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Clin Chem exam 2 > Hepatobiliary - bilirubin, cholestasis, and functional mass > Flashcards

Hepatobiliary - bilirubin, cholestasis, and functional mass Flashcards

1
Q

What bilirubin tests are sensitive or insensitive to artifact like lipemia or hemolysis?

A

Total bilirubin = sensitive
Bu - insensitive
Bc - insensitive

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2
Q

What is the more sensitive way of measuring bilirubin?

A

bilirubin subfractions Bu and Bc

more reliable than Bt

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3
Q

What is another name for unconjugated bilirubin? Why?

A

Indirect

When we run the assay to measure Bu, we indirectly measure it by adding alcohol to solubalize it

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4
Q

What is another name for conjugated bilirubin? Why?

A

Direct

We directly measure it with the assay

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5
Q

What is the approximate half life for Bd? Why?

A

3-10 days

So long because it depends on the half life of the protein it is bound to.

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6
Q

How can you calculate the Bd of a sample with bichem results?

A

Bt - Bu - Bc = Bd

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7
Q

Although conjugated bilirubin is synonymous with direct bilirubin, what do we mean when we say direct bilirubin in the lab?

A

Direct bilirubin in the lab = Bc + Bd

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8
Q

What is the disadvantage of a direct bilirubin reading in the lab?

A

With cholestasis, direct bilirubin values remain elevated longer than Bc because of the influence of Bd – this can mislead clinicians to think that active cholestasis is still present.

Not able to distinguish b/w active and previous cholestasis

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9
Q

What is the extended bilirubin profile?

A

measures Bt, Bu, Bc, Bd

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10
Q

What are the three types of hyperbilirubinemia?

A

Pre-hepatic
Hepatic
Post-hepatic

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11
Q

Can cholestasis be pre-hepatic?

A

NO

hepatic or post hepatic cause!

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12
Q

What is the classic pattern for pre-hepatic hyperbilirubinemia?

A

increase in Bu and no increase in Bc (or at least proportionately very little Bc)

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13
Q

What are two major mechanisms for pre-hepatic hyperbilirubinemia?

A
  1. hemolytic disease

2. decreased uptake of Bu (decreased hepatocytes or decreased functional mass)

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14
Q

What is the mechanism to get increased Bu due to hemolytic disease w/o Bc increase?

A

Bu uptake by a healthy liver is not easily overwhelmed!

For Bu to increase before Bc – severe hemolysis –> hypoxic injury –> comprise hepatocyte uptake function

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15
Q

How can hemolytic disease lead to both Bu and Bc increase in the blood – suggesting cholestasis?

A

Uptake of Bu and conjugation may exceed ability to excrete Bc into bile canaliculi –> increase Bc in plasma

Hypoxic injury –> swelling –> physical obstruction of bile outflow

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16
Q

What is the rate limiting step in conjugation/excretion?

A

ability to excrete Bc into bile canaliculi

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17
Q

What is the pattern seen for intrahepatic hyperbilirubinemia?

A

Mixture of increased Bc and Bu – Bc will usually predominate in all except horses

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18
Q

What is the mechanism for intrahepatic hyperbilirubinemia?

A

intraheptaic cholestasis –> backup of Bc into the blood

hepatocytes are compromised in ability to take up Bu –> increase Bu in blood

19
Q

Why is the pattern for intrahepatic hyperbilirubinemia least specific?

A

Chronic prehepatic or posthepatic can appear as intraheptic.

If there is no evidence of prehepatic (hemolysis) or posthepatic, call it intrahepatic.

20
Q

What is the classic pattern of post-hepatic hyperbilirubinemia?

A

almost exclusively Bc

21
Q

What is the mechanism for post-hepatic hyperbilirubinemia?

A

Obstruction of common bile duct (tumor, stone, pancreatitis) –> backup of Bc into blood

If acute – Bc may be elevated before cholestasis induces increase production of ALP or GGT

22
Q

What happens with post-hepatic hyperbilirubinemia progression?

A

secondary hepatocellular injury –> may interfere with Bu uptake –> mixed pattern –> can no longer be differentiated from intrahepatic

23
Q

What are most sensitive for cholestasis in the dog?

