Hyperlipemia in Miniature Horses

By Mary Boyce

 

Hyperlipemia is a syndrome characterized by negative energy balance and rapid mobilization of peripheral adipose tissue. Fatty acids infiltrate the liver and triglycerides accumulate in the plasma, resulting in elevated serum triglyceride levels and impaired hepatic function. Reduced feed intake or anorexia is usually the cause of hyperlipemia.

Hyperlipemia has been documented in miniature horses, miniature donkeys and ponies as both a primary disease process and a secondary complication of a primary systemic disease. Hyperlipemia in ponies is most frequently a primary disease associated with obesity, pregnancy, lactation, stress, and transportation. Secondarily, hyperlipemia may result from any systemic disease that produces a negative energy balance, such as enterocolitis, parasitism, gastric impaction, or colic. Clinical signs vary widely and are usually a reflection of the primary disease. The most common clinical signs are anorexia and lethargy, but weakness, ataxia, depression, diarrhea, jaundice, and ventral edema have also been noted. Prognosis for survival in miniature horses can be as low as 50% in some cases or as high as 78% in others. Because the majority of cases of hyperlipemia in miniature horses occur secondarily to primary systemic disease, the nature and severity of the primary disease is a major determinate of survival.

Most cases of hyperlipemia are associated with reduced food intake. During fasting, adipose tissue triglycerides are broken down by a hormone sensitive lipase to glycerol and free fatty acids. A significant portion of the fatty acids are taken up by the liver where they may be completely oxidized via the TCA cycle, used for ketone production, or reesterified to triglycerides. Triglycerides either accumulate in the liver or are released into the plasma as very low density lipoproteins (VLDL). In equids, triglyceride production is emphasized over ketone formation, therefore, lipemia rather than ketosis dominates the response to prolonged fasting (Naylor).

Lipoprotein lipase, also a hormone sensitive enzyme, is attached to the luminal side of capillary vessels in adipose, muscle, heart, and other tissues. Triglycerides in plasma VLDL are hydrolyzed to fatty acids and glycerol which are transported into peripheral tissues. Lipoprotein lipase activity in hyperlipemic ponies has been found to have twice the activity of nonlipemic ponies (Watson and Burns), so the excess serum triglyceride concentration in hyperlipemia appears to be the result of increased hepatic production rather than impaired function of lipoprotein lipase.

A prolonged increase of serum triglyceride concentration is associated with lipid accumulation in the liver, kidney, myocardium, and skeletal muscles, and this impairs the function of these organs. Postmortem examination of hyperlipemic miniature horses has revealed fatty infiltration of the liver and kidneys. These organs appear pale or swollen and are often greasy in texture. In severe cases of hyperlipemia, the liver is ruptured. Lipemic changes may also be seen in unclotted blood. Nearly all blood-clotting factors are formed by the liver, so disease of the liver can greatly depress the clotting system.

Hyperlipemia arose as a secondary complication of a primary systemic disease in the majority of miniature horse cases reviewed in this article. Enterocolitis, or inflammation of the colon, was found to be one the most common primary diseases (Mogg). Clinical signs include fever, diarrhea, dehydration, anorexia, depression and endotoxemia. Another common primary disease was colic, or acute abdominal pain due to smooth muscle peristalsis. In the case studies reviewed, colic was induced by gastric impaction, small colon impaction, gastrointestinal tract ulceration, and duodenitis/proximal jejunitis (Moore, Mogg). Dehydration, anorexia, fever, and pain are common clinical signs of colic. Feed intake was reduced in each case of enterocolitis and colic, either intentionally or by anorexia. Other primary diseases identified include parasitism, septicemia, postpartum peritonitis, laminitis, primary hepatopathy, edematous, crusting labial lesions, hypocalcemic tetany, esophageal obstruction and pituitary adenoma.

Because the observed clinical signs were for the most part related to the primary disease, it is difficult to determine specific clinical signs for hyperlipemia in miniature horses. Case studies of primary hyperlipemia in ponies consider anorexia a consistent feature of the condition. Dullness, depression and lethargy have been observed as well (Watson). This coincides with the prevalence of anorexia and lethargy observed in miniature horses. The mean duration of clinical signs before hospitalization were 2.4 days (Mogg) and 5.1 days (Moore) in miniature horses, and 10 +/-7 days in ponies (Watson). The duration of clinical signs prior to diagnosis of hyperlipemia can be short which suggests that serum triglycerides can accumulate in a brief period of time.

