Liver Document - Lab Abnormalities

What are the two primary enzymes indicating hepatocellular damage?

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Which enzyme is more liver-specific in dogs and cats?

ALT

Where is ALT located within hepatocytes?

In the cytosol, released during cell membrane injury or necrosis.

What other tissues contain ALT?

Skeletal muscle (minor amount) — mild increases possible in muscle injury.

Where is AST located?

In mitochondria and cytoplasm of hepatocytes and muscle cells.

What does AST elevation suggest when ALT is also high?

Active or severe hepatocellular necrosis.

What if AST is high but ALT is normal?

Consider muscle disease or hemolysis.

What is the half-life of ALT in dogs vs cats?

Dogs: 2.5d, ~60 hours; Cats: unknown

What does normalization of ALT indicate?

Either recovery or end-stage disease (few viable hepatocytes left)

Concept: ALT/AST ↑ = ____; ALP/GGT ↑ = ___

hepatocellular injury, 

cholestasis

What are the two main enzymes associated with cholestasis?

Alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT).

What are the main sources of ALP in dogs?

Liver, bone, and corticosteroid-induced isoenzyme.

Which ALP isoenzyme is unique to dogs?

Corticosteroid-induced ALP (C-ALP) — induced by endogenous or exogenous steroids.

What is the significance of ALP in cats?

Very specific but poorly sensitive — short half-life (~6 hours).

Why can a small ALP increase be significant in cats?

Indicates marked hepatobiliary disease (esp. lipidosis or cholangitis).

What is the relationship between ALP and GGT in feline hepatic lipidosis?

ALP >> GGT (GGT often normal or only slightly increased).

What is the relationship between ALP and GGT cholangitis or biliary disease?

GGT ≥ ALP.

What causes increased ALP besides liver disease?

Bone growth, hyperthyroidism (cats), Cushing’s disease, corticosteroids, anticonvulsants.

Where is GGT localized in the liver?

Bile duct epithelium and canalicular membranes.

When are both ALP and GGT elevated?

In cholestatic or biliary obstruction (esp. dogs).

What are the two forms of bilirubin?

Unconjugated (indirect) and conjugated (direct).

Where is bilirubin conjugated?

In hepatocytes via UDP-glucuronyl transferase.

What are the three major mechanisms of hyperbilirubinemia?

Prehepatic, hepatic, and posthepatic.

What causes prehepatic hyperbilirubinemia?

Excess RBC breakdown (hemolysis).

What causes hepatic hyperbilirubinemia?

Defective uptake, conjugation, or excretion by hepatocytes.

What causes posthepatic hyperbilirubinemia?

Biliary obstruction or cholestasis.

What is the pattern of bilirubin elevations in cholestasis?

Conjugated (direct) bilirubin predominates.

Why is bilirubinuria always significant in cats?

Cats have high renal threshold for bilirubin — any bilirubinuria is abnormal. Suggestive of hemolysis or hepatic disease.

What does bilirubinuria in dogs indicate?

May be normal in concentrated urine from males, but otherwise suggests cholestasis or hemolysis.

What are bile acids and where are they synthesized?

Amphipathic molecules synthesized in hepatocytes from cholesterol.

What is the main role of bile acids?

Aid in fat digestion and regulate bile flow.

What happens to bile acids during normal enterohepatic circulation?

Absorbed in ileum, returned to liver via portal vein, and efficiently cleared by hepatocytes.

What causes increased serum bile acids?

Decreased hepatic clearance (hepatocellular dysfunction) or portosystemic shunting.

How are bile acids tested?

Paired preprandial and 2-hour postprandial samples.What is a normal bile acid range in dogs?

What is a normal bile acid range in dogs?

< 25 µmol/L (typically < 10 fasting, < 20 postprandial).

When are both pre- and postprandial bile acids high?

Hepatocellular dysfunction or portosystemic shunt.

When is only postprandial increased?

Partial obstruction or reduced gallbladder contraction.

Why may bile acids remain normal in extrahepatic obstruction?

Complete blockage prevents bile acid absorption from gut.

Why is albumin a useful indicator of hepatic function?

It’s exclusively synthesized by the liver — low levels reflect chronic dysfunction.

