Disorders of IRON Metabolism DR. AKIF AHSAN Assistant Professor

Dept. of Biochemistry JNMC, AMU, Aligarh

OBJECTIVES By the end of this session you should be able to:

Enumerate the causes of Fe deficiency. 1. Enumerate the EARLY manifestations of Fe deficiency.

2.

Enumerate the manifestations of severe prolonged Fe deficiency.

3.

Describe the pathogenesis & enumerate the manifestations of primary hemochromatosis.

4.

Enumerate the causes of secondary hemochromatosis.

5.

FA T I GU E W EA KN E S S D I ZZ I N ES S SHORTNESS OF BREATH

CONJUNCTIVAL PALLOR S KI N PA LLOR

- A N E M I A -

Anemia is a medical condition in which the RBC count or hemoglobin is less than normal.

NORMAL ANEMIA

Most common cause of anemia is…

IRON DEFICIENCY

Causes of Iron Deficiency

Inadequate intake Malabsorption Blood loss

Infancy Adolescence Pregnancy

Steatorrhea Celiac disease Gastrectomy Lead poisoning

Hookworm infestations Nephrosis Hemorrhoids Peptic ulcer

Early Manifestations

Earliest change: Depletion of body iron stores.

↑ transferrin & ↓ transferrin saturation

↓ plasma iron

Microcytic hypochromic anemia

Poikilocytosis

↓ hemoglobin

Severe prolonged deficiency leads to

Koilonychia

Angular stomatitis

Glossitis

Pharyngeal & esophageal webs

Atrophic gastritis

Partial villus atrophy

Koilonychia

Angular Stomatitis (Cheilosis)

Glossitis

Pharyngeal & esophageal webs

Pharyngeal & esophageal webs

IRON TOXICITY

Iron Toxicity / Overload

Hemochromatosis (Hemosiderosis)

Primary

Secondary

Ferritin, serum iron & % saturation of TIBC are increased.

Primary Hemochromatosis

Mutation of HFE gene

Hepcidin level decreases

Iron absorption increases

Inhibits release of HEPCIDIN from liver.

Fe2+

Fe2+

Fe2+

DMT 1

Ferroportin Ferroportin

Intestinal mucosal cells Spleenic macrophages HEPCIDIN

HFE gene mutation

Non-functional HFE protein

Clinical Manifestations

Diabetes

Hepatomegaly / Cirrhosis

Bronze colored skin pigmentation

Cardiomegaly / CHF

Bronze Diabetes

Due to Iron deposition in different organs

Bronze Diabetes

Secondary Hemochromatosis

Severe chronic hemolysis

Repeated blood transfusions

Excessive parenteral iron supplements

Excessive dietary iron

MCQ

a) ↓ Transferrin saturation b) ↓ TIBC c) Hypochromic anemia d) Poikilocytosis

All are seen in iron deficiency, EXCEPT:

[KEY: b]

MCQ

a) Mutation in HFE gene b) ↓ Hepcidin level c) ↓ transferrin saturation d) ↑ Iron absorption

All are true about primary hemochromatosis, EXCEPT:

[KEY: c]

MCQ

a) Both A and R are true and R is the correct explanation of A.

b) Both A and R are true but R is NOT the correct explanation of A.

c) A is true but R is false. d) A is false but R is true. e) Both A and R are false

Assertion: Iron toxicity is seen in primary hemochromatosis.

Reason: Ferritin increases in primary hemochromatosis.

[KEY: b]

CAN YOU ??? Enumerate the causes of Fe deficiency. 1. Enumerate the EARLY manifestations of Fe deficiency.

2.

Enumerate the manifestations of severe prolonged Fe deficiency.

3.

Describe the pathogenesis & enumerate the manifestations of primary hemochromatosis.

4.

Enumerate the causes of secondary hemochromatosis.

5.