iron Deficiency Anemia 2006 - columbia.edu€¦ · Iron Deficiency Anemia/Anemia of Chronic Disease...

Iron Deficiency Anemia/Anemia of Chronic Disease

Tuesday, February 10, 2004 – 10:00 am

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IRON DEFICIENCY ANEMIA/ ANEMIA OF CHRONIC DISEASE

ANEMIADefinition

• Decrease in the number of circulating red blood cells

• Most common hematologic disorder by far



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ANEMIACauses

• Blood loss• Decreased production of red blood cells

(Marrow failure)• Increased destruction of red blood cells

– Hemolysis

• Distinguished by reticulocyte count– Decreased in states of decreased production– Increased in destruction of red blood cells

ANEMIACauses - Decreased Production

• Cytoplasmic production of protein– Usually normocytic (MCV 80-100 fl) or

microcytic (MCV < 80 fl)

• Nuclear division/maturation– Usually macrocytic (MCV > 100 fl)



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ANEMIACauses - Cytoplasmic Protein Production

• Decreased hemoglobin synthesis– Disorders of globin synthesis– Disorders of heme synthesis

• Heme synthesis– Decreased Iron– Iron not in utilizable form– Decreased heme synthesis

IRON DEFICIENCY ANEMIAPrevalence

Country Men (%) Women(%)

PregnantWomen (%)

S. India 6 35 56N. India 64 80Latin America 4 17 38Israel 14 29 47Poland 22Sweden 7USA 1 13



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IRON

• Functions as electron transporter; vital for life• Must be in ferrous (Fe+2) state for activity• In anaerobic conditions, easy to maintain

ferrous state• Iron readily donates electrons to oxygen,

superoxide radicals, H2O2, OH• radicals• Ferric (Fe+3) ions cannot transport electrons or

O2

• Organisms able to limit exposure to iron had major survival advantage

IRONBody Compartments - 75 kg man

Stores1000 mg

Tissue170 mg

Red Cells2400 mg

4 mgAbsorption < 1 mg/day

Excretion < 1 mg/day



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IRON CYCLE

Fe

Fe

FeFeFe Ferritin

Hemosiderinslow

FeFe

Fe FeFe

Fe

Fe Fe

Fe

Ferritin Ferritin

Tran

sfer

rin R

ecep

tor

RBC PRECURSOR

CIRCULATING RBCs

Fe Fe

TRANSFERRIN

MONONUCLEARPHAGOCYTES

INTRACELLULAR IRON TRANSPORT

H+ H+

H+H+Lysosome

Fe+2

Fe+2

Transferrin

Transferrin receptor



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IRONCauses of Iron Deficiency

• Blood Loss– Gastrointestinal Tract– Menstrual Blood Loss– Urinary Blood Loss (Rare)– Blood in Sputum (Rarer)

• Increased Iron Utilization– Pregnancy– Infancy– Adolescence– Polycythemia Vera

• Malabsorption– Tropical Sprue– Gastrectomy– Chronic atrophic gastritis

• Dietary inadequacy (almost never sole cause)• Combinations of above

DAILY IRON REQUIREMENTS

0 2

10 14 20 27 29 32 34 40 49 55 65

Males

0

0.5

1

1.5

2

2.5

Abs

orbe

d Ir

on

Req

uire

men

t (m

g/da

y)

Age

Males Females

Pregnancies



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IRON ABSORPTION

0

2

46

810

12

1416

Iron

(m

g/da

y)

Iron in Diet IronSolubilized

Iron Uptake Iron Absorbed

GI ABSORPTION OF IRON



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FERRITIN/TRANSFERRIN REGULATION

IRON ABSORPTION

0.01

0.1

1

10

100

Iron Absorbed (mg/day)

0.1 1 8 10 20 80 100 200Iron Ingested (mg/day)



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IRON DEFICIENCY ANEMIAProgression of Findings

• Stainable Iron, Bone Marrow Aspirate• Serum Ferritin - Low in Iron Deficiency• Desaturation of transferrin• Serum Iron drops• Transferrin (Iron Binding Capacity) Increases• Blood Smear - Microcytic, Hypochromic;

Aniso- & Poikilocytosis• Anemia



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IRON STORESIron Deficiency Anemia

Stores0 mg

Tissue170 mg

Red Cells1500 mg

3 mgAbsorption 2-10 mg/day

Excretion Dependent on Cause



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IRON DEFICIENCYSymptoms

• Fatigue - Sometimes out of proportion to anemia

• Atrophic glossitis• Pica• Koilonychia (Nail spooning)• Esophageal Web

IRONCauses of Iron Deficiency

• Blood Loss– Gastrointestinal Tract– Menstrual Blood Loss– Urinary Blood Loss (Rare)– Blood in Sputum (Rarer)

• Increased Iron Utilization– Pregnancy– Infancy– Adolescence– Polycythemia Vera

• Malabsorption– Tropical Sprue– Gastrectomy– Chronic atrophic gastritis

• Dietary inadequacy (almost never sole cause)• Combinations of above



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IRON REPLACEMENT THERAPYResponse

• Usually oral; usually 300-900 mg/day• Requires acid environment for

absorption• Poorly absorbed

IRON THERAPYResponse

• Initial response takes 7-14 days• Modest reticulocytosis (7-10%)• Correction of anemia requires 2-3 months• 6 months of therapy beyond correction of

anemia needed to replete stores, assuming no further loss of blood/iron

• Parenteral iron possible, but problematic



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ANEMIA OF CHRONIC DISEASEFindings

• Mild, non-progressive anemia (Hgb c. 10, Hct c. 30%

• Other counts normal• Normochromic/normocytic (30%

hypochromic/microcytic)• Mild aniso- & poikilocytosis• Somewhat shortened RBC survival• Normal reticulocyte count (Inappropriately low for

degree of anemia)• Normal bilirubin• EPO levels increased but blunted for degree of

anemia

ANEMIA OF CHRONIC DISEASECauses

• Thyroid disease• Collagen Vascular Disease

– Rheumatoid Arthritis– Systemic Lupus Erythematosus– Polymyositis– Polyarteritis Nodosa

• Inflammatory Bowel Disease– Ulcerative Colitis– Crohn’s Disease

• Malignancy• Chronic Infectious Diseases

– Osteomyelitis– Tuberculosis

• Familial Mediterranean Fever



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IRON STORESAnemia of Chronic Disease

Stores2500 mg

Tissue170 mg

Red Cells1100 mg

1 mg

Absorption < 1 mg/day

Excretion < 1 mg/day

IRON CYCLEAnemia of Chronic Disease

Fe

Fe

FeFeFe Ferritin

Hemosiderinslow

MONONUCLEARPHAGOCYTESFe

Fe

Fe Fe

Fe

Ferritin Ferritin

Tran

sfer

rin R

ecep

tor

RBC PRECURSOR

CIRCULATING RBCs

Fe Fe

TRANSFERRIN

IL-1/TNF



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IRON DEFICIENCY versus ACD

Serum Iron Transferrin Ferritin

Iron Deficiency

ACD



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SUMMARYIron-Related Anemias

• Most common anemia• Symptom of pathologic process• Primary manifestation is hematologic• Treatment requires:

– Replacement therapy– Correction of underlying cause (if possible)

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