Flashcards in Laboratory diagnostics of liver disease Deck (60):
Name 4 enzymes used to indicate hepatocellular damage
ALT, AST, SDH, GLDH.
These are leaked directly from hepatocytes and indicate damage/necrosis of these cells
Does a blebosome indicate reversible or irreversible damage?
What is ALT most commonly used for? Describe its rate of increase/decrease
dogs and cats.
Will increase within 12 hours of injury, peaks at 1-2 days and decreased over the next 2-3 weeks.
Is ALT used in large animals?
No - hepatic ALT activity i n large animals is very low so use SDH or GLDH. GLDH is considered liver specific but assays for use in small animals are rarely available.
What should you check if AST is increased?
Look at CK to determine if liver or mm problem is the underlying cause
Describe how CK levels change after injury.
It will increase within 1-2 hours of mm injury, peak at 6-12 hours and decrease over next 24-48 hours. If persistently elevated indicates ongoing damage. AST and ALT will increase more slowly
Define cholestasis. Which enzymes indicate this?
obstruction of bile flow with regurgitation of biliary substances into the blood. Enzymes = ALP and GGT
Where does ALP come from?
bile duct epithelium. increases with cholestasis. also found in boune so increased in young growing animals. Steroid induced isoform in dogs only not cats (so any increase in this species is significant).
Where is GGT derived from?
bile duct epithelium. also found in renal tubular cells so could be found in urine (not blood) if renal tubular damage is present
What is GGT used for?
it is a more sensitive indicator of cholestasis in large animals - ALP has a very wide range
Where can GGT be found in relation to neonates?
in the colostrum so will be increased in nursing animals
Measures of hepatic function - 7
bilirubin, albumin, urea, glucose, cholesterol, ammonia, bile acids
Describe bilirubin metabolism.
bilirubin is a RBC breakdown molecule, it is not water soluble, therefore it needs a carrier molecule (albumin) so it forms conjugated albumin in the liver. This is converted into urobilinogen (enters GIT) and is excreted in urine but some enters enterohepatic circulation (gives yellow colour to plasma). Stercobilinogen is found in GIT and is excreted in faeces.
How does fasting in horses affect bilirubun levels?
fasting for 24 hours or more will produce an increase in bilirubin
When might you see bilirubinaemia? 2
haemolysis and choelstasis
Describe bilirubinuria - normal?
low levels of bilirubin can be found normally in dog urine. Canine renal tubular epithelium can conjugate bilirubin.
Bilirubinuria in the cat is not normal and is always a significant finding. This may be present before elevation of bilirubin levels are detected in the plasma.
What are ammonia and urea both products of?
How much urea passes back into the GIT and how much is renally excreted?
25% to gut. 75% to renal excretion.
What should you do if urea is increased in the blood test?
Check urine for kidney problem - urea is used primarily to evaluate the renal system as its main route of excretion is via the kidneys.
What should you do if urea if found to be decreased in the blood?
Check the liver (major loss of function is indicated by this clinical sign). This is associated with decreased synthesis.
If ammonia levels are increased, what might you see? What should you do?
ammonium biurate crystals in the urine. run an ammonia tolerance test.
What does the ammonia tolerance test measure?
the liver's ability to maintain normal blood levels of ammonia both at rest and in response to challenge (an assessment of hepatic function)
Is glucose a sensitive indicator of hepatic function?
No - decreases in glucose production only occur with end-stage liver disease and there are other causes of hypoglycaemia (neoplasia and bacterial sepsis)
What might cause hyperglycaemia? 2
stress (mild increase) and DM
Where is cholesterol synthesised? When might it increase/decrease?
liver and excreted in bile (may increase or decrease with hepatic disease).
increases with cholestasis due to decreased excretion and endocrine disorders (DM and HAC) and varies inversely with T4 (increased with HYPOthyroidism and decreased with HYPERthyroidism).
decreases with hepatic failure due to decreased synthesis.
