Erythropoiesis & Iron Deficiency Anemia PDF 2024-2025

Dr.Mona Taalab 2024- 2025 Erythropoiesis and general aspects of anemia Hematopoiesis is the process of blood cells formation 1 ...

Dr.Mona Taalab 2024- 2025 Erythropoiesis and general aspects of anemia Hematopoiesis is the process of blood cells formation 1  Dr.Mona Taalab 2024- 2025 Stages of erythrocyte development: The reticulocytes: give rise to the mature enucleated erythrocyte, after one day of circulation in the peripheral blood. Through differentiation nucleoli disappear, nucleus condenses and finally extruded, the cell size is reduced and large amounts of hemoglobin (Hb) are synthesized. 2  Dr.Mona Taalab 2024- 2025 Structure of hemoglobin: Each red blood cell contains several hundred million hemoglobin molecules which transport oxygen~ 250 million molecules /cell Hemoglobin molecule consists 4 chain, each formed of Heme & polypeptide chain (globin). Each Heme molecule consists of porphyrin ring + iron (Fe+2). 3  Dr.Mona Taalab 2024- 2025 Types of hemoglobin molecules: Hemoglobin A (HbA): makes up about 95%-98% of hemoglobin found in adults; it contains two alpha beta protein chains. Hemoglobin A2 (Hb A 2 ): makes up about 1.5%-3.2% of hemoglobin found in adults; it has two alpha. Hemoglobin F (Hb F): makes up about 1%.of hemoglobin found in adults; it has two alpha gamma ( ) protein chains. A primary function of erythrocytes is to: Transport oxygen from the lungs to the tissues and organs in the body. This means that red cell mass represents the oxygen carrying capacity of the body. The normal red blood cell lifespan is 120 days. 4  Dr.Mona Taalab 2024- 2025 Definition of anemia: Reduction in the hemoglobin concentration, RBCs and hematocrit values below normal for age and sex Values: ( according to WHO) Less than 13g/dl in adult males Less than 12g/dl in adult females Normal adult red cell values Male Female Hemoglobin(g/dl) 14 – 16 gm/dl 13- 15 gm/dl PCV (HCT) 40-52 % 36-48% Red cell count (x1012 /l) 4.5-6.5 3.9-5.6 MCV(fL) 80-95 MCH (pg) 27-34 MCHC(g/dL) 30-35 Reticulocytic count (x109 /L) 0.5-2.5% (50x109/l, -150x109/l) 5  Dr.Mona Taalab 2024- 2025 Classification of anemias: I. Etiological classification. II. Morphological classification. I. Etiological classification: A) Anemia due to decreased RBCs formation. Decreased BM function: Aplastic anemia ( hereditary or acquired; Acquired form: Idiopathic or secondary to drugs, infections, …etc.). BM infiltration: leukemia, lymphoma …etc. Decrease of substances essential for hematopoiesis (deficiency anemia). Iron deficiency anemia. Megaloblastic: vitamin B 12 and folic acid deficiency. B) Anemia due to excess RBCs loss: Hemorrhagic anemia Hemolytic anemia C) Other causes: Anemia of chronic disorders (ACD) Anemia due to endocrinal disorders. Anemia due to renal failure. Anemia due to liver disease. Anemia due to collagen disease 6  Dr.Mona Taalab 2024- 2025 II. Morphological classification: 1) Microcytic hypochromic anemia: MCV MCH MCHC Causes: Iron deficiency anemia Thalassemias. Lead poisoning. Sideroblastic anemia (some cases). Anemia of chronic disease (2/3 of the cases.) 