Hemoglobin Large protein MW 64000 4 polypeptides 2  chains and 2 β chains Each chain heme, an iron-containing pigment The iron ion in heme is able to reversibly bind an oxygen molecule. O2 can bind to Hb at the lungs and then be released at the tissues

Hemoglobin Synthesis Normal hemoglobin production dependent upon Adequate iron supply iron is delivered to the RBC precursor by transferrin. It goes to the mitochondria where it is inserted into protoporphyrin to form heme. Adequate synthesis of protoporphyrins In the mitochondria Adequate globin synthesis. Ribosomes

Hemoglobin synthesis 2 succinyl CoA +2 glycine → Pyrrole 4 pyrroles → Protoporphyrin IX Protoporphyrin IX + Fe++→ Heme Polypeptide chains of globin are produced by ribosomes Heme + Polypeptide → Hemoglobin chain (Alpha chain or beta chain) 2 alpha chains + 2 beta chains → Hemoglobin A

Hemoglobin

Hemoglobin

Hemoglobin 92-95% Hb A  3-5% Hb A1c  2-3% Hb A2  1-2% Hb F

Absolute values Total count Size Hemoglobin contents ♂ 5000,000 ± 300,000 ♀ 4700,000 ± 300,000 Size Diameter =7.8 µ Outer edges = 2.5 µ Centre = 1 µ Hemoglobin contents 34 % of cell volume ♂14-16.5 g/dl of whole blood ♀12-15 g/dl of whole blood

Absolute values Hematocrit O2 carrying capacity MCV 80-100 fl ♂ 40-50 % ♀ 37-47 % O2 carrying capacity Each molecule carries 4 O2 1 G Hb 1.34 ml 100 ml of blood ♂ 20 ml ♀ 19 ml MCV 80-100 fl MCH 27-34 pg MCHC 31-35 g/dl

Anemia

Anemia means deficiency of hemoglobin in blood either due to few RBCs in blood or too little hemoglobin in the cells.

Anemia anemia is a functional inability of the blood to supply the tissue with adequate O2 for proper metabolic function. anemia is not a disease, but rather the expression of an underlying disorder or disease.

Anemia Quantitative and/or qualitative deficiency of RBC ↓ No of RBCs ↓ Amount of Hb ↓ O2 carrying capacity

Anemia Anemia may develop: When RBC loss or destruction exceeds the maximal capacity of bone marrow RBC production When bone marrow production is impaired

Anemia Various diseases and disorders are associated with anemia include: Nutritional deficiencies External or internal blood loss Increased destruction of RBCs Ineffective or decreased production of RBCs Abnormal hemoglobin synthesis Bone marrow suppression by toxins, chemicals, radiation, Infection Bone marrow replacement by malignant cells

Normal RBCs

Types of Anemia Blood loss anemia Aplastic anemia Megaloblastic anemia Hemolytic anemia

Classification of Anemia Nutritional anemia Pernicious anemia Aplastic anemia Renal anemia Blood loss anemia Hemolytic anemia Congenital anemia

Classification of anemias Anemias may be classified morphologically based on the average size of the cells and the hemoglobin concentration into: Macrocytic Normochromic, normocytic Hypochromic, microcytic

Nutritional Anemia Iron deficiency anemia ↓ intake of iron ↓ absorption of iron Chronic blood loss ↑ demand of iron (e.g. pregnancy) No of cells may be normal ↓ iron → ↓ Hb → ↓ size of cells (microcytic) ↓ iron → ↓ Hb → ↓ colour (Hypo chromic) (brittle spoon shaped nails- koilonychias- is a common feature)

Microcytic RBC

Micocytic Hypochromic anemia

Nutritional Anemia Magaloblastic anemia ↓ dietary Vitamin B12 ↓ intrinsic factor ↓Folic acid Maturation failure Cells- bigger ( megaloblasts) Cell membrane – fragile → easy rupture Hb contents - normal

Pernicious Anemia Maturation failure anemia ↓ Vit. B12 due to poor absorption from GIT ↓ intrinsic factor in the stomach Autoimmune destruction of parietal cells Atrophy of gastric mucosa Gastrectomy Megaloblastic anemia Cell membrane fragile → easy rupture

Macro ovalocyte

Aplastic Anemia Failure of bone marrow to produce RBCs Aplasia of the bone marrow Bone marrow may be destroyed Radiation e.g X-rays, gamma rays, nuclear bomb explosion Chemicals e.g.benzene, arsenic, chloramphenicol. quinine, gold salts, benzene, radium etc Bacterial toxins Tuberculous invasion HIV infections Invasion of bone marrow by cancer cells Chemotherapy for cancer

