Iron deficiency anemia anemia of chronic disease
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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.

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IRON DEFICIENCY ANEMIA/ ANEMIA OF CHRONIC DISEASE

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Iron deficiency anemia anemia of chronic disease

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

ANEMIADefinition

  • Decrease in the number of circulating red blood cells

  • Most common hematologic disorder by far


Anemia causes

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


Anemia causes decreased production

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)


Anemia causes cytoplasmic protein production

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 anemia prevalence

IRON DEFICIENCY ANEMIAPrevalence


Iron deficiency anemia anemia of chronic disease

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


Iron body compartments 75 kg man

Stores1000mg

Tissue500 mg

Red Cells2300 mg

IRONBody Compartments - 75 kg man

Absorption < 1 mg/dayExcretion < 1 mg/day

3 mg


Iron cycle

CIRCULATING RBCs

MONONUCLEARPHAGOCYTES

Fe

Fe

Fe

Fe

Fe

Fe

Transferrin Receptor

Ferritin

Fe

Fe

Fe

Fe

Ferritin

Fe

Ferritin

Fe

slow

Hemosiderin

Fe

Fe

RBC PRECURSOR

Fe

Fe

TRANSFERRIN

IRON CYCLE


Intracellular iron transport

INTRACELLULAR IRON TRANSPORT

Fe+2

Transferrin

Transferrin receptor

H+

H+

Lysosome

Fe+2

H+

H+


Iron causes of iron deficiency

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

DAILY IRON REQUIREMENTS

Pregnancies


Iron absorption

IRON ABSORPTION


Gi absorption of iron

Fe

Fe

Fe

Fe

Fe

Fe

Fe

TRANSFERRIN

GI ABSORPTION OF IRON

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Ferritin

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe


Ferritin regulation

IRE

Ferritin

HIGH IRON

IREBindingProtein

Fe

Fe

Fe

+

Fe

Fe

Fe

Fe

Fe

IRE

FerritinMessage

LOW IRON

Fe

Fe

IREBindingProtein

Ribosome

Fe

FERRITIN REGULATION


Transferrin regulation

IRE

Transferrin

LOW IRON

IREBindingProtein

Fe

Fe

Fe

+

Fe

Fe

Fe

Fe

Fe

Transferrin

Message

IRE

HIGH IRON

Fe

Fe

IREBindingProtein

Ribosome

Fe

TRANSFERRIN REGULATION

Fe


Iron absorption1

IRON ABSORPTION


Iron deficiency anemia progression of findings

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 stores iron deficiency anemia

Tissue500 mg

Red Cells1500 mg

IRON STORESIron Deficiency Anemia

Stores0 mg

Absorption 2-10 mg/dayExcretion Dependent on Cause

3 mg


Iron deficiency symptoms

IRON DEFICIENCYSymptoms

  • Fatigue - Sometimes out of proportion to anemia

  • Atrophic glossitis

  • Pica

  • Koilonychia (Nail spooning)

  • Esophageal Web


Iron causes of iron deficiency1

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 replacement therapy response

IRON REPLACEMENT THERAPYResponse

  • Usually oral; usually 300-900 mg/day

  • Requires acid environment for absorption

  • Poorly absorbed


Iron therapy response

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


Anemia of chronic disease findings

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


Anemia of chronic disease causes

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


Iron stores anemia of chronic disease

Stores2500 mg

Tissue500 mg

IRON STORESAnemia of Chronic Disease

Absorption < 1 mg/dayExcretion < 1 mg/day

1 mg

Red Cells1100 mg


Iron cycle anemia of chronic disease

CIRCULATING RBCs

MONONUCLEARPHAGOCYTES

Fe

Fe

Ferritin

Fe

Fe

Fe

Fe

Fe

Fe

Transferrin Receptor

Ferritin

Ferritin

Fe

slow

Fe

Hemosiderin

RBC PRECURSOR

Fe

Fe

IL-1/TNF

TRANSFERRIN

IRON CYCLEAnemia of Chronic Disease


Iron deficiency versus acd

IRON DEFICIENCY versus ACD

Serum Iron

Transferrin

Ferritin

Iron Deficiency

ACD


Summary iron related anemias

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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