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, an accumulation of lipids in the blood. Hyperlipemia occurs most commonly in ponies, miniature horses, and donkeys and less frequently in standard-size adult horses. The 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.

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. Hyperlipemia secondary to a systemic disease can occur in horses of any age and in any condition. Secondary hyperlipemia is more common than primary hyperlipemia in miniature breeds. Female, stressed, and obese donkeys are at highest risk of developing hyperlipemia regardless of pregnancy status. Hyperlipemia occurs most commonly in winter and spring, when pasture nutrition may be compromised yet caloric intake is maximal because of cold weather and late gestational requirements.

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.

Hepatic lipidosis, or fatty liver disease, is a complex metabolic disease that occurs primarily in dairy cattle. In goats, hepatic lipidosis has been associated with cobalt deficiency. Histologic lesions are consistent with those characteristic of white liver disease in sheep.

Clinical signs of hyperlipemia are nonspecific and variable and may not relate to loss of liver function. They include depression, anorexia, weakness, 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 observed. Plasma 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—especially triglycerides, nonesterified fatty acids, and very-low-density lipoproteins—are increased. Donkeys have higher plasma triglyceride concentrations than do other equids. Hypoglycemia is a common finding in ponies but not in miniature horses with hyperlipemia. The total bile acid concentration is often normal. Prothrombin time (PT) and partial thromboplastin time (PTT) may be prolonged. Sorbitol dehydrogenase (SDH) and AST activities may be normal or increased. BUN and creatinine concentrations vary. Anorexia can lead to hypokalemia. Animals may become neutropenic with increased band neutrophils. Concurrent pancreatitis has been reported rarely.

A prolonged increase in serum triglyceride concentrations is associated with lipid accumulation in the liver, kidneys, myocardium, and skeletal muscles, impairing the 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 the 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 occur. 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 beta-hydroxybutyrate; high activity levels of gamma-glutamyl transferase (GGT) and AST; and hypoproteinemia.

• Grossly abnormal fatty-looking plasma or serum

• Measurable increases in plasma lipids without grossly visible changes

Hyperlipemia, blood sample

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Courtesy of Dr. Sameeh M. Abutarbush.

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

• Treatment of the underlying condition when hyperlipemia is secondary to systemic disease

• Administration of intravenous fluids containing glucose

• Increasing dietary quality and intake

Correction of the underlying disease, administration of intravenous fluids, and nutritional support are the most essential factors in the treatment of hyperlipemia. Nutritional support reverses the negative energy balance, increases serum glucose concentrations, promotes endogenous insulin release, and inhibits the mobilization of peripheral adipose tissue. A polyionic electrolyte solution containing supplemental dextrose (7.5-9.0 g/kg/hour IV) and potassium (potassium chloride at 20–40 mEq/L IV, administered at no more than 0.5 mEq/kg/hour) should be administered 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.

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 may be 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 clinical signs of abdominal discomfort. Body weight, total fluid intake, and fecal consistency should be monitored daily. In animals that survive, hyperlipemia usually resolves in 3–10 days; however, enteral feeding should be continued, even if tapered gradually, until voluntary feed intake is adequate.

Totally anorectic horses may be treated with partial parenteral nutrition in which the lipid portion of the conventional total-parenteral-nutrition 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 do 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 treatments. Insulin decreases the mobilization of peripheral adipose tissue by stimulating lipoprotein lipase activity and by inhibiting adipocyte hormone–sensitive lipase activity. The appropriate dosage of insulin for horses has not been well established, and it depends on the type of insulin used. When insulin is administered, response to treatment, 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 the treatment of hepatic lipidosis.

Heparin is used in the treatment of hyperlipemia because it promotes peripheral use of triglycerides and enhances lipogenesis via stimulation of lipoprotein lipase activity. Heparin may be given intravenously or subcutaneously (but not intramuscularly), with recommended dosages of 150 IU/kg SQ or IV as a loading dose, followed by 125 IU/kg SQ or IV q 8-12 hours. Dosage adjustments are made based on monitoring of activated partial thromboplastin time. Use of heparin is questionable when hepatic production of triglycerides is increased and the peripheral removal of triglycerides is not impaired. 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. The prognosis is often poor in ponies, standard-size horses, and camelids.