Malassimilation Syndromes in Large Animals

Maldigestion syndromes are uncommon and poorly understood in large animals. They can be caused by alterations in gastric function or activity of rumen microflora, insufficient grinding and rumination, abnormal bacterial proliferation in the small intestine, or a decrease or lack of small intestinal brush border enzyme activity (eg, lactase deficiency).

Less likely causes include drug-induced alteration in secretion or excretion of bile salts and deficiency or inactivation of pancreatic lipase. Changes in bile salt concentration may not impair digestion in adult herbivores but may exacerbate diarrhea in milk-fed neonates. Surgical resection of the distal small intestine may facilitate bacterial overgrowth with associated bile salt abnormalities.

Lactose is a disaccharide composed of glucose and galactose. The enzyme lactase, which catalyzes the degradation of lactose into its components, is localized in the small intestinal brush border of foals and calves. The degradation is necessary to facilitate absorption.

Primary lactase deficiency is inherited as an autosomal recessive trait in humans; however, its occurrence and mode of inheritance in large animals is poorly documented. Acquired or secondary lactase deficiency seems to be more common than primary lactase deficiency in large animals.

Secondary lactase deficiency has been described in foals, calves, and crias as a result of intestinal mucosal changes induced by viral, protozoal, and bacterial enteritis. Sloughing of the small intestinal epithelial cells, loss of villous tips, and loss of some or all of the crypt cells contribute to some degree of lactase deficiency because of loss of lactase-secreting epithelial cells. Morphological changes can include partial villous atrophy, crypt hyperplasia, and infiltration of the lamina propria.

Osmotic diarrhea in lactase-deficient foals and calves occurs because of increased undigested/unabsorbed nutrients entering the caudal intestines, subsequently increasing bacterial fermentation, concentration of osmotically active particles, and retention of intestinal water and electrolytes.

A number of diseases can induce a malabsorption syndrome by altering the normal absorptive mechanisms of the small intestine. Malabsorption commonly occurs in animals with GI disease. It may arise from structural or functional disorders of the small intestine or have a multifactorial etiopathogenesis.

Malabsorption is often present concurrently with enteric protein loss. Either can cause loss of nutrients in the feces and subsequent weight loss.

Malabsorption is not synonymous with diarrhea in any species; however, diarrhea may be a common clinical feature. Function of the large intestine may be secondarily altered because of changes in the small intestine. Transient diarrhea can occur as abnormal quantities of carbohydrates, protein, fatty acids, and bile acids enter the large intestine in the ileal effluent. These substances can directly or indirectly enhance intestinal secretion or decrease absorption rates. Malabsorption of nutrients can result from insufficient absorptive surface area, an intrinsic defect in the mucosal or submucosal morphology of the intestinal wall, or obstruction of blood and lymphatic vessels.

Rotavirus infection in younger animals can cause destruction of intestinal villous epithelial cells, which results in maldigestion due to decreased activity of brush border disaccharidase enzymes and in malabsorption due to decreased absorptive surface area. Coronavirus and cryptosporidia infection may have similar effects. (See also Intestinal Diseases in Ruminants.)

A decreased absorptive surface area can also result from small intestinal resection (short bowel syndrome) or from villous atrophy due to granulomatous enteritis.

Local infiltrative or inflammatory disease, edema, or lymphatic obstruction (granulomatous enteritis, lymphosarcoma) secondary to local or systemic causes can interfere with the ability of the intestinal wall to absorb nutrients. Inefficient absorption also may develop because of increased mucosal permeability caused by cellular damage.

Metabolic abnormalities may alter the epithelial cells and decrease the available energy for active transport and maintenance of the carrier proteins or brush border enzymes.

Congenital deficiencies of enzymes normally present on the microvilli are not well recognized in large domestic animals. However, neonates and ruminants have low maltase activity, and ruminants especially lack sucrase. In most mammalian species, lactase activity declines with age.

