Regulation of fat metabolism in the adipocyte is modulated by blood glucose concentration as well as hormonal, neural and pharmacological mechanisms. A previously obese individual undergoing starvation is at increased risk for lipolysis. Many cats developing hepatic lipidosis (HL) are obese.
Fat in the liver is of five types: triglycerides (TG), phospholipids, lipoproteins, cholesterol and cholesterol esters. Lipid vacuolation in lipidosis is predominantly composed of triglycerides. They accumulate in the liver when the rate of hepatic synthesis exceeds their dispersal.
The development of lipid vacuoles within hepatocytes does not directly have a noxious effect on the cell. It is believed that the lipid accumulation reflects an underlying metabolic disorder. For example, any systemically ill person is expected to have some fat vacuoles in their hepatocytes.
Unrestricted release of fatty acids from excessive adipose fat promotes lipidosis because up to one third of mobilized fat may be residing in the liver at one time. Therefore, in these cats, lipidosis may reflect the liver's inability to match fat dispersal with delivery from systemic sources. An imbalance between essential lipoprotein components will also interfere with fat dispersal. Given the complexity of lipid metabolism, it is, however, unlikely that one pathogenesis explains HL in all affected individuals.
Obese female cats are at greatest risk of developing hepatic lipidosis. Cats of any age may be affected; most commonly cats are between 4-15 years of age. Domestic shorthair cats are breed predisposed; this finding could be a reflection of this breed's greater incidence in the population.
Clients bring their cat in because of weight loss or anorexia, vomiting, lethargy and weakness. While fat may become depleted on the limbs and dorsal trunk, abdominal and thoracic fat stores remain spared.
Physical examination findings
Palpable, rounded liver margins
Fat depletion dorsally with abdominal and thoracic fat spared
Diagnosis and treatment RULE #1 with yellow cats: - FEED FIRST, DIAGNOSE LATER! - Lack of nutrients promotes lipolysis and glycogenolysis. This fuels the already imbalanced TG dispersal mechanisms. Protein is essential for this process, in order to make lipoproteins VLDL, thus protein restriction is contra-indicated unless encephalopathy is present.
Feeding a minimum of 50 kcal/kg ideal body weight/day of a good quality, calorie dense diet is essential. Protein should be > 30% of calories. Don't use carbohydrates instead of fat, as these cats are already prone to insulin resistance. Arginine is an essential amino acid in the cat (easy to remember: Carnitine-Arginine-Taurine = CAT). Arginine is needed for normal detoxification of nitrogen. Cage resting cats with HL may reduce muscle release of ammonia, thus may be beneficial.
Protein restriction should only be considered in the cat with hepatic encephalopathy (uncommon). If HE is present, then lactulose (0.25-2 ml/kg to effecting soft stools), plus metronidazole (7.5 mg/kg PO q12h) are indicated.
The underlying problem in a lipidotic cat is their dysfunctional lipoprotein and lipid metabolism, particularly in the transport and accumulation of VLDL (very low density lipoprotein)...i.e., fatty acids. In a starving cat, adipocyte lipolysis is promoted due to reduced glucose availability, decreased insulin concentrations, increased concentrations of growth hormone and glucocorticoids. The fatty acids are taken into the liver where, in a healthy liver, they are oxidized to ketone bodies or re-esterified to triglycerides (TG). In the lipidotic liver, increased TG storage occurs and ketone metabolism may be altered, resulting in ketonuria. One way to check if these ketones are from lipolysis, rather than diabetes, is to run a serum betahydroxybutarate level. Of course, confirmation of diabetes can be made via a) history and clinical findings, along with b) serum fructosamine or glycosylated hemoglobin levels to differentiate stress induced hyperglycemia/glucosuria.
RULE #2 of yellow cats: - FLUIDS! - Treat and prevent dehydration with a non-lactate and non-glucose containing fluid. Lactate metabolism requires hepatic input. Glucose requires hepatic metabolism. Hydration is critical; dehydration decreases hepatic circulation, which impairs detoxification. It also increases the urea in the gut, which results in azotemia, increased ammonia production and absorption. Constipation (often a result of dehydration) allows prolonged contact with endotoxic materials in the gut. A dehydrated cat with severe liver disease will feel very ill as he/she is, in essence, undergoing a continuous ammonia challenge test. Pectin and lactulose may be beneficial as pectin traps H+ and lactulose incorporates N into bacteria.
CBC and Biochemistries
There are characteristic red cell changes, poikilocytosis, in liver disease. These include schistocytes, acanthocytes, elliptocytes, echinocytes, blister cells and keratocytes.
