LIVER DISEASE, METABOLISM, AND DIGESTION IN LLAMAS AND ALPACAS

David E Anderson, DVM, MS, Diplomate ACVS
College of Veterinary Medicine
The Ohio State University
Columbus, Ohio

Significance of Liver Disease in Camelids

The incidence of liver disease in llamas and alpacas is unknown, but this disease appears to be common in North America. In a survey of llamas and alpacas admitted to the Veterinary Teaching Hospital at Ohio State University between January 1, 1993 and December 31, 1995, 19 cases of liver disease were found (Table 1). In a survey of the Veterinary Teaching Hospital at Oregon State University, 31 cases of hepatic lipidosis were found during a 7-year period (Tornquist et al 1999). Although fatty liver disease is often observed during necropsy examination of llamas and alpacas, primary liver disease has been infrequently diagnosed.

Metabolism

Llamas and alpacas have the metabolic demands of milk, neonate, and fiber production. North American breeders attempt to achieve a birthing interval of 12.5 months for llamas and alpacas. Thus, females are usually bred within 30 days after birthing. Also, the fiber coat is harvested annually. Thus, concurrent lactation, gestation, and fiber coat growth occur. This requires significant protein and energy, placing the animal at risk for metabolic decompensation similar to that seen in sheep or goats having multiple fetuses or dairy cattle of high lactation potential.

Llamas and alpacas are unique compared with true ruminants. Forestomach production of volatile fatty acids (acetate, propionate, and butyrate) are produced in similar concentration as ruminants, but plasma concentration of ketone bodies (b-hydroxybutyrate and acetoacetate) are lower and blood glucose concentrations are higher than that of domestic ruminants (Vallenas et al 1971). Hepatic ketogenesis appears to be the primary mechanism for ketone body production (similar to dogs and humans), where as alimentary ketogenesis is the primary mechanism in ruminants (Emmanuel 1980; Emmanuel et al 1978). Also, llamas and alpacas absorb greater amounts of glucose from the forestomachs compared with true ruminants. These metabolic differences suggest that camelids have greater gluconeogenic and lesser ketogenic pathways compared with true ruminants. Thus, llamas and alpacas manifest disturbances of energy metabolism similarly to both ruminants (ketosis) and monogastric species (hyperlipidemia) (Anderson et al 1994).

Although llamas and alpacas are more efficient in digestion of poor quality roughage, they are similar to sheep in the digestion of high quality roughage (Dulphy et al 1997, Dulphy et al 1998). When llamas and sheep were offered hay, hay and barley, hay and soybean meal, or hay and soybean meal and barley, llamas had higher dry matter, organic matter, and neutral detergent fiber digestibilities compared with sheep (Duplhy et al 1997). Intake and digestibility was positively related to the crude protein content of the roughage, but negatively related to the neutral detergent fiber content (Dulphy 1998). Efficiency of digestion may be related to greater stability of pH in the first two forestomach compartments and to greater cellulolytic activity (Dulphy 1997). Llamas appear to be able to efficiently buffer acidic solutions within the first forestomach chamber particularly when high concentrations of volatile fatty acids are present (Rubsamen and Engelhardt 1978).

When llamas were compared with sheep for forage selection, llamas selected a higher proportion (48 to 75 %) of coarse forages compared with sheep (37 to 68 %) (Genin et al 1994). Also, sheep selected a greater proportion (25 to 45 %) of soft herbs and grasses compared with llamas (8 to 25 %). Thus, feeding practices in North America may contribute to placing llamas and alpacas at a disadvantage to cope with metabolic deficits. Owners frequently feed pelletized feed or grain mixes at a rate of 20 to 40 % of daily dry matter intake. This constant, ready source of energy may alter the forestomach microflora and down regulate hepatic enzyme pathways. The effect of this would be to loose the inherent efficiency of the forestomach digestive process of camelids and, therefore, make them less able to cope with abrupt changes in metabolic function.

Maintenance energy requirement

Russel and Redden (1997) studied the effects of nutrition on fiber production. In that study, alpacas were fed two different diets in a crossover design model. Diets were formulated to provide 0.67 x MER (maintenance energy requirement) or 2.0 x MER. The authors assumed MER to be 0.44 MJ / kg M0.75 which had been used in sheep models. Alpacas fed 0.295 MJ / kg M0.75 (0.67 x MER) lost weight during the study period at a rate of ®¢ 69 g/day. Fiber growth rate was approximately 186 um/day. Alpacas fed 2.0 x MER gained weight at a rate of 70 g/day. Fiber growth rate was 223 um/day. Thus, 0.44 MJ / kg M0.75 / day seemed to be a reasonable estimate of MER. In other studies, Newman and Paterson (1994) estimated the MER for alpacas at 0.276 MJ / kg M0.75 / day and von Engelhardt and Schneider (1977) estimated Mer for llamas at 0.256 MJ / kg M0.75 / day. Thus, variations in MER estimates exist and may be related to different foodstuffs, trace mineral composition, and environmental conditions. The effect of concentrate feeding on MER was demonstrated when Carmean et al (1992). Llamas were fed a diet containing 50 % oat hay and 50 % pelletized concentrate feed at a rate of 1.6 % body weight as dry matter per day. The authors calculated MER for these llamas at 0.353 MJ / kg M0.75 / day. This provides further evidence that digestive efficiency may be lower with higher quality feeds.

