of feces. Diarrhea may be a sign of a primary gastrointestinal (GI) disease or a nonspecific response to sepsis, toxemia, or disease of another organ system.

Under normal circumstances a large volume of essentially isotonic fluid enters the proximal GI tract daily. Most of this fluid is resorbed, and only a small percentage is ultimately passed with the feces. The fluid comes from dietary intake and from endogenous secretions of the upper digestive tract. The total daily volume exchanged exceeds that of the animal's total extracellular fluid volume. Normally absorption just exceeds secretion; therefore small changes in rate of absorption or secretion can result in diarrhea. In the horse most water resorption occurs in the cecum and large colon, and diarrhea in the horse (other than neonates) usually involves some abnormality in the lumen or wall of the large intestine.

Normal fecal color is tan, brown, or greenish, depending on diet. The adult horse normally produces 11 to 13 kg of fecal material per day (24 to 29 lbs of body weight per day) while on a diet of grass hay and 3 lb of oats.¹ Fecal output is as high as 20 kg/day (44 lbs/day) in horses fed a mixture of alfalfa and orchard grass ad libitum.² Horses with chronic watery diarrhea can produce up to 214 g/kg of body weight per day,¹ which is >90 L of diarrhea in a 450-kg horse.

Cattle normally produce 15 to 28 kg of feces per day with a water content of about 75% to 85% on a diet of grass hay.³ Fluidity of cattle feces can increase markedly in animals on lush green feed. Sheep and goat feces contain only 50% to 60% water.³ Fluid feces in the cow and unformed feces in the horse, goat, and sheep are nonspecific signs that often accom­pany sepsis or illness other than a primary gastrointestinal disease.

Animals with chronic diarrhea rarely develop severe dehydra­tion because they compensate for increased fecal water losses by increasing water consumption by an equivalent amount. Normal water consumption in the horse on a hay diet in a mild ambient temperature environment is about 24 to 30 L/ day, whereas cattle consume 30 to 60 L/day based on 10 kg of dry matter feed intake. Water and feed intake do not increase linearly with increasing body size, but by multiplying body weight in kilograms to the 0.75th power (BW kg⁰⁷⁵) by a base factor (≈200 mL for water). Thus a 500-kg horse requires 21 L of water. The effect of temperature on water intake is dramatic and not linear; as ambient temperatures rise close to 37° C (98° F), water intake per kilogram of dry matter increases much more rapidly than at lower temperatures. Exercise and loss through sweat, particularly in the horse, can dramatically increase salt and water requirements.

Mechanisms of Diarrhea

The following six major mechanisms produce diarrhea (Box 7.1):

• Decreased or damaged absorptive surface area (malabsorption)

• Increased numbers of osmotically active particles within the intestinal lumen

• Increased volume of secretion of solutes and water

• Abnormal intestinal motility resulting in decreased transit time, as with systemic inflammatory response syndrome (SIRS)

• Increased blood-to-lumen pressure as in heart failure or acute or chronic inflammatory bowel diseases

• Gastrointestinal inflammation, as occurs with peritonitis

The common net result is an increase in fecal water.

Decreased surface area is mainly a result of villous blunting (atrophy) and/or microvillous damage in the small intestine, which lead to malabsorption. Both occur to some degree with most enteric diseases, and regeneration of surface area from crypt cells with healing is accompanied by a gradual decrease in the volume of diarrhea. Diseases in which this is a major

■ BOX 7.1

■ BOX 7.2

Mechanisms of Diarrhea

Malabsorption (villous atrophy)

Osmotic overload Secretion

Abnormal motility

Increased blood-to-lumen hydraulic pressure Inflammation

Decreased transit time

mechanism include neonatal diseases such as rotavirus and coronavirus enteritis,⁴ cryptosporidiosis, acute inflammatory disease such as salmonellosis, and chronic diseases such as Johne's disease and other granulomatous bowel diseases.