In horses, malabsorption is commonly caused by the following:

• Inflammatory or infiltrative disorders:

  • diffuse lymphosarcoma of the small intestine (alimentary lymphoma)

  • enteritis due to eosinophilic, lymphocytic-plasmacytic, or basophilic infiltrate

  • multisystemic eosinophilic epitheliotropic enterocolitis

  • granulomatous enteritis (inflammatory bowel disease)

  • equine proliferative enteropathy caused by Lawsonia intracellularis infection (weanling foals, yearlings)

  • intestinal ischemia and damage due to migration of Strongylus vulgaris larvae, small strongyles, or Strongyloides westeri (foals) infection

  • cryptosporidiosis

  • postinfarction inflammation

  • amyloid-associated gastroenteropathy

  • multiple abscesses in the bowel

  • tuberculosis

  • histoplasmosis

  • intestinal Rhodococcus equi infection

  • invasive enterocolitis (Salmonella spp infection)

• Biochemical or genetic abnormalities:

  • congenital or acquired lactase deficiency (lactose intolerance)

  • dietary-induced enteropathy

  • monosaccharide transport defect

  • pancreatic exocrine insufficiencies

• Diseases causing inadequate absorptive area:

  • villous damage or atrophy due to viral infection (rotavirus, coronavirus) or bacterial enteritides in foals

  • cryptosporidiosis

  • intestinal resection

• Cardiovascular disorders:

  • congestive heart failure

  • intestinal ischemia

• Lymphatic obstruction:

  • lymphosarcoma

  • mesenteric lymphadenopathy

  • intestinal lymphangiectasia

  • impaired lymphatic drainage due to a lymph node abscess

  • thoracic duct obstruction

• Miscellaneous:

  • drug-induced conditions

  • heavy metal toxicosis

  • zinc deficiency

In cattle, malabsorption syndromes are less frequently documented but likely occur most often in calves with diarrhea. Diseases that cause malabsorption syndromes in ruminants include diarrhea caused by viruses, bacteria, or protozoa in calves and young stock. These inflammatory changes often result in maldigestion and malabsorption.

Another major group of cattle affected by malabsorption syndrome is older cattle with Mycobacterium avium paratuberculosis infection (Johne’s disease).

Rare underlying reasons for malabsorption in ruminants include local or generalized ischemia, protein malnutrition, congestive heart failure, lymphatic obstruction, parasitism (eg, trichostrongylosis of sheep and cattle), and tuberculosis.

Oral antimicrobials can cause an imbalance in GI tract flora and interfere with digestion and intestinal absorption of nutrients. Treatment with high doses of ampicillin, neomycin, or tetracycline significantly decreases and delays glucose absorption during oral glucose tolerance tests in calves.

South American camelids (also termed New World camelids) can be affected by most conditions that cause malabsorption syndrome in ruminants. Virus-caused diarrhea (coronavirus infection) is particularly a problem in young crias. Intestinal protozoal infection (eg, Eimeria macusaniensis) can result in weight loss and hypoproteinemia due to malabsorption during either the prepatent or patent phase of infection. Severe debilitation caused by coccidiosis most commonly occurs in young animals; however, chronic malabsorption caused by chronic enteritis can also occur in adult llamas and alpacas, which typically shed high numbers of the pathogen.

In swine, malabsorption is poorly documented; however, proliferative enteropathy (L intracellularis infection) can result in malabsorption. In piglets, an amylase deficiency can result in starch malabsorption during the immediate postweaning period. Diarrhea of other origin (eg, Escherichia coli infection) may cause malabsorption syndrome in piglets.

Clinical signs of malassimilation syndrome are variable, depending on the underlying disease condition and the presence or absence of concurrent protein-losing enteropathy.

Malassimilation syndromes frequently result in a negative energy balance, and subsequently in weight loss,muscle wasting, and possibly low serum protein concentrations. Therefore, chronic weight loss or decreased growth rate is a typical clinical sign.

Appetite of affected animals can be normal, increased, or decreased and is therefore not very helpful as a diagnostic parameter. Polyphagia may occur because of insufficient nutrient absorption to stimulate the satiety centers. In small intestinal malabsorption, decreased feed intake or anorexia is present more commonly because the primary disease process causes loss of appetite.

Feces are frequently normal in consistency and volume. Diarrhea might be present but is not a consistent feature. In adult animals, small intestinal disease must be rather extensive before diarrhea develops, because the colon can compensate and absorb the increased fluid load. This is especially the case in llamas and alpacas. In adult horses and ruminants, diarrhea indicates involvement of the large intestine. In young animals in which colonic function is not yet fully developed, diarrhea can occur with both small intestinal and large intestinal disease.

