Malassimilation is a defect in the ability of the GI tract to incorporate nutrients into the body either due to malabsorption or maldigestion. Malabsorption is the failure of passage of nutrients from the lumen of the bowel into the bloodstream, while maldigestion is the failure of intraluminal degradation of dietary constituents due to a defect in pancreatic exocrine function, bile acid content, or brush border enzymes. Maldigestion alone is an infrequent cause of malassimilation in large animals. Maldigestion syndromes are uncommon in horses compared with other domestic species. The equine pancreas secretes only low concentrations of digestive enzymes and probably plays a small role in nutrient digestion. Some disease processes involve both maldigestion and malabsorption, such as is seen in young animals with lactase deficiency. Diseases of malabsorption are much more common in horses than are diseases of maldigestion.
Etiology and Pathogenesis
Many diseases, by altering the normal absorptive mechanisms of the small intestine, induce a malabsorption syndrome. In horses, these include the following: 1) 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); Lawsonia intracellularis (weanling foals, yearlings); intestinal ischemia and damage due to migration of Strongylus vulgaris larvae, small strongyles, or Strongyloides westeri (foals) infection; cryptosporidia; postinfarction inflammation; amyloid Aassociated gastroenteropathy; multiple abscessation in the bowel; tuberculosis; histoplasmosis; intestinal Rhodococcus equi infection; invasive enterocolitis (Salmonella spp); 2) biochemical or genetic abnormalities—congenital or acquired lactase deficiency (lactose intolerance), dietary-induced enteropathy, monosaccharide transport defect, pancreatic exocrine insufficiencies; 3) diseases causing inadequate absorptive area—villous damage or atrophy due to viral infection (rotavirus, coronavirus) or bacterial enteritides in foals, cryptosporidia, intestinal resection; 4) cardiovascular disorders—congestive heart failure, intestinal ischemia; 5) lymphatic obstruction—lymphosarcoma, mesenteric lymphadenopathy, intestinal lymphangiectasia, abscessation, thoracic duct obstruction; and 6) miscellaneous—drug-induced, heavy metal toxicosis, zinc deficiency.
Malabsorption syndromes in cattle are poorly documented but likely are seen most frequently in calves with diarrhea. Diseases that cause malabsorption syndromes in ruminants and swine include viruses (rotavirus, coronavirus), cryptosporidia, local or generalized ischemia, protein malnutrition, small-intestinal resection (short-bowel syndrome), congestive heart failure, lymphatic obstruction, parasitism (trichostrongylosis of sheep and cattle), tuberculosis, and Johne's disease in ruminants and proliferative enteropathy (Lawsonia intracellularis) in swine. Oral antibiotics may alter absorptive epithelial cells and cause an imbalance in GI tract flora. Treatment with high doses of ampicillin, neomycin, or tetracycline significantly decreases and delays glucose absorption during oral glucose tolerance tests in calves.
Camelids are affected by many of the same conditions that cause malabsorption syndrome in ruminants. Coronavirus is particularly a problem in young crias. Eimeria macusaniensis, during either the prepatent or patent phase of infection, may result in weight loss, hypoproteinemia, and severe debilitation in affected young and adult camelids.
Maldigestion syndromes are uncommon and poorly understood in large animals. They may be due to alterations in gastric function or activity of rumen microflora, abnormal bacterial proliferation in the small intestine, or a decrease or lack of small-intestinal brush border enzyme activity (lactase deficiency). Less likely causes include drug-induced alteration in secretion or excretion of bile salts (induced by drugs or by hepatic or intestinal disease), or deficiency or inactivation of pancreatic lipase. Changes in bile salt concentration may not impair digestion in the adult herbivore but may exacerbate diarrheal states in milk-fed neonates. Surgical resection or bypass of the distal small intestine may facilitate bacterial overgrowth with associated bile salt abnormalities.
