Hyperlipemia and Hepatic Lipidosis in Large Animals

Poor feed quality or decrease in feed intake, particularly during a period of high-energy requirement (eg, pregnancy, systemic disease), may result in hyperlipemia syndrome. Hyperlipemia is seen most commonly in ponies, miniature horses, and donkeys and less frequently in standard-size adult horses. Pathogenesis of hyperlipemia is complex, with a negative energy balance triggering excessive mobilization of fatty acids from adipose tissue, leading to increased hepatic triglyceride synthesis and secretion of very-low-density lipoproteins, concomitant hypertriglyceridemia, and fatty infiltration of the liver. The biochemical etiology of hyperlipemia is overproduction of triglyceride rather than failure of triglyceride catabolism.

Onset of disease is associated with stress, decreased feed intake, fat mobilization and deposition in the liver, and overproduction of triglycerides, which may be precipitated by insulin resistance. In ponies, hyperlipemia is usually a primary disease process associated with obesity, pregnancy, lactation, stress, or transportation. Hyperlipemia may develop secondary to any systemic disease that results in anorexia and a negative energy balance. Secondary hyperlipemia is more common than primary hyperlipemia in miniature breeds. Hyperlipemia secondary to a systemic disease can be seen in horses of any age and in any condition. Female, stressed, and obese donkeys are at highest risk of developing hyperlipemia regardless of pregnancy status. Hyperlipemia is most commonly seen in winter and spring.

Alpacas and llamas may develop hyperlipemia and ketonuria in late stages of gestation or secondary to disease states. Adult camelids and even young crias are susceptible to hepatic lipidosis during disease states.

Fatty liver disease is a complex metabolic disease seen primarily in dairy cattle. See Fatty Liver Disease of Cattle.

In goats, hepatic lipidosis has been associated with cobalt deficiency. Histologic lesions are consistent with those characteristic of white liver disease in sheep.

Signs of hyperlipemia are nonspecific and variable and may not relate to loss of liver function. They include lethargy, weakness, inappetence, decreased water intake, and diarrhea. Often, there is a history of prolonged anorexia, rapid weight loss, and previous obesity. Emaciation, ventral edema, colic, and trembling may be seen. Serum biochemical values and coagulation testing in miniature horses and ponies with hyperlipemia indicate that impaired hepatic function is common. Affected animals have grossly opalescent blood and lipemic plasma. The blood concentrations of all lipids are increased, especially triglycerides, nonesterified fatty acids, and very-low-density lipoproteins. Donkeys have higher plasma triglyceride concentrations than do other equids. Hypoglycemia is a common finding in ponies but not in miniature horses with hyperlipemia. Total bile acid concentration and BSP^® clearance are often normal, but BSP clearance may be prolonged in some animals. Activated partial thromboplastin time and one-stage prothrombin time may be prolonged. AST and sorbitol dehydrogenase (SDH) may be normal or increased. Increased creatinine, isosthenuria, and metabolic acidosis may develop secondary to renal disease. BUN and creatinine concentrations are variable. Anorexia can lead to hypokalemia. Animals may become neutropenic with increased band neutrophils. Concurrent pancreatitis has been reported.

Prolonged increase in serum triglyceride concentrations is associated with lipid accumulation in the liver, kidneys, myocardium, and skeletal muscles, impairing function of these organs. The liver and kidneys become friable, and death may result from acute hepatic rupture.

Alpacas and llamas may develop hyperlipemia and ketonuria in late stages of gestation, during lactation, or secondary to disease states. Nonspecific clinical signs include lethargy, anorexia, and recumbency. Hypertriglyceridemia, hypercholesterolemia, increased SDH activity, metabolic acidosis, azotemia, and ketonuria may be seen. Secondary renal failure may develop. Camelids appear to be similar to both horses (hyperlipidemia) and cattle (ketosis) in their response to severe energy imbalance in late gestation. Hepatic lipidosis is the most common liver disease found in llamas and alpacas. Camelids of various ages and energy requirements are susceptible, and the pathogenesis is multifactorial. Common clinical findings include anorexia; weight loss; high concentrations of bile acids, nonesterified fatty acids, and β-hydroxybutyrate; high activities of γ-glutamyl transpeptidase or transferase (GGT) and AST; and hypoproteinemia.