Clinical signs of malassimilation can also include exercise intolerance, lethargy, and variable thirst.

Vital signs are usually normal until late in the disease. Pyrexia can occur with inflammatory and neoplastic conditions.

Abdominal pain can result from bowel inflammation, mesenteric or mural abscesses or adhesions, or partial obstruction.

Ascites, dependent edema, and weakness may develop later in the disease process, especially if enteric protein loss is present.

Skin and ocular lesions, vasculitis,arthritis, hepatitis, and renal disease may indicate immunological reactions, particularly with inflammatory bowel disease. Skin lesions with malabsorption-related dermatosis include a thin coat, patchy alopecia, and focal areas of scaling and crusting that are often symmetrically distributed.

Foals and calves with lactose intolerance commonly have diarrhea, a poor growth rate, and an unthrifty appearance. Some animals experience flatulence, mild abdominal discomfort, or bloating after milk ingestion. In young animals with acquired lactase deficiency, clinical signs (eg, diarrhea, dehydration, weight loss) and clinicopathological alterations (eg, acidosis, hypoglycemia. and electrolyte abnormalities) are indistinguishable from those of the primary enteropathy. The condition of the animal may improve quickly, and diarrhea may resolve when milk is no longer fed.

• History and clinical examination

• Laboratory testing, often extensive

Small intestinal malabsorption cannot be determined by clinical examination or by routine laboratory data. However, clinical examination may lead to a presumptive diagnosis after more common causes of weight loss have been excluded. Determination of the primary underlying pathological process is necessary to establish an appropriate treatment regimen and prognosis.

A thorough history should focus on duration of condition, precipitating factors, nutritional history, deworming and routine health care program, and previous or concurrent diseases, as well as the number, age, and proximity of other affected animals.

A thorough physical examination should be performed to correlate physical findings with clinical signs and history. In adult horses and cattle, rectal palpation is performed to determine the presence of intra-abdominal masses, enlarged lymph nodes, adhesions, abnormal positioning or thickening of bowel segments, or abnormalities in the cranial mesenteric artery. The kidneys, bladder, and related structures should also be evaluated.

A CBC and serum biochemical analysis (eg, concentrations or total protein, albumin, fibrinogen, glucose, cholesterol, bilirubin, ketone bodies, and fatty acids, as well as activities of CK, AST, and glutamate lactate dehydrogenase) help determine general health status of the animal; presence of inflammation or an infectious process; involvement of body systems; and metabolic, electrolyte, and serum protein status.

Urinalysis, abdominocentesis, and fecal examination for parasite ova, larvae, protozoa, and occult blood should also be performed to exclude more common causes of weight loss. Additionally, urinalysis should be performed to assess whether glucose or protein is being excreted via urine, which could be a further cause of chronic weight loss.

Plasma protein electrophoresis, fecal pH measurement, bacteriological culture, and immunological studies might be indicated. Intracolonic fermentation of poorly absorbed carbohydrates will often decrease the fecal pH in foals and calves. Protein-losing enteropathy can be diagnosed presumptively by excluding other causes of protein loss, such as renal disease or loss into a third space (peritoneum, pleural space), and by excluding the possibility of decreased albumin production due to another condition, such as liver disease.

Standard and contrast radiography of the bowel might be feasible in foals and small ponies, calves, and South American camelids.

Abdominal ultrasonography is a useful diagnostic tool to determine bowel-wall thickness and intestinal motility, as well as the presence of excess fluid in the abdominal cavity, masses, adhesions, abnormal positioning of bowel in the abdominal cavity, and vascular lesions in the cranial mesenteric artery.

When malassimilation is suspected, a carbohydrate absorption test may be performed to assess small intestinal function. In horses, gastroscopy to diagnose lesions in the stomach (eg, granulomas, tumor, ulcers) and duodenum or retention of ingesta should be performed before absorption tests are performed. The intestinal disorder must be diffuse and/or must affect the delivery to and transit through the small intestine for absorption tests to be diagnostic. An abnormal or flattened absorption curve is suggestive of small intestinal dysfunction. However, a flattened absorption curve can also be caused by other conditions.

