3.hemoglobin PRESENTATION POWER POINT PPT

HEAMOGLOBIN PRESENTATION

1. Hemoglobin

2. Preview Introduction Structure Synthesis Functions Important definitions Catabolism of hemoglobin Different varieties of hemoglobin MCQS

3. Introduction

4. Cytoplasm of erythrocytes contain an O2 binding protein. It consists of the protein GLOBIN & pigment HEME. Erythrocytes precursors synthesize Hb . Hb is 1 st appear in erythropoiesis of stage IV . Hb is centrally localized in RBC.

5. Disadvantages of free Hb If Hb was dissolved in plasma, it would lead to……. 1 ) Increase in the viscosity of plasma, hence of whole blood, so BP will rise . 2) Increase in the osmotic pressure of plasma to 100 mmHg 3) Hemogobinuria leads to renal damage 4) Free Hb is taken up & rapidly destroyed by tissue- mcrophages system

6. Normal Hb concentration: a) At birth : 23 gm% b) at end of 3 months : 10.5 gm% c) at end of 1 year: 12.5 gm% d) Male : 15.5 gm% (14-18 gm %) e) Female : 14 gm% ( 12- 15.5 gm%) When blood is equilibrated with 100% O2, normal Hb becomes 100% saturated . 1gm/dl Hb when fully saturated, combine with 1.34 ml O2. O2 carrying capacity of blood . male : 21 ml/dl female: 18 ml/dl

7. Structure of Hb

8. MW: 68,000 Two parts: 1) structure of globin : -Two alfa & two beta chains. 2) structure of heme : - iron- porphyrin complex. a) porphyrin neucleus : - four pyrrole rings - these rings are joined together by 4 methine bridge (=CH-). - Carbon atoms of methine bridge are labelled alfa , beta, gamma, delta

9. b) iron: - Ferrous form - Each ferrous ion combine loosely & reversibly with O2. - Combination of heme with O2 is called oxygenation but not oxidation. why? Because after combination of O2 iron in the heme stays in ferrous state. So, O2 doesn’t become ionic O2 but is carried as a molecular O2 1 molecule of Hb can carry 4 O2 molecules

10. Synthesis

11. 1) Protein : -for globin formation 2) Iron : -for heme formation 3) Copper : -for absorption, mobilization, & utilization of iron 4) Cobalt : -for vit . B12 synthesis & erythropoietin production. 5) Calcium : -for iron absorption. 6) Vitamins : -for synthesis of nucleic acid

12. Functions

13. 1) Transport function: 2) Buffer function : - responsible for 70% buffering power of blood 3) Additional NO binding site:

14. Important definitions

15. 1) Oxyhemoglobin : - Hb reacts with O2 - Its affinity is influenced by pH, temp., concentration of 2-3 DPG etc. 2) Carbamino -hemoglobin: - Hb reacts with CO2 3) Deoxygeneted Hb : - Hb from which O2 has been removed. 4) Glycosylated Hb : - Glucose is attached to terminal valine in beta chain - Level of HbA1c in the blood is increases in poorly control pt of DM.

16. Oxy & deoxyhaemoglobin

17. 5) Carboxyhemoglobin : - CO reacts with Hb . 6) Methaemoglobin : - when reduced or oxygenated Hb is exposed to various drugs or oxydising agents, ferrous is oxidized to ferric form. Disadvantage: - it cant unite reversibly with O2. - it is dark coloured , Produce mimic cyanosis

18. Catabolism of Hb

19. Old RBCs are destroyed by ‘ tissue- macrophage system ’ 1) Kupffer cells of liver 2) alveolar macrophage in the lung 3) osteoclast in bones 4) microglia in brain 5) lymphnode 6) spleen 0.3 gm of Hb is destroyed and 0.3 gm synthesized every hour

20. Variation of Hb

21. 1) Physiological varieties A) Adult Hb : a) Haemoglobin A: - it is the normal Hb in adults represents about 97% of total Hb . -it is composed of 2 α and 2 β chain b) Haemoglobin A2: - minor adult Hb , comprised 3% of normal adult Hb . Composed of 2 α and 2 δ chains c) HbF (fetal Hb ): - main Hb during fetal life and about 60% of normal Hb at birth then disappear gradually. It is composed of 2 α and 2 γ chains. - Hb F has greater affinity for O2 than HbA so ensure O2 transfer from maternal circulation to fetus RBCs through placenta.