Lactose is a disaccharide composed of glucose and galactose. The small-intestinal brush border enzymes of foals and calves include lactase, which catalyzes the degradation of lactose into its component monosaccharides that are then absorbed. Primary lactase deficiency is inherited as an autosomal recessive trait in humans, but its occurrence and the mode of inheritance in large animals is poorly documented. Acquired or secondary lactase deficiency is more common. It is seen in foals, calves, and possibly 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 result in some degree of lactase deficiency due to loss of lactase-secreting epithelial cells. Morphologic changes may include partial villous atrophy, crypt hyperplasia, and infiltration of the lamina propria. Osmotic diarrhea in lactase-deficient foals and calves occurs due to increased undigested/unabsorbed nutrients entering the lower bowel, increased bacterial fermentation, increased concentration of osmotically active particles, and retention of water and electrolytes in the intestine.
Malabsorption is commonly seen in animals with GI disease. It may arise from structural or functional disorders of the small intestine or be multifactorial. Often, malabsorption is seen concurrently with enteric protein loss. Either may cause loss of nutrients in the feces and weight loss. Malabsorption is not synonymous with diarrhea in any species, although diarrhea may be a feature. Function of the large intestine may be secondarily altered due to changes in the small intestine. Transient diarrhea may result as abnormal quantities of bile acids, fatty acids, and carbohydrates enter the large bowel in ileal effluent. These substances can directly or indirectly enhance secretion or decrease absorption rates.
Malabsorption of nutrients may result from insufficient absorptive surface area, an intrinsic defect in the mucosal or submucosal morphology of the intestinal wall, or lymphatic obstruction. Rotavirus infection in younger animals may 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 may have similar effects. 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 may interfere with the ability of the intestinal wall to absorb nutrients. Inefficient absorption also may develop due to 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 that are normally present on the microvilli are not well recognized in domestic animals. However, neonates and ruminants have low levels of maltase, and ruminants lack sucrase. In most species, lactase levels decline with age.
Clinical signs are variable, depending on the underlying disease condition and the presence or absence of concurrent protein-losing enteropathy. A negative energy balance, weight loss, and possibly low serum protein concentrations characterize malassimilation syndromes. Chronic weight loss or reduced growth rate is the predominant clinical sign. Frequently, enteric protein loss may also be present and prove more debilitating than malabsorption.
Appetite of affected animals may be normal, increased, or decreased. Polyphagia may be seen due to failure of assimilated nutrients to stimulate satiety centers. More commonly with small-intestinal malabsorption, hypophagia or anorexia is present because the primary disease process causes loss of appetite. Feces are frequently normal in consistency and volume. Diarrhea may be present but is not a consistent feature. In mature animals, small-intestinal disease may be extensive before diarrhea develops because the colon can compensate and absorb the increased fluid load. In adult horses and ruminants, diarrhea indicates large-intestinal disease. In young animals in which colonic function is not yet fully developed, diarrhea is seen with small-intestinal and large-intestinal disease.
Clinical signs may also include poor condition, muscle wasting, exercise intolerance, normal or lethargic attitude, and variable thirst. Vital signs are usually normal until late in the disease. Pyrexia may be seen with inflammatory and neoplastic conditions. Abdominal pain may result from bowel inflammation, mesenteric or mural abscesses, 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 immunologic reactions, particularly with inflammatory bowel disease. Skin lesions seen with malabsorption-related dermatosis include a thin hair coat, patchy alopecia, and focal areas of scaling and crusting that are often symmetrically distributed.
Foals and calves with lactose intolerance commonly have diarrhea, poor growth rate, and an unthrifty appearance. Some may experience flatulence, mild abdominal discomfort, or bloating after intake of milk. In young animals with acquired lactase deficiency, clinical signs (diarrhea, dehydration, weight loss) and clinicopathologic alterations (acidosis, hypoglycemia, electrolyte abnormalities) may be indistinguishable from those of the primary enteropathy. The animal's condition may improve quickly, and diarrhea may resolve when milk is withdrawn or replaced with enzymatically treated milk.
The carcass is thin to emaciated, depending on the duration and severity of the malassimilation disease. Specific lesions depend on the primary underlying disease process. Overt signs of malabsorption do not always correlate with gross and histopathologic changes, emphasizing the importance of functional disorders.
