Liver Clin Path Flashcards
describe indicators of liver function
on chem panel:
1. decreased albumin
2. decreased cholesterol
3. decreased urea nitrogen
4. decreased glucose
5. increased bilirubin
elsewhere:
-decreased coagulation factors: prolonged PT/PTT
confirmatory testing
-increased ammonium
-increased bile acids
describe albumin
- represents nearly half of total serum protein
-contributes to oncotic pressure - liver is the site of all albumin synthesis
-loss of 60-80% liver function leads to hypoalbuminemia - if liver does not efficiently clear foreign proteins and antigens, globulins will increase as part of the inflammatory response
- protein profile confounded by effects of comorbidities
describe protein/albumin alteration differentials (7)
- liver dysfunction*:
-albumin: decreased
-globulins: normal to increased - protein-losing nephropathy:
-albumin: decreased
-globulins: normal - protein losing enteropathy*:
-albumin: decreased
-globulins: decreased - hemorrhage:
-albumin: decreased
-globulins: decreased - inflammation:
-albumin: decreased
-globulin: increased - dehydration*:
-albumin: increased
-globulins: increased - lymphoid neoplasia:
-albumin: normal to decreased
-globulins: normal to increased
describe urea nitrogen
- healthy hepatocytes convert ammonium to urea
- less synthesis of urea with liver dysfunction
-concurrent azotemia can complicate this picture
describe urea nitrogen alteration differentials
- liver dysfunction*: decreased
- low protein diet: decreased
- young animal: decreased
- urea cycle problem: decreased
- azotemia: increased
describe cholesterol
- healthy hepatocytes make cholesterol
- less synthesis of cholesterol with liver dysfunction
-but cholestasis blocks clearance and causes cholesterol increases
-so liver dysfunction AND cholestasis = murky
describe cholesterol alteration differentials (7)
- liver dysfunction: decreased
- protein losing enteropathy: decreased
- cholestasis: increased
- protein losing nephropathy: increased
- hyperthyroidism: increased
- pancreatitis: increased
- endocrinopathies: increased
describe glucose
- healthy liver helps to maintain fasting blood glucose
- with a marked reduction in functional liver mass, normal blood glucose cannot be maintained
-at least 75% of liver mass must be lost before hypoglycemia occurs (one of the last changes to appear)
-if glucose is the only one of the 5 markers affected, spend more time investigating other causes of low glucose bc liver is less likely to be the porblem
describe glucose alteration differentials
- liver dysfunction: decreased
-late in dysfunction!! - excess insulin: decreased
- hypoadrenocorticism: decreased
- sepsis: decreased
- starvation: decreased
- delayed separation of cells from serum after collection: decreased
describe bilirubin
- pigment produced by heme degradation
-a normal process! - total bilirubin = unconjugated bilirubin + conjugated bilirubin
describe hyperbilirubinemia
- pre-hepatic: hemolysis
- hepatic:
-anorexia (horses)
-decreased functional mass
-intrahepatic blockages - post-hepatic:
-decreased secretion into biliary system
-post-hepatic cholestasis or pancreatic disease
describe bilirubin in fasting horses
- fasting/anorexia induces increases in bilirubin within one day
-anorexia = struggle to take up bilirubin into hepatocytes (a glucose dependent process in HORSES) - total bilirubin concentration as high as 12mg/dL in horses
-won’t necessarily see hypoglycemia with this state of anorexia
describe bilirubinuria
- conjugated bilirubin passes easily through the glomerular filtration barrier and is then excreted in the urine
- dogs have low renal threshold for bilirubin
-especially males!
-in male dogs, bilirubinuria occurs before hyperbilirubinemia - cats have higher renal threshold
-hyperbilirubinemia occurs before bilirubinuria
-bilirubinuria is more significant in cats than dogs
-if see in urine in cat, CHECK THE BLOOD
describe bilirubin formation in “other species”
- typically formed by catalytic reduction of biliverdin by biliverdin reductase
- BR almost completely lacking in birds
- BR activity low in rabbits
- biliverdin is major bile pigment in these species
don’t really test in these species
“what we can test they dont have and what they have we cant test”
describe bile acids and ammonium testing to confirm a functional issue with the liver
bile acids:
1. pre and post prandial samples: small animals
2. baseline sample: horses, ruminants, some birds
3. increased bile acids (post-prandial or baseline sample) due to abnormal circulation (shunting), dysfunctional liver, and cholestasis
ammonium:
1. baseline sample
2. special sample handling: degrades so fast
3. increased ammonium due to abnormal circulation (shunting) or dysfunctional liver
4. not affected by cholestasis
describe damage enzymes
- soluble cytosolic enzymes
-released with hepatocyte damage or necrosis
-blood increases can be seen in hours - include: ALT, AST, SDH
- species differences = panels vary
describe ALT
- alanine aminotransferase
- blood increases
-hepatocellular damage: best for dogs and cats, not much liver activity in large animals
-skeletal muscle damage: horses, ruminants, pigs, birds; in small animals, a tremendous amount of muscle damage necessary for increase (CK is best enzyme for muscle damage in everyone!!)
- decreased or normal ALT is not always good
-declining activity may represent a scarcity of viable hepatocytes (chronic liver disease) even if injury persists - increased ALT is not always bad
-can increase during recovery when active regeneration is occurring
describe AST
- aspartate aminotransferase
- blood increases:
-hepatocellular damage: inflammation, hypoxia, toxins, trauma, neoplasia
-muscle damage: skeletal and cardiac
-hemolysis
- species:
-routinely used to detect liver damage in horses and cattle
-less popular in dogs and cats; use ALT instead
- cytosolic and mitochondrial forms; could indicate more severe injury but LESS specific for liver than ALT
describe SDH
- sorbitol dehydrogenase
- hepatocellular damage
-most liver specific BUT unstable in vitro so VERY short half life
-low sensitivity in chronic liver disease
describe cholestatic enzymes
- membrane bound
- cholestasis is NOT the only cause for blood increases of these enzymes
- increases take days instead of hours
- includes ALP and GGT
- species differences so panels vary
describe ALP
- alkaline phosphatase
- total ALP: comprised of liver, bone, and corticosteroid induced in DOGS ONLY
- blood increases:
-cholestasis
-bone remodel, young growers
-induction by drugs/steroids in DOGS ONLY
describe GGT
- gamma glutamyl transferase
- blood increases:
-cholestasis
-steroids: dogs only, minimal
-colostrum ingestion: dogs, sheep, cattle
–NOT cat and horse
sum up liver enzymes
- serial measurements are much more helpful than one value
- decreased values not USUALLY clinically significant
- increased enzymes do NOT indicate a loss of lover function