Water is a vital nutrient for digestion and metabolic processes. Marcilese et al (1994) determined water turnover in llamas. In winter, body water was estimated as 659 ml/kg with a daily water turnover of 116 ml/ kg0.82. In spring and summer, daily water turnover was increased. Daily water turnover in lactating llamas in summer was approximately 396 ml/kg0.82 and that of non-lactating llamas was 260 ml/ kg0.82.

Liver Disease Other than Hepatic Lipidosis

Although hepatic lipidosis is the most common liver disease found in llamas and alpacas (Tournquist et al 1999; Anderson et al 1994; Jonsson and Rozmanec 1997), bacterial, viral (Galbreath et al 1994), and fungal (Fowler et al 1992; Muir and Pappagianis 1982) hepatopathy, intoxication (Junge and Thornburg 1989), neoplasia (Potter and Young 1994; Cebra et al 1995), and parasite migration (liver fluke) also have been documented. Cholangiohepatitis may be most often caused by Salmonella or E coli, but Listeria sp. and Clostridium sp. (Clostridium perfringens, Tyler et al 1996; Clostridium novyi, DE Anderson, unpublished data) infections also have been diagnosed. Cholangiohepatitis is assumed to be caused by reflux from the duodenum via the biliary system and may be associated with enteritis or disturbances of intestinal motility. Llama adenovirus infection has been reported to cause pneumonia and hepatitis. Fungal hepatitis has been reported to occur as part of systemic coccidioidomycosis resulting in pyogranulomas in the liver parenchyma. Toxic hepatopathy has been associated with copper toxicosis and was associated with diets containing a copper:molybdenum ratio of approximately 16.6:1. Hepatic necrosis associated with halothane anesthesia has been reported in one alpaca (Groom et al 1995). Reported cases of hepatic neoplasia affecting llamas and alpacas include lymphosarcoma, hemangiosarcoma, and adenoma (Cebra et al 1995, Potter and Young 1994).

Anamnesis

Llamas and alpacas with liver disease usually demonstrate vague clinical signs. These signs may include apparent depression, lethargy, increased periods of recumbency, and decreased appetite. Occasionally diarrhea or abdominal discomfort are observed. Often, owners report that the animal became separated from the herd or refused to eat their daily concentrate feed ration. Frequently, environmental changes are reported by the owner and may include changes in diet, addition or removal of herd mates, traveling to shows, sales, or to a new farm, recent breeding activity, and importation and quarantine. Other risk factors may include obesity, emaciation, hyperthermia, and hypothermia.

Physical Examination

A thorough physical examination is required to rule-out common causes of illness in camelids such as: endo- and ecto-parasites, gastrointestinal disturbance, ulceration of the forestomach compartments, malnutrition, social hierarchy stress, dental problems (e.g. tooth root abscess, malocclusion), neurologic disease (meningeal worm, trauma, infection), and pneumonia. Body condition scoring is done to determine appropriateness of body weight (Hilton et al 1998). Rectal temperature, heart rate and rhythm, respiratory rate and pattern, forestomach motility frequency and pattern, fecal consistency and color, urine color and clarity, peripheral lymph node palpation, and oral examination are the minimum data base. Clinical signs of acute, severe abdominal pain may be seen in camelids suffering from rapidly progressive liver disease. These patients must be accurately differentiated from surgical diseases because the stress of surgery (immunosuppression) and general anesthesia (decreased hepatic blood flow) may be detrimental to patients with liver disease. Advanced liver disease may result in hepatic encephalopathy. Clinical signs observed during hepatic encephalopathy include ataxia, blindness, seizures, head pressing, opisthotonus, recumbent, and death.

Diagnostic Tests

Often, clinical signs of liver disease in llamas and alpacas are vague. Therefore, complete blood cell count and serum biochemistry analyses are recommended for those animals demonstrating abnormal clinical signs without an apparent cause. Age and species adjusted normal values for selected hematology (Table 3) and serum biochemistry (Table 4) variables should be used.

Although serum activity of AST, ALP, and ALT may be elevated in llamas and alpacas with liver disease, these enzymes are inconsistent in the magnitude of elevation relative to the severity of disease. Serum activity of SDH is a more reliable indicator of liver parenchymal disease and serum activity of GGT is a more reliable indicator of biliary tract disease in llamas and alpacas. Serum activity of AST and CPK reflect muscle injury and may provide some assessment of how long and how often the camelid has been recumbent. Creatinine and BUN allow evaluation of hydration and renal function. These should be interpreted with concurrent assessment of urine specific gravity. Rising BUN and creatinine despite supportive therapy may indicate renal lipidosis and is an indicator of poor prognosis for survival. Cholesterol and b-hydroxybutyrate are useful indicators of fat mobilization. Serial evaluation is most useful as an aide in assessment of response to treatment.