2) Normocytic normochromic anemia: MCV N MCH N MCHC N Causes: Hemolytic anemias except thalassemia Hemorrhagic anemia (acute blood loss) Bone marrow failure or infiltration by( leukemia, lymphoma, carcinoma, etc…) Anemia of chronic disease (1/3 of cases) Renal insufficiency ( due to erythropoietin deficiency). Mixed deficiency 3) Macrocytic anemia: MCV > 95 fL Causes: Megaloblastic: Vitamin B12, folic acid deficiency. Non megaloblastic: 7  Dr.Mona Taalab 2024- 2025 Alcohol, pregnancy, liver diseases, smoking, reticulocytosis, hypothyroidism, Myelodysplastic neoplasm (MDS), multiple myeloma. Clinical manifestations of anemia Depends on: Speed of onset. Severity of anemia. Age of patient. Underlying diseases especially CVS. A) Symptoms: 1) CVS: Low COP symptoms. Exertional dyspnea & palpitation. Angina and intermittent claudication. Symptoms of heart failure in severe cases. 2) Neurological: Lack of concentration. Headache, tinnitus, blurring of vision. 3) Skeletal: Bone ache Easy fatigability. 4) Genital: Menstrual disturbance especially amenorrhea. Decreased Libido. 8  Dr.Mona Taalab 2024- 2025 B) Signs: 1- Pallor: detected in palm and palmer creases, nail bed, tongue and inner conjunctiva. Differential diagnosis of other causes of pallor …. (SBE, Rh fever, MI, Myxedema, hypopituitarism ). 2- CVS Tachycardia (hyperdynamic circulation). Hemic murmur: on aortic, soft midsystolic, no thrill. Water hummer pulse. Capillary pulsation. Congestive Heart failure 3- Oedema LL: Increased capillary permeability. Heart Failure. Specific signs according to cause e.g.: Koilonychia (spooned shaped nails), angular stomatitis Iron deficiency anemia Jaundice :- Hemolytic, Megaloblastic anemia Bone deformity & mongoloid facies Thalassemias. Leg ulcer sickle cell anemia Purpura & infection BM failure & infiltration Beefy red tongue painful tongue megaloblastic anemia Pain & parasthesia vitamin B12 deficiency (subacute combined degeneration) 9  Dr.Mona Taalab 2024- 2025 Laboratory investigations 1) RBCs indices: Normocytic, microcytic, macrocytic 2) Reticulocytic count: (n= 0.5-2%) Increased in : Hemolytic anemia, Hemorrhagic anemia, Anemia under treatment Decreased in : Bone marrow failure or infiltration 3) WBCs & Platelets: Decrease in pancytopenia: causes: Aplastic anemia Hypersplenism Myelofibrosis BM infiltration (lymphoma, leukemia, carcinoma) Megaloblastic anemia Hairy cell leukemia PNH ( Paroxysmal Nocturnal Hemoglobinuria) 4) Bone marrow examination: indications: pancytopenia leukocytosis: to diagnosis of acute and chronic Leukemias Diagnosis of bone marrow infiltration e.g: lymphoma, carcinoma and multiple myeloma. Cases of refractory anemia. 10  Dr.Mona Taalab 2024- 2025 Investigation according to morphology I. Microcytic anemia: A) Iron profile S. Iron : (90 – 150 g%) S. ferritin : (20 – 250 ng/dl) Total iron binding capacity (TIBC): (280 – 400 g%) In iron deficiency anemia: S. Iron & ferritin decreased TIBC: increased In Anemia of chronic disease: S. Iron decreased TIBC decreased S. ferritin normal or increased in some cases. In thalassemias: Increased in serum iron & ferritin. In sideroblastic anemia: S. Iron S. ferritin TIBC N BMA: ringed sideroblast B) Hb electrophoresis: In Thalassemia ( increased HbF or HbA2), Sickle cell anemia.