Iron Metabolism

Question 1

Describe the methods for assaying body iron stores

Answer 1

Complete Blood Count, Hematocrit, Hemoglobin, Ferritin levels

Question 2

Describe the basis for and consequences of: microcytic anemia, hypochromic anemia, and sideroblastic anemia.

Answer 2

Microcytic Anemia: Mcv is below 80 indicating rbcs are too small; Low Hematocrit
Hypochromic Anemia: The rbcs are too pale indicating a low hemoglobin and iron content.
Sideroblastic Anemia: is a genetically inherited disorder that results in problems with heme production. Histologically, it is characterized by the presence of a sideroblast – an erythrocyte containing visible ferritin granules.

Question 3

Hemochromatosis

Answer 3

An overdosing of iron from 2 mechanisms.
1. Genetic defect: leading to an inability to metabolize iron. As a result, iron is preferentially absorbed by intestinal cells and transported systemically in the blood. Since iron is not easily excreted, iron accumulates in numerous compartments of the body

2. Hemosiderosis: refers to a type of iron overload as a result of multiple blood transfusions. This is common in patients diagnosed with Cooley’s anemia (a type of β-thalassemia)

Question 4

How do we get iron?

Answer 4

Must be ingested in the diet.

Question 5

What are sources of heme iron?

Answer 5

Liver, meat and fish; Easily absorbed

Question 6

What are the sources of non-heme iron?

Answer 6

Plant sources; Not easily absorbed

Question 7

Which oxidation state of iron is most easily absorbed?

Answer 7

Ferrous iron (+2), is more easily absorbed than Ferric iron (+3)

Question 8

How do you most easily increase absorption of ferric iron?

Answer 8

Simultaneously ingest Vitamin C.

Question 9

Describe the Iron absorption process

Answer 9

1. Intake using ATP
2. Ferrous iron taken by chelator.
3. Apoferritin takes ferrous iron and becomes Ferritin by oxidizing iron.
4. Ferritin gives ferric iron to Apotransferrin.
5. Apotransferrin reduces iron and becomes Transferrin.
6. Transferrin receptor receives transferrin and releases it inside the cell.

Question 10

How do mucousal cells lose iron?

Answer 10

The slough off into the digestive tract.

Question 11

What role does Transferrin play?

Answer 11

Decreases Iron toxicity and directs iron to transferrin receptors.

Question 12

How is transferrin and its receptor taken into the cell?

Answer 12

Endocytosed as a vesicle

Question 13

What are the 3 fates of endocytosed iron?

Answer 13

1. Incorporated into heme.
2. Incorporated into non-heme
3. Stored as ferric iron in hemosiderin (long term) or ferritin (short term).

Question 14

What is the Iron responsive element?

Answer 14

A sequence of nucleoties on transferrin receptor mRNA that form a stem-loop .

Question 15

What is the Iron responsive protein?

Answer 15

It binds to IRE in the absence of iron.

Question 16

Explain the interaction between IRP and IRE with iron.

Answer 16

In low iron concentrations, IRPs bind IREs, this protects the mRNA from degradation; Resulting in translation of the transferrin receptor. In high iron concentrations, IRPs bind iron and can’t bind the transferrin receptor mRNA; Leaving mRNA unprotected and freely degradable by RNAses

Question 17

How do you measure the amount of iron in the body?

Answer 17

1. CBC, HCT, RBC count, hemoglobin, ferritin,
2. Measuring plasma by releasing iron from transferrin.
3. Measuring total iron binding capacity

Question 18

How do you measure total iron binding capacity?

Answer 18

1. Release all iron from transferrin.
2. Saturate transferrin with iron so and immediately measure the amount of iron bound (direct)
3. (Plasma iron/ TIBC) * 100 = %transferrin saturation

Question 19

What is the normal range for %transferrin saturation?

Answer 19

20-50

Question 20

What are the 4 conditions in which iron may be elevated?

Answer 20

Hemochromatosis, Hemosiderosis, Hemolytic disease, and Pernicious anemia

Question 21

What are the 3 conditions in which iron may be below normal?

Answer 21

Iron deficiency, Active Hematopoiesis, and late stage pregnancy.

Question 22

How are serum iron levels, TIBC, %saturation, and serum ferritin values affected in high iron circumstances?

Answer 22

Serum Fe and Serum ferritin levels rise; TIBC is unaffected and %saturation is greater than 50%.

Question 23

How are Serum iron levels, TIBC, %saturation and serum ferritin values affected in low iron circumstances?

Answer 23

Serum Fe and Serum ferritin levels decrease; TIBC is unaffected and %saturation is lower than 20%.

Question 24

What are the two mechanisms of hemochromatosis?

Answer 24

1. A genetic defect leading to an inability to metabolize iron. Iron then accumulates in blood causing an overdose.
2. Hemosiderosis results in multiple blood transfusions. Commonly found in B-thalassemia.

Question 25

What is sideroblastic anemia?

Answer 25

A genetically inherited disorder that results in problems with heme production. Characterized by sideroblasts (rbc with visible ferritin granules as a consequence of failed heme biosynthesis).

Question 26

Whats the mode of inheritance of sideroblastic anemia?

Answer 26

X-linked recessive