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Clin Chem 2 > Bilirubin/cholestasis/fxn mass > Flashcards

Bilirubin/cholestasis/fxn mass Flashcards

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1
Q

3 fractions of total bilirubin in dry reagent assays

A
  1. Unconjugated
  2. Conjugated
  3. Delta
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2
Q

Hyperbilirubinemia vs cholestasis

A

Hyperbilirubinemia

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

Interpreting cholestasis in horse

A

-

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4
Q

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

A

Dog:
ALP > GGT > Urine Bilirubin > Bc

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

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5
Q

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

A

-

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6
Q

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

A
  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
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7
Q

Total bilirubin

A
  • Measures all forms
  • sensitive to artifact
    • hemolysis
    • lipemia (non-fasted)
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8
Q

Unconjugated bilirubin measurements

A 
aka Indirect 
- soluble in alcohol to measure it
       = indirect approach
- soluble in plasma w/ protein binding
- insensitive to artifact
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9
Q

Causes for ↑ Bu

A

↓ hepatocyte uptake

↑ production (hemolysis

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10
Q

Causes for ↑ Conjugated bilirubin

A
  • Specific for cholestasis!

* * correction of cholestasis –> <24hr correction

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11
Q

Delta bilirubin

A
    • calculated
  • indicates PREVIOUS cholestasis
  • 1/2 life depends on protein binding half life (covalently bound)
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12
Q

Direct bilirubin measurements

A

Conjugated + Delta bilirubin

  • water soluble forms are measured
  • stays ↑ longer than Bc
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13
Q

Pre-hepatic pattern

A 
↑ Bu
1. Hemolytic disease
       • healthy liver not easily overwhelmed
       • --> hepatic compromise (ALT ↑)
       • --> swelling (GGT, Bc ↑)
2. Decreased uptake
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14
Q

What is the rate limiting step in hemolysis?

A

enzymatic conjugation of bilirubin in hepatocytes

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15
Q

If Bu & Bc are both ↑

A

ambiguous pattern

  • chronic pre/post-hepatic
  • acute intrahepatic
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16
Q

Intra-hepatic pattern

A
  • least specific pattern
  • Bc predominately ↑ & Bu ↑
    • except in horse
    • intraheptaic cholestasis –> Bc backup in blood
    • ↓ hepatocyte uptake –> Bu in blood
17
Q

Post-hepatic pattern

A
  • Almost entirely Bc
  • Obstruction of bile ducts –>back up of Bc
  • If acute –> ↑ Bc BEFORE induced enzymes (ALP/GGT)
  • chronicity –> hepatocellular injury
18
Q

Sensitivity for cholestasis in DOG

A

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 ↑
19
Q

Sensitivity for cholestasis in CAT

A

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
20
Q

Why could you see ↑ GGT/ALP w/o ↑ Bc?

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

- bile still excreted –> Bc stays normal in blood

21
Q

Sensitivity for cholestasis in HORSES

A

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

22
Q

How do you interpret ↑ direct bilirubin?

A

> 25% of Bt = cholestasis

23
Q

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

A
  • Pre-hepatic hyperbilirubinemia
    • fasting –> ↓ uptake –> 5x ↑Bu
    • ↓ 80% w/in 12 hrs
24
Q

Causes for ↓ BUN

A
  1. ↑ GFR

2. ↓ Hepatic fxn

25
Q

Causes for ↓ Albumin / ↑ Globulin

A
  1. ↓ hepatic fxn

2. Active inflammation

26
Q

Causes for ↓ cholesterol

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

Clin Chem 2 (6 decks)

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