Inflammation can be accompanied by increased mucous production and increases in size of membrane pores, through which tissue fluids and serum proteins leak into the lumen. This is associated with increased capillary and lymphatic hydraulic pressures. Both acute (salmonellosis) and chronic (Johne's) inflammatory bowel diseases are protein-losing enteropathies. Low plasma protein concentrations, particularly low albumin, are often found (unless hypovolemia and hemoconcentration are present). Bowel inflammation often results in transudation and exudation of serum proteins, blood, and/or mucus, resulting in dysentery (bloody diarrhea). In addition to salmonellosis, dysentery may also commonly be seen with enterotoxemia caused by Clostridiumperfringens, types A, B, or C; Clostridium difficile; Lawsonia intracellularis⁵; attaching effacing Escherichia coli; Campylobacter jejuni; coccidiosis; malignant catarrhal fever (MCF); arsenic toxicity; and oak toxicity. Inflammation results in malabsorption, maldigestion, osmotic effects, and, in acute disease, changes in intestinal motility. Because most water absorption in the horse occurs in the cecum and colon, inflammatory typhlitis and colitis are the major causes of diarrhea in the adult horse (Boxes 7.2 and 7.3). The neonatal foal commonly develops small intestinal enteritis.

Irritation of the bowel with a foreign body such as sand may result in either low-grade recurrent colic or diarrhea or both.

Osmotic diarrhea results from any disease causing maldiges­tion and/or malabsorption. Any osmotically active solute can produce diarrhea in normal animals if given in quantities sufficient to surpass the intestinal capacity for digestion or absorption. Disaccharides are natural examples. Osmotic cathartics such as dioctyl sodium sulfosuccinate (DSS) hold water in the intestine and act as fecal softeners. Magnesium phosphates and sulfates and other divalent and trivalent cations and anions are poorly absorbed and thus are effective laxatives and cathartics.

Osmotic diarrhea can be associated with ingestion of osmoti­cally active and poorly absorbed solutes, overloading of the intestine with carbohydrates or lipids beyond the amount that

Causes of Diarrhea in Horses^a

Common Causes

Colitis or typhlitis

Salmonellosis

Enteritis, unknown cause

Potomac horse fever (equine monocytic ehrlichiosis) Endotoxemia or gram-negative sepsis

Overfeeding or sudden change in diet

Clostridium difficile

Clostridium perfringens

Parasites (ascarids, large and small strongyles)

Less Common Causes

Eosinophilic gastroenteritis

Renal failure, uremia

Necrotizing enterocolitis

Heart failure

Enterotoxemia (C. perfringens, mainly type A)

Lawsonia intracellularis (mainly foals and weanlings), proliferative enteropathy

Intestinal lymphosarcoma

Cathartics or laxatives

Parasympathomimetics

Chronic granulomatous bowel disease

Proximal enteritis

Peritonitis

Intussusception

Sand, gravel, or enterolith in gut lumen

Gut stenosis

Antibiotic use

Gastroduodenal ulcers

Rhodococcus equi, gut infection (mainly foals) Cryptosporidiosis (mainly foals)

Giardiasis (mainly foals)

Toxins or poisonous plants (see Box 7.3)

Uncommon Causes

Hepatic failure Cholelithiasis

Vascular aneurysm

Combined immunodeficiency

Agammaglobulinemia

Lactose intolerance (mainly foals) Campylobacter jejuni (mainly foals)

Colorectal polyps Anaphylaxis

Vitamin A deficiency

Tularemia

Snake bite, insect or spider sting or bite

Histoplasmosis Hydroallantois Hyperlipidemia Internal abdominal abscess

Pheochromocytoma

Viral arteritis

Sarcoidosis

Addison disease

Malignancy

Grass sickness (exotic)

Glanders (exotic)

Besnoitiosis (globidiosis) (exotic)

^aSee Chapter 17 for information on neonates.

can be digested and absorbed, sudden dietary changes resulting in marked shifts in gut flora and resulting bacterial action on ingested substrate (e.g., grain overload), or bowel disease in which surface area is diminished or digestion interfered with in some manner. Lactase deficiency, secondary to rotavirus or C.

