Hemochromatosis (Dbouk)

Question 1

Iron absorption predominantly occurs in:

Answer 1

duodenum (Enterocytes)

Question 2

Regulates Fe export into circulation

Answer 2

Ferroportin

located at basolat surface of enterocytes + macrophages

Question 3

Complex which forms at the surface of hepatocytes + senses serum iron concentrations:

Complex which induces production of Hepcidin:

Answer 3

HFE and TFr1

HFE and TFr2

Question 4

Regulation of Fe absorption and release when excess Fe? When insufficient Fe?

Answer 4

1. Hepcidin is expressed and binds to ferroportin
2. Ferroportin is internalized (no Fe uptake into circulation)
3. No hepcidin produced
4. Ferroportin -> absorption of Fe from intestine

Question 5

Hepcidin expression is induced by:

Hepcidin expression is decr when:

Answer 5

excess iron and inflammation

Fe is deficient

Question 6

Mutations in HFE decrease Hepcidin expression leading to:

Answer 6

incr intestinal Fe absorption via up-regulation of ferroportin

Question 7

What organs are most affected in Hemochromatosis?

Answer 7

Liver
Heart
Pancreas
Thyroid

(tissues with High Transferrin Receptors)

Question 8

Epidemiology of Hemochromatosis
Type 1:
Type 2:

Answer 8

Both = Caucasians

1: > 40 yrs men, > 50 yrs women
2: 10-15 yo

Question 9

Mutation associated w/ Hemochromatosis 
Type 1:
Type 2:
Type 3:
Type 4:

Answer 9

1: C282Y/C282Y (= ↓ sensing of actual Fe stores)
2: HAMP & HJV genes (= low hepcidin)
3: Transferrin Receptor mutation
4: Ferroportin mutation (= decr ability to export Fe out of hepatocytes)

Question 10

Clinical Symptoms of Hemochromatosis

Type 1:

Answer 10

fatigue, Hypertrophic Osteoarthritis in 2nd/3rd MP joint, cirrhosis, HCC

Question 11

Clinical Symptoms of Hemochromatosis

Type 2:

Answer 11

Cardiomyopathy and Heart failure, Hypogonadism, Hypertrophic Osteoarthritis

Question 12

Clinical Symptoms of Hemochromatosis

Type 3:

Answer 12

Cirrhosis, Liver cancer, hypogonadism, Hypertrophic Osteoarthritis

Question 13

What indirect markers of Fe overload should be measured if Hemochromatosis is suspected?

Answer 13

Transferrin saturation (> 45%= suspect Fe overload)

Serum ferritin (= excess storage Fe)

Question 14

What confirms a dx of hemochromatosis?

Answer 14

Presence of homozygous C 282Y

Question 15

Role of Liver Biopsy in dx of hemochromatosis?

Answer 15

Diagnose Hemochromatosis in the absence of HFE mutation (type II, III)

**also = assess damage

Question 16

How do you treat patients with elevated ferritin?

Answer 16

therapeutic phlebotomies

Iron Chelating Agents (once Fe in nml range; binds Fe and removes through urine)

avoid vit C, decr etoh

Question 17

What should be performed for all 1st degree relatives of patients w/ Hemochromatosis?

Answer 17

Ferritin/TS and HFE mutation analysis

Question 18

WHat is the response to therapy in hemochromatosis?

Answer 18

• Improved survival if initiated before cirrhosis/diabetes
• Reversal of fibrosis (but not cirrhosis)
• Improved glycemic control
• Improved cardiac function
• Reduction in portal HTN (in cirrhotics)
• Elimination of HCC risk (if started prior to cirrhosis)
• Reduction in skin pigmentation