EXAM #2: LIVER PATHOLOGY Flashcards Preview

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Flashcards in EXAM #2: LIVER PATHOLOGY Deck (73)
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1

What are the four most common causes of chronic liver disease in US? (List in order of prevalence)

1) Hepatitis C
2) Alcoholic liver disease
3) Non-alcoholic fatty liver disease
4) Hepatitis B

2

What is meant by hepatocyte integrity?

Membrane integrity of hepatocytes

****When damaged, hepatocytes are "leaky"****

3

What are the two classic liver lab tests?

AST
ALT

*****Finding these enzymes in the serum indicates that there has been damage to the hepatocytes that have made them "leaky"*****

4

What three lab tests test hepatocyte function? What happens to these tests with impaired liver function?

1) Serum albumin--decreased
2) Prothrombin time--increased
3) Serum ammonia--increased

5

What lab tests are associated with obstructed bile flow?

1) ALP
2) 5'-Nucleotidase (5'-NT)
3) GGT

6

What are the two types of bilirubin? What is the difference between direct and indirect bilirubin?

- Conjugated= Direct, has sugar moieties added and can be excreted
- Unconjugated= Indirect, no sugar moieties

*****Unconjugated is "indirect" b/c it is an indirect measurement (Total- conjugated= unconjugated)*****

7

What is the normal serum total bilirubin level?

0.1-1.2 mg/dL

8

What are the clinical manifestations of hyperbilirubinemia?

- Jaundice
- Cholestasis= slowing of the flow of bile

9

How high does the serum bilirubin need to be for there to be clinical symptoms?

Carvenale= greater than 2 mg/dL

Pathoma= greater than 2.5 mg/dL

10

Outline normal bilirubin metabolism.

1) RBCs are consumed by splenic macrophages
2) Protoporphyrin (from heme) is converted into UNCONJUGATED bilirubin (UCB)
- Heme oxygenase= Biliverdin
- Biliverdin reductase= Unconjugated Bilirubin
3) UCB binds albumin and is carried to the liver
4) In the hepatocyte ER, UCB is CONJUGATED to CB, via Uridine Glucuronyl Transferase (UGT)
5) CB is transferred to bili canaliculi via MDR-2 and MDR-3 transporters to form bile
6) Bile is stored in the gallbladder
7) Bile is released into the duodenum
8) Intestinal flora convert CB to UROBILINOGEN in the bowel
9) Urobilinogen is oxidized to STERCOBILIN and UROBILIN

11

What enzyme conjugates UCB in the hepatocyte?

UGT, Uridine Glucuronyl Transferase
- Adds one sugar to bilirubin i.e. monoglucuronides
- OR adds 2x sugars to make diglucuronides

(UGT1A1)

12

What heme degradation product gives stool its color?

Sterocobilin

13

What heme degradation product gives urine its color?

Urobilin

14

What is the etiology of hyperbilirubinemia seen in extravascular hemolysis or ineffective erythropoiesis?

- Increased UCB b/c of heme degradation
- UCB overwhelms liver's ability to conjugate

15

What is the lab finding in extravascular hemolysis/ ineffective erythropoiesis?

Elevated UCB

16

What are the clinical features of extravascular hemolysis/ ineffective erythropoiesis?

1) Dark urine due to increased urine UROBILINOGEN
2) Increased risk for pigmented bilirubin gallstones (excess UCB must eventually be converted to CB--hyperaccumulation of which can cause gallstones)

****Note that UCB is NOT water soluble and will NOT be in urine****

17

What is the etiology of physiologic jaundice of the newborn?

Newborns have transiently low UGT (UCB-->CB)

18

What is the lab manifestation in physiologic jaundice of the newborn?

Elevated UCB

19

What is the clinical manifestation of physiologic jaundice in the newborn?

Possible kernicterus
- UCB is fat soluble
- Deposits in the basal ganglia and causes neurologic deficits/death

20

How is physiologic jaundice of the newborn treated?

Phototherapy, which makes UCB more water souble

****Note that phototherapy does NOT conjugate UCB*****

21

What is the etiology of Gilbert Syndrome?

Mildly low UGT activity due to a promoter mutation

22

What is the inheritance pattern of Gilbert Syndrome?

Autosomal recessive

23

What lab finding is associated with Gilbert Syndrome?

Elevated UCB

24

What are the clinical features associated with Gilbert Syndrome?

1) Predominantly asymptomatic
2) STRESS e.g. severe infection causes hyperbilirubinemia

25

What is the etiology of Crigler-Najjar Syndrome Type I?

Autosomal recessive absence of UGT

26

What is the lab finding in Crigler-Najjar Syndrome?

Extremely elevated UCB

27

What are the clinical manifestations of Crigler-Najjar Syndrome?

Kernicterius that is typically fatal

28

How does Crigler-Najjar Syndrome Type 2 differ from Type 1?

Type 2=
- AUTOSOMAL DOMINANT with variable penetrance
- Moderate decrease in UGT activity
- Only occasional kernicterus

****NOTE that this is TREATED WITH PHENOBARBITAL*****

29

What is the etiology of Dubin-Johnson Syndrome?

Autosomal recessive mutation in MDR-2 transporter that impairs CB transfer to bile canaliculi

30

What lab finding is associated with Dubin-Johnson Syndrome?

Elevated CB