Clinical diagnosis of hyperlipemia is often based on the signalment, history, clinical signs, and gross observation of a white to yellow discoloration of the plasma in equids. Plasma or serum triglyceride >500 mg/dL confirm the diagnosis. Cholesterol may be increased, indicating an increase in lipoprotein. Nonesterified fatty acids, very-low-density lipoproteins, and β-hydroxybutyrate (camelids) may also be increased. Laboratory evidence of hepatic dysfunction is supportive.

Correction of the underlying disease, IV fluids, and nutritional support are the most essential factors in treatment of hyperlipemia. Nutritional support reverses the negative energy balance, increases serum glucose concentrations, promotes endogenous insulin release, and inhibits mobilization of peripheral adipose tissue. A polyionic electrolyte solution containing supplemental dextrose (50 g/hr/450 kg) and potassium (potassium chloride at 20–40 mEq/L) should be given IV to hypoglycemic, hypokalemic horses. Glucose administration may cause refractory hyperglycemia in animals with insulin resistance. Glucose concentrations, renal function, urine output, and serum electrolyte concentrations should be monitored closely. IV fluids and glucose must be administered cautiously in camelids with hepatic lipidosis, because many are already hypoproteinemic, and glucose regulation in camelids is often challenging. Intermittent bolus administration of polyionic IV fluids rather than continuous infusion may more effectively maintain hydration without exacerbating existing hypoproteinemia.

Voluntary enteral nutrition is preferred if the affected animal will consume adequate quantities of nutritionally valuable feeds; however, most will not. Frequent feedings of a high-carbohydrate, low-fat diet are preferred. In animals with inadequate oral intake, supplemental tube feeding is necessary. Commercially available high-calorie enteral formulations provide adequate short-term nutritional support. Recipes for home-prepared, liquid tube-feeding diets for horses are also available. Small frequent feedings are required to meet caloric needs without overloading the GI tract. Animals should be observed after each feeding for signs of abdominal discomfort. Body weight, total fluid intake, and fecal consistency should be monitored daily. In animals that survive, hyperlipemia usually resolves in 5–10 days, but enteral feeding should be continued until voluntary feed intake is adequate. Enteral nutritional supplementation and treatment of the primary disease often reverses hyperlipemia in miniature horses and donkeys but less frequently in ponies.

For totally anorectic horses, partial parenteral nutrition may be used. The lipid portion of the solution is omitted. Blood glucose concentration should be monitored at least twice daily to ensure that euglycemia is maintained and that substantial hyperglycemia (≥180 mg/dL) is avoided.

In camelids, partial parenteral nutrition with enteral supplementation can be used to maintain adequate energy intake and minimize further fat mobilization. Because of the distinct metabolism of camelids, parenteral nutrition products must contain higher amounts of amino acids (relative to nonprotein calories) than traditional formulations used in other species. Glucose concentrations must be carefully monitored, because camelids do not assimilate exogenous glucose well.

Exogenous insulin administration is recommended for treatment of iatrogenic hyperglycemia and hyperlipemia, especially when these conditions are resistant to more conventional therapies. Insulin decreases mobilization of peripheral adipose tissue by stimulating lipoprotein lipase activity and by inhibiting adipocyte hormone–sensitive lipase activity. The appropriate dosage of insulin to be used in horses has not been well established. When insulin is used, response to therapy, including blood glucose concentrations, must be closely monitored and the insulin dosage adjusted accordingly. Insulin administration may fail to lower serum triglyceride or glucose concentrations in hyperlipemic animals when an insulin-resistant state is present. Insulin treatment in camelids has reportedly been effective in treatment of hepatic lipidosis.

Heparin is used in treatment of hyperlipemia because it promotes peripheral utilization of triglycerides and enhances lipogenesis via stimulation of lipoprotein lipase activity. Heparin may be given IV or SC, with recommended dosages of 40–100 IU/kg, bid. Use of heparin is questionable in affected animals with increased hepatic production of triglycerides and without impaired peripheral removal of triglycerides. Heparin administration may potentiate bleeding complications and is contraindicated in animals with coagulopathies from liver dysfunction.

Nutritional supplementation to prevent hyperlipemia is indicated in miniature horses and donkeys, ponies, horses, and camelids with systemic disease associated with hypophagia and high metabolic demands.

Clinical biochemical variables are not useful prognostic indicators of survival in ponies with hyperlipemia. In most instances, survival depends on the ability to successfully treat the primary disease. Prognosis is often poor in ponies, standard-size horses, and camelids.