iron deficiency anemia/ anemia of chronic disease
DESCRIPTION
IRON DEFICIENCY ANEMIA/ ANEMIA OF CHRONIC DISEASE. Maj Gen Muhammad Ayyub MBBS (Pesh), Ph.D (London), FRC Path (UK), Army Medical College, Rawalpindi. ANEMIA Definition. Decrease in the number of circulating red blood cells Most common hematologic disorder by far. ANEMIA Causes. - PowerPoint PPT PresentationTRANSCRIPT
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IRON DEFICIENCY ANEMIA/ ANEMIA OF CHRONIC
DISEASE
Maj Gen Muhammad AyyubMBBS (Pesh), Ph.D (London),
FRC Path (UK), Army Medical College, Rawalpindi
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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
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ANEMIACauses - Decreased Production
• Cytoplasmic production of protein– Usually normocytic (MCV 80-100 fl) or
microcytic (MCV < 80)
• 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
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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
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IRONBody Compartments - 75 kg man
Stores1000mg
Tissue500 mg
Red Cells2300 mg
3 mgAbsorption < 1 mg/day
Excretion < 1 mg/day
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IRON CYCLE
Fe
Fe
FeFeFe Ferritin
Hemosiderinslow
Fe
Fe
Fe FeFe
Fe
Fe Fe
Fe
Ferritin Ferritin
Tra
nsfe
rrin
Rec
epto
r
RBC PRECURSOR
CIRCULATING RBCs
Fe Fe
TRANSFERRIN
MONONUCLEARPHAGOCYTES
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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
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DAILY IRON REQUIREMENTSPregnancies
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IRON ABSORPTION
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GI ABSORPTION OF IRON
FeFe
FeFe
Fe FeFe
FeFe
Fe
Fe
Fe
Fe
Fe
Fe
FeFe
Fe
Fe
Fe
Ferritin
Fe Fe
TRANSFERRIN
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FERRITIN REGULATION
LOW IRON
Ribosome
IRE FerritinMessage
Fe Fe
Fe
IREBindingProtein
Fe Fe
Fe
Fe IREBindingProtein
Fe
Fe Fe Fe+
HIGH IRONFerritinIRE
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TRANSFERRIN REGULATION
HIGH IRON
Ribosome
IRE TransferrinMessage
Fe Fe
Fe
IREBindingProtein
Fe Fe
Fe
Fe IREBindingProtein
Fe
Fe Fe Fe+
LOW IRONTransferrinIRE
Fe
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IRON ABSORPTION
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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
Tissue500 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
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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
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IRON REPLACEMENT THERAPYResponse
• Usually oral; usually 300-900 mg/day
• Requires acid environment for absorption
• Poorly absorbed
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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
anemia)• Normal bilirubin• EPO levels increased but blunted
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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• Renal Failure
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IRON STORESAnemia of Chronic Disease
Stores2500 mg
Tissue500 mg
Red Cells1100 mg
1 mg
Absorption < 1 mg/day
Excretion < 1 mg/day
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IRON CYCLEAnemia of Chronic Disease
Fe
Fe
FeFeFe Ferritin
Hemosiderinslow
MONONUCLEARPHAGOCYTESFe
Fe
Fe Fe
Fe
Ferritin Ferritin
Tra
nsfe
rrin
Rec
epto
r
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)