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anaemia general, IDA.pptx

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DrAshish Chaudhary

Anemia is defined as a reduction in red blood cells or hemoglobin. Iron deficiency anemia is the most common nutritional disorder worldwide, affecting toddlers, adolescent girls, and women of childbearing age at higher rates in developing countries. It results from inadequate dietary iron intake relative to iron losses and needs. Diagnosis is based on microcytic hypochromic blood cells, low serum iron, ferritin and transferrin saturation, and high total iron binding capacity. Treatment involves oral or parenteral iron supplementation to replenish iron stores.

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anaemia general, IDA.pptx
Anemia
Definition • Reduction of the total circulating red cell mass below normal limits • Reduced --- oxygen-carrying capacity of the blood tissue hypoxia • usually diagnosed  reduction in the hematocrit (packed red cells : total blood volume) / hemoglobin concentration
• Classification 1. underlying mechanisms (etiological) 2. morphological
Normal, mature RBCs are biconcave, disc-shaped, anuclear cells measuring approximately 7-8 microns in diameter on a peripheral blood smear with an internal volume of 80-100 femtoliters (fL).
Morphologic • normocytic, microcytic, or macrocytic • normochromic or hypochromic • Shape • Microcytic hypochromic --disorders of hemoglobin synthesis (most often iron deficiency) • Macrocytic anemias --maturation defect • Normochromic, normocytic -- diverse etiologies specific abnormalities of red cell shape (visual inspection on PS)
• Mean cell volume--- average volume of RBC (fL) • Mean cell hemoglobin--- Average content HB (pg) • Mean cell hemoglobin concentration-- average concentration of HB (gm/deciliter) • Red cell distribution width--- coefficient of variation of RBC volume
anaemia general, IDA.pptx
• Classification of Anemia According to Underlying Mechanism • BLOOD LOSS • INCREASED RED CELL DESTRUCTION (HEMOLYSIS) • DECREASED RED CELL PRODUCTION
anaemia general, IDA.pptx
anaemia general, IDA.pptx
• MC– anemias of red cell underproduction  nutritional deficiencies • extrinsic causes
anaemia general, IDA.pptx
Iron Deficiency Anemia • most common nutritional disorder in the world • clinical signs and symptoms ---- mostly related to inadequate hemoglobin synthesis • higher in developing countries • toddlers, adolescent girls, women of childbearing age • normal iron metabolism
Iron Metabolism • normal diet -- about 10 to 20 mg of iron form of heme contained in animal products, inorganic iron – vegetables • 20% of heme iron, 1% to 2% of nonheme ---absorbable • total body iron content -- about 2.5 gm - F , 6 gm -- M
Iron --- recycled between the functional and storage pools --- transferrin
• Free iron -- highly toxic • binding of iron in storage pool --- ferritin or hemosiderin • Ferritin --- ubiquitous protein-iron complex  liver, spleen, bone marrow, and skeletal muscles • Liver--- parenchymal cells; other tissues --spleen BM macrophages • Plasma transferrin or breakdown of red cells • Intracellular ferritin --cytosol or lysosomes-- ferritin aggregate into hemosiderin granules • iron-overloaded cells stored in hemosiderin
• plasma ferritin -- derived from storage pool  correlate well with iron stores • iron deficiency -- serum ferritin is below 12 µg/L • iron overload -- 5000 µg/L may be seen • Iron balance is maintained by regulating the absorption of dietary iron in the proximal duodenum • 1 to 2 mg lost each day through the shedding of mucosal and skin epithelial cells
anaemia general, IDA.pptx