■ BOX 7.3

Toxic Causes of Diarrhea in Horses^a

Phenylbutazone or other nonsteroidal antiinflammatory drug toxicity

Blister beetle toxicity (cantharidin)

Salt poisoning

Selenium toxicity

Slaframine toxicity (slobber factor)

Amitraz toxicity

Propylene glycol toxicity

Dioctyl sodium sulfosuccinate toxicity

Sulfur toxicity

Phosphorus toxicity

Nicotine (Black Leaf 40) toxicity

Reserpine toxicity

Arsenic toxicity

Mercury toxicity

Monensin, lasalocid, or salinomycin toxicity Organophosphate toxicity

Iron

Plant Toxins

Oleander poisoning

Japanese yew (Taxus cuspidata) poisoning

Castor bean poisoning Avocado poisoning

Thorn apple (Datura stramonium) toxicity

Potato poisoning

Heath (Ericaceae) poisoning

Algae poisoning

Acorn or oak poisoning

Hypericum (St. John's wort, Klamath weed) poisoning Agrostemma githago (corn cockle) poisoning Mycotoxicosis

Pimelea poisoning (St. George disease) (exotic) Monkshood

Buttercup

Death camas

Datura

Foxglove

Hoary alyssum

^aSee additional lists at www.vet.cornell.edu/consultant.

difficile infections, may result in osmotic diarrhea in foals⁶ and probably also in neonatal ruminants. This results in increased concentration of undigested and/or unabsorbed nutrients enter­ing the lower bowel, increased bacterial fermentation, and an increase in the concentration of osmotically active particles. Unfavorable electrochemical gradients prevent resorption of water. Mucosal digestive enzyme levels are often decreased with any disease involving the small intestine, resulting in maldigestion. When osmotic diarrhea is suspected in mature animals, dietary modification to basic roughage should be tried as part of the nonspecific therapy.

Secretory diarrheas are most important in neonates⁴ (e.g., enteropathogenic E. coli), but many strains of Salmonella that are associated with colitis in large animals may also produce enterotoxins that stimulate secretion. Enterotoxins act by stimulating cyclic adenosine monophosphate (AMP) or other intracellular messengers to promote secretion of chloride, sodium, and other electrolytes into the gut lumen. Water is carried with these electrolytes and osmotically retained. The hallmark of secretory diarrheas is the large volume of feces produced.

Examples of secretory diarrheas are enterotoxigenic E. coli, many strains of Salmonella, and C. perfringens. Salmonella and other invasive microorganisms produce inflammation that may induce prostaglandin-mediated secretion as well. Salmonella typhimurium translocates Salmonella effector proteins into epithelial cells and causes diarrhea.⁷ Secretion may occur with viral diarrhea by a different mechanism, as damaged mature (absorbing) villous cells are replaced by immature (secreting) crypt cells.⁸ An example of viral secretory enteritis is rotavirus.

Decreased intestinal transit time, associated with increased peristalsis and/or decreased segmentation, appears to occur in many bowel diseases because of bowel irritation. Peritonitis is a major cause of bowel inflammation and should always be explored as a contributing cause of diarrhea, especially when fecal output volume is scant. Abnormal motor patterns have been demonstrated to occur with many infectious diarrheas and may be a bowel response to irritation and/or increased intraluminal volume. Elimination of gut contents thus appears to be a normal gut defense mechanism against infection and should not be pharmacologically alleviated in acute infectious diarrheas. Primary motility disorders of animals are not well recognized; diarrhea associated with nervous or excited animals may be the best example of this type. In general, fecal volume associated with motility disorders is not great.

Increased hydraulic or hydrostatic pressure, from the blood to the intestinal lumen, also decreases net fluid absorption. These can result from decreased oncotic pressure (hypoalbuminemia), increased capillary hydrostatic pressure (heart failure or portal hypertension as with liver disease), or decreased lymphatic drainage associated with inflamed or blocked lymph vessels or nodes (lymphosarcoma). These mechanisms are most commonly associated with chronic diarrhea, but acute inflammation can also result in diarrhea associated with this mechanism.

Two or more of these mechanisms are probably at work in most diarrheal diseases. Therapy of diarrhea is therefore nonspecific and supportive, except when the actual causative agent can be identified and is treatable. Diagnosis of a specific causative agent is most important when diarrhea is caused by an infectious agent so that appropriate therapeutic steps can be taken before chronicity develops, spread of disease can be prevented, and an accurate prognosis can be made.