Small-intestinal malabsorption cannot be determined by clinical examination or by routine laboratory data. More common causes of weight loss must be excluded before a diagnosis of a malassimilation syndrome can be made. Determination of the primary underlying disease process is also necessary to establish an appropriate treatment regimen and prognosis.
A complete history should focus on duration of condition, precipitating factors, nutritional history, deworming and routine health care program, previous or concurrent diseases, as well as the number, age, and proximity of other affected animals. A thorough physical examination is performed to correlate physical findings with clinical signs and history. 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, fibrinogen, and serum chemistry panel aid in determining the animal's general health status; 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. Plasma protein electrophoresis, fecal pH, culture, leukocyte count, and immunologic studies may be indicated. Intracolonic fermentation of malabsorbed carbohydrates will often reduce 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 (eg, as in liver disease). Standard and contrast radiography of the bowel may be feasible in foals and small ponies. Ultrasonography is useful in determining bowel wall thickness and intestinal motility, as well as the presence of excess fluid, 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. For absorption tests to be diagnostic, the intestinal disorder either must be diffuse or must affect the delivery to and transit through the small intestine. An abnormal or flattened absorption curve is suggestive of small-intestinal dysfunction. Gastroscopy to eliminate the presence of lesions in the stomach (granulomas, tumor, ulcers) and duodenum or retention of ingesta should be done before absorption tests are performed, because either may cause a delay or flattening of the absorption curve.
Although absorption tests may indicate malassimilation is present, an etiologic diagnosis requires a biopsy of intestinal mucosa and possibly lymph node. In some cases rectal biopsy may reveal focal or diffuse inflammatory infiltration. Culture of the biopsy and fecal examination for leukocytes and epithelial cells may confirm the presence of salmonellae or other invasive organisms. In many cases, laparoscopy or exploratory celiotomy is required to obtain the intestinal or lymph node biopsy. Surgery may not be advisable in a debilitated animal because wound healing is poor, and dehiscence is a potential problem. If undertaken, intestinal and lymph node biopsies should be obtained for culture, histopathology, enzymology, and immunology. 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 the d-glucose and d-xylose absorption tests. These tests may be useful in assessing small-intestinal function in preruminant calves, foals, crias, and mature horses. Oral carbohydrate tolerance studies are not useful in ruminants because the sugar is degraded in the rumen. 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 influenced by cellular uptake and metabolism of glucose, as well as by intestinal absorption. The d-xylose absorption test more directly measures intestinal absorptive capacity and is not influenced by endogenous factors and intestinal enzymatic activity. However, d-xylose is more expensive, and availability of both xylose and laboratories that can perform plasma xylose determinations is limited.
Glucose or galactose may inhibit the absorption of d-xylose; therefore, fasting is necessary before the test is performed. The protocols of both tests require prolonged fasting, which may be deleterious to sick young foals and calves. The results of both tests are also affected by gastric emptying rate, small-intestinal transit time, and the animal's diet and length of fasting period before testing. The shape of the d-xylose absorption curve is influenced by renal clearance, hypoxia, anemia, systemic bacterial infections, and IgG concentrations in foals. Age of the animal being evaluated also affects absorption and digestion of glucose, lactose, and xylose. Therefore, the control animals must be within a few days of age of the affected animal if reference ranges are not available for its age group.
A delayed peak in the absorption curve of both d-glucose and d-xylose tests may result from delayed gastric emptying resulting from hypertonicity of the glucose or xylose mixture, excitement, pain, retained gastric contents, changes in GI transit time and motility, or partial obstruction. A flat absorption curve may be seen in a horse with normal absorptive capacity due to a transient decrease in intestinal blood flow or to bacteria in the lumen of the small intestine that metabolize the test sugar. Xylose rapidly equilibrates with many body fluids (eg, ascites), which lowers the blood concentration of xylose and may give a flat curve. Indications for an oral d-xylose absorption test in foals, calves, and possibly crias include persistent diarrhea not attributable to infectious agents, poor growth despite normal intake, and other signs of maldigestion (repeated episodes of gas colic, bloating, ileus).