• Luminal nonheme- iron --Fe3+ (ferric)  reduced to Fe2+ (ferrous) iron by ferrireductases cytochromes and STEAP3. • apical membrane b (DMT1). • non-heme iron  inhibited by substances in the diet that bind and stabilize Fe3+ iron and enhanced by substances that stabilize Fe2+ iron • less than 5% of dietary nonheme iron , about 25% of the heme iron derived from hemoglobin, myoglobin, and other animal proteins is absorbed. • Heme iron -metabolized to release Fe2+ iron, which enters a common pool with nonheme Fe2+ iron
• duodenal cells  transport to the blood / storage as mucosal iron • Fe2+ transported  basolateral enterocyte membrane by ferroportin • Fe2+ iron to Fe3+ iron iron oxidases hephaestin and ceruloplasmin. • Fe3+ transferrin red cell progenitors in the marrow • DMT1  lysosomal membranes into the cytosol of red cell precursors in the bone marrow • Ferroportin release of storage iron from macrophages
Iron absorption is regulated by hepcidin synthesized and released from liver • Hepcidin --bind to ferroportin • hepcidin levels rise iron trapped within duodenal cells  lost --- vice versa • Ferroportin also suppresses iron release from macrophages • pathogenesis of anemia of chronic diseases
• anemia of chronic disease  inflammatory mediators that increase hepatic hepcidin production • Mutation in TMPRSS6 • hepcidin  low in both primary and secondary hemochromatosis
Etiology • 1 mg daily requirement • As -10% to 15% absorbed RDA is 7 to 10 mg –M, 7 to 20 mg for F • Heme iron is much more absorbable than inorganic iron • Absorption of inorganic iron  enhanced by ascorbic acid, citric acid, amino acids, and sugars in the diet • inhibited by  tannates (found in tea), carbonates, oxalates, and phosphates
anaemia general, IDA.pptx
Pathogenesis
anaemia general, IDA.pptx
Morphology
anaemia general, IDA.pptx
anaemia general, IDA.pptx
Laboratory tests • 1.BLOOD PICTURE AND RED CELL INDICES • i) mild to moderate to marked (HB less than 6 g/dl) • ii) Red cells. hypochromic and microcytic, and there is anisocytosis and poikilocytosis • Hypochromia generally precedes microcytosis • Target cells, elliptical forms and polychromatic cells are often present • RBC count is below normal
• iii) Reticulocyte count normal or reduced but may be slightly raised (2-5%) • iv) Absolute values • Low MCV (below 50 fl) • low MCH (below 15 pg) • low MCHC (below 20 g/dl) • High RDW • v) Leucocytes usually normal • vi) Platelets slightly to moderately raised
• BONE MARROW FINDINGS • i) Marrow cellularity. Increased due to erythroid hyperplasia (M:E ratio decreased) • ii)Erythropoiesis. – micronormoblasts • iii) Other cells. Myeloid, lymphoid and megakaryocytes normal • iv) Marrow iron. Iron staining (Prussian blue reaction) --low
3.BIOCHEMICAL FINDINGS • i) The serum iron level is low (normal 40-140 μg/dl); it is often under 50 μg/dl. • ii) Total iron binding capacity (TIBC) is high (normal 250- 450 μg/dl) and rises to give less than 10% saturation (normal 33%) • iii) Serum ferritin is very low (normal 30-250 ng/ml) • iv) Red cell protoporphyrin is very low (normal 20-40 μg/dl) • v) Serum transferrin receptor protein --- raised in iron deficiency due to its release in circulation
anaemia general, IDA.pptx
anaemia general, IDA.pptx
Clinical Features • signs and symptoms --- underlying cause of the anemia • depletion of iron-containing enzymes--- koilonychia, alopecia, atrophic changes in the tongue and gastric mucosa, and intestinal malabsorption • Pica , periodically move their limbs during sleep • Esophageal webs + microcytic hypochromic anemia + atrophic glossitis  Plummer-Vinson syndrome
anaemia general, IDA.pptx
• Treatment • Oral • Parenteral
anaemia general, IDA.pptx