In mature horses, small intestinal diseases such as granu­lomatous bowel disease or duodenitis/proximal jejunitis (anterior enteritis) may not be associated with diarrhea, and diseases of the stomach almost never cause diarrhea. Most significant diarrheal disease in adult horses involves the large colon because this is the principal site of water absorption. The exception to this is the neonatal foal, in which primarily small intestinal diseases such as rotavirus infection and cryptosporidiosis may cause severe diarrhea.

The frequency of defecation is usually increased when diarrhea is present, and defecation frequency is highest when the colon or rectum is irritated. When these areas are involved, tenesmus (straining) may result. Tenesmus can also occur with hepatic failure in ruminants and in horses and ruminants with rectal tears or strictures, vaginitis, retained placenta, dystocia, intussusception, urolithiasis, perirectal abscesses, rabies, and diseases involving the nervous system when there is retention of feces or urine. Severe rectal irritation can lead to straining and rectal prolapse.

In ruminants, abnormalities such as grain overload (toxic indigestion) resulting in ruminal osmotic changes can produce diarrhea, as can changes in abomasal pH such as occur with type II ostertagiasis. Diarrhea in ruminants is frequently caused by forestomach problems (Boxes 7.4 and 7.5). The colon and

^aRinderpest was a cause of diarrhea in ruminants until 2011, when it was eradicated worldwide. B, Bovine; O, ovine.

remainder of the distal bowel are involved in diseases such as salmonellosis. Gram-negative infections and resulting endo­toxemia, found in conditions such as coliform mastitis and septic metritis, are relatively common causes of nonspecific diarrhea.

Foals with septicemia also commonly develop nonspecific diarrhea associated with SIRS.

Diarrhea may be 1) a manifestation of a primary disease (bovine viral diarrhea [BVD]; Johne’s disease; C. difficile, sal­monellosis); 2) one of the signs of a generalized disease (MCF, uremia); or 3) secondary to toxemia (coliform mastitis, septic metritis, septicemia, salmonellosis).

Nonspecific Fluid Therapy for Diarrhea

Dehydration, electrolyte losses, and acid-base abnormalities can occur rapidly when diarrhea is present. Treatment to correct these problems is an important component of nonspecific therapy in animals with diarrhea. Often the cause of diar­rhea remains undetermined, yet correction of hypovolemia, dehydration, and acid-base and electrolyte abnormalities can result in a return to normal systemic function, particularly if the diarrhea is acute and severe. Fluids and electrolytes can be given orally or parenterally. Oral fluids can be given rapidly and inexpensively but only if dysmotility is not present. Oral fluids should be isotonic or hypotonic. The degree of dehydration should be estimated as a percentage of body weight. Mild dehydration is usually considered less than 5%; moderate, 5% to 8%; and severe, over 8%. Thus a severely dehydrated 450-kg patient with an estimated 10% dehydration (weakness, cold extremities, sunken eyes, decreased urine output, decreased elastic skin rebound, weak pulse, rapid heart rate) may require up to 45 L of fluids over time. Boluses of 10 to 20 mL/kg of isotonic crystalloid can be administered IV until signs of shock abate or plateau.

The optimal means of determining electrolyte status is to analyze a plasma or serum sample before initiating fluid therapy. Electrolyte requirements can be estimated; with diarrhea, mixed water and electrolyte losses occur, so sodium-containing fluids are usually required to replace lost sodium and improve blood volume (see also Critical Care and Fluid Therapy, Chapter 44). Unless the acid-base status can be measured, the safest sodium-containing fluids are balanced polyionic fluids such as PlasmaLyte A, PlasmaLyte 148, Hartmann’s solution, or lactated Ringer's solution. Normal saline is a satisfactory alternative in many cases, but the relatively high concentration of chloride ions in saline can aggravate a preexisting metabolic acidosis through raising chloride concentration, producing a hyper­chloremic metabolic acidosis (HCMA), and therefore saline should be used sparingly. In calves with severe metabolic acidosis, use of fluids containing sodium bicarbonate is indicated. In horses, it is best not to include large quantities of sodium bicarbonate in fluids unless there is laboratory evidence that a significant strong ion metabolic acidosis exists (such as hyperchloremia). Flow rates for administering isotonic

^aSee additional lists at www.vet.cornell.edu/consultant.