Although absorption tests might indicate the presence of malassimilation, an etiological diagnosis requires a biopsy of intestinal mucosa and possibly lymph node. In some cases, rectal biopsy can reveal focal or diffuse inflammatory infiltration. Bacteriological culture of the feces, biopsy samples, and fecal examination for leukocytes and epithelial cells can confirm the presence of salmonellae or other invasive organisms.

In some cases, laparoscopy or exploratory celiotomy is required to obtain intestinal or lymph node biopsies. Surgery might not be advisable in a debilitated animal, because wound healing is poor and dehiscence is a potential problem. If surgery is undertaken, intestinal and lymph node biopsies should be obtained for culture and for histological, enzymological, and immunological evaluation. Because of the risk and cost of obtaining appropriate tissue samples, malassimilation syndrome is often presumptively diagnosed with the aid of absorption tests.

Clinically applicable absorption tests include d-glucose and d-xylose. These tests can help assess small intestinal function in preruminant calves, foals, crias, and mature horses. Indications for an oral absorption test in foals, calves, and possibly crias include persistent diarrhea not attributable to infectious agents, poor growth despite normal intake, and other clinical signs of maldigestion (repeated episodes of gas, colic, bloating, ileus). In monogastric animals, the test solution is administered into the stomach. In ruminants and South American camelids, the forestomachs must be bypassed (esophageal groove, abomasocentesis) because otherwise the sugars are metabolized by the forestomach flora; however, oral carbohydrate tolerance studies are not frequently used in ruminants.

The d-glucose absorption test has the advantages of being easy and inexpensive, and methods to determine blood glucose concentrations are available in most clinical laboratories. The main disadvantage is that results are not only a function of intestinal absorption but also are strongly influenced by the intensive cellular uptake and metabolism of glucose after it has been absorbed.

The d-xylose absorption test more directly measures intestinal absorptive capacity and is not influenced by endogenous factors and intestinal enzymatic activity, respectively. Disadvantages are that d-xylose is more expensive, and the number of commercial laboratories that perform plasma xylose determinations is limited. However, d-xylose concentrations can be measured using photometric techniques, which do not require special equipment and can be performed in a clinical laboratory.

Glucose or galactose can inhibit the absorption of d-xylose; therefore, fasting is necessary before the test is performed in horses and preruminant calves. The protocols of both tests require prolonged fasting, which can be deleterious to sick young foals and calves. The results of both tests are also affected by gastric emptying rate (d-xylose has also been used to estimate abomasal emptying rate in cattle), small intestinal transit time, diet, and length of fasting period before testing. The shape of the absorption curve is influenced by renal clearance, hypoxia, anemia, systemic and intestinal bacterial infections, and IgG concentrations in foals. The age of the animals also affects absorption and digestion of glucose, lactose, and d-xylose. Therefore, the control animals must be within a few days of the affected animal's age if reference ranges are not available for its age group.

A delayed peak in the absorption curve of both the d-glucose and d-xylose tests may be due to delayed gastric emptying resulting from hypertonicity of the glucose or xylose solution, excitement, pain, retained gastric contents, changes in GI transit time and motility, or partial obstruction. Further sedation of the animal decreases GI motility and, secondarily, the absorption. A flat absorption curve may also be observed in animals with normal absorptive capacity due to a transient decrease in intestinal blood flow or to bacteria in the lumen of the small intestine metabolizing the test sugar. The test substance rapidly equilibrates with many body fluids (eg, ascites), which lowers the blood concentration of xylose and may result in a flat curve.

• Supportive treatment and care

• Special feeding requirements

The etiology of the primary underlying disease process must be determined before specific therapy for malassimilation syndrome can be initiated. Specific therapy for most causes of malassimilation is not available, except for lesions due to parasite damage. Anticoccidial and larvacidal deworming treatments might improve the condition; however, complete healing and return to full absorption capacity are not always achievable, depending on the damage.

Anti-inflammatory agents (NSAIDs, eg, ketoprofen in swine, horses, ruminants, and South American camelids; meloxicam in horses, cattle, small ruminants, South American camelids, and swine) or corticosteroids (eg, dexamethasone) can also help decrease the inflammatory response within the affected bowel. Supportive care and absorption of nutrients from more caudal parts of the intestine must be encouraged until the intestinal epithelium recovers and new villous cells are produced. Maturation and healing of the intestinal absorptive surfaces can take weeks to months in severe cases.

