1. OXIGEN & CARBON DIOXIDE TRANSPORT Biochemistry Departement Medical Faculty Of Andalas University Padang

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3. 3 Oxygen Transport

4. Total Body Oxygen Stores Oxygen in the Lung (~500 ml O 2 ). Oxygen in the Blood (~850 ml O 2 ). Oxygen in the Cells (very little except Mb-bound).

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6. At the Lung Level

7. At the Tissue Level

8. Oxygen Is Carried in Blood in 2 Forms Bound to hemoglobin in red blood cells. Dissolved in plasma. Normally insignificant.

9. 9 Hemoglobin Each “heme” molecule is capable of binding with 1 O 2 molecule and each “globin” molecule is capable of binding with 1 CO 2 molecule. So, each molecule of Hb can bind to either 4 molecules of O 2 and 1 molecule of CO 2 100 ml of blood has about 15 gm of Hb, at Hct = 0.45

10. 10 Binding of O 2 to 4 heme sites given by:

11. 11 Oxygen as Oxyhemoglobin Each gram of Hb can store about 1.34 ml of O 2 : 1 L of blood (150 gm of Hb) can store about 208 ml of O 2  Oxygen Capacity of Hb. With normal cardiac output, about 1040 ml of O 2 can be carried in blood per minute. (4 times of the metabolic demands).

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14. O 2 Saturation. Units: percent. Fraction or percentage of all the hemoglobin binding sites that are currently occupied by oxygen.

15. 15 Oxygen Saturation of Hb

16. Four (5-6?) Things Change Oxyhemoglobin Affinity 1.Hydrogen Ion Concentration, [H + ] 2. Carbon Dioxide Partial Pressure, PCO 2 3. Temperature 4. [2,3-DPG] 5. Special Case: Carbon Monoxide 6. Hemoglobin variants

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18. 18 Factors Affecting Hb-O 2 Affinity: Summary Hydrogen Ion: –Increased H + (decreased pH) increases H + binding to Hb and reduces O 2 affinity (HbO 2 +H +  HbH + +O 2 ). Carbon Dioxide (Bohr effect): –Increased P CO2 increases CO 2 binding to Hb and reduces O 2 affinity (increased O 2 delivery to tissue). –Increased P CO2 increases H + and reduces O 2 affinity (fixed acid Bohr effect). Temperature and 2,3-DPG (diphosphoglycerate): –Increased temperature and 2,3-DPG reduces O 2 affinity.

19. Effect of CO & Anemia on Hb-O 2 Affinity Normal blood with Hb=15 gm/dl, anemia with Hb=7.5 gm/dl, and normal blood with 50% HbCO (carboxyhemoglobin).

20. Exercise Increase temperature Increased PCO 2 and Decreased pH (acidosis)

21. 2,3-DPG 2,3-DPG is a glycolytic intermediate –accumulates to uniquely high levels in RBCs -Increased 2,3-DPG right shift -Decreased 2,3-DPG left shift Increased 2,3-DPG associated with hypoxia.

22. Conditions with Increased 2,3-DPG acclimatization to high altitudes. chronic lung disease; emphysema. anemia. hyperthyroidism. right to left shunt. congenital heart disease. pulmonary vascular disease.

23. Blood Bank Storage CPD (citrate phosphate dextrose) Storage 2,3-DPG depletion O.D.C. left-shifted oxygen Oxygen unloading impaired

24. 24 Carbon Dioxide Transport

25. 25 At the Tissue Level

26. 26 At the Lung Level

27. 27 Carbon Dioxide Transport CO 2 is transported in blood in dissolved form, as bicarbonate ions, and as protein-bound carbamino compound. Protein-bound CO 2 (carbamino compounds): Amount of CO 2 stored as carbamino compounds is about 21 ml/L (4% of the total art CO 2 ).

28. 28 Carbon Dioxide Transport A majority amount of CO 2 is transported in the form of bicarbonate ions (HCO 3 - ): Amount of CO 2 in HCO 3 - form at P CO2 =40 mmHg is about 420 ml/L (90% of the total arterial CO 2 ).

29. 29 Carbon Dioxide Transport Haldane Effect: Increasing O 2 -saturation reduces CO 2 content and shifts the CO 2 dissociation curve to right. This is because, increasing P O2 leads to : –Decrease in the formation of carbamino compound. –Release of H+ ions from the hemoglobin and resulting in dehydration of HCO 3 -.

30. 30 Carbon Dioxide Dissociation Curve CO2 O2 2 2 Over the normal physiological range (P CO2 = 30 to 55 mmHg and P O2 = 40 to 100 mmHg), the CO 2 equilibrium curve is nearly linear. But, O 2 equilibrium curve is highly nonlinear.

32. Bicarbonate in RBCs. Carbonic anhydrase is present in RBCs CO 2 forms carbonic acid which dissociates to H + and HCO 3 - Released H + is buffered by histidine residues (imidazole group) Percent of the total PaCO 2 : 70%

33. Carbamino Compounds in RBCs. Approximately 30% of RBC contents is Hb CO 2 forms carbamino hemoglobin Released H + is buffered by histidine residues (imidazole group) Percent of the total PaCO 2 : 23 %

34. CO 2 Formation in Plasma Carbamino compounds – CO 2 binds the amine groups of plasma proteins to form carbamino compounds.

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37. Chloride Shift (Hamburger Shift) Newly formed HCO 3 - passes out of RBC Cl - diffuses into RBC to maintain electroneutrality –Chloride shift is rapid –Complete before the RBCs exit capillary

38. 38 Tissue-Gas Exchange: Summary Gas exchange processes in the peripheral organs are essentially opposite those in the lungs. O 2 is released from the capillary blood to the tissues and diffuses to the mitochondria energy (ATP) through cellular metabolism. CO 2 diffuses from the tissues to the blood stream and is transported to the lungs for elimination. The exchange of O 2 and CO 2 in the blood-tissue exchange unit depends on P O2, P CO2, and also on O 2 and CO 2 saturation curves.

39. 39 Resources BIOEN 589: Integrative Physiology. Download 24 jan 05. Kennelly, PJ., Rodwell, V W. Proteins: Myoglobin & Hemoglobin. In: Harper’s Illustrated Biochemistry. 27th Ed. 41- 8. Miliefsky, M. Respiratory System Ch.23. Download 24 Nov 10. Sheardown, H. Blood Biochemistry. McMaster University. Download 20 Mei 07. Irvin, CG. Respiratory Physiology. Lecture 4A CO2 Transport. In: MEDICAL PHYSIOLOGY 30. Download 22 Jun 09. Marks, DB., Marks, AD., Smith CM. Basic medical biochemistry: a clinical approach. 1996. Dalam: B.U. Pendit, penerjemah. Biokimia Kedokteran Dasar: Sebuah Pendekatan Klinis. Eds. J. Suyono., V. Sadikin., L.I. Mandera. Jakarta: EGC, 2000 R.K. Murray, D.K. Granner, P.A. Mayes, V.W. Rodwell Harper’s Biochemistry. 27th ed. McGraw-Hill Companies, New York. 2006.