intravenous fluids should be monitored, with close attention to perfusion parameters, in order to avoid fluid overload, pulmonary edema, and excessive diuresis. When the patient is shocky, flow rates close to 20 mL/kg/h or faster may be required for the initial administration of isotonic crystalloid fluids, but in general rates below 5 to 10 mL/kg/h are desirable, especially once hypovolemic shock has been addressed. Fluid overload is detrimental, and therefore frequent reassessment of the patient should be made. Hypertonic saline (7% NaCl) may be given rapidly intravenously at a dose of 4 to 5 mL/kg once. When a colloid fluid is required to combat low plasma protein concentrations, hetastarch or plasma can be used. Hetastarch is available as 6% hetastarch in a balanced electrolyte or normal saline solution. A dose of 10 mL/kg should not be exceeded for hetastarch because of development of dose­dependent coagulopathies. The use of hetastarch in human critical care has recently been questioned. A meta-analysis has suggested an increase in renal disease and mortality in patients treated with hetastarch.⁹ How this applies to large animals is unknown, but creatinine should be monitored closely. See Neonatal Diarrhea, Chapters 17 (section on Neonatal Foals) and 20 (section on Neonatal Ruminants); Fluid and Electrolyte Balance, Chapter 22; and Fluid Therapy, Chapter 44 for more details on fluids and acid-base balance.

Approach to Diagnosis of Diarrhea in the Horse (for Neonates, See Chapter 17)

1. Take history. Especially note change in diet, deworming program, housing and management, and whether diarrhea is acute or chronic. Note appetite, whether animal is drinking an adequate volume of water, and whether salt is available. Note whether it is a single or multiple case, if there are concurrent diseases, or if other medications or exposure to toxins are involved. Most antimicrobials have been associated with diarrhea in horses at times, but especially lincomycin and erythromycin. Antimicrobials should be discontinued if diarrhea develops during admin­istration. Most pathogenic bacterial and protozoal agents rely on altered intestinal microflora to proliferate in the gut and cause diarrhea. Note whether nonsteroidal anti­inflammatory drugs such as phenylbutazone were used before the development of diarrhea. Many causes of diarrhea can be eliminated from consideration on the basis of history. Find out about housing and whether animals have access to pasture or natural water sources or are stall confined. For example, Potomac horse fever would be considered in horses with access to or living near water sources in endemic areas.

2. Perform physical examination. Take vital signs (these are often normal in chronic cases). Perform rectal examination unless an infectious contagious agent is suspected, especially if diarrhea is scant in volume. Note body condition score (see Chapter 9). Systemic signs of endotoxemia, SIRS, hypovolemia, and dehydration often accompany acute colitis, including salmonellosis, equine monocytic ehrlichiosis (Potomac horse fever), clostridiosis, and many other acute diseases.

3. Examine feces. Perform gross inspection; note whether blood or fibrin is present (see list of causes of dysentery).

a. Gram stain of feces. A predominance of gram-positive rods may indicate an anaerobic overgrowth such as occurs with C. difficile infections, although this is not highly sensitive or specific. Perform microscopic examination for ova and protozoa, especially for chronic cases.

b. Perform multiple cultures for Salmonella, C. difficile⁰⁰ and C. perfringens if onset is acute, if animal is febrile, or if feces contain fibrin and mucus. A commercial polymerase chain reaction (PCR) test can be used as an aid to evaluate for the presence of salmonellosis.¹¹ Cultures for C. difficile should be performed on selective media (cycloserine-cefoxitin-fructose agar). Recently Brachyspira pilosicoli has been isolated from the feces of weanlings with chronic diarrhea.¹² This agent warrants further investigation as a cause of diarrhea and failure to thrive in young horses. Fecal PCR and serology for Lawsonia intracellularis should be performed on young horses (including young adults) with hypoproteinemia, unthriftiness, and variable diarrhea.

