Transport of gases

1. Transport of gases Dr. Kalpana

2. At the end of class students should be able to: • Describe the processes of oxygen transport in blood. • Draw a labelled diagram of oxy-Hb dissociation curve. • Explain the factors affecting oxy-Hb dissociation curve. • Mention the significance of P50 • Explain the importance of Bohr effect

3. Partial pressure of gases(mm Hg) in different parts of respiratory system

4. Oxygen transport

5. Gaseous transport • O2 consumption by body = 250ml/min • CO2 excretion by body = 200ml/min

6. Oxygen transport

7. Oxygen transport • 2 forms • Physical form –Dissolved form in plasma as simple solution • Chemical form –Combination with Hemoglobin

8. Physical form (or) Dissolved form in plasma • Account for about 1 to 2 % of O2transport. • Amount of O2 is o.3 ml per 100 ml of blood/100 mmHg PO2.

9. Significance of dissolved form • Dissolved form determine PO2 in the blood-combining capacity of Hb. • When O2 carrying capacity of Hb is affected-this form content is increased -necessary O2 for tissue

10. Chemical form (oxy-hemoglobin) • Normal Hb level = 15gm/dl • With full saturation (100%) O2 carrying capacity of Hb = 1.34 ml/ gm of Hb • O2 carrying capacity of 100ml blood = • 1.34 x 15 = 20.1ml/dl (with 100% Hb sat.) • Arterial blood (PO2 of 97mm Hg) with 97.5% Hb saturation (due physiological shunt) = 19.8 ml/dl

11. Hemoglobin (Hb) • Molecular weight = 68,000 • Consists of 4 Heme (with a ferrous ion in each) & conjugate with 4 polypeptide chains • Each ferrous ion combine with a molecule of Oxygen • Each Hb molecule carry 4 molecule of O2 (Hb4O8) • This oxygenation & de oxygenation are so rapid require <0.01sec

12. The iron stays in the ferrous state, the reaction is oxygenation. • Hb4 + O2 Hb4O2 • Hb4O2 + O2 Hb4O4 • Hb4O4 + O2 Hb4O6 • Hb4O6 + O2 Hb4O8 • The reaction is rapid, requiring less than 0.01s.

13. O2 dissociation curve • Method of determination: • 5 ml of blood placed in 250 ml of tonometer • Fill the tonometer with known concentration of O2. • Shake for 20 minutes in water bath at 37.5oc • After that measure % of Hb saturation in the blood • The result of saturation is plotted against that ofPO2.

14. Oxygenation of Hb • Combination of O2 with Hb depend on PO2. • The relationship between PO2 & Hb saturation is not linear but “sigmoid shape”. • The curve obtained by plotting the Hb saturations against their various PO2 is – Oxygen dissociation curve • (Or Oxy-Hb dissociation curve • Or Hb dissociation curve)

16. O2 dissociation curve • Sigmoid in shape • Having three phases– • Phase 1 -- Slow ascend (between 0 to 10 mm Hg of PO2.) • Phase 2 --Steep ascend (between 10 to 50 mm Hg) & • Phase 3 -- Plateau (between 70 to 100 mm Hg of PO2.)

17. 3 important points in O2 dissociation curve are -- Arterial point -- PO2 of 100 mm Hg & Hb saturation of 97.5% Venous point --PO2 of 40 mm Hg & Hb saturation of 75% P50 --PO2 of 28 mm Hg & Hb saturation of 50% P50 – is the partial pressure at which 50% Hb saturation occur When P50 – increases O2 affinity decreases

18. Basis or Reason for sigmoid shape • Heme to Heme interaction • Configuration change of Hb

19. Advantages of sigmoid shape curve Plateau phase –safety factor -significant decrease in lung function allows normal saturation of Hb. -oxygen content and saturation remain fairly constant inspite of wide fluctuations in alveolar PO2 Steep phase –Helps to deliver more O2 in case of body’s requirement

20. The oxyhemoglobin dissociation curve is shifted either left or right by various factors • Shift of the curve to left indicates acceptance of oxygen by hemoglobin • Shift of the curve to right indicates dissociation of oxygen from hemoglobin

21. Factors shifting O2 dissociation curve to left 1. In the fetal blood – fetal hemoglobin has got more affinity for oxygen than adult hemoglobin 2. Decrease in hydrogen ion concentration and increase in pH (alkalinity)

22. Factors shifting O2 dissociation curve to right (less O2 affinity) In the blood level -- • Increase in temperature • Increase in H+ ion concentration ( pH) • Increase in CO2 • Increase in 2,3-DPG level

23. Bohr’s effect • Decrease O2 affinity due to decrease in pH of blood is called Bohr’s effect • Normally decrease in pH of blood occur due to increase in CO2 content of blood – Hence, increase in blood CO2 shifts the O2 dissociation curve to right can also be called Bohr’s effect.

24. Significance of Bohr’s effect • Takes place at tissue level • Helps in unloading & O2 delivery to tissue • Most of Hb unsaturation (O2 delivery) to tissue occur due to decrease in PO2. • Extra 1 to 2% of unsaturation of Hb (and resulting O2 delivery) is due to increase in PCO2

25. 2,3-Diphosphoglycerate (2,3-DPG) • Metabolic byproduct of glycolysis • It is a highly charged anion • Bind with β-chain of Deoxy-Hb • HbO2 + 2,3-DPG  Hb-2,3-DPG + O2 • Increase in concentration of 2,3-DPG causing more & more O2 liberation • Thereby decrease oxygen affinity with Hb

26. Factors decrease 2,3-DPG level • Acidosis (inhibit glycolysis) • Fetal Hb (γ-chain of fetal Hb has poor binding capacity for 2,3,DPG) • Stored blood (due decrease in metabolism)

27. Factors increase 2,3-DPG level • Hormones –Thyroid hormone, GH & androgen • Exercise –increase metabolism • High altitude –(secondary due to alkalosis with half life of 6 hours) • Anemia • Diseases causing chronic hypoxia

28. Factors shift O2 dissociation curve to left (increased affinity) • Decrease in temperature • Decrease in H+ ion concentration ( pH) • Decrease in CO2 level • Fetal Hb • CO poisoning

29. 5. Fetal Hemoglobin Advantage Increased O2 release to the fetal tissues under the hypoxic condition.

30. Carbon monoxide • CO shifts the curve to left due to inhibition of synthesis of 2,3 DPG. Affinity of CO to combine with Hb is 200 times the O2. • Carboxy-Hb • Myoglobin • It takes up oxygen readily at low pressure. • Rectangular hyperbola.

32. Summary

33. References • Comprehensive Textbook of Medical physiology (Vol 2 first edition) G K Pal • Text book of medical physiology (Vol 2 6 th edition) A K Jain AEJ