Bilirubin/cholestasis/fxn mass

Question 1

3 fractions of total bilirubin in dry reagent assays

Answer 1

1. Unconjugated
2. Conjugated
3. Delta

Question 2

Hyperbilirubinemia vs cholestasis

Answer 2

Hyperbilirubinemia

1. Pre-hepatic
2. Hepatic
3. Post hepatic – Cholestasis

Question 3

Interpreting cholestasis in horse

Answer 3

-

Question 4

Rank diagnostic tests according to typical pattern of sensitivity for detecting cholestasis

Answer 4

Dog:
ALP > GGT > Urine Bilirubin > Bc

Cat/Horse:
GGT > ALP > SERUM Bc > urine bilirubin

Question 5

What are the exceptions to the ranking cholestasis tests? Whats the significance?

Answer 5

-

Question 6

List test results from routine profile that is altered w/ ↓ fxn’l mass
Mechanisms for each.

Answer 6

1. BUN (Urea)
   • ↓ ammonia metabolism
2. Proteins must rule out Active inflammation
   • Albumin ↓
   • Globulin varies - commonly ↑
   -↓ Kupffer cells –> GI Ag processed in LN
   –> Ig production
   - ↓ Ig clearance in liver –> longer 1/2 life
3. Glucose
   • ↓ ↓ during fasting – lack of glycogen stores
   -longer insulin 1/2 life
   –> lack of uptake –> seizures
   • ↑ Post-prandial – ↓ hepatic uptake
4. Cholesterol
   • ↓ synth
   • < 75 in dog – pathoneumonic for liver fxn
5. Unconjugated Bilirubin
   • ↓ Bu uptake –> ↑ Bu in serum
6. Coagulation
   • 10, 9, 7, 2
7. Microcytic, normochromic (non-anemic)
   • Portosystemic shunts –> ↓ iron metabolism
   –Target cells (lipid loading)
8. Ammonium biurate (Urine) & Isosthenuria
   • ↑ circulating ammonia –> crystals
   • tyrosine / leucine crystals possible

Question 7

Total bilirubin

Answer 7

• Measures all forms
• sensitive to artifact
  • hemolysis
  • lipemia (non-fasted)

Question 8

Unconjugated bilirubin measurements

Answer 8

aka Indirect 
- soluble in alcohol to measure it
       = indirect approach
- soluble in plasma w/ protein binding
- insensitive to artifact

Question 9

Causes for ↑ Bu

Answer 9

↓ hepatocyte uptake

↑ production (hemolysis

Question 10

Causes for ↑ Conjugated bilirubin

Answer 10

• Specific for cholestasis!

* * correction of cholestasis –> <24hr correction

Question 11

Delta bilirubin

Answer 11

• • calculated
• indicates PREVIOUS cholestasis
• 1/2 life depends on protein binding half life (covalently bound)

Question 12

Direct bilirubin measurements

Answer 12

Conjugated + Delta bilirubin

• water soluble forms are measured
• stays ↑ longer than Bc

Question 13

Pre-hepatic pattern

Answer 13

↑ Bu
1. Hemolytic disease
       • healthy liver not easily overwhelmed
       • --> hepatic compromise (ALT ↑)
       • --> swelling (GGT, Bc ↑)
2. Decreased uptake

Question 14

What is the rate limiting step in hemolysis?

Answer 14

enzymatic conjugation of bilirubin in hepatocytes

Question 15

If Bu & Bc are both ↑

Answer 15

ambiguous pattern

• chronic pre/post-hepatic
• acute intrahepatic

Question 16

Intra-hepatic pattern

Answer 16

• least specific pattern
• Bc predominately ↑ & Bu ↑
  • except in horse
  • intraheptaic cholestasis –> Bc backup in blood
  • ↓ hepatocyte uptake –> Bu in blood

Question 17

Post-hepatic pattern

Answer 17

• Almost entirely Bc
• Obstruction of bile ducts –>back up of Bc
• If acute –> ↑ Bc BEFORE induced enzymes (ALP/GGT)
• chronicity –> hepatocellular injury

Question 18

Sensitivity for cholestasis in DOG

Answer 18

ALP > GGT > Urine Bilirubin > Bc
• enzymes before Bc backup
• low renal threshold
• collateral bile flow – prevent significant bilirubin back up

• • Except:
• Acute post-hepatic obstruction
  - Bc back up precedes enzyme ↑

Question 19

Sensitivity for cholestasis in CAT

Answer 19

GGT > ALP > SERUM Bc > urine bilirubin
• Higher renal threshold

• *Except:
  
  1. Acute Post-hepatic obstructions (Bc > enzymes)
  2. Hepatic LIPIDOSIS - ALP&raquo_space;> GGT
  3. Fxn’l cholestasis
     - exrahepatic endotoxins interfere with enzyme production

Question 20

Why could you see ↑ GGT/ALP w/o ↑ Bc?

Answer 20

• Small area of bile back up –> ↑ induced enzymes

- bile still excreted –> Bc stays normal in blood

Question 21

Sensitivity for cholestasis in HORSES

Answer 21

GGT > ALP > Bc > urine bilirubin (Same as cat)

• ALP & Bc = Cholestasis specific
• GGT sensitive but NOT Specific!
- liver specific but not cholestasis
• Bu = major bilirubin fraction always

Question 22

How do you interpret ↑ direct bilirubin?

Answer 22

> 25% of Bt = cholestasis

Question 23

If a horse is fasted for a few days, what would you expect to see in the blood work?

Answer 23

• Pre-hepatic hyperbilirubinemia
  • fasting –> ↓ uptake –> 5x ↑Bu
  • ↓ 80% w/in 12 hrs

Question 24

Causes for ↓ BUN

Answer 24

1. ↑ GFR

2. ↓ Hepatic fxn

Question 25

Causes for ↓ Albumin / ↑ Globulin

Answer 25

1. ↓ hepatic fxn

2. Active inflammation

Question 26

Causes for ↓ cholesterol

Answer 26

1. ↓ hepatic fxn 
       • mild to severe 
       • severe =pathoneumonic
2. Severe malnutrition
3. Lymphangectasia 
        • severe pooling of lymph in GI