CBC is evaluated for evidence of bacterial infection and protein loss. The presence of hypoproteinemia is common in llamas and alpacas affected with liver disease. This may be the result of forestomach ulcers, renal losses, decreased hepatic production, or extravascular loss associated with increased vascular permeability. Increasing PCV concurrent with a decreasing T.P. is an indicator of a grave prognosis.

Forestomach fluid analysis should be done to rule-out digestive disturbances (e.g. grain overload). Fluid from the first forestomach compartment may be obtained via orogastric intubation or by percutaneous aspiration (Navarre et al 1999). Fluid analysis should include pH, bacterial fermentation capacity assessed by new methylene blue reduction test, and microscopic examination for density, diversity, and activity of protozoa. A fecal occult blood test should be performed to aid in diagnosis of bleeding into the gastrointestinal tract.

Investigation of Etiology

Diagnosis of the cause of liver disease in camelids can be an exercise in frustration, and histopathologic examination of the liver tissue is necessary for accurate diagnosis. Percutaneous liver biopsy is the procedure of choice for obtaining diagnostic specimens (Wells et al 1997, Anderson et al 1998). A modified Lee-White clotting time (whole blood added to a clean glass tube containing no preservatives; normal < 10 minutes, usually < 5 minutes) should be determined before liver biopsy is performed. Liver biopsy samples may be used for histopathology, virology, bacteriology, and toxicology (element analysis). If possible, viral cultures should be plated on llama origin cell lines (Mattson 1997). Recently, a picornavirus has been identified from llamas suffering diabetes mellitus and hepatic lipidosis (Stehman 1997). This has been associated with insulin dependent diabetes mellitus and eventual ketoacidosis and death. Paired serum titers for picornavirus and llama adenovirus should be done to rule-out active viral infection. A thorough herd evaluation should be done to rule-out subclinical causes of stress or metabolic disturbance. This should include fecal examination for parasite eggs, diet analysis, and water analysis. If warranted, mineral element analysis should be done using a representative sample of the herd.

Treatment Strategy

Symptomatic treatment is directed at supportive care unless a more specific diagnosis can be determined. Antibiotics and anti-inflammatory drugs may be indicated for treatment of suspected bacterial hepatitis or secondary infections. Administration of glucocorticoids, particularly dexamethasone, is contraindicated in llamas and alpacas with liver disease. One current theory is based on steroid interference with the action of insulin on hepatocytes. Fluid therapy (IV or PO), parenteral nutrition, and vitamin and mineral supplementation are useful for treatment of hepatic lipidosis. Intravenous fluids must be administered cautiously because camelids readily become profoundly hypoproteinemic with liver disease. Intermittent bolus administration of IV fluids, rather than continuous infusion, has proven to be useful in maintaining hydration without exacerbation of hypoproteinemia. Voluntary consumption of water containing electrolytes is preferable to IV administration in most cases. Ulcer prophylaxis should be used to prevent development of bleeding ulcers. Proton pump inhibitors such as omiprazole (2 mg/kg body weight, PO, q12h) are preferred because H-2 receptor blocking drugs such as cimetidine have little effect on acid production in llamas and alpacas (Drew et al 1992). Sucralfate (1 gram per 30 kg, PO, q12h) may be useful when ulcers are present, but this drug is not expected to have any preventative effect. If appetite is suppressed, transfaunation (0.5 to 1-liter rumen fluid from a cow) is a potent appetite stimulant. Other appetite stimulant options include B complex, lose dose butorphanol (0.02 mg/kg, S.C.), and offering a variety of feeds including frequent grazing. Camelids may become recumbent when isolated in a stall. These animals should be walked, grazed, and a companion animal kept with them to prevent this cycle from starting. Use of a companion animal is beneficial to prevent apparent depression commonly associated with isolation from the herd, but the companion should be one with which the animal is familiar.

Prevention of Liver Disease

Extensive investigations performed at Ohio State University of camelids affected with liver disease have usually identified a common source of stress. These have included malnutrition, parasitism, changes in management, environment, or feed sources, or changes in hierarchy structure. The diversity and theoretical nature of these risk factors make recommendations for prevention difficult. Probably, the most significant factor in the prevention of liver disease is to prevent sustained stress. A detailed review of on-farm activities should be done and should include assessment of all foodstuffs including grass, hay, trace mineral supplement, feed supplement, and water source (Waldridge and Pugh 1997).

Table 1.

Table 2.

Table 3.

*Fowler et al 1989

Table 4.

*Fowler et al 1989
†Simons et al 1993
‡Andreasen et al 1998
**Anderson, unpublished data, Ohio State University, 1999.

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