Liver Disease Lab Dx Flashcards
What 3 substances can be used to evaluate the liver?
- Enzymes
- Metabolites
- Function tests
Give 4 enzymes which indicate hepatocellular damage. Why are they seen in association with hepatocellular damage?
- ALT
- AST
- SDH
- GLDH
> leak directly from cells when hypoxia/oxidants/mitochondrial toxins -> ATP depletion -> membrane “blebbing” and production of blebosomes or necrosis of the cell
> levels increase rapidly with cell damage as substances already produced and contained in cells
Which is the most common enzyme looked at in cats and dogs? When will levels rise/fall? Is it liver specific?
ALT - also found in muscle but only at v. low levels
- ^ within 12hours injury
- peak 1-2d
- falls over 2-3w
Is the same most common enzyme analysed in large and small animals?
No - ALT activity in large animals is very low
- Use SDH or GLDH
- GLDH = liver specific but rarely available to look at in smallies
Which hepatocellular enzyme is found in high levels but is not liver specific? Where else is it found?
AST - also derived from muscle and RBCs in fairly high concentration (~= ALT)
Which enzyme is muscle specific? When will levels rise/fall?
CK (more rapid changes) - ^ within 1-2hrs - Peak 6-12hrs - Decrease over 24-48hrs > If persistently high indicates ongoing damage
Give 2 enzymes that indicate cholestasis. Where are they derived from?
- ALP
- GGT
> derived from bile duct epithelium (amongst oher places)
Define cholestasis
Obstruction of bile flow with regurgitation of biliary substances into he blood
Where else is ALP found and hwo may this influence results?
> Bone - will be higher in young growing animals
> Steroid induced isoform in DOGS only (due to stress or dugs)
In which species is any increase in ALP particularly significan?
Cats (no steroid induced isoform, short half life)
What is the most common cause of ALP in cats?
Hyperthyroidism
When would “induction” related increases be seen vs “leakage”?
Induction eg. after steroid injection = 1 week later
Leakage = instantaneously
Which enzyme is a more sensitice indicator of cholestasis in large animals?
GGT (ALP has a v. large range)
Where is GGT found other than bile duct epithelium?
- Colostrum -> ^ in nursing animals
- renal tubular cells -> urine if tubular damage present
How can differences in ALT and ALP be remembered?
- alT = trauma [not related to liver FUNCTION]
- alp = production [induction]
Give 7 measures of hepatic FUNCTION
- bilirubin
- albumin
- urea
- glucose
- cholesterol
- ammonia
What is the average lifespan of a red blood cell?
120d
Outline the pathway of RBC breakdown
- RBC breakdown
- Hbg -> bilirubin (not water soluable
- Albumin bound unconjugated bilirubin transported in blood -> liver, dissociates
- Hepatocytes uptake and conjugate -> bile -> gut
- Converted to urobiligen and stercobiligen for excretion
How does dogs metabolism of bilirubin differ to other species?
Capable of excreting small amouns of unconjugated bilirubin directly from he kidneys
Why is serum/plasma yellow?
Bilirubin”
In which species does bilirubin increase dramatically with fasting?
Horses (fasting >24 huors)
What effect on bilirubin levels would ^ haemolysis have a) initially? b) longterm?
a) ^ UNconjugated bilirubin
b) ^ conjugated aswell (due to rate limiting step being excretion -> bile)
What is the rate limiting step of bilirubin metabolism?
excretion -> bile
In which species is low level bilirubinuria found normally?
Dogs (canine renal tubular epithelium can conjugate bilirubin)
In which species is bilirubinaemia always significant?
Cats (may be seen before ^ levels deeced in the blood)
What are he 2 products of protein metabolism?
Ammonia and Urea (ammonia derived from gut, travels -> liver via poral circulation and converted to urea)
Which system does v/^ urea in the blood/urine(?) indicate a problem in? What else may be seen with liver disease?
v = liver
^ = kidney
- ammonium biurate crystals in urine due to high ammonia levels
Are glucose levels often affected by hepatic disease?
- Not sensitive - decreases only with end stage liver disease
- hypoglyceamia caused by neoplasia and bacterial sepsis
- hyperglycaemia caused by stress and diabetes mellitits
Is cholesterol a useful biomarker of liver function?
NO! Can be
- increased (cholestasis and v excretion)
- decreased (v synthesis)
- the same if both parts diseased!
> ^ with endocrine disorders (DM, Cushings)
> varies inversely with T4 (^hypothyroidism, v hyperthyroidism)
WHy are bile acids recycled in enterohepatic recirculation?
High energy for production
How is bile acid concentration used to monitor hepatic function in different species?
- measure fasted
- measure post-prandial
> tests hepatic uptake - horses: measure single sample as no gall bladder
- not often used in ruminants (range too wide)
What 2 major pathologic processes does ^ [BA] indicate?
- v clearance from portal blood, v functional mass [ie. not being reuptaken by hepatocytes] or PSS
- v BA excretion via bile ( Obstructive cholestasis)
Which parameter can be measured to evaluate hepatic function but rarely is?
Ammonium (NH4+) concentration [indications similar to bile acids]
- test not feasible as stability poor
Are liver enzymes and function tests sufficient to determine the undelying cause of liver lesion?
No - FNA or biopsy required
Look at lecture for other lab findings to take into account