What causes hypoalbuminemia in liver disease?

Decreased synthesis due to hepatocellular loss.

What other mechanisms can reduce albumin?

Protein-losing enteropathy/nephropathy, malnutrition, or blood loss.

Why is albumin often normal in acute hepatic injury?

Long half-life (8–10 days in dogs) — changes lag behind acute injury.

How can low albumin contribute to ascites?

Reduces plasma oncotic pressure → fluid leakage into abdomen.

What other metabolic change may occur with liver failure?

Hypoglycemia due to depleted glycogen and impaired gluconeogenesis.

What diseases can cause hyperglycemia secondary to hepatic dysfunction?

Cushing’s, diabetes mellitus, or stress response.

What is the relationship between cholesterol and hepatic function?

The liver synthesizes, stores, and excretes cholesterol — both hyper- and hypocholesterolemia may occur.

What causes hypercholesterolemia in liver disease?

Cholestasis (impaired excretion of cholesterol into bile).

What causes hypocholesterolemia?

Severe hepatic failure (reduced synthesis) or portosystemic shunts.

Why is cholesterol often low in congenital shunts?

Decreased hepatic synthesis due to diverted portal flow.

Why is the liver critical for coagulation?

It produces all major clotting factors (except VIII) and anticoagulants (protein C, S, antithrombin).

Which tests evaluate hepatic synthetic function?

PT (extrinsic) and aPTT (intrinsic).

What does prolonged PT or aPTT suggest?

Reduced hepatic synthesis of clotting factors or vitamin K deficiency.

Why can cholestasis cause coagulopathy?

Decreased bile → poor fat absorption → vitamin K malabsorption → factor II, VII, IX, X deficiency.

How can coagulopathy caused by cholestasis be prevented?

Vitamin K1 supplementation (SC 3 doses q12h before biopsy or surgery).

What does prolonged PTT alone suggest?

Early factor deficiency; monitor before procedures.

What is antithrombin III’s role?

Hepatic anticoagulant — low levels may cause hypercoagulability and thrombosis.

Cholestasis → ___ → ___

vitamin K deficiency → hemorrhage risk

Chronic hepatic failure → ___ + ___

prolonged PT/PTT, low AT III

Why does ammonia accumulate in liver disease?

Impaired conversion to urea via the urea cycle in hepatocytes.

What are hepatic causes to hyperammonemia?

some forms of portosystemic shunting, severe hepatitis, severe hepatic necrosis, diffuse hepatic neoplasia, cirrhosis

What test can detect impaired hepatic detoxification?

Ammonia tolerance test or resting plasma ammonia.

Why is the ammonia tolerance test risky?

May precipitate encephalopathy in compromised patients.

What pre-analytic factors can falsely increase ammonia?

Delayed processing, poor sample handling, or patient struggling during draw.

What diseases cause hyperammonemia besides hepatic failure?

Congeintal deficiencies in argininosuccinate synthetase (in dogs, rare), dietary arginine deficencies (in anorectic cats),

Urease-producing urinary tract infections and GI bleeding.

What neurologic sign is strongly suggestive of hyperammonemia?

Episodic disorientation, drooling, or seizures post-meal.

What is the mainstay of therapy for hyperammonemia?

Lactulose (acidifies colon and traps ammonia) ± antibiotics.

What urine findings suggest hepatic disease?

bilirubinuria, ammonium biurate crystals, low specific gravity

What do ammonium biurate crystals indicate?

Portosystemic shunt or severe hepatic dysfunction.

What are typical USG findings in hepatic disease?

Hyposthenuria or isosthenuria due to altered medullary concentration gradients or PU/PD.

Why may BUN be low in liver disease?

Impaired urea synthesis from ammonia.

How can low BUN affect clinical signs?

Reduces medullary hypertonicity → polyuria.

ALT/AST ↑ =

Hepatocellular injury

ALP/GGT ↑ =

Cholestasis

Bilirubin ↑ =

Icterus (pre-, hepatic, post-)

Bile acids ↑ =

Functional or shunting

Low albumin/glucose =

Chronic/late failure

Prolonged PT/PTT =

Coagulopathy

Ammonia ↑ =

Encephalopathy

Ammonium biurate crystals =

Shunt