Calves and foals with acquired lactase deficiency after diarrheal disease (viral, bacterial, protozoal) often respond well to supportive care (correction of acid-base, electrolyte, and glucose abnormalities) and feeding of enzymatically treated milk until the small intestinal mucosa has regenerated. Foals and calves should be fed small amounts of high-quality roughage or grain (if they are able to tolerate it) to help meet their energy needs; however, enteral feeding should be continued whenever possible.

Young foals and calves that do not tolerate feedings of milk or enzymatically treated milk might benefit from short-term (< 24 hours) withdrawal of milk. These animals need alternative sources of energy and nutrients, such as short-term (≤ 24 hours) feeding of glucose-containing electrolyte solutions or, in more severe cases, partial or total parenteral nutrition. Dietary change to a soy-based, non–lactose-containing milk replacer and early weaning are advised for animals with nonresponsive lactose intolerance.

Treatment of inflammatory bowel disease in horses has been attempted but is often unsuccessful, even with aggressive corticosteroid administration. Sulfasalazine and isoniazid have been recommended; however, their usefulness is unproved.

Similarly, the usefulness of dimethyl sulfoxide in the treatment of intestinal amyloidosis is unknown.

Animals with anaerobic or aerobic bacterial overgrowth may respond to antimicrobial administration. Adequate penetration of antimicrobials into inflammatory bowel lesions (R equi in foals) is doubtful. L intracellularis in foals has been successfully treated with long-term administration of antimicrobials (erythromycin, azithromycin, clarithromycin, chloramphenicol, oxytetracycline, doxycycline) and aggressive supportive care (fluids, plasma), as dictated by the animal’s clinical condition.

Any treatment attempt of cattle with clinical signs of Johne’s disease has proved to be unsuccessful; slaughter or euthanasia is recommended.

Eimeria macusaniensis infections in affected South American camelids may successfully be treated if diagnosed early. Treatment currently involves administration of amprolium, sulfonamides, ponazuril, or toltrazuril with appropriate supportive care.

Horses with malabsorption due to a disease process or after small bowel resection must be fed a diet that optimizes digestion of feeds in the large intestine. The diet should provide easily absorbed protein, carbohydrates, fat, and water-soluble vitamins and maintain mineral balance. Increased concentrate:forage ratios decrease digestion of feeds in the large intestine and should be avoided.

Horses benefit from a fiber-based diet. To enhance digestion in the large intestine, easily fermentable roughages (eg, alfalfa) should be fed. High-quality fiber, metabolized in the cecum and colon to volatile fatty acids, may partially compensate for small intestinal losses.

In young animals, the diet may be supplemented with milk protein, provided that lactase deficiency is not present. Fat may be added to the diet to enhance caloric intake. Calcium, magnesium, phosphate, zinc, copper, and iron might need to be supplemented because they are absorbed in horses in the small intestine only. Water-soluble (especially vitamin B₁₂) and fat-soluble vitamins should be supplemented parenterally as needed. Excessive supplementation, which could lead to toxicosis, should be avoided.

Horses that will not eat may have to be force-fed via nasogastric tube. The horse should be fed small, frequent meals to take advantage of the limited remaining absorptive ability of the small intestine without overloading it.

Preruminant calves that are repeatedly tube-fed can develop ruminal acidosis due to deposition of fermentable feed material into the rumen (rumen drinker) rather than the abomasum.

Partial or total parenteral nutrition might be necessary for animals that refuse to eat or that cannot tolerate assisted enteral feeding. However, total parenteral nutrition is expensive and difficult to continue long-term in horses or even impossible in ruminants.

Efforts should be made to determine an etiological diagnosis once malassimilation has been confirmed so that an accurate prognosis can be given and appropriate therapy prescribed.

Most conditions causing malassimilation in adult large animals warrant a poor prognosis, and treatment is commonly unsuccessful. However, parasitic infection of the bowel or its blood supply can respond to anthelmintic therapy. Occasionally, a non-neoplastic infiltration of the bowel responds to corticosteroids; however, the response may be transient. Calves, foals, and kids with lactase deficiency can respond well to supportive care and dietary management.

The prognosis for horses with malabsorption due to inflammatory bowel disease is poor; most reported cases have been fatal.

Malassimilation in production animals results in decreased yield and subsequent culling, often without the problem being diagnosed.

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