22. Adult haemoblobin Hb A Hb A 2 Hb F structure a 2 b 2 a 2 d 2 a 2 g 2 Normal % 96-98 % 1.5-3.2 % 0.5-0.8 %

23. 2) Haemoglobinopathies Abnormal formation of Hb . Due to disorders of Globin Synthesis Two main types : 1) Formation of abnormal polypeptide chain e.g.- Sickle cell Anaemia 2) Suppression of synthesis of polypeptide chain e.g - Thalassaemia

24. Sickle Cell anemia Sickle Cell Anemia is a genetic disorder that is characterized by the formation of hard, sticky, sickle-shaped red blood cells, in contrast to the biconcave-shaped red blood cells (RBCs) found in “normal” individuals. This disease is caused by a mutation in hemoglobin.

25. Basic abnormality: Valine replaces glutamate in the 6 th position of β chain. Is common in African blacks Hb crystallizes & takes sickle shape under hypoxic conditions. Increased tendency towards haemolysis. Heterozygous : Half the circulating hemoglobin is abnormal and half is normal. Have sickle cell trait Homozygous : all of the hemoglobin is abnormal. Develop the full blown disease

26. Anemia - reduced O 2 carrying capacity of the blood Abnormal hemoglobin in RBCs : Sickle Cell - one amino acid in the beta chains is wrong . In low O 2 conditions the beta chains form stiff rods which cause RBCs to sickle blocking small vessels.

27. Hb -S polymerizes at low O2 tensions, and this causes the red cells to become sickle-shaped, hemolyze , and form aggregates that block blood vessels. Severe hemolytic anaemia

28. 2) Thalassemia The name is derived from the Greek words Thalasso = Sea" and " Hemia = Blood " in reference to anemia of the sea. Thalassemia is a group of inherited disorders of hemoglobin synthesis characterized by a reduced or absent output of one or more of the globin chains of adult hemoglobin They are hereditary hemolytic diseases in which the synthesis of either α - or β - globin chain is reduced/absent.

29. a) Alpha Thalassemia: - mutations in the alpha chain of the hemoglobin molecule. Major: all four alpha chain genes are deleted, which is so severe that death can occur in utero (prior to birth). Minor: two alpha chain genes are deleted Silent Carrier State ,Mild .

30. 2) Beta ( ß ) thalassemia : -Synthesis of of β -chains is decreased or absent whereas synthesis of α -chains is normal and will combine with δ -chains giving excess of HbA 2 ( α 2 δ 2 ) or it may combine with γ -chains producing excess of HbF ( α 2 γ 2 ). - There are 3 types categorized according to severity: Thalassemia minor Thalassemia intermedia Thalassemia major

31. Difference b/w major & minor Major ß thalassaemia Less common Homozygous transmission Moderate to severe Total absence of ß chain synthesis HbF markedly increase Life span: shorter, death occurs at 17 th year Minor ß thalassaemia More common Heterozygous transmission Mild Partial synthesis of ß chain Normal or mild increase Longer, survives up to adult life

32. MCQ

33. ` 1) Hb iron combine with ….. a) molecular O2 rather than ionic O2 b) both molecular as well as ionic O2 c) O2 attached to 2,3 DPG d) superoxide radicals 2) Each Hb molecule carries how many O2 molecules? a) 2 b) 4 c) 6 d) 8

34. 3) Affinity of Hb for O2 is influenced by all of the following except …… a) Ph b) Potassium c) temperature d) 2,3 DPG 4) Exposure of Hb to oxidizing agent results in…… a) ferric form to oxidize to ferrous form b) formation of methaemoglobin c) cyanosis d) formation of deoxygenated Hb

35. 5) Index of O2 carrying capacity of blood is… a) 2,3 DPG level in RBC b) iron content in Hb c) Hb concentration in the blood d) total iron content in Hb 6) Sickle cell anaemia , false ststement is….. a) RBCs fragility increases b) RBCs are sickle shaped c) blood flow to tissues decreases d) manifests as mild anaemia