JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2021
D-M11 (NP)

 

 

Signalment (JPC Accession # 2287584):  6-year-old female donkey

 

HISTORY:  1-week history of anorexia, depression, and weakness; in late gestation.  On physical exam: increased heart and respiration rates, dehydration, and dependent edema.  The serum was grossly lipemic.

 

HISTOPATHOLOGIC DESCRIPTION:  Liver:  Diffusely the hepatocytes are markedly enlarged by a discrete clear cytoplasmic vacuole (lipid) up to 20um in diameter that flattens and peripheralizes the nucleus (vacuolar degeneration, lipid type).  Multifocally, vacuoles of adjacent hepatocytes coalesce.  There are few hepatocytes that are shrunken and hypereosinophilic with nuclear pyknosis (single cell death).  Diffusely, sinusoids are collapsed.  Multifocally, portal areas contain few lymphocytes, plasma cells, and rare neutrophils.  The capsule is minimally thickened by fibrous connective tissue, and the liver has a rounded contour.

 

MORPHOLOGIC DIAGNOSIS:  Liver, hepatocytes:  Vacuolar change, lipid-type, diffuse, severe, breed unspecified, donkey (Equus asinus), equine.

 

CONDITION:  Hepatic lipidosis, hyperlipemia syndrome, equine hyperlipidemia, fatty liver disease

 

GENERAL DISCUSSION:

• Hepatic lipidosis is the abnormal accumulation of triglycerides within hepatocytes
• Hepatic lipidosis most often affects ponies (Shetland ponies are predisposed), donkeys, miniature horses, cattle, cats, sheep (pregnant, obese, or lactating), and is a characteristic finding in rabbits with gastric trichobezoar
• Usually secondary to an event that causes anorexia
• Rapid clinical course with high mortality in ponies
• Obesity is an important risk factor, primarily in felines

 

PATHOGENESIS:

• Hepatic lipidosis occurs when triglycerides, neutral fats, and cholesterol accumulate faster than their metabolic degradation or release as lipoproteins; these excess lipids are deposited as intra hepatocellular droplets; VLDL is the primary lipoprotein in the blood of hyperlipemic ponies
• Hepatic lipidosis can occur as the result of one or a combination of the following mechanisms:
• Excessive delivery of free fatty acids either from the gut or from adipose tissue
• Increased mobilization of fat is the most common cause of lipidosis in domestic animals
• Decreased beta-oxidation of fatty acids to ketones and other substances because of mitochondrial injury (toxins, hypoxia)
• Impaired synthesis of apoprotein (e.g. CCL₄ toxicity, aflatoxicosis)
• Impaired combination of triglycerides and protein from lipoprotein (uncommon)
• Impaired secretion of lipoproteins from the hepatocyte (uncommon)
• Insulin resistance: Proposed underlying cause in ponies;  increased steroid hormones interfere with insulin function; stress (increased cortisol) and increased progesterone during pregnancy may exacerbate the problem;  insulin resistance results in increased lipolysis and free fatty acids, leading to hypertriglyceridemia

 

TYPICAL CLINICAL FINDINGS:

• Depression, anorexia, weakness, colic, pasty feces, icterus
• Hepatic rupture is a frequent cause of death
• Ponies may also manifest signs of hepatic encephalopathy or terminal DIC
• Clinical pathology: Increased plasma triglycerides (primarily VLDL), increased alkaline phosphatase, GGT, LDH, and SDH, lipemic serum and blood, metabolic acidosis, DIC in severe cases, increased ammonia (Azevedo, J Vet Diagn Invest. 2019)

 

TYPICAL GROSS FINDINGS:

• Enlarged greasy yellow liver, bulges on cut surface, floats in formalin
• Enlargement of the liver may cause rupture of the liver capsule
• Lipidosis may also involve the heart, skeletal muscle, kidney, adrenal cortex
• Hemorrhage and infarction if DIC is present

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Swollen hepatocytes that contain variably sized discrete lipid vacuoles that often displace the nucleus to the periphery

 

DIAGNOSIS:

• Plasma triglyceride levels > 500 mg/dl
• Special stains: Oil red-O, Sudan IV

 

DIFFERENTIAL DIAGNOSIS:

• Endocrinopathies: Hyperlipidemia and fatty liver may occur with diabetes mellitus, hypothyroidism, hyperadrenocorticism
• Hepatotoxins: Usually cause necrosis in addition to fatty change

 

COMPARATIVE PATHOLOGY:

