Laboratory Diagnosis of Liver Disease Flashcards
How can the liver be evaluated?
Enzymes
Metabolites
Function tests
What enzymes indicate hepatocellular damage?
Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Sorbitol dehydrogenase (SDH) Glutamate dehydrogenase (GLDH)
These are leaked directly from the hepatocytes and indicate damage or necrosis of these cells
Which liver is most commonly used in dogs and cats to indicated hepatocellular damage?
ALT
- Will increase within 12 hours of injury
- Peak at 1-2days
- Decrease over 2-3weeks
GLDH
Considered to be liver specific but assays for smallies rarely available
What is the sequence of events of hepatocellular damage?
- ATP depletion due to hypoxia or mitochondrial toxins
- Membrane damage due to oxidants or other agents
- NECROSIS
- Membrane blebbing
Why are SDH and/or GLDH used to indicate damage in large animals?
Hepatic ALT activity is very low
What pattern of AST and ALT would you expect in an animal that had undergone muscle damage?
Increased AST
Slight increased ALT
Check creatinine kinase levels as more muscle specific
Describe the pattern of CK following muscle injury…
Increased within 1-2hours of injury
Peaks at 6-12 hours
Decreases over the following 24-48hours
What does persistent elevation of CK indicate?
Persistent muscle damage
What is cholestasis?
Obstruction of bile flow with regurgitation of biliary substances into the blood
What enzymes indicate cholestasis?
ALP - Alkaline phosphatase
GGT - Gammaglutamyltransferase
Where is alkaline phosphatase (ALP) found?
Derived from the bile duct epithelial
Bone (so increased in growing animal)
Where has ALP been isolated in dogs?
Kidney Liver Bone Placenta Intestines Sterioids
What can cause an increased ALP in dogs?
Age Breed Drug induced Cushing's Primary hepatic biliary disease Systemic disorders Bone related disorders
What other compound could be mistaken for ALP? In which species?
Steroid isoform (dogs) Not found in cats, so any increase in ALP is always significant (e,g hyperthryoid)
Why does ALP increase? How is it different from ALT?
Some ALP ready formed on membrane. An induced induces ALP production by the cells (-1week)
ALT is released due to trauma
Where is gammaglutamyltransferase (GGT) found?
Bile duct epithelium
Colostrum
Increased in nursing animals
Renal tubular cells
can be found in urine (not blood) if renal tubular damage is present
What can be used to measure hepatic function?
Bilirubin Albumin Urea Glucose Cholesterol Ammonia Bile acids
How is bilirubin metabolised?
- Broken down RBC releases BU (not water soluble)
- Bound to albumin in blood
- Enters liver (but must be unbound from albumin)
- Metabolised and conjugated - becomes water soluble
- Enters canaliculi (rate limiting step)
- Bile -> gut
- Bacteria act on conjugated BU and forms urobilirubin or stercobilirubin
- Taken up by receptors in ileum, enters hepatic portal vein and re-enters liver or blood stream
- Urobilinogen and albumin bound in blood where it passes through the kidneys and is excreted as unbound bilirubin or urobilinogen
What does bilirubinuria indicate?
Low levels are normal in the dog
In the cat, always significant
What can cause increases in cholesterol?
Cholestasis due to decreased excretion
Hepatic disease (but may decrease)
Post prandial
Endocrine disorders including diabetes mellitus and hyperadrenocorticism
Increases variation with T4
+ Increased with hypothyroidism
- Decreased with hyperthyroidism
What can cause decreases in cholesterol?
Hepatic failure
decreased synthesis
Hyperthyroidism
Is a change in blood glucose a reliable indicator for hepatic disease?
No; decreases only with end stage disease
+ Hyperglycaemia may be caused by stress and DM
- Hypoglycaemia also caused by sepsis, neoplasia, starvation
What is the basis of the bile acid test?
Measure fasting and postprandial
During the fasting stage, bile acid are stored in the gall bladder, released after feeding.
Measure singularly in the horse as no gall bladder
Why do you need to be careful when measuring ammonium concentration?
It has very low stability.