d-Xylose Absorption Test
This test measures absorptive capacity of the small-intestinal mucosa because functional enterocytes actively transport xylose across the mucosa and into the bloodstream. Subnormal absorption supports a diagnosis of malabsorption. Age and diet also affect xylose absorption in normal horses. Foals <3 mo old have a higher peak concentration of xylose after administration than adults. Adult horses maintained on a high-roughage, low-energy diet have a higher peak concentration of xylose after administration than those fed a high-energy diet. Food deprivation can alter d-xylose absorption in horses without overt GI tract disease. This effect must be considered when interpreting results in horses that are anorectic regardless of cause.
d-Xylose (0.5–1 g/kg in a 10% solution) is administered via nasogastric tube to a horse that has been fasted overnight (18–24 hr). Heparinized venous blood samples are collected before xylose administration (time 0) and at 30-min intervals afterward for 4 hr (±6 hr sample). Expected peak values (20–25 mg/dL) should occur between 60 and 120 min after dosing. The normal curve should have a bell shape or inverted V shape with a definable peak plasma xylose concentration 1–2 hr after administration. Peak absolute plasma values should be ≥15 mg/dL above baseline values in normal horses.
d-Glucose Absorption Test
Glucose absorption curves are steeper in pasture-fed horses than in those fed a higher energy ration. Lower peak values are seen in horses on a high-concentrate ration. The length of the pretest fast influences the absorption curve. Prolonged fasting may delay or decrease peak glucose concentration, thus giving a false-positive result. In two studies, >90% of adult horses with evidence of “total” glucose malabsorption had severe infiltrative lesions of the small intestine. The majority of horses (18/25) classified with “partial” glucose malabsorption also had obvious pathologic abnormalities of the small intestine.
Performance of the d-glucose absorption test is similar to that of the d-xylose absorption test except samples are collected into sodium fluoride tubes. In normal horses, blood glucose concentrations should peak 90–120 min after administration. This peak should be >85% above the resting glucose level. Reportedly complete malabsorption is defined as a peak <15% above resting concentrations; partial malabsorption is defined as a peak 15–85% above resting levels. One of the major disadvantages to the oral glucose absorption test is that using the conventional protocol, sampling is over a 6-hr period. One reported modified protocol requires only 2 test samples at 0 and 120 min after administration. This modification reportedly did not affect the reliability of the test result.
Oral Lactose Tolerance Test
Diagnosis of acquired lactase deficiency is usually presumptive based on history, clinical signs, and confirmation of presence of associated pathogens. Definitive diagnosis can be made with an oral lactose tolerance test. Lactose is hydrolyzed within the brush border of the small-intestinal enterocytes by lactase to constituent d-glucose and galactose before it is absorbed. Oral lactose tolerance testing is directed specifically at assessing whether lactase activity is present or not. Adult horses (>3 yr old) are lactose intolerant, and the test is unsuitable for ruminants. The oral lactose tolerance test is of value in evaluating young foals and preruminant calves with diarrhea or poor growth. Lactose intolerance has been documented in foals, calves, and kids.
An oral lactose tolerance test does not distinguish maldigestion from malabsorption and requires fasting for several hours. Feeding enzymatically treated milk to animals suspected of being lactose intolerant may be tried before subjecting animals to the lengthy fast (12–18 hr) required before this test is performed. Before performing an oral lactose intolerance test, grain and hay should be withheld from the dam and foal for 18 hr. The calf or foal should be prevented from nursing (muzzled) for ≥4 hr before administering d-lactose at 1 g/kg as a 20% solution via nasogastric tube; the muzzle should be kept in place for the duration of the test. Blood samples are collected into fluoride oxalate tubes for determination of blood glucose concentrations at 30 min and immediately before and at 30-min intervals for 3–4 hr after dosing. Blood glucose concentration should be double that of the resting values within 60–90 min of lactose administration. Peak glucose concentrations should be ≥35 mg/dL higher than baseline in healthy foals. Abnormal results suggestive of lactose intolerance include a delayed, prolonged, or lack of rise in blood glucose concentration from baseline.
