04b: Liver Stuff

Question 1

Liver disease longer than (X) period of time is considered chronic

Answer 1

X = 6 months

Question 2

Patients considered to be in fulminant hepatic failure presented with which symptoms only (X) weeks after onset of liver disease.

Answer 2

X = 6

Encephalopathy, hypoglycemia, hypoalbuminemia, low coag factors

Question 3

The jaundice seen in liver disease is almost always associated with which other symptom?

Answer 3

Dark urine (due to high direct BR)

Question 4

T/F: pruritis and maculopapular rash are important features of liver disease

Answer 4

False - rash-less pruritis is

Question 5

T/F: liver disease symptoms include hypercoaguable states

Answer 5

True - decreased synthesis of antithrombin III, Protein C and S

Question 6

List the key clinical signs that make liver disease in a patient obvious.

Answer 6

1. Jaundice
2. Muscle wasting
3. Ascites
4. Palmar erythema
5. Spider angioma

Question 7

Enlargement of the spleen in the setting of liver disease is usually due to:

Answer 7

portal hypertension

Question 8

A cirrhotic liver feels (X) upon palpating

Answer 8

Firm and nodular

Question 9

Liver function tests usually include (X) hepatocellular enzymes and (Y) canalicular enzymes.

Answer 9

X = AST, ALT
Y = ALP, GGT

Question 10

Most commonly used tests of hepatic synthetic function include:

Answer 10

1. Albumin

2. PT (replaced by INR)

Question 11

Most commonly used tests of hepatic excretory function include:

Answer 11

BR

Question 12

(ALT/AST) is less specific to liver since it is also found in high concentrations in (X) cells.

Answer 12

AST

Pancreas, RBCs, muscle, kidney

Question 13

An increase in (AST/ALT) that’s out of proportion to (AST/ALT) suggests alcoholic hepatitis/drug-induced injury.

Answer 13

AST&raquo_space; ALT

Likely due to extra-hepatic release as well

Question 14

Increased levels of alkaline phosphatase is found as result of extra-hepatic reasons such as:

Answer 14

1. bone disease (Paget’s)
2. pregnancy
3. intestinal injury (ischemia).

Question 15

Increased levels of alkaline phosphatase (with normal AST/ALT) is found as result of hepatic diseases such as:

Answer 15

1. Bile duct obstruction

2. Cholestatic liver diseases (primary biliary cirrhosis, sclerosing cholangitis, drug-induced cholestatic liver injury)

Question 16

Hepatic cause for high ALP can be confirmed with (X) test.

Answer 16

X = GGT (should see parallel increase)

Question 17

GGT is a (specific/sensitive) test for liver injury.

Answer 17

Sensitive (but not specific for any one disease since elevated in nearly all forms of liver disease)

Question 18

T/F: liver disease can be ruled out with normal serum albumin levels.

Answer 18

False - long half-life of albumin means acute liver disease in patient may present with normal albumin

Question 19

Based on the (short/long) half life of (X), which test is extremely useful for monitoring liver function in patients with acute liver injury?

Answer 19

Short;
X = clotting factors

PT/INR

Question 20

List examples of diseases that present with hepatitic pattern of disease (high ALT/AST).

Answer 20

1. Viral/autoimmune hepatitis

2. Acute drug toxicity (ex: acetaminophen)

Question 21

List the most common diseases that would cause AST/ALT rise over 1000!

Answer 21

1. Viral hepatitis
2. Drug/toxin-mediated hepatitis
3. Ischemic hepatitis

Question 22

“Mixed” (cholestatic and hepatitic) pattern of liver disease is only really seen in which cases?

Answer 22

chronic diseases (cirrhosis, some cases of metastasis)

Question 23

What are some causes for cholestatic pattern of liver disease (high ALP/GGT)?

Answer 23

1. Bile duct obstruction
2. Metastatic disease to liver
3. Infiltrative disorders
4. Granulomatous disease
5. Autoimmune (preferentially affecting biliary ductules)

Question 24

BR is formed from breakdown of:

Answer 24

Heme:

1. Myoglobin
2. Hemoglobin
3. Cytochromes

Question 25

T/F: Liver is major site of BR production.

Answer 25

False - spleen! 70-80% BR from hemoglobin from senescent RBCs

Question 26

In ecchymoses (bruises), (X) process is occurring in (Y) cells.

Answer 26

``` X = Heme breakdown and BR formation Y = macrophages ```

Question 27

BR formation: here is converted to (X) by (Y). What color is (X)?

Answer 27

``` X = biliverdin Y = heme oxygenase ``` Blue/green

Question 28

Biliverdin is converted to (X) via cytosolic (Y).

