clinpath hepatobil (strandberg) Flashcards
What does tissue diagnostic enzymology tell you?
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
Leakage (injury) enzymes
- 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
Leakage (injury) enzymes
Alanine Aminotransferase (ALT)
- 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
Leakage (injury) enzymes
Aspartate Aminotransferase (AST)
- 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)
Leakage (injury) enzymes
Creatinine Kinase (CK)
increased due to muscle injury or hepatocellular damage
- serum CK source = skeletal and cardiac muscle
Leakage (injury) enzymes
Sorbitol Dehydrogenase (SDH)
- cattle and horses (much more specific than AST in these species)
- tissue source = liver
- better than ALT compared to in dogs/cats
Induced Enzymes
Induced/cholestatic enzymes
- attached to cell membranes
- increase due to cellular stress and are slower to manifest
- cholestasis increases relase of these enzymes
- ALP, GGT
Induced Enzymes
Alkaline Phosphatase (ALP)
- source
- isoenzymes
- 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
Induced Enzymes
4 Causes of increased ALP
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)
Induced Enzymes
Gamma Glutamyl Transferase (GGT)
- 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
Evidence of primary hepatocellualr injury versuus primary cholestasis
primary hepatocellualr injury: leakage enzymes elevated to greatest degree (ALT, AST)
primary cholestasis: induced enzymes elevated to greatest degree (GGT, ALP)
When will hypoalbuminemia and hypoglycemia be detected?
Not until 60-80% (albumin) and > 70% (glucose) of hepatic function is lost
hypoalbuminemia is almost always seen in dogs with chronic liver disease
Where is cholesterol excreted
in the bile
When will you see hypercholesterolemia versus hypocholesterolemia
Hyper: cholestasis
Hypo: hepatocelluar damage
many animals with liver failure will have normal serum cholesterol
What forms unconjugated bilirubin?
Metabolism of hemoglobin
unconjugated bilirubin is transported to the liver once attached to albumin, and then hepatocytes conjugate it
When is indirect/unconjugated bilirubin greater than direct/conjugated bilirubin?
Bi > Bd
- hemolysis/internal hemorrhage
- fasting/anorexia in LAs (esp. horses)
Horses: no food -> decr. glucose available for conjugation of Bi into Bd
When is direct/conjugated bilirubin greater than indirect/unconjugated bilirubin?
- obstructive cholestasis
- functional cholestasis (sepsis)
Causes of elevated serum bile acids
- 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!
When is running a bile acids test most useful?
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
When will ammonia levels be elevated?
- 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
