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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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)
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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)
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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IRON DEFICIENCY versus ACD
Serum Iron Transferrin Ferritin
Iron Deficiency
ACD
Iron Deficiency Anemia/Anemia of Chronic Disease
Tuesday, February 10, 2004 – 10:00 am
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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)