IRON DEFICIENCY ANEMIA

INTRODUCTION

Iron distribution
- Functional iron is present in enzymes, Hb and myoglobin
- Iron is stored as ferritin and hemosiderin in BM macrophages
- Women have less iron stores than men (due to menses)
Iron absorption and regulation

Gastric acid frees elemental iron from food (this is why achlorhydria iron
availability)
Iron from plants is in a nonheme or oxidized form (ferric, Fe3+) and cant be
absorbed in the duodenum and must be converted by cytochrome B in the
duodenal mucosa into reduced iron (Fe2+) to be reabsorbed by divalent metal
transporter 1 (DMT1)
Iron from meat is in a heme or reduced form (ferrous, Fe2+) and is directly
absorbed in the duodenum by heme carrier protein 1
Absorbed iron is stored as mucosal ferritin or it enters the ferroportin 1 port and
is immediately converted by hephaestin or ceruloplasmin to ferric iron (Fe3+) so
that it can bind to transferrin in the blood
Transferrin brings iron to developing erythroid precursors in the marrow.
Iron absorption is dependent on body total iron stores, which is reected by the
amount of iron bound to transferrin

Nutshell Course

Transferrin with iron binds to transferrin receptors in immature precursor cells

of normal enterocytes, which serve as iron sensors in the duodenum
HFE gene (hemochromatosis gene) protein product in the sensor cells acting
with the transferrin receptor causes dierentiation of these cells into mature
enterocytes that absorb iron
HFE protein product also regulates the production of hepcidin (hormone
synthesized in the liver which determines absorption and release of iron)
Iron depletion transferrin-bound iron binding to transferrin receptors in
enterocytes hepcidin synthesis upregulation of ferroportin 1 iron
reabsorption in the duodenum to bind to transferrin & iron release from BM
macrophages to bind to transferrin for erythropoiesis
Iron excess transferrin-bound iron binding to transferrin receptors in
enterocytes hepcidin synthesis down regulation of ferroportin 1 iron
accumulates in enterocytes (eventually shed into the bowel) & iron release
from BM macrophages (iron blockage)
The following condition hepcidin and iron absorption:a. Normal menstrual cycle
b. Pregnancy and lactation
c. All types of anemia

EPIDEMIOLOGY

Iron deficiency anemia is the

MCC of reactive
thrombocytosis and the MC
presentation of celiac disease
and it may be a treatable
cause of restless leg syndrome

MC overall anemia
MC nutritional deficiency worldwide

Bleeding:
- PUD (MCC of GI bleeding in adult men)
- Polyps/colorectal cancer (MCC of GI bleeding in elderly >50 years)
- Meckel diverticulum (in children)
- Hemorrhagic gastritis (e.g., NSAIDs use)
- Hookworm infestations
iron utilization:
- Menorrhagia, pregnancy and lactation are the MCCs of iron deficiency in women
<50 years
- In infants and children, iron is needed for tissue growth and expansion of blood
volume in developing fetuses
iron intake: MCC of iron deficiency in young children
iron absorption: E.g., celiac disease and post-gastric surgery
Intravascular hemolysis causing hemoglobinuria: E.g., microangiopathic
hemolytic anemia and PNH
Others: Prematurity and frequent phlebotomy

CAUSES

CLINICAL FINDINGS

General features of anemia: Pallor of the skin, conjunctiva and skin creases
Features of chronic iron deficiency:
- Pica: Carving for nonfood substances (e.g., clay and ice chips pagophagia)

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Koilonychia: Spooning of the fingernails

Esophageal web (Plummer-Vinson syndrome) dysphagia for solids but not
liquids
Achlorhydria
Glossitis (inflammation of the tongue) and angular cheilosis (inflammation of the
corners of the mouth)
In iron deficiency anemia, all lab studies

LAB FINDINGS

DDx

MCV
serum iron and iron saturation
serum ferritin (the best screening test )
TIBC and RDW
Microcytic and normocytic cells are present with
central area of pallor and anisocytosis
serum free erythrocyte protoporphyrin (FEP)
Trombocytosis: To blood viscosity and prevent highoutput heart failure
Eosinophilia: In hookworm infestations
Anemia of chronic disease (ACD): See Table
Lead poisoning: Presents with FEP, basophilic
stippling, and lead lines on the gums)
. Thalassemia minor: See Table

become abnormal before anemia is

present

Sequence of iron deficiency is as follow:

absent iron stores in BM serum
ferritin serum iron TIBC & iron
saturation normocytic normochromic
and microcytic hypochromic anemia

A therapeutic trial of iron may be

diagnostic of iron deficiency:
Reticulocytosis from iron typically begins
3-5 days after iron therapy followed by
in Hb

TREATMENT

Oral iron
Parenteral iron carries the risk of anaphylaxis and should be used only if oral iron
isnt tolerated
Lack of response to iron therapy indicates:
- Noncompliance (MCC)
- Continued blood loss
- Iron is not being absorbed
- Wrong diagnosis (e.g., . Thalassemia minor)

IMAGE LIBRARY

Koilonychia

Peripheral blood smear in iron deficiency anemia. Note the

enlarged central area of pallor in the RBCs (arrows) and the
size variation, which explains the RDW

Nutshell Course