Answer 28

``` X = BR Y = Biliverdin reductase ```

Question 29

T/F: both biliverdin and BR are water insoluble.

Answer 29

False - biliverdin water soluble

Question 30

Which structural feature of BR accounts for its poor water solubility?

Answer 30

Intramolecular H bonds

Question 31

T/F: unconjugated BR is transported to liver bound to albumin

Answer 31

True

Question 32

T/F: Hepatic uptake of BR is rate-limiting in its metabolism.

Answer 32

False - very rapid carrier mediated uptake

Question 33

Once BR enters hepatocyte, (X) regulate its cytosolic diffusion and prevent efflux back into plasma.

Answer 33

X = ligandins and FA binding proteins (bind to BR)

Question 34

BR conjugating enzyme:

Answer 34

UGT (BR Uridine diphosphate glucoronosyltransferase)

Question 35

BRDG transported across (X) and into biliary tree via which transporter?

Answer 35

X = canalicular membrane MRP2 transporter

Question 36

In the gut, bacteria have which effect on BRDG?

Answer 36

1. Deconjugation (back to BR) | 2. Reduction (to urobilinogen)

Question 37

T/F: Urobilinogen is yellow.

Answer 37

False - colorless

Question 38

T/F: Urobilinogen is mainly excreted by the kidneys.

Answer 38

False - only 2%

Question 39

Urine urobilinogen (increases/decreases) when there's total bile duct obstruction.

Answer 39

Decreases/disappears

Question 40

Urine urobilinogen is increased in which general disease states?

Answer 40

BR overproduction (ex: hemolysis)

Question 41

Jaundice with no bilirubinuria usually means that the serum bilirubin is (conjugated/unconjugated). Why?

Answer 41

Unconjugated (can't be excreted in urine); conjugated BR would be excreted by kidney if significant amounts were circulating in serum

Question 42

DDx for conjugated hyperbiliruminemia.

Answer 42

Mnemonic: BICH 1. Bile duct obstruction 2. Inherited (Dubin-Johnson, Rotor's) 3. Cholestatic disease 4. Hepatitis

Question 43

Dubin-Johnson follows (X) inheritance pattern and involves point mutation in gene for (Y). Highest incidence in which ethnic group?

Answer 43

``` X = AR Y = MRP2 protein (nonfunctional) ``` Iranian Jews

Question 44

24 y.o. M presents with upper resp tract infection and jaundice. He reports this has happened before when he had the flu. Serum BR is 4 mg/dL and mostly conjugated. Likely diagnosis is (X).

Answer 44

X = Dubin-Johnson Syndrome

Question 45

In (X) inherited etiology of hyperbilirubinemia, liver tissue is darkly pigmented, often black.

Answer 45

X = Dubin-Johnson Syndrome

Question 46

DDx for unconjugated hyperbiliruminemia.

Answer 46

1. Hemolysis 2. Ineffective erythropoeisis 3. Neonatal/breast milk jaundice 4. Drug-induced 5. Inherited (Crigler-Najjar, Gilbert's)

Question 47

T/F: Over 90% of newborns have high BR levels with over 50% becoming jaundiced.

Answer 47

True

Question 48

T/F: Hemolysis usually causes severe elevation of BR (over 10 mg/dL).

Answer 48

False - usually mild between 1-4 mg/dL

Question 49

Why might ineffective erythropoeisis be a cause for (conjugated/unconjugated) hyperbilirubinemia?

Answer 49

RBC destruction in bone marrow leads to large BR load

Question 50

Crigler-Najjar Syndrome is inherited in (X) pattern involving (Y) protein.

Answer 50

``` X = AR Y = UGT (conjugates BR) ```

Question 51

Crigler-Najjar Type I: (X) protein is (defective/absent) and therapy involves (Y).

Answer 51

X = UGT Absent (severe, death by 18 mo) Y = liver transplant

Question 52

Crigler-Najjar Type II: (X) protein is (defective/absent) and therapy involves (Y).

Answer 52

X = UGT Defective (mild form, survival to adulthood) Y = Phenobarbital therapy (increases expression of UGT)

Question 53

Patient with Crigler-Najjar Type II presents with jaundice. You would expect urine BRDG to be (low/normal/high).

Answer 53

Normal (high circulating BR is unconjugated)

Question 54

Gilbert's Syndrome is condition characterized by (constant/intermittent) (conjugated/unconjugated) hyperbilirubinemia. Which protein involved?

Answer 54

Intermittent (bouts); unconjugated UGT (levels either reduced or protein defective with reduced activity)

Question 55

T/F: Gilbert's Syndrome patients typically don't require Rx.

Answer 55

True