c. An evaluation for C. difficile and C. perfringens toxins (with fecal enzyme-linked immunosorbent assays [ELISAs] or a stool cytotoxin assay for C. difficile) should be made if the diarrhea is temporally associated with antibiotic administration. Several ELISA kits are avail­able for identification of toxins A (enterotoxin) and B (cytotoxin) of C. difficile in feces. A stool cytotoxin cell culture is available for toxin B.^13,14 Toxin B cell culture testing is considered the gold standard.¹⁵

d. Isolates of C. perfringens should be examined for the ability to produce alpha, beta, epsilon, and beta 2-toxins because certain strains may be associated with gastrointestinal disease.^16,17 Type C C. perfringens isolates have been associated with the most severe disease in horses and foals and elaborate both alpha and beta toxin. Gene sequences for these toxins are found by PCR once the isolates are cultured. Commercial veterinary diagnostic laboratories now offer PCR for the C. perfringens gene sequences directly in horse feces as part of diarrhea PCR panels. In addition, a commercial fecal ELISA is available for detection of alpha-toxin, beta-toxin, and epsilon-toxin in feces directly at the California Animal Health and Food Safety Laboratory (San Bernardino). This allows diagnosis of C. perfringens, types A (alpha toxin) and C (alpha and beta toxins). Recently, NetFtoxin-producing type A C. perfringens isolates have been linked to severe, necrotizing enterocolitis in foals.¹⁸

e. Fecal occult blood (if positive, see list of causes of melena and blood in feces).

f. Fecal osmolality, sodium, and potassium concentrations (optional). Electrolyte concentration in feces is roughly twice the sodium plus potassium. When this value is much lower than the measured osmolality of the feces, the difference is an osmolar gap caused by osmotically active nonelectrolytes such as lactose, and osmotic diarrhea is confirmed.

g. Check for sand by placing some feces in a bucket of water or rectal palpation sleeve, mixing thoroughly, and decanting the water or inspecting the bottom for sedimentation of sand. If a radiographic unit with the appropriate power capability is available, abdominal radiographs should be taken to detect the presence and amount of sand. Ultrasound of the ventral abdomen can be used to diagnose the presence of sand, although this requires considerable expertise.

A PCR test for feces is available at University of Minnesota Diagnostic Laboratory at www.vdl.umn.edu and the University of California Molecular Labora­tory at www.vetmed.ucdavis.edu/vme/taqmanservice/ (see Chapter 29 for complete list) for detection of L. intracellularis, organisms in weanlings and yearlings with diarrhea, weight loss, general malaise, and hypoalbu- minemia.¹⁹ Also see serum test described later. Young adult horses can also develop disease from Lawsonia.¹²⁰

h. Rhodococcusequi can cause diarrhea in 3-week to 6-month- old foals. Diagnostic tests include cultures of transtracheal aspirates, abdominal fluid cytology and culture, abdominal ultrasonography, and ruling out other etiologies of diar­rhea. Fecal PCR should also be performed.²¹

i. If all other cultures are negative and an infectious cause of diarrhea is suspected, the feces should be cultured for Aeromonas species and C. perfringens (see earlier).^22,23

4. Obtain blood for the following database:

a. Complete blood count (CBC; includes fibrinogen and plasma protein concentrations). Increased fibrinogen concentration indicates inflammation. Decreased protein concentrations indicate protein-losing enteropathy. Thrombocytopenia may indicate a coagulopathy. Neutropenia with or without a toxic, left shift (imma­ture neutrophilia) is often present with infectious and inflammatory causes of acute colitis, indicating SIRS. Increases in packed cell volume (PCV) and red cell mass are often present, indicating hemoconcentration and/or splenic contraction in horses.

b. Acid-base analysis should be performed if the condition is acute and the horse is dehydrated or toxic. Although acid-base values are not useful diagnostically in terms of specific etiology, they allow for initiation of proper acid base and electrolyte supportive therapy.

5. Test serum for the following:

a. Electrolyte (Na, K, Cl, Mg, Ca, HCO₃) concentrations, including ionized calcium.

b. Serum creatinine and blood urea nitrogen (BUN) concentrations—prerenal azotemia is common as a result of dehydration; check again after rehydration. Acute kidney injury is also common. Serum chemistries should be evaluated for liver and other organ disease. Liver enzymes are frequently elevated during and for a period following acute toxic diarrhea.

c. Albumin and globulin concentrations; hypoalbuminemia is seen with chronic protein-losing enteropathies such as inflammatory bowel disease (e.g., granulomatous enteritis), phenylbutazone toxicity (right dorsal colitis), hypobiotic cyathostomiasis, Lawsonia intracellularis infec­tion, and acute colitis conditions (such as salmonellosis).