How do you measure bile acid concentration? Species differences?
2 readings - fasted levels and post-prandial. except horses where you have one sample - no gall bladder. not used in ruminants as the range is too wide.
what are the 2 main pathologic processes that cause bile acid concentration to increase in plasma?
-decreased BA clearance from portal blood (decreased functional hepatic mass or PSS)
-decreased BA exrection via bile (obstructive cholestasis)
On what grounds does the BA challenge test work?
adds increased work-load (challenge) to the BA system
What is 'blood ammonia'?
mostly NH4+ and very little NH3. Usually plasma and not blood
Why might ammonia's poor stability cause problems?
false increases and false decreases
Why might you get hyperammonaemia? 3
-decreased NH4+ clearance from the portal blood (decreased functional mass and PSS)
-urea cycle defect
-increased NH4+ intake (NH4+ tolerance test)
= spur cells. they are spiculated RBCs with projections of varying sizes and surface distribution. they appear contracted, dense and irregular
Hepatic lesions associated with acanthocytosis - 2
hemangiosarcoma and lipid metabolism defect
Pathogenesis - acanthocytosis
possibly vascular trauma, altered lipid composition of RBC membrane
Hepatic lesion causes of anaemia
hepatitis --> decreased functional mass
Codocytes, also known as target cells or Mexican hat cells, are red blood cells that have the appearance of a shooting target with a bullseye.
Hepatic lesion that would cause codocytes to be present on CBC
decreased functinal mass
Pathogenesis - codocyte formation
altered lipid composition on RBC membrane
Hepatic lesions associated with microcytosis 2
decreased functional mass or PSS
Pathogenesis - microcytosis
possibly decreased transferrin production and thus decreased delivery of iron to RBC precursors
What other lab tests should you do when evaluating the liver (other than enzymes, metabolites and function tests)? 3
-Others (coagulation assay, faecal exam, peritoneal fluid assays)
What signs of liver problems might you see with UA? 4
-ammonium biurate crystalluria
-hyposthenuria or isosthenuria
Why might you see ammonium biurate crystalluria?
decreased functional mass
Pathogenesis of - ammonium biurate crystalluria?
inadequate fixing of NH4+ into urea and decreased conversion of uric acid to allantoin
Hepatic lesion associated with bilirubinuria - 2
cholestasis and decreased Bc transport
Pathogenesis - bilirubinura
inadequate biliary excretion of bilirubin
Lesion associated with hyposthenuria or isosthenuria
decreased functional mass
Excretion of urine of low specific gravity due to an inability of the tubules of the kidneys to produce concentrated urine
excretion of urine that has not been concentrated by the kidneys and has the same osmolality as that of plasma.
Pathogenesis - hyposthenuria or isosthenuria
decreased renal medullary tonicity due to decreased urea concentration; increased NH4+ excretion may inhibit concentrating mechanism
Lesion associated with urate crystalluria
decreased functional mass
Pathogenesis - urate crystalluria
decreased conversion of uric acid to allantoin
What result of a coagulation assay suggest that there is a hepatic lesion?
increased PTT or PT
What hepatic lesion may cause increased PTT or PT? 2
cholestasis or decreased functional mass
Pathogenesis - increased PTT or PT? 3
-decreased vitamin K dependent coagulation factors due to impaired intestinal absorption of vitamin K.
-Decreased clearance of inhibitors of coagulation factors such as FDP.
-decreased production of most coagulation factors.
Cause of steatorrhea
Pathogenesis - steatorrhea
defective lipid digestion because bile acids not delivered to the intestine
What might be an indicator of hepatic disease on a peritoneal fluid analysis? Why might you see this? 2
transudate. decreased functional mass. cirrhosis
Pathogenesis - transudate from the peritoneal cavity 4
-increased Na+ and H20 retention,
-decreased plasma oncotic pressure,
-decreased lymphatic drainage.