Measurement of serum triglyceride concentration appears to be the best method of diagnosing hyperlipemia. The standard criterion for diagnosis is serum triglyceride concentration in excess of 500 mg/dL. The mean peak of serum triglyceride concentration in 14 hyperlipemic miniature horses was 1,320 mg/dL, with a range of 493-2,830 mg/dL (Mogg), and 2,122.4 mg/dL, (range, 1,337-3,004 mg/dL), in 9 miniature horses and miniature donkeys (Moore). Prior to 1994, in the study done by Mogg, et al, serum triglyceride concentrations were determined using a lipase/glycerol dehydrogenase method on an automated discrete chemistry analyzer. In 1994 triglyceride concentrations were determined by use of a lipase/glycerol kinase/L-alpha-glycerophosphate oxidase method on a dry-slide automated discrete chemistry analyzer. In the study done by Moore, et al, serum triglyceride concentrations were determined with a reagent kit (Boehringer Mannheim) on an automated discrete analyzer (Boehringer Mannheim/ Hitachi 747).

Other biochemical parameters used for diagnosis of hyperlipemia are high levels of serum cholesterol concentrations, increased activity of gamma-Glutamyl transferase, increased concentration of bilirubin and creatinine, low levels of blood glucose, and development of metabolic acidosis. High serum cholesterol is an indication of increased fat metabolism. Tests of serum enzyme activities, such as gamma-Glutamyl transferase, help quantify the degree of active liver destruction. High plasma creatinine concentration is most likely the result of decreased renal profusion (prerenal azotemia). Azotemia has an inhibitory affect on lipoprotein lipase, resulting in decreased uptake of triglycerides in peripheral tissues. An increased plasma concentration of bilirubin is an indication of possible damage to liver cells, i.e. free bilirubin is not being converted to conjugated bilirubin in the liver. Hypoglycemia decreases insulin release which results in promotion of lipid mobilization from adipose tissue and decreased triglyceride removal from blood. Dehydration, renal dysfunction, and the buildup of ketone bodies are all possible causes of metabolic acidosis.

While the biochemical tests presented above can be used to diagnose hyperlipemia or may point to hepatic impairment, they are not useful prognostic indicators of survival. High serum triglyceride concentration is indicative of severe hyperlipemia, but in the case studies reviewed there did not appear to be a positive correlation between triglyceride levels and mortality rate. Miniature horses with high triglyceride levels (3,004 mg/dL) survived (Moore), while some with triglyceride levels below 1,500 mg/dL did not survive (Mogg). Necropsy examination revealed severe hepatic lipidosis in miniature donkeys and miniature horses that showed biochemical evidence of hepatic impairment. For example, 2 miniature donkeys with diffuse hepatic and renal lipidosis had glutamyl transferase concentrations of 57 IU/dL and 987 IU/dL, with the normal range being 15-35 IU/dL. Creatinine levels were 2.3 mg/dL and 1.3 mg/dL, with 0.9-1.4 mg/dL as a reference (Moore). Elevated glutamyl transferase and creatinine concentrations in ponies were found in 17/18 and 14/18 cases respectively (Watson). Evidence of hepatic lipidosis was also observed in miniature horses that were successfully treated, so liver damage due to hyperlipemia appears to be reversible in some cases.

Treatment of hyperlipemia in miniature horses consists of specific treatment of the primary disease, nutritional support, fluid therapy, and drug therapy. The aim is to eliminate the negative energy balance and its cause, and to hasten the removal of triglycerides from the blood. Nutritional support is considered the most important factor in treatment of hyperlipemia because it reverses the negative energy balance, increases serum glucose concentrations, promotes endogenous insulin release, and inhibits mobilization of peripheral adipose tissue (Moore). Nutritional support most commonly consists of intravenous or enteral administration of dextrose, enteral administration of commercially prepared, low-residue diets, and feeding high carbohydrate concentration gruels. Feed given in small portions at frequent intervals minimizes risk of gastric reflux, bloat, colic, or diarrhea. Intravenous fluids are administered concurrently for correction of dehydration, electrolyte disorders, and acid-base imbalances.

Insulin is used in treatment of hyperlipemia to block mobilization of adipose tissue and to facilitate removal of triglycerides from the blood. Insulin inhibits the hormone sensitive lipase that converts adipose tissue triglyceride to glycerol and fatty acids, thus decreasing the triglyceride mobilization from adipose tissue. Insulin also activates lipoprotein lipase which converts VLDL to free fatty acids and glycerol in peripheral tissues; it increases triglyceride uptake in peripheral tissues. Exogenous insulin administration may not be effective in all cases. Anti-lipolytic insensitivity to exogenous insulin has been demonstrated in ponies with clinical hyperlipemia (Forhead). This peripheral insulin resistance can be exacerbated by obesity, pregnancy, and stress (Jeffcott).

Combinations of insulin and glucose can be used but there are reports that this therapeutic regime may result in severe lactic acidosis and a poor recovery rate. A treatment in which insulin administration is combined with glucose and galactose administration on alternate days is reported to give better results than either glucose and insulin, or heparin treatments (Naylor).

