3.3.3 Pathophysiology: Liver as a Metabolic Organ

Question 1

What is a basic criteria to make a diagnosis of Wilsons?

Answer 1

KF rings and low ceruloplasmin

Question 2

What is the King’s college criteria for tylenol toxicity ALF?

Answer 2

Question 3

What are the two important mutations in HFE gene?

Answer 3

Cys282Tyr

H63Asp

Question 4

How will a patient with tylenol toxicity present in clinic?

Answer 4

Question 5

What is this an image of?

Answer 5

Liver biopsy with copper stain

Question 6

What are some criteria to diagnose A1-antitrypsin deficiency?

Answer 6

Early onset emphysema

Serum protein electrophoresis - low alpha 1-AT

Variable hepatic disease syndromes (attached image)

Question 7

What is this an image of?

Answer 7

a1 - AT deficiency

Protein polymers accumulation in the cells

Question 8

Wilson disease most often affects what age of people and presents similar to what?

Answer 8

Affects children age 10-13

Presents similar to acute hepatitis

Question 9

What is this an image of?

Answer 9

Hemachromatosis - iron accumulation in hepatocytes

Question 10

What are the important genetic characteristics of Hereditary Hemochromatosis? (4)

Answer 10

Autosomal recessive - HFE gene

Homozygote frequency - 1 in 300

Heterozygote freq - 8-14%

HFE gene on chromosome 6

Question 11

How can serum copper levels present in a patient with Wilson disease?

Answer 11

Total may be increased due to increased free copper

Question 12

What can lead a physician to make a diagnosis of hemochromatosis?

Answer 12

Elevated serum ferritin levels

Abnormal liver enzymes

Iron saturation greater than 50%

DNA test 9 HFE Cys282Tyr

Liver biopsy - prussian blue for iron

Question 13

What are some of the criteria required to make a diagnosis of tylenol toxicity?

Answer 13

Marked elevation in plasma hepatic enzyme levels > 5000 IU/L

Increased prothrombin time

AST levels tend to be higher than ALT

Question 14

What is the genotype associated with A1-AT deficiency

Answer 14

PiZZ

PiMZ

PiMM is normal

Question 15

What is the cause for accumulation of copper in organs from Wilson disease?

Answer 15

Genetic defect which encodes a metal transporting ATPase. This leads to reduced hepatic excretion of copper. Copper is not incorperated into ceruloplasmin

Question 16

What is the Kayser-Fleischer ring?

Answer 16

A copper ring deposited in decemet’s membrane

Need slit lamp to see

Question 17

Alpha-1 antitrypsin is an inhibitor of what proteolytic enzyme?

Answer 17

Elastase

Question 18

What is the important pathophysiology of hemochromatosis?

Answer 18

Increased absorption of iron from the diet

Iron overload and eventual fibrosis and organ failure

Question 19

Why can Tylenol be toxic?

Answer 19

It can react and create NAPQ1 which will bind covalently with hepatocyte macromolecules, producing hepatic cell lysis. Usually this is delt with by glutathione, but once these are depleted, NAPQ1 will wreak havoc

Question 20

How will patients with hemochromatosis present in clinic?

Answer 20

Asymptomatic until ages 45-50

Iron is stored in liver and other organs

There is multiorgan involvement

Question 21

Is iron overload an acute process or long term process?

Answer 21

Long term

Question 22

How will alpha1- antitrypsin present in an infant vs early childhood vs adolescence/adults?

Answer 22

Infancy - prolonged obstructive jaundice; elevated transaminases and symptoms of cholestasis

Early childhood - Elevated transaminase, asymptomatic hepatomegaly, severe liver dysfunction

Adolescence/adults - Chronic active hepatitis; cryptogenic cirrhosis; portal hypertension; hepatocellular carcinoma

Question 23

What are some of the neuropsychiatric manifestations of Wilson’s disease?

Answer 23

Seizures and pseudobulbar palsy

Question 24

What are a few drugs that can be used to treat Wilson Disease?

Answer 24

D-penicillamine

Trientine hydrochloride

Zinc acetate

Question 25

Late stage hemachromatosis will present with what additional finding on liver biopsy?

Answer 25

There will be fibrosis and nodule formation of liver tissue

Question 26

What can also put a person at increased risk for tylenol toxicity?

Answer 26

Taking medications that use the same CYP

Question 27

What are the characteristic liver findings associated with hemochromatosis?

Answer 27

Hepatomegaly

Mild elevations of serum aminotransferases and alk phosphatase

Decompensated cirrhosis

Increased risk of liver cancer

Question 28

Where is alpha1 antitrypsin produced? What is its major target?

Answer 28

IN the liver and major target is neutrophil elastase

Question 29

What are some circumstances that drastically increase a patients risk for tylenol toxicity?

Answer 29

Chronic alcohol abuse

Malnutrition

Question 30

What is the importance of phlebotomy for patients with hemachromatosis?

Answer 30

Removal of blood - which in turn will remove iron from the body

Occurs weekly