Renal Anemia Renal diseases (CRF) → ↓ Erythropoietin ↓ Erythropoietin → → ↓ Production of erythrocytes

Hemorrhagic Anemia Acute blood loss anemia Chronic blood loss anemia Normocytic Normochromic ↓ RBC count ↓ Hb/cmm of blood Chronic blood loss anemia Microcytic Hypochromic

Normocytic RBC

Normochromic & Hypochromic cells

Hemolytic Anemia Erythroblastosis Fetalis Sickle cell anemia Congenital spherocytosis Hemolysis due to Infections like malaria, septicemia Chemicals like lead, hemolysins Agglutinins (Jaundice is common feature in hemolytic anemia)

Erythroblastosis fetalis Rh negative mother Rh positive fetus Mother exposed to positive cells during first delivery Antibodies formed against positive cells Severe anemia in subsequent fetus Blast cells in the blood

Erythroblastosis fetalis

Erythroblastosis fetalis

Sickle cell anemia Sickle-cell anemia – results from a defective gene coding for an abnormal hemoglobin called hemoglobin S (Hb S) Alpha chains are normal, beta chain is defective Hb S has a single amino acid substitution in the beta chain Valine is substituted for Glutamic acid at position 6 Low oxygen → Precipitation and crystallization of Hb S → Sickling & hemolysis of RBC Sickle cell disease crises – a vicious cycle Hb S precipitate and cells aggregate may block small blood vessels leading to necrosis

Sickle cells

Hereditary spherocytosis One of the congenital anemia RBC are spherical instead of being biconcave Decreased deformability Cannot withstand compression Hemolysis in tight vascular beds

Spherocytes

Thalassemia Cooley’s anemia or Mediterranean anemia Impaired α or β chain synthesis due to genetic abnormality α thalassemia Decreased, defective or absent α chain β thalassemia (more common) Decreased, defective or absent β chain

Effects of anemia ↓ viscosity Easy flow of blood ↑ blood flow in all the tissues ↓O2 →vasodilatation ↑ COP ↑ work load on heart May → cardiac failure

Common clinical features in anemia Pale skin, lips, conjunctiva, mucous membrane, koilonychias etc Increased HR, COP, murmurs Increased Respiration rate, breathlessness Anorexia, nausea , vomiting, Headache, lack of concentration, irritability, lethargy, lack of energy, fatigue Menstrual disturbances, menorrhagia, oligomenorrhea, amenorrhea

Summary of variations in color and size

Polycythemia An increase in RBC mass is called polycythemia and it may lead to an increase in blood viscosity. Polycythemia Relative polycythemia due to decreased plasma volume e.g. in dehydration. Absolute polycythemia due to actual increase in RBC mass. This may occur in disorders that prevent adequate tissue oxygenation

failure of oxygen delivery to the tissues (cardiac failure) Secondary Polycythemia tissues become hypoxic because of too little oxygen in the breathed air high altitudes, failure of oxygen delivery to the tissues (cardiac failure) RBC count commonly rises to 6 to 7 million/ mm 3 30 percent above normal.

Physiological polycythemia occurs in natives who live at altitudes of 14,000 to 17,000 feet, where the atmospheric oxygen is very low The blood count -- 6 to 7 million/mm3 to perform continuous work even in a rarefied atmosphere

Polycythemia Vera (Erythremia) Pathological condition/tumorous condition RBC count --- 7 to 8 million/mm3 hematocrit --- 60 to 70 percent instead of the normal 40 to 45 percent genetic aberration in the hemocytoblastic cells blast cells no longer stop producing RBCs when too many cells are already present viscosity of the blood increases to10 times that of water---engorgement of capillaries

EFFECT OF POLYCYTHEMIA ON THE CIRCULATORY SYSTEM greatly increased viscosity of the blood --- blood flow very sluggish---decreases venous return to the heart blood volume is greatly increased in polycythemia which tends to increase venous return cardiac output in polycythemia is normal because these two factors more or less neutralize each other

The arterial pressure is also normal (1/3, the arterial pressure is elevated) The color of the skin depends to a great extent on the quantity of blood in the skin subpapillary venous plexus blood passes sluggishly through the skin capillaries deoxygenated hemoglobin ---bluish coloration

Chronic blood loss leads to which type of anemia a) megaloblastic anemia b)microcytic hypochromic anemia c) normocytic, normochromic anemia

Megaloblastic anemia is due to which of the following a) folic acid deficiency b) Iron deficiency c)Vitamin C deficiency

In sickle cell anemia, a)Alpha chains are faulty b)Beta chains are faulty c)Gamma chains are faulty

Thank-you Questions ??