Heparin is another hormone used to hasten the removal of triglycerides from the blood. Like insulin, heparin promotes peripheral utilization of triglycerides and enhances lipogenesis via stimulation of lipoprotein lipase. Heparin is a powerful anticoagulant, though, and can potentially cause bleeding complications. Production of normal coagulation factors may be impaired due to fatty infiltration of the liver, so heparin should be used with care. As a precaution, blood clotting tests should be performed during therapy.

The mean time for resolution of hyperlipemia in miniature horses was 7 days (Moore) and approximately 9 days in ponies (Watson). In patients that survived, serum triglyceride concentrations fell below 500 mg/dL and clinical signs of hyperlipemia were absent. There were no reported signs of liver damage in recovered miniature horses, donkeys, or ponies, but post-hyperlipemic biochemical data was not available for hepatic analysis in any of the case studies reviewed.

The success rate of treatment for hyperlipemia in miniature horses appears to be dependent on the severity of the primary disease. Survival was 78% in a study of miniature horses and miniature donkeys with secondary hyperlipemia (Moore). The 2 miniature donkeys that died had impactions that resulted in gastrointestinal tract rupture. The primary diseases were successfully treated in the remainder of the cases, as was the hyperlipemia. Regarding case studies that had 50% to 60% mortality rates, the primary diseases may have been more severe or may have remained undetected for longer periods of time (Mogg, Watson). All miniature horses with peak serum triglyceride concentration greater than 1,200 mg/dL died in one study (Mogg), but other cases have not shown the same relationship (Watson, Jeffcott, Moore). Necropsy of hyperlipemic equids with triglyceride concentrations above 2,000 gm/dL has revealed diffuse hepatic and renal lipidosis, so there does seem to be a correlation between high triglyceride levels and hepatic dysfunction.

Most cases of hyperlipemia can be prevented by maintaining feed intake. Enteral feeding of commercially prepared diets are recommended for miniature horses with enterocolitis, colic, or other anorexia-induced primary diseases. Enteral nutritional support can also be provided for patients with gastric or colon impaction, but should be used with caution so as not to exacerbate intestinal blockage. For cases of obesity or laminitis, feeding a half-maintenance ration is advised rather than complete feed withdrawal.

Examination of case studies involving hyperlipemia in miniature horses is somewhat limited due to the rarity of hyperlipemia in equids in general. In many cases the cost of biochemical tests, hospitalization, and treatment is prohibitive and the patient is euthanized. For the majority of miniature horses that were diagnosed with hyperlipemia, survival was determined by the nature and severity of the primary disease. The various biochemical parameters were valuable in diagnosis of hyperlipemia and hepatic impairment, but they were not useful indicators of survival. Primary systemic diseases that cause negative energy balance and rapid mobilization of adipose tissue must be recognized, and nutritional, fluid, and supportive therapy must be provided for the patient to survive.

References

Forhead AJ. Relationship between plasma insulin and triglyceride concentrations in hypertriglyceridaemic donkeys. Research in Veterinary Science. 1994;56:389-392.

Jeffcott LB, Field JR, McLean JG, et al. Glucose tolerance and insulin insensitivity in ponies and standardbred horses. Equine Veterinary Journal. 1986;18:97-101.

Mogg TD and Palmer JE. Hyperlipidemia, hyperlipemia, and hepatic lipidosis in American Miniature Horses: 23 cases (1990-1994). Journal of the American Veterinary Medical Association. 1995;207:604-607.

Moore BR, Abood SK, Hinchcliff KW. Hyperlipemia in 9 Miniature Horses and Miniature Donkeys. Journal of Veterinary Internal Medicine. 1994;8:376-381.

Naylor JM. Hyperlipemia. In: Robinson NE. Current Therapy in Equine Medicine 2. Philadelphia, PA: W. B. Saunders Company; 1987:114-116.

Watson TDG, Burns L, Love S, et al. Plasma lipids, lipoproteins and post-heparin lipases in ponies with hyperlipaemia. Equine Veterinary Journal. 1992;24:341-346.

Watson TDG, Murphy D, Love S. Equine hyperlipaemia in the United Kingdom: Clinical features and blood biochemistry of 18 cases. The veterinary Record. 1992;131:48-51.

Other Sources

Guyton AC. Textbook of Medical Physiology, 7th edition. Philadelphia, PA: W. B. Saunders Company; 1986.

Jeffcott LB, Field JR. Current concepts of hyperlipaemia in horses and ponies. The Veterinary Record. 1985;116:461-466.

Pearson EG, Maas J. Hyperlipemia/Hyperlipidemia in Ponies. In: Smith BP. Large Animal Internal Medicine. St. Louis, MO: C. V Mosby Company; 1990:862-863.

Vale MM. The Illustrated Veterinary Encyclopedia for Horsemen. Grand Prairie, TX: Equine Research, Inc.; 1998.

Zubay JL. Biochemistry, 4th edition. Dubuque, IA: Wm. C. Brown Publishers; 1998.

 

Copyright 1999 Mary Boyce and Koni Stone

 

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