• Cats: Feline fatty liver syndrome is an idiopathic syndrome of hepatic lipidosis that typically affects obese and anorectic cats; these cats develop hepatic failure, icterus, and hepatic encephalopathy; elevated ALP is more severe than GGT; adipokine concentrations are altered: increased concentrations of adiponectin (related to liver disease) and leptin (specifically related to hepatic lipidosis)
• Chickens: Fatty liver hemorrhagic syndrome (FLHS) is a common noninfectious cause of mortality in laying backyard chickens; abundant coelomic fat reserves and an enlarged, pale, tan to yellow, friable liver with subcapsular and parenchymal hematomas and hemorrhages
• Small ruminants: White liver disease caused by dietary deficiencies of vitamin B12 and cobalt; hepatic lipidosis and ceroid deposition start in the centrilobular areas; anemia and icterus are common
• Ox, bison: Ketosis results from impaired carbohydrate and volatile fatty acid metabolism; in pregnant and lactating ruminants, the continual demand for glucose and amino acids may result in ketosis when fat metabolism becomes excessive; bovine fatty liver syndrome (physiologic fatty liver/fat cow syndrome) occurs most often in obese, periparturient dairy cattle and rarely beef cattle and is precipitated by an event that causes anorexia
• Camelids: Hepatic lipidosis may be induced by anorexia, weight loss and can be associated with hepatic encephalopathy
• Rabbits: Watanabe rabbits have a single-gene defect in the gene encoding for low-density lipoprotein receptor; develop hypercholesterolemia on a low-cholesterol diet; hepatic lipidosis is a characteristic finding in rabbits with gastric trichobezoar (hairballs)
• Non-human primates: Fatal fasting syndrome of older, obese macaques that are stressed and anorectic; hepatic lipidosis is accompanied by renal tubular fatty change, subcutaneous and intracavitary fat necrosis and pancreatic acinar degeneration
• Other periparturient animals: Due to negative energy balance and mobilization of fatty acids; hepatic pathways for oxidation of fatty acids and VLDL formation are overwhelmed, and fat accumulates in the liver
• Neonates: Fatty liver is normal in neonates of species in which the milk is rich in fat
• Captive nondomestic felids (tigers, cougars, lions): hepatocellular vacuolar change was the most common lesion among the 90 animals necropsied
• Hepatic lipodystrophy of Galloway calves: fatal liver disease affected a small portion of the breed; histologic findings include fibrosis, lipidosis, and bile duct hyperplasia

 

REFERENCES:

1. Azevedo CN, Lidbury JA, Jeffery U. Effects of marked hypertriglyceridemia and lipid clearance techniques on canine biochemistry testing. J Vet Diagn Invest. 2019 Jul;31(4):546-553.
2. Bain PJ. Liver. In: Latimer KS, ed. Duncan and Prasse’s Veterinary Laboratory Medicine Clinical Pathology. 5th ed. Ames, IA: Wiley-Blackwell; 2011:225-226.
3. Bernard JM, Newkirk KM, McRee AE, Whittemore JC, Ramsay EC. Hepatic lesions in 90 captive nondomestic felids presented for autopsy. Vet Pathol. 2015;52(2):369-376.
4. Brown DL, Van Wettere AJ, Cullen JM. Hepatobiliary system and exocrine pancreas.  In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:457.
5. Burden FA, Toit ND, Hazell-Smith E, Trawford AF. Hyperlipemia in a population of aged donkeys: description, prevalence, and potential risk factors. J Vet Intern Med. 2011;25:1420–1425.
6. Conwelll R. Hyperlipaemia in a pregnant mare with suspected masseter myodegeneration. Vet 2010; 166: 116-117.
7. Cullen JM, Stalker MJ. Liver and biliary system.  In: Maxie MG, eds. Jubb Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2, 6th ed., Philadelphia, PA: Elsevier Saunders; 2016:276-278.
8. Kramer JA, et al. The Common Marmoset as a Model for the Study of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Vet Pathol. 2015;52(2):404.
9. Mazaki-Tovi M, et al. Alterations in adipokines in feline hepatic lipidosis. J Vet Intern Med. 2013;27(2):242.
10. Miller MA, Zachary JF. Mechanisms and morphology of cellular injury, adaptation, and death.  In:  McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:25, 28-29.
11. Palmer MV, Olsen SC. Hepatic lipidosis in pregnant captive American bison (Bison bison). J Vet Diagn Invest. 2002;14:512-515.
12. Pillitteri CA, et al. Hepatic encephalopathy associated with hepatic lipidosis in llamas (Lama glama). Vet Pathol. 2013;50(1):177.
13. Smith GW. Hepatic lipidosis. In:  Smith BP, eds. Large Animal Internal Medicine. 5th ed. St. Louis, MO: Mosby Elsevier; 2015:861-866.
14. Trott KA, et al. Fatty liver hemorrhagic syndrome in the backyard chicken: a retrospective histopathologic case series. Vet Pathol. 2014;51(4):787.
15. Wieland M, Mann S, Hafner-Marx A, Ignatius A, Metzner M. Hepatic lipodystrophy in Galloway calves. Vet Pathol. 2017;54(3):467-474.

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