Hepatobiliary system Flashcards
3 major types of hepatic abnormalities
- Hepatocellular injury
- Cholestasis
- Functional mass abnormality
3 tests to detect hepatocellular injury
w/ advantages / disadvantages
- active injury
1. ALT
2. AST
3. SDH
- active injury
Most specific test for Large animal hepatocellular injury
SDH
What tests provide info about hepatocellular injury in Lg animal?
AST, SDH
Serum ALP in cat/horse
- ** ANY ↑ is significant!!!!–> cholestsis**
1. Short 1/2 life = 6 hrs
2. Nearly all hepatic - Liver ALP is 3x lower than in dog
** Queens –> mild ↑ = Placental?
What does ↑ GGT mean in LgA vs SmA
Lg – Primarily Cholestasis (hepatocellular injury)
Sm – ONLY cholestasis!
Enzyme pattern in neonates
ALP
• ↑ due to osteoblast activity
GGT
• ↑ due to passive transfer (NOT foals!)
With hepatocellular injury, does magnitude of enzyme correlate w/ severity?
NO
- mild diffuse lesions –> large increases
- focal/mulifocal necrosis –> about the same enzyme level (but irreversible damage)
- severe /chronic injury –> depletion of enzymes
Why is injury a better term than “enzyme leakage”?
- Reversable lesions –> Blebbing –> release of membrane-bound cytosolic fragments –> break down and release in circulation
- Irreversible injury/necrosis –> holes big enough for enzymes to leak out (& other important e-lytes) –> cellular death
Are injury and cholestasis related?
Yes
- Injured cells often swell –> compressing biliary canaliculi –> 2° mild cholestasis
- Cholestasis –> bile acids –> detergent action to cellular membrane –> hepatocellular injury
Is hepatocellular injury assoc’d w/ ↓ fxn’l mass?
No. Common to have ↑ in injury markers, w/o change in fxn’l mass
What biochemical changes are assoc’d w/ cholestasis?
- ↑ bile products (blood/urine)
- Bilirubin
- bile acids - ↑ Membrane bound enzymes
- ALP
- GGT
2 general mechanisms for ↓ functional mass
* how do you distinguish between them?
- ↓ number of viable hepatocytes
• severe injury, cirrhosis, atrophy, neoplasia, lipidosis - Vascular anomaly (bypass liver)
** when ↓ fxn’l mass is determined –> additional testing/imaging needed
What amount of liver mass needs to be lost in order to be detected biochemically?
70-80%
Why would you see ↑ in gamma globulins?
- ↓ Ag clearing by Kupffer cells
2. ↑ Ig 1/2-life
What are 4 important factors influencing enzyme interpretations?
- Tissue specificity
- Circulating 1/2 life
- Sequential data
- Localization of enzyme and expression
Which liver enzymes are located in cytosolic/mitochondria?
Are they constitutive or induced?
ALT, AST, SDH
- constitutive - Set conc in cytoplasm
** Hepatocellular injury!
Which liver enzymes are located in cell membrane?
Are they constitutive or induced?
ALP, GGT
- Induced overtime
** cholestasis
ALT Tissue
Alanine Amino-Transferase
Dog & cat -- cell injury
- HEPATOCYTES ( > specific than AST)
- (muscle occasionally --MILD)
- Severe muscle injury
- congenital myopathy
Not used in LA
ALT 1/2 life
Dog
- ~2.5 Days
Cat
- 3.5 hrs ** more significant if high!
AST Tissue
Aspartate Amino-Transferase
- HEPATOCYTES & MUSCLES & RBC’s
- Cellular injury –Cytosol & mitochondria
- higher values assoc’d w/ cell death (mito)
**cannot be used alone
AST 1/2 life
Dog / cat
24 hrs
Horse
4-7 Days
ALP tissue
Alkaline phosphase
• inducible enzyme of hepatocytes in response to cholestasis
• 2 isoforms modified into tissue specific forms
- Tissue Unspecific isoenzyme
- Intestinal isoenzyme
• cALP = Dog specific (coricosteroid-induced)
ALP 1/2 life
Dog
- 3 days
Cat (horse) –nearly all hepatic
- 6 Hrs
Isoforms of Tissue unspecific isoenzyme
- Hepatic (canicular surfaces)
- Bone (osteoblasts)
• significant in diff Isoforms
Isoforms of Intestinal Isoenzyme
- Intestinal (extremely short half life)
- Corticosteroid-induced hepatic (cALP)
• dog only
• Corticosteroids OR Anticonvulsants
• possible to ↑ w/ cholestasis too
Interpreting ↑ ALP
> 4 fold ( 600 mg/dl )
• Pure cholestasis (hALP)
• Pure isoenzyme induction (cALP)
- mild ↑
• Mixed (Drug assoc’d hepatopathy)
- hALP & cALP
Neonatal ALP
Foal, Calf, Puppy
1-2 wks –> Moderate/marked ↑ ALP (1,-3,000)
4 wks –> moderate ↑ ALP (800-900)
• osteoblast activity (bALP)
–> declines to 200-300 by 6 months
GGT Tissue
Gamma Glutamyltransferase
- inducible enzyme of BILE DUCT EPITHELIAL CELLS > hepatocytes
** Small animal
• Cholestasis Specific!!
** Lg Animal
• 1° cholestasis
• also mild w/ injury
• Biliary hyperplasia
GGT 1/2 life
3 days (horse/dog/cat)
Neonatal GGT values
↑ colostral GGT
• in CALVES/ LAMBS (dogs & cats)
• 5 fold ↑ in first 24hrs
• indirect confirm passive transfer
SDH tissue
Sorbitol dehydrogenase (Iditol dehydrogenase)
• Cytosol of HEPATOCYTES
- liver specific (all species)
• substituted for ALT in Lg animal panels
SDH 1/2 life
VERY SHORT
• single insult --> return to reference interval in 2-5 days
• unstable in serum (even if frozen)
-- run w/in 8-12 hrs
-- 25% ↓ in 1wk if frozen