Lack of an appropriate rise in blood glucose concentration after lactose administration may be due to maldigestion or malabsorption. Therefore, if the lactose tolerance test is abnormal, a d-glucose or d-xylose absorption test should be performed to determine whether malabsorption or maldigestion alone is the problem. Casein hypersensitivity is distinguished from lactose intolerance by assessing the animal's response to enzymatically treated and untreated milk. Definitive confirmation of lactase deficiency is through direct measurement of mucosal lactase activity in the intestinal tissue. However, this is rarely undertaken in the clinical setting because a surgical biopsy of the mucosa is required.
A hydrogen breath test has also been described for detection of carbohydrate malabsorption in horses. In a clinical study, diseased horses showed higher fasting breath hydrogen levels than did normal horses. Usefulness of this test in clinical practice is yet to be determined.
The etiology of the primary underlying disease process must be determined before specific therapy can be initiated. Specific therapy for most causes of malassimilation is not available, except for lesions due to parasite damage. Larvacidal dewormings with ivermectin, moxidectin, or high-dose fenbendazole may be corrective. Anti-inflammatory agents (eg, NSAID, corticosteroids) may also be beneficial in decreasing the inflammatory response within the affected bowel.
Malabsorption and chronic weight loss in horses may follow viral enteritis. Sloughing of the villous tips with loss of intestinal epithelial cells results in insufficient intestinal absorptive surface for adequate uptake of nutrients from the gut. Supportive care and facilitation of nutrient absorption from the hindgut must be encouraged until the intestinal epithelium recovers and new villous cells are produced. Maturation and healing of the intestinal absorptive surfaces may 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 that can tolerate it should be fed small amounts of high-quality roughage or grain to help meet their energy needs. Although enteral feeding should be continued whenever possible, young foals and calves that will not tolerate feedings of milk or enzymatically-treated milk may benefit from short-term (<24 hr) withdrawal of milk. These animals need alternate sources of energy and nutrients such as short-term feeding (≤24 hr) 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, but their usefulness is unproven. Similarly, the usefulness of dimethyl sulfoxide in the treatment of intestinal amyloidosis is unknown. Animals with anaerobic or aerobic bacterial overgrowth as a problem may respond to antimicrobial administration. Adequate penetration of antimicrobials into inflammatory bowel lesions (Rhodococcus equi in foals and Johne's disease in ruminants) is doubtful. Successful treatment of Lawsonia intracellularis in foals has been achieved with longterm administration of antimicrobials (erythromycin, azithromycin, clarithromycin, chloramphenicol, oxytetracycline, doxycycline) and aggressive supportive care (fluids, plasma) as dictated by the animal's clinical condition. Eimeria macusaniensis infections in affected camelids may successfully be treated if diagnosed early. Treatment currently involves administration of amprolium and/or ponazuril 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-to-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 if lactase deficiency is not present. Fat may be added to the diet to enhance caloric intake. Calcium, magnesium, phosphate, zinc, copper, and iron may need to be supplemented because they are absorbed in the horse only in the small intestine. 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 with a gruel 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 may develop ruminal acidosis due to deposition of fermentable feed material into the rumen rather than the abomasum. IV feeding, using partial or total parenteral nutrition, may be necessary for animals that refuse to eat or for those that cannot tolerate force-feeding. However, parenteral nutrition is expensive and difficult to continue on a longterm basis.
Efforts should be made to determine an etiologic 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 infestation of the bowel or its blood supply can respond to anthelmintic therapy. Occasionally, a non-neoplastic infiltration of the bowel may respond to corticosteroids, but the response may be transient in some cases. Calves, foals, and kids with lactase deficiency may respond well to supportive care and dietary management. Prognosis for horses with malabsorption due to inflammatory bowel disease is poor; most reported cases have been fatal.
Last full review/revision March 2012 by Susan D. Semrad, VMD, PhD, DACVIM