Albumin is produced exclusively by the liver, and has a half-life in normal dogs estimated at ~8 days. Because the normal liver is estimated to maintain albumin synthesis at 33% maximal capacity, it has much reserve capability. The role of albumin as a transport molecule is essential for maintaining normal drug-receptor interactions. In liver disease, transport functions of albumin may decline, increasing risk of adverse drug reactions (more free or unbound drug). Albumin's large role in maintaining colloid osmotic pressure reflects its lower molecular weight compared to other plasma proteins and its higher intravascular concentration. In inflammation or malnutrition, albumin may increase its transcapillary escape rate; this augments redistribution of albumin and onset of hypoalbuminemia in patients with necroinflammatory liver disease, long before development of ascites.
Albumin also functions as a scavenger of oxygen radicals and other oxidizing agents. These antioxidant effects may be compromised in necroinflammatory liver disease and fulminant hepatic failure. Any disease processes promoting an oxidative environment (eg, diabetes mellitus, renal disease, hepatic insufficiency) can irreparably damage the albumin molecule, leading to an accelerated rate of albumin turnover (synthesis and catabolism).
Early trends toward hypoalbuminemia usually reflect systemic inflammation (negative acute phase effect). Only in severe hepatic insufficiency (eg, chronic progressive hepatitis) is synthetic failure a driving force causing hypoalbuminemia. Glomerular disease or protein-losing enteropathy must be excluded as a cause of hypoalbuminemia; glomerular causes are associated with a urine protein:creatinine ratio >3 and hypercholesterolemia.
Total bilirubin >2.5–3.0 mg/dL results in clinical icterus. Bilirubin concentrations can increase due to prehepatic causes (eg, hemolysis), hepatic causes (impaired uptake, intracellular transport, glucuronide conjugation, or canalicular elimination), or extrahepatic cholestasis (EHBDO, biliary tree rupture). Total bilirubin concentrations vary markedly with different disease processes. Concentrations are highest in dogs with hemolytic disorders and in cats with HL and EHBDO. Bilirubinuria can be detected in normal dogs because of their ability to conjugate bilirubin in the kidney (low renal threshold). However, bilirubinuria in cats is always abnormal and should be investigated. Fractionation of total bilirubin into direct (conjugated) and indirect (unconjugated) moieties offers little diagnostic utility.
Common causes of hyperbilirubinemia include: increased hemoprotein liberation (eg, hemolytic anemia, ineffective erythropoiesis, body cavity hemorrhage), bile duct occlusion, ruptured biliary tract, intrahepatic cholestasis, impaired hepatobiliary bilirubin processing, and sepsis, among others. Jaundiced dogs and cats presenting with regenerative anemia should be tested for hemolytic disorders, including immune-mediated hemolytic anemia, Heinz body hemolysis, zinc toxicity, and erythroparasites (including hemotrophic Mycoplasma [cats, dogs] and Babesia [dogs]). Bilirubin covalently bound to albumin (biliprotein complexes) remains in the circulation and is not excreted in urine. Chronic retention can impart tissue jaundice in the absence of bilirubinuria long after a cholestatic disorder has resolved.
BUN and Creatinine
There is no characteristic change in BUN or creatinine concentrations with liver disorders except that low values are seen with portosystemic shunting and in dogs on restricted protein diets formulated to reduce signs of HE. BUN reflects numerous systemic variables including hydration status, nutritional support, enteric bleeding, tissue catabolism, and the hepatic capacity to detoxify ammonia. Anorexia, a low-protein diet, or hepatic insufficiency can result in low normal to subnormal concentration of BUN, while increased values relative to creatinine may reflect dehydration or enteric bleeding. A low BUN and often a low creatinine can be associated with portosystemic shunting. Increased water turnover increases glomerular filtration rate up to 2-fold and contributes to PU/PD in these patients. Reduced hepatic synthesis of creatinine also contributes to low creatinine in patients with hepatic insufficiency, considering that creatinine depends on hepatic synthesis of creatine in the transmethylation pathway. Compared to BUN, serum creatinine concentrations are less affected by dietary protein intake.
Hypoglycemia is uncommon in acquired liver disease except end-stage cirrhosis or fulminant liver failure. The inability to store hepatic glycogen or convert glycogen to glucose is more common in neonates and juvenile small-breed dogs with congenital portosystemic shunts. Other causes of hypoglycemia, including sepsis, insulinoma, iatrogenic insulin overdose, rare glycogen storage disorders, or paraneoplastic effects of large primary hepatic neoplasia (canine hepatocellular carcinoma or adenoma) or other tumors should be considered.
All cells in the body except RBC can synthesize cholesterol for intra-cellular use. Cholesterol used in plasma lipoproteins is synthesized only in the liver and distal small intestine. Bile provides the major excretory pathway for cholesterol. A low serum cholesterol concentration may reflect endocrine, metabolic, and nutritional factors as well as hepatic insufficiency and portosystemic shunting. Nonhepatic disorders associated with hypocholesterolemia include hypoadrenocorticism, maldigestion/malabsorption, severe starvation, cachexia, sepsis, and hyperthyroidism (cats); hepatic causes include portosystemic shunting (congenital or acquired) and severe hepatic insufficiency (eg, in fulminant hepatic failure). High cholesterol is more common in ill animals and requires careful consideration of potentially related nonhepatic disorders including hypothyroidism, diabetes mellitus, pancreatitis, nephrotic syndrome, idiopathic dyslipidemias, and rarely a postprandial effect. Hypercholesterolemia is usually observed in EHBDO and some animals with diffuse intrahepatic cholestasis and hepatic regeneration.
Last full review/revision March 2012 by Sharon A. Center, DVM, DACVIM