( increased HbS) II. Normocytic anemia: Reticulocytic count: Increased in cases of Hemolysis and hemorrhage 11  Dr.Mona Taalab 2024- 2025 Decreased in case of BM failure BMA in patients with Aplastic anemia: Decreased in bone marrow cellularity with increased fatty spaces. Investigations of hemolytic anemia: Serum bilirubin (indirect), urine urobilinogen, fecal stercobilinogen, serum haptoglobin, reticulocytosis, BMA: Hypercellular, erythroid hyperplasia. Investigations of hemolytic anemia according to type: Hereditary: HB electrophoresis: Hemoglobinopathies Sickling test for sickle anemia Osmotic fragility hereditary spherocytosis Enzyme assay GP6D assay. Acquired: Direct Coombs’ test autoimmune hemolytic anemia (AIHA). Ham’s test PNH (hemolysis of RBCs at low PH serum). III. Macrocytic: MCV 95 fL Exclude alcoholism, hypothyrodism & other causes of macrocytosis For Megaloblastic anemia: Serum Folic acid & B12 level. BMA: Megaloblastic changes and erythroblasts are large and show failure of nuclear maturation. Schilling test: radioactive cobalt 57Co absorption test Gastric function test & gastric acidity Therapeutic test: correction with vitamin B12 & folic acid 12  Dr.Mona Taalab 2024- 2025 Iron deficiency anemia Iron deficiency anemia is the most common cause of anemia & it’s the most important cause of microcytic hypochromic anemia. Site of iron absorption: Duodenum Factors affecting iron absorption: 1- Factors enhancing iron absorption: Haem iron Ferrous form Acids (HCL- vitamin C) Reduced serum hepcidin Ineffective erythropoiesis Hereditary haemochromatosis 2-Factors reducing iron absorption: In organic iron Ferric form Alkalis- antacids Inflammation Increased serum hepcidin Decreased erythropoiesis 13  Dr.Mona Taalab 2024- 2025 Clinical features: General signs of anemia. Painless glossitis, angular stomatitis. Brittle, ridge or spooned shaped nails (koilonychia). Dysphagia as a result of pharyngeal webs (paterson-kelly or Plummer-Vinson syndrome). Pica: unusual dietary cravings In children: irritability, poor cognitive function and psychomotor instability. Causes of iron deficiency: I. Chronic blood loss: Uterine. Gastrointestinal: e.g. DU, OV, partial gastrectomy, carcinoma of stomach, caecum, colon rectum, colitis, piles. Rarely hematuria, hemoglobinuria. II. Increased demands: prematurity growth pregnancy. III. Malabsorption. IV. Poor diet. Laboratory findings: CBC: Microcytic, hypochromic anemia. Blood film: Pencil cells & aniso pokilocytosis Reticulocytic count decreased in relation to severity of anemia Platelets count increased especially in chronic blood loss Serum iron decreased & TIBC increased. 14  Dr.Mona Taalab 2024- 2025 Serum ferritin :decreased Serum transferrin receptor: increased. Red cell protporphyrin: increased & red cell ferritin decreased. BM: decreased iron from macrophages & from erythroblasts Investigation of the cause: E.g. occult blood test upper & lower GIT endoscopy, urine analysis, pelvic U/S, chest x-ray Treatment: I. Treatment of the cause. II. Iron therapy: 1) Oral iron: A- The best is ferrous sulphate 67mg elemental iron. – Given on an empty stomach. – S/E: abdominal pain, constipation. B- Ferrous gluconate: contain less elemental iron. C- Ferrous fumarate. Oral iron given for long enough both to correct anemia & to replenish body iron stores i.e. 6 months. The Hb should raise at rate 1-2 g/dl every 3-4w. Causes of failure of response to oral iron: Continuing hemorrhage. Failure to take tablets. Wrong diagnosis. Mixed deficiency. Malabsorption. 15  Dr.Mona Taalab 2024- 2025 Parenteral iron: Ferric hydroxide – sucrose by slow intravenous infusion Iron dextran slowly intravenous injection or infusion. Iron sorbitol deep intramuscular. N.B: used after failure of oral iron, malabsorption, intolerance to oral essential to replete body stores rapidly. S/E :hypersensitivity Dose in milligrams (target Hb – Actual Hb) X body weight X 0.24 + 500 mg. 16