clinpath hepatobil (strandberg)

Question 1

What does tissue diagnostic enzymology tell you?

Answer 1

Increased serum enzyme activity correlates directly to serum enzyme concentration, and tells about leakage from injured cells or increased production of the enzyme – does NOT provide info on tissue/organ function

Question 2

Leakage (injury) enzymes

Answer 2

• escape from cytosol following lethal or sub-lethal cellular injury
• degree of elevation DOES NOT correlate to severeity of tissue injury!
• hepatic: ALT, AST, SDH

Question 3

Leakage (injury) enzymes

Alanine Aminotransferase (ALT)

Answer 3

• tissue source = liver, skeletal & cardiac muscle
• primary enzyme in SA to determine hepatocellular injury; NOT useful in horses and cattle
• can be increased with severe skeletal and cardiac muscle damage

Question 4

Leakage (injury) enzymes

Aspartate Aminotransferase (AST)

Answer 4

• tissue source = hepatocytes, skeletal muscle, erythrocytes
• primary enzyme in horses & cattle to determine hepatocellular injury
• tends to parallel ALT; AST also returns to baseline quicker than ALT
• may increase due to muscle injury (look at CK) or hemolysis (Hgb, blood smear)

Question 5

Leakage (injury) enzymes

Creatinine Kinase (CK)

Answer 5

increased due to muscle injury or hepatocellular damage
- serum CK source = skeletal and cardiac muscle

Question 6

Leakage (injury) enzymes

Sorbitol Dehydrogenase (SDH)

Answer 6

• cattle and horses (much more specific than AST in these species)
• tissue source = liver
• better than ALT compared to in dogs/cats

Question 7

Induced Enzymes

Induced/cholestatic enzymes

Answer 7

• attached to cell membranes
• increase due to cellular stress and are slower to manifest
• cholestasis increases relase of these enzymes
• ALP, GGT

Question 8

Induced Enzymes

Alkaline Phosphatase (ALP)
- source
- isoenzymes

Answer 8

• sourced from many tissues
• is a part of the hepatobiliary system & increases with cholestasis

2 main isoenzymes (different structures produced in different regions of the body) = intestinal & tissue non-specific
- Intestinal: cALP – can be induced by corticosteroids in DOGS (only dogs have this isoenzyme!!)
- Tissue non-specific isoenzymes: LALP (liver) and bALP (bone)

cALP, LALP and bALP = main sources of serum ALP

ALP is most sensitive in DOGS

Question 9

Induced Enzymes

4 Causes of increased ALP

Answer 9

1. hepatobiliary disease (cholestasis – dogs– )
2. osteoblastic activity in young, growing animals (or bone neoplasia, fracture healing – bALP)
3. induction by drugs (exo- and endogenous corticosteroids; anticonvulsants like phenobarb – cALP)
4. post-colostrum ingestion (puppies; kittens and lambs, NOT foals)

Question 10

Induced Enzymes

Gamma Glutamyl Transferase (GGT)

Answer 10

• sourced from many tissues
• is a part of the hepatobiliary system & increases with cholestasis
• more sensitive but less specific in cats (vice versa for dogs)
• more sensitive than ALP in horses & cattle

Question 11

Evidence of primary hepatocellualr injury versuus primary cholestasis

Answer 11

primary hepatocellualr injury: leakage enzymes elevated to greatest degree (ALT, AST)

primary cholestasis: induced enzymes elevated to greatest degree (GGT, ALP)

Question 12

When will hypoalbuminemia and hypoglycemia be detected?

Answer 12

Not until 60-80% (albumin) and > 70% (glucose) of hepatic function is lost

hypoalbuminemia is almost always seen in dogs with chronic liver disease

Question 13

Where is cholesterol excreted

Answer 13

in the bile

Question 14

When will you see hypercholesterolemia versus hypocholesterolemia

Answer 14

Hyper: cholestasis
Hypo: hepatocelluar damage

many animals with liver failure will have normal serum cholesterol

Question 15

What forms unconjugated bilirubin?

Answer 15

Metabolism of hemoglobin

unconjugated bilirubin is transported to the liver once attached to albumin, and then hepatocytes conjugate it

Question 16

When is indirect/unconjugated bilirubin greater than direct/conjugated bilirubin?

Answer 16

Bi > Bd
- hemolysis/internal hemorrhage
- fasting/anorexia in LAs (esp. horses)

Horses: no food -> decr. glucose available for conjugation of Bi into Bd

Question 17

When is direct/conjugated bilirubin greater than indirect/unconjugated bilirubin?

Answer 17

• obstructive cholestasis
• functional cholestasis (sepsis)

Question 18

Causes of elevated serum bile acids

Answer 18

• abnormalities of portal circulation (PSS)
• decreased functional hepatic mass (diffuse liver diseases)
• decreased excretion of BA into bile (any causes of intraphepatic or post-hepatic cholestasis)

Serum bile acids will ALWAYS INCREASE in cholestasis; only test bile acids if cholestasis has been ruled out and you need to assess hepatic function!

Question 19

When is running a bile acids test most useful?

Answer 19

When you suspect liver disease but not proven with routine tests (e.g., elevated hepatic enzymes but normal bilirubin//non-icteric)

-bile acids will ALWAYS be increased in cholestasis; only run bile acids if the patient does NOT have cholestasis, but you still strongly suspect hepatic disease

Question 20

When will ammonia levels be elevated?

Answer 20

• abnormal blood flow in portal circulation (e.g., PSS)
• markedly decreased hepatic functional mass (> 60% loss)

is NOT altered by cholestasis (unlike serum bile acids)

Ammonia: by-product of the metabolism of AA and other nitrogen-rich compounds -> ammonia gets removed via enterohepatic circulation -> ammonia gets transformed into urea in liver