It is believed that alterations in cholesterol and phospholipid metabolism affect red cell membranes making them less flexible. Additionally, alterations in the liver structure change the structure red cells pass through (sinusoids), allowing the red cells to fracture and fragment. Oxidative stress on the red cell membrane plays a role as well.
The classical biochemical pattern is an increased SAP, a less increased alt with bilirubinemia/-uria and normal or only slight increase in ggt.
BUT! 75% of cats have HL secondary to some other condition.
RULE #3 of yellow cats: - LOOK FOR THE UNDERLYING CAUSE OF THE LIPIDOSIS - Ultrasound to assess liver, pancreas, stomach, small and large bowel to determine if there is "triaditis" (inflammation of the liver, pancreas and bowel), disease of the gall bladder and biliary tree, etc. It is important to try to determine which cats have concurrent pancreatitis, because in one study, 38% of cats with HL had concurrent histopathologic acute pancreatitis. The recovery rate of cats with acute pancreatitis was 20% rather than >50% of cats with HL alone. Note: most people report a much higher recovery rate of 50-80% of cats with lipidosis and I want YOU to be getting upwards of 80% recovery! When you have a patient with hepatic lipidosis, primary or secondary...the point is to feed first, diagnose later. A hyperechoic liver is supportive of lipidosis but could also be indicative of lymphoma. Therefore we need to biopsy or aspirate the liver.
Fine needle aspirate cytology may reveal hepatic lipidosis without revealing the underlying cause of the disease. Using a "passive" technique provides better samples. If the patient is stable enough and once coagulation factors and electrolyte abnormalities are corrected, consider exploratory surgery to collect wedge biopsies of the liver for histopathology as this gives the best samples (and information). It also allows you to collect other organ samples and place a gastrotomy or esophagostomy tube.
RULE #4 of yellow cats: - FEEDING VIA LARGE BORE TUBE INCREASES CHANCE OF SURVIVAL - Esophageal or gastric tubes are easily placed and maintained.
RULE #5 - VOMITING! - For vomiting patients, metoclopramide is more effective and less neuropathic when given by constant rate infusion (1-2 mg/kg cri IV over 24 hours). Other drugs that can be used for the prevention of vomiting include dimenhydrinate, diphenhydramine, prochlorpromazine, chlorpromazine, ondansetron and dolasetron.
For volume induced vomiting, "trickle feed" by putting the diet into an empty fluid bag and running it by constant slow drip through the g-tube.
RULE#6: - SUPPLEMENTATION WITH L-CARNITINE - 250-500mg PO q24h increases the chance of recovery. L-carnitine is an essential cofactor of fatty acid (fa) metabolism. Sources are meat and dairy. L-carnitine transforms free long chain fa and prevents accumulation of free fa in the hepatocyte cytoplasm as well as acetyl groups in the mitochondria.
RULE#7 - CORRECT SERUM POTASSIUM - Aggressive attention to and correction of serum hypokalemia is essential; hypokalemia is a negative predictor for survival.
RULE#8 - VITAMIN K SUPPLEMENTATION - 50% of cats with HL have prolonged PIVKA (Proteins Induced in Vitamin K Absence or Antagonism) times or other prolonged coagulation tests and require Vit K1 therapy. It takes cats < 7 days to become Vit K deficient. Cats who have been on antibiotics may have fewer organisms in their bowels to make Vit K. Vitamin K is absorbed in the proximal small bowel and recycled by the liver (Vit K epoxidase cycle). Thus, in small bowel disease (such as IBD induced fat malabsorption), as well as in liver diseases (especially in hepatic lipidosis), low Vitamin K levels may predispose to occult coagulopathies. Factors II, VII, IX and X, as well as protein C and protein S (antithrombotic proteins) are Vit K dependent. Supplementation is most effective using Vit K1. If the patient is jaundiced or nauseous, then the Vit K1 must be given SC rather than orally because intestinal absorption is poor (0.5-1.0 mg/kg q24h X 3-4 days or until coagulation normalizes.)
RULE#9 - SUPPLEMENTATION WITH TAURINE - 250-500 mg/day is valuable as this is an essential amino acid in the cat. Taurine may be hepatoprotective and is required for bile conjugation. It plays a role in membrane stability and function. Cats with HL are taurine wasting in their urine. Anorexia causes a decrease in serum taurine levels.
RULE#10 - SUPPLEMENT WATER SOLUBLE VITAMINS - Thiamine supplementation is indicated in cats with ventroflexion of the neck if serum potassium levels are normal. Vit B12 is required for lipoprotein production.
RULE#11 - AVOID UNNECESSARY DRUGS in cats with hepatic disorders and reduce doses given.