Iron disorders

lecture 2

Where is iron stored in the body?

macrophages and normoblasts

Describe the six steps of iron absorption.

1. iron is ingested and digested as Fe³⁺

2. Fe³⁺ is reduced to Fe²⁺ by HCl

3. Fe²⁺ is absorbed into mucosal cells

4. Fe²⁺ is oxidized back to Fe³⁺

5. some of the Fe³⁺ goes into cells as ferritin

6. some of the Fe³⁺ binds to transferrin in circulation

How can marrow cells receive iron?

from plasma transferrin or macrophages

Which population has a high prevalence of IDA?

children (infants - 2y/o)

What are some causes of IDA?

• rapid growth

• pregnancy

• chronic blood loss

• dietary deficiency

• faulty iron absorption

In the CBC, what values are abnormal for IDA?

decreased Hct, Hgb, RBCs, MCV

increased RDW

microcytic/hypochromic cells

What four iron tests can help diagnose IDA?

1. serum iron

2. saturated iron

3. serum ferritin

4. TIBC

What is serum iron? How is it impacted in IDA?

serum iron is the iron bound to transferrin in circulation

in IDA: decreased

What is saturated iron? How is it impacted in IDA?

the percentage of transferrin that is bound by iron

in IDA: <15% saturation

How can we calculate saturated iron?

(serum iron/transferrin) * 100%

What is serum ferritin? How is it impacted in IDA?

the stored iron within cells

in IDA: decreased

Which iron test is the most sensitive indicator of IDA?

serum ferritin

What is TIBC? How is it impacted in IDA?

total iron binding capacity, the total amount of transferrin that can bind to iron

in IDA: increased

What are the abnormal lab values of iron tests in IDA all together?

decreased: serum iron, saturated iron, ferritin

increased: TIBC

What test differentiates between IDA and ACD (anemia of chronic disorders)?

soluble transferrin receptor test

What is the difference between IDA and ACD?

in IDA, there is an actual decrease in iron, in serum and in storage

in ACD, there is a normal amount of iron, but it is skewed in ferritin as hepcidin blocks the release of iron into circulation

What would bone marrow look like in IDA?

small normoblasts with frayed margins

no iron storage granules seen (blue coloring)

hypochromic cells

What are the three stages of IDA?

1. iron depletion

2. iron deficiency erythropoiesis

3. IDA

What events take place in iron depletion?

iron is mobilized from storage

• decreased ferritin

• increase GI absorption

• increased transferrin

What events take place in iron deficiency erythropoiesis?

saturated transferrin falls below 15%

sideroblasts decrease

heme synthesis slows down

RBC protoporphyrin increases

What events take place in IDA?

cells turn from normocytic/normochromic to microcytic/hypochromic

What is thalassemia?

disorder where the body does not make enough hemoglobin

What is sideroblastic anemia?

impaired iron utilization in erythropoiesis, leading to a buildup of iron

What are the iron labs for sideroblastic anemia?

increased: serum iron, ferritin, saturated iron, bone marrow iron

decreased: TIBC

What iron values (serum iron and saturated iron) correlate to iron excess?

over 200 mg/dL of serum iron and 100% saturation of iron

What is hemochromatosis?

condition that arises due to chronic overexposure of iron

What are the signs of hemochromatosis?

joint pain, fatigue, pain, weakness, liver and cardiac failure, diabetes

What is the cause of primary familial hemochromatosis?

abnormality of HFE gene on chromosome 6

What characteristic is seen in sideroblastic anemia?

siderotic granules and pappenheimer bodies

What are causes of hereditary sideroblastic anemia?

abnormal ALAS enzyme, vitamin B6 deficiency

What are causes of acquired sideroblastic anemia?

idiopathic, tumors, drugs (isoniazid), lead, chloramphenicol, ethanol

What does the mutation of HFE gene do?

increases iron absorption into epithelial cells, pushing tons of iron into circulation

What are the labs for primary familial hemochromatosis?

increased: serum iron, ferritin, saturated iron, bone marrow iron

decreased: TIBC