d. Specific immunoglobulin (Ig) A, IgM, and IgG con­centrations; immunodeficient individuals may have chronic diarrhea. Specific immunoglobulin concentra­tions may be altered with lymphoma or multiple myeloma. Elevated globulins may indicate the presence of chronic disease.

e. PCR for Neorickettsia risticii (Potomac horse fever) in whole blood and feces samples. Both blood and feces should be tested, in order to increase the sensitivity of detection. Paired sera for Neorickettsia risticii titer following acute diarrhea with fever can also be performed, but this is rarely performed since availability of PCR testing.

f. Clotting times (prothrombin time [PT] and partial thromboplastin time [PTT] or activated clotting time [ACT]) should be monitored as indicators of coagu­lopathies such as disseminated intravascular coagulation (DIC) in horses with acute typhlocolitis. Antithrombin concentrations can be monitored for the risk of throm­boses, particularly in horses with hypoproteinemia.

6. Perform abdominocentesis, especially if signs of colic are present. Evaluate cytology, protein, and fibrinogen values in chronic cases to rule out peritonitis, tumors, and mesenteric abscess.

7. Perform function and absorption tests in chronic diarrhea cases, especially when weight loss is present.

a. Oral glucose or xylose small intestine absorption tests (see Chapter 32) for chronic cases, particularly if a high index of suspicion of malabsorption exists because of hypoalbuminemia. If tests indicate malabsorption, either biopsy the gut (duodenum through duodenoscopy) or rectum or assess the response to treatment following larvicidal anthelmintic treatment.

b. Perform liver function tests such as measurement of serum bile acid concentrations if liver involvement is suspected as a result of increased liver enzyme concentra­tions and/or hypoalbuminemia. Liver enzymes are increased in many cases of enterocolitis and in these cases do not necessarily indicate primary liver disease (see Chapter 33). Secondary liver disease may occur secondary to endotoxemia or altered hemodynamics, as well as cholangiohepatitis.

8. Examine tissue.

a. Rectal or intestinal (duodenal) biopsy for microscopic examination and fluorescent antibody for immune- mediated diseases (also culture for Salmonella). Rectal mucosal histopathology is particularly useful in horses with hypoalbuminemia or weight loss.²⁴

b. Detection of C. perfringens beta 2-toxin from type A or beta toxin from type C isolates can be performed by immunohistochemistry of gut mucosa and is diag­nostic on biopsy or postmortem specimens.²⁵ NetF toxin is a recently recognized virulence factor in some type A isolates¹⁸.

c. Liver biopsy if indication of significant or persistent liver disease, especially in chronic cases.

9. Toxicology.

a. Blood lead, liver lead, and liver arsenic concentrations can be measured if toxicity is suspected.²⁶

b. High-pressure liquid chromatography or gas chromatography-mass spectrometry can be used to detect cantharidin (blister beetle toxin) in urine or gastrointestinal contents in endemic areas or when hay is imported from those areas.^23,27

c. Urine, serum, and gastrointestinal contents can be evaluated for the presence of oleandrin toxins using thin-layer chromatography. Oleander toxicity should be suspected in animals with diarrhea, colic, arrhythmias, and renal disease.²⁸

10. Evaluate response to treatment with undiagnosed chronic diarrhea.

a. Alter diet to simple grass hay. Alternatively, a complete pelleted diet can be tried, especially if right dorsal colitis or maldigestion/malabsorption is suspected, as well as in horses that are normal clinically and have normal clinicopathologic results, but that have increased fecal water. Psyllium mucilloid (4 oz), and 1 to 2 cups of corn oil can be added to the daily diets of horses with right dorsal colitis.^29,30

b. Stop nonsteroidal drugs such as phenylbutazone if right dorsal colitis is a possible cause of loose feces.

c. Transfaunation with fecal (or colon or cecum if available) contents from a healthy animal that has been tested negative for Salmonella and other fecal pathogens can be tried, especially when dysbiosis of the microbiome is suspected.

d. Attempt to classify by rectal biopsy; many changes are nonspecific.

If lymphocytic, lymphoplasmacytic, or granulomatous enteritis is diagnosed: Administer 0.04 to 0.06 mg/kg IM or IV dexamethasone per day, tapering down to 0.02 mg/kg in 5 to 7 days; if response is favorable, continue with 1 to 1.5 mg/kg prednisolone PO per day, taper over 2 months.

