Hepatobiliary system

Question 1

3 major types of hepatic abnormalities

Answer 1

1. Hepatocellular injury
2. Cholestasis
3. Functional mass abnormality

Question 2

3 tests to detect hepatocellular injury

w/ advantages / disadvantages

Answer 2

• • active injury
    1. ALT
    2. AST
    3. SDH

Question 3

Most specific test for Large animal hepatocellular injury

Answer 3

SDH

Question 4

What tests provide info about hepatocellular injury in Lg animal?

Answer 4

AST, SDH

Question 5

Serum ALP in cat/horse

Answer 5

• ** 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?

Question 6

What does ↑ GGT mean in LgA vs SmA

Answer 6

Lg – Primarily Cholestasis (hepatocellular injury)

Sm – ONLY cholestasis!

Question 7

Enzyme pattern in neonates

Answer 7

ALP
• ↑ due to osteoblast activity
GGT
• ↑ due to passive transfer (NOT foals!)

Question 8

With hepatocellular injury, does magnitude of enzyme correlate w/ severity?

Answer 8

NO

• mild diffuse lesions –> large increases
• focal/mulifocal necrosis –> about the same enzyme level (but irreversible damage)
• severe /chronic injury –> depletion of enzymes

Question 9

Why is injury a better term than “enzyme leakage”?

Answer 9

• 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

Question 10

Are injury and cholestasis related?

Answer 10

Yes

1. Injured cells often swell –> compressing biliary canaliculi –> 2° mild cholestasis
2. Cholestasis –> bile acids –> detergent action to cellular membrane –> hepatocellular injury

Question 11

Is hepatocellular injury assoc’d w/ ↓ fxn’l mass?

Answer 11

No. Common to have ↑ in injury markers, w/o change in fxn’l mass

Question 12

What biochemical changes are assoc’d w/ cholestasis?

Answer 12

• ↑ bile products (blood/urine)
  - Bilirubin
  - bile acids
• ↑ Membrane bound enzymes
  - ALP
  - GGT

Question 13

2 general mechanisms for ↓ functional mass

* how do you distinguish between them?

Answer 13

1. ↓ number of viable hepatocytes
   • severe injury, cirrhosis, atrophy, neoplasia, lipidosis
2. Vascular anomaly (bypass liver)

** when ↓ fxn’l mass is determined –> additional testing/imaging needed

Question 14

What amount of liver mass needs to be lost in order to be detected biochemically?

Answer 14

70-80%

Question 15

Why would you see ↑ in gamma globulins?

Answer 15

1. ↓ Ag clearing by Kupffer cells

2. ↑ Ig 1/2-life

Question 16

What are 4 important factors influencing enzyme interpretations?

Answer 16

1. Tissue specificity
2. Circulating 1/2 life
3. Sequential data
4. Localization of enzyme and expression

Question 17

Which liver enzymes are located in cytosolic/mitochondria?

Are they constitutive or induced?

Answer 17

ALT, AST, SDH
- constitutive - Set conc in cytoplasm

** Hepatocellular injury!

Question 18

Which liver enzymes are located in cell membrane?

Are they constitutive or induced?

Answer 18

ALP, GGT
- Induced overtime

** cholestasis

Question 19

ALT Tissue

Answer 19

Alanine Amino-Transferase
Dog & cat -- cell injury
- HEPATOCYTES ( > specific than AST)
- (muscle occasionally --MILD)
       - Severe muscle injury
       - congenital myopathy 

Not used in LA

Question 20

ALT 1/2 life

Answer 20

Dog
- ~2.5 Days

Cat
- 3.5 hrs ** more significant if high!

Question 21

AST Tissue

Answer 21

Aspartate Amino-Transferase

• HEPATOCYTES & MUSCLES & RBC’s
• Cellular injury –Cytosol & mitochondria
  - higher values assoc’d w/ cell death (mito)

**cannot be used alone

Question 22

AST 1/2 life

Answer 22

Dog / cat
24 hrs

Horse
4-7 Days

Question 23

ALP tissue

Answer 23

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)

Question 24

ALP 1/2 life

Answer 24

Dog
- 3 days

Cat (horse) –nearly all hepatic
- 6 Hrs

Question 25

Isoforms of Tissue unspecific isoenzyme

Answer 25

1. Hepatic (canicular surfaces)
2. Bone (osteoblasts)
   • significant in diff Isoforms

Question 26

Isoforms of Intestinal Isoenzyme

Answer 26

1. Intestinal (extremely short half life)
2. Corticosteroid-induced hepatic (cALP)
   • dog only
   • Corticosteroids OR Anticonvulsants
   • possible to ↑ w/ cholestasis too

Question 27

Interpreting ↑ ALP

Answer 27

> 4 fold ( 600 mg/dl )
• Pure cholestasis (hALP)
• Pure isoenzyme induction (cALP)
- mild ↑
• Mixed (Drug assoc’d hepatopathy)
- hALP & cALP

Question 28

Neonatal ALP

Answer 28

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

Question 29

GGT Tissue

Answer 29

Gamma Glutamyltransferase
- inducible enzyme of BILE DUCT EPITHELIAL CELLS > hepatocytes

** Small animal 
      • Cholestasis Specific!! 
** Lg Animal 
      • 1° cholestasis
      • also mild w/ injury
      • Biliary hyperplasia

Question 30

GGT 1/2 life

Answer 30

3 days 
(horse/dog/cat)

Question 31

Neonatal GGT values

Answer 31

↑ colostral GGT
• in CALVES/ LAMBS (dogs & cats)
• 5 fold ↑ in first 24hrs
• indirect confirm passive transfer

Question 32

SDH tissue

Answer 32

Sorbitol dehydrogenase (Iditol dehydrogenase)
• Cytosol of HEPATOCYTES
- liver specific (all species)
• substituted for ALT in Lg animal panels

Question 33

SDH 1/2 life

Answer 33

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