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anaemia general, IDA.pptx

  • 3. Definition • Reduction of the total circulating red cell mass below normal limits • Reduced --- oxygen-carrying capacity of the blood tissue hypoxia • usually diagnosed  reduction in the hematocrit (packed red cells : total blood volume) / hemoglobin concentration
  • 4. • Classification 1. underlying mechanisms (etiological) 2. morphological
  • 5. Normal, mature RBCs are biconcave, disc-shaped, anuclear cells measuring approximately 7-8 microns in diameter on a peripheral blood smear with an internal volume of 80-100 femtoliters (fL).
  • 6. Morphologic • normocytic, microcytic, or macrocytic • normochromic or hypochromic • Shape • Microcytic hypochromic --disorders of hemoglobin synthesis (most often iron deficiency) • Macrocytic anemias --maturation defect • Normochromic, normocytic -- diverse etiologies specific abnormalities of red cell shape (visual inspection on PS)
  • 7. • Mean cell volume--- average volume of RBC (fL) • Mean cell hemoglobin--- Average content HB (pg) • Mean cell hemoglobin concentration-- average concentration of HB (gm/deciliter) • Red cell distribution width--- coefficient of variation of RBC volume
  • 9. • Classification of Anemia According to Underlying Mechanism • BLOOD LOSS • INCREASED RED CELL DESTRUCTION (HEMOLYSIS) • DECREASED RED CELL PRODUCTION
  • 12. • MC– anemias of red cell underproduction  nutritional deficiencies • extrinsic causes
  • 14. Iron Deficiency Anemia • most common nutritional disorder in the world • clinical signs and symptoms ---- mostly related to inadequate hemoglobin synthesis • higher in developing countries • toddlers, adolescent girls, women of childbearing age • normal iron metabolism
  • 15. Iron Metabolism • normal diet -- about 10 to 20 mg of iron form of heme contained in animal products, inorganic iron – vegetables • 20% of heme iron, 1% to 2% of nonheme ---absorbable • total body iron content -- about 2.5 gm - F , 6 gm -- M
  • 16. Iron --- recycled between the functional and storage pools --- transferrin
  • 17. • Free iron -- highly toxic • binding of iron in storage pool --- ferritin or hemosiderin • Ferritin --- ubiquitous protein-iron complex  liver, spleen, bone marrow, and skeletal muscles • Liver--- parenchymal cells; other tissues --spleen BM macrophages • Plasma transferrin or breakdown of red cells • Intracellular ferritin --cytosol or lysosomes-- ferritin aggregate into hemosiderin granules • iron-overloaded cells stored in hemosiderin
  • 18. • plasma ferritin -- derived from storage pool  correlate well with iron stores • iron deficiency -- serum ferritin is below 12 µg/L • iron overload -- 5000 µg/L may be seen • Iron balance is maintained by regulating the absorption of dietary iron in the proximal duodenum • 1 to 2 mg lost each day through the shedding of mucosal and skin epithelial cells
  • 20. • Luminal nonheme- iron --Fe3+ (ferric)  reduced to Fe2+ (ferrous) iron by ferrireductases cytochromes and STEAP3. • apical membrane b (DMT1). • non-heme iron  inhibited by substances in the diet that bind and stabilize Fe3+ iron and enhanced by substances that stabilize Fe2+ iron • less than 5% of dietary nonheme iron , about 25% of the heme iron derived from hemoglobin, myoglobin, and other animal proteins is absorbed. • Heme iron -metabolized to release Fe2+ iron, which enters a common pool with nonheme Fe2+ iron
  • 21. • duodenal cells  transport to the blood / storage as mucosal iron • Fe2+ transported  basolateral enterocyte membrane by ferroportin • Fe2+ iron to Fe3+ iron iron oxidases hephaestin and ceruloplasmin. • Fe3+ transferrin red cell progenitors in the marrow • DMT1  lysosomal membranes into the cytosol of red cell precursors in the bone marrow • Ferroportin release of storage iron from macrophages
  • 22. Iron absorption is regulated by hepcidin synthesized and released from liver • Hepcidin --bind to ferroportin • hepcidin levels rise iron trapped within duodenal cells  lost --- vice versa • Ferroportin also suppresses iron release from macrophages • pathogenesis of anemia of chronic diseases
  • 23. • anemia of chronic disease  inflammatory mediators that increase hepatic hepcidin production • Mutation in TMPRSS6 • hepcidin  low in both primary and secondary hemochromatosis
  • 24. Etiology • 1 mg daily requirement • As -10% to 15% absorbed RDA is 7 to 10 mg –M, 7 to 20 mg for F • Heme iron is much more absorbable than inorganic iron • Absorption of inorganic iron  enhanced by ascorbic acid, citric acid, amino acids, and sugars in the diet • inhibited by  tannates (found in tea), carbonates, oxalates, and phosphates
  • 31. Laboratory tests • 1.BLOOD PICTURE AND RED CELL INDICES • i) mild to moderate to marked (HB less than 6 g/dl) • ii) Red cells. hypochromic and microcytic, and there is anisocytosis and poikilocytosis • Hypochromia generally precedes microcytosis • Target cells, elliptical forms and polychromatic cells are often present • RBC count is below normal
  • 32. • iii) Reticulocyte count normal or reduced but may be slightly raised (2-5%) • iv) Absolute values • Low MCV (below 50 fl) • low MCH (below 15 pg) • low MCHC (below 20 g/dl) • High RDW • v) Leucocytes usually normal • vi) Platelets slightly to moderately raised
  • 33. • BONE MARROW FINDINGS • i) Marrow cellularity. Increased due to erythroid hyperplasia (M:E ratio decreased) • ii)Erythropoiesis. – micronormoblasts • iii) Other cells. Myeloid, lymphoid and megakaryocytes normal • iv) Marrow iron. Iron staining (Prussian blue reaction) --low
  • 34. 3.BIOCHEMICAL FINDINGS • i) The serum iron level is low (normal 40-140 μg/dl); it is often under 50 μg/dl. • ii) Total iron binding capacity (TIBC) is high (normal 250- 450 μg/dl) and rises to give less than 10% saturation (normal 33%) • iii) Serum ferritin is very low (normal 30-250 ng/ml) • iv) Red cell protoporphyrin is very low (normal 20-40 μg/dl) • v) Serum transferrin receptor protein --- raised in iron deficiency due to its release in circulation
  • 37. Clinical Features • signs and symptoms --- underlying cause of the anemia • depletion of iron-containing enzymes--- koilonychia, alopecia, atrophic changes in the tongue and gastric mucosa, and intestinal malabsorption • Pica , periodically move their limbs during sleep • Esophageal webs + microcytic hypochromic anemia + atrophic glossitis  Plummer-Vinson syndrome

Editor's Notes

  • #16: catalase and the cytochromes ,,, liver and mononuclear phagocytes
  • #17: , transferrin is about one third saturated with iron, yielding serum iron levels that average 120 µg/dL in men and 100 µg/dL high-affinity receptors
  • #24: hepatic transmembrane serine protease that normally suppresses hepcidin