Eosinophilic infiltrate: Administer larvicidal anthel­mintic dose of fenbendazole plus corticosteroids.

e. Transfusion with plasma (1 to 2 mL/kg) in young horses 2 to 12 months of age that may need some additional proteins, antithrombin, or immunoglobulin. Synthetic colloids such as hetastarch can be used in animals with reduced colloid osmotic pressure (hypoalbuminemia); check especially if edema is present. Hetastarch (6%) has been used at 10 mL/kg, and this dose should not be exceeded daily because of risks of dose-dependent coagulopathies.³¹ Hetastarch has been associated with adverse effects in human patients, including renal injury and mortality in some studies.⁹

f. Horses with Potomac horse fever often respond favorably to systemic treatment with tetracycline.

g. Metronidazole (15 mg/kg PO q 8 h) can be used empiri­cally, especially if an anaerobic overgrowth is suspected, C. difficile orperfringens has been diagnosed, or when the diarrhea is secondary to antibiotic use.³² Metronidazole can be administered intravenously in horses with reflux.

Approach to Diagnosis of Diarrhea in Ruminants (for Neonates, See Chapter 20)

1. Take history. Especially note diet, appetite, previous deworming and vaccinations, and whether it is an indi­vidual or herd problem. In animals younger than 1 year of age, Coccidia, Ostertagia, or other helminths should be strongly considered. Determine if onset is acute or chronic. If chronic, first consider diseases such as parasitism, Johne's disease, copper deficiency (molybdenosis), selenium deficiency, liver failure, and other diseases of individual cows such as bovine leukosis virus (BLV), amyloidosis, heart failure, or uremia.

2. Perform physical examination. Especially note weight loss, fever, systemic signs, rumen activity, and oral lesions. Perform rectal examination. In most acute-onset diseases, vital signs are abnormal and systemic involvement or oral lesions (especially with BVD) may be obvious.

3. Examine feces.

a. Gross inspection

b. Microscopic examination for ova and parasites

c. Culture for Salmonella if animal is febrile or feces appear inflammatory (fibrin or mucus)

d. Check for fecal occult blood

e. Culture or other diagnostic test for Mycobacterium avium subsp. paratuberculosis, if weight loss is a problem (especially if a herd problem in animals older than 2 years of age)

4. Take rectal scrapings of mucous if weight loss and chronic diarrhea are present.

a. Make thin smear on glass slide for acid-fast staining for M. avium subsp. paratuberculosis. Examine under oil immersion lens

5. Test for BVD if any oral lesions or other relevant clinical signs. See Chapter 32 for available tests.

6. Obtain blood for the following:

a. Plasma proteins

b. Fibrinogen

c. In acute cases, electrolytes and acid-base status

d. If a herd problem, copper and selenium status

7. Test serum for the following:

a. BUN

b. Liver enzymes (γ-glutamyltransferase [GGT] and sorbitol dehydrogenase [SDH])

c. Albumin and globulin values

d. Agar gel immunodiffusion (AGID) for BLV (single animals); request gp51 and p24 antibody status (see Chapter 37).

e. If Johne's disease is suspected, perform ELISA test or other relevant test (see Chapter 32).

8. Perform paracentesis. Paracentesis rules out gross perito­nitis, but many false-negatives are possible as a result of focal or fibrinous peritonitis.

9. Perform urinalysis for protein to rule out consideration of amyloidosis or other multisystemic immune-mediated disease. Because ruminants normally have a urine pH of 8 or higher, most dipstick tests will give a trace or a 1+ positive reading for urine protein even when the animal's urine is normal.

10. Examine tissue. Perform rectal, intestinal, or mesenteric lymph node biopsy for acid-fast stain for Johne's disease, for culture for Salmonella, BVD, and for presence of lymphosarcoma.

11. Perform feed analysis (herd problem only); check copper, molybdenum, and selenium levels.

a. Toxins suspected (e.g., mercury, arsenic)

12. Tap abomasum for increased pH; rule out type II ostertagiasis.

13. Perform necropsy (herd problem only).

a. Pick severely affected individual to examine thoroughly.