A

ALP > GGT > urine bilirubin > serum bilirubin (Bc)

24
Q

What are most sensitive for cholestasis in horse and cat?

A

GGT > ALP > serum Bc > urine bilirubin

25
Q

Why is urine bilirubin seen before serum bilirubin in dogs?

A

Normal levels are too low to measure in blood

Low renal threshold allows Bc to overflow into urine before serum Bc is detectable

26
Q

What should you consider in a dog that has increased Bc before increase in enzymes?

A

Acute post-hepatic obstructions

27
Q

What are the primary exceptions for sensitivity for cholestasis in cats?

A
  1. acute post hepatic obstruction – Bc precedes enzymes
    * *** 2. Hepatic lipidosis - large elevations of ALP with normal or mildly increased GGT: not pathognomonic but very suggestive
  2. Functional cholestasis (uncommon) - extrahepatic dz such as FIP or septicemia: Bc may increase alone or may precede enzymes
28
Q

What is the primary way of dx FIP in cats?

A

liver biopsy

29
Q

What are the most specific measures of cholestasis (intra or post hepatic) in adult horses?

A

ALP or Bc

30
Q

When does increase ALP occur in neonatal horses?

A

first year

31
Q

What is the difference b/w ALP and GGT in cholestasis in horses?

A

ALP - specific measure!

GGT - sensitive, not specific: may indicate injury

32
Q

What is unique about equine bilirubin?

A

regardless of the process, Bu is (almost) always the major bilirubin fraction in horses
ANY increase in Bc = cholestasis

33
Q

What are the pre-hepatic hyperbilirubinemia causes in horses?

A
  1. Hemolytic disease (increase production)
  2. Decreased uptake
    - fasting hyperbilirubinemia (major cause)
    - hepatocellular injury/decreased functional mass
34
Q

How can you tell if there is a fasting hyperbilirubinemia in horses?

A

5x increases in Bu w/in 2.5-5.5 days of fasting

should decrease by 80% w/in 12 hours after eating

35
Q

When the bilirubin profile is Bt, Bu, Direct (Bc+Bd) what is suggestive of cholestasis?

A

direct > 25% of Bt = cholestasis

36
Q

What bilirubin profile is best to look at cholestasis?

A

Bt, Bu, Bc, and Bd (purdue does this!)

37
Q

What are the two distinct types of conditions that cause decreased functional mass?

A
  1. Loss of functional hepatocytes

2. Vascular shunts that bypass hepatocytes (congenital or aquired)

38
Q

What may cause loss of functional hepatocytes?

A

Severe cirrhosis – small liver
fibrosis – small liver
infiltrative process damaging and/or replacing hepatocytes (neoplasia, lipidosis) – big liver

39
Q

What may be seen on biochemistry with decreased hepatic functional mass?

A
  1. Decreased BUN w/ normal or decreased creatinine depending on medullary washout situation
  2. Decrease albumin
  3. Increase globulins: decreased clearance during antigenic stimulation
  4. Decrease globulins: decrease non-Ig protein production
  5. Fasted glucose levels decreased: hepatic glycogen stores are decreased
  6. Post-parandial glucose levels increase - decreased hepatic uptake
  7. Decrease cholesterol
  8. Decrease Bu – decrease uptake/fewer receptors
40
Q

What is the half life of albumin in dogs and cats? Horses?

A

Dogs and cats: 8-10 days

Horses: 21 days

41
Q

What two things do you have to rule out with hypoproteinemia before assuming it’s decrease hepatic functional mass?

A

Renal loss

GI loss

42
Q

What is almost pathognomonic for decrease hepatic functional mass in dogs?

A

cholesterol < 75 mg/dl

43
Q

Besides what is seen on biochemistry, what else may be seen with decrease hepatic functional mass?

A
  1. Decreased vitamin K dependent clotting factors (II, VII, IX, X) – prolonged PT/PTT
  2. Microcytic, normochromic, normal hematocrit – abnormal Fe metabolism in presence of normal Fe stores
  3. target cells w/o significant anemia or regeneration
  4. ammonia biurate crystals – increased circulating ammonia
  5. tyrosine and leucine crystals (maybe)– severe liver dz: not indicative of decreased fnx mass
  6. polyuria +/- non concentrated USG - medullary washout

Clin Chem exam 2 (6 decks)

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