2. Oxygen Transport by Blood LECTURE 20 By Dr. Khaled Khalil Assistant Professor of Human Physiology

3. At the end of this session, the student should be able to:  Describe the forms in which oxygen is transported in the blood.  Define oxygen partial pressure (tension), oxygen content, oxygen capacity and percent hemoglobin saturation.  Illustrate and describe oxyhemoglobin dissociation curve.  Describe factors affecting shape of oxyhemoglobin dissociation curve (shift to right and shift to left).  Describe the diffusion of oxygen from capillary blood to tissues and different factors affecting it. GUYTON & HALL Textbook of Medical Physiology, 12 th edition, page: 495-502.

4. O 2 is present in the blood in two forms: I. Physical solution: 1- Each 100 ml of arterial blood contains 0.3 ml of O 2 dissolved physically in plasma. 2- Each 100 ml of venous blood contains 0.13 ml of O 2 dissolved physically in plasma. II. Chemical combination: More than 98% of the O 2 is bound to hemoglobin of the red blood cells.

5. I. Physical solution: Although it is small amount but it has the following significance:

6. It determines the rate and direction of oxygen flow. As O 2 diffuses from high pressure to low pressure, physically dissolved O 2 acts as a pathway for the supply of O 2 to and from hemoglobin. When the blood reaches the tissues, it is this small amount that is first transported to the cells and then, it is replaced rapidly by more oxygen liberated from Hb. It determines the rate and direction of oxygen flow. As O 2 diffuses from high pressure to low pressure, physically dissolved O 2 acts as a pathway for the supply of O 2 to and from hemoglobin. When the blood reaches the tissues, it is this small amount that is first transported to the cells and then, it is replaced rapidly by more oxygen liberated from Hb.

7. HemoglobinHemoglobin - It is an oxygen carrying pigment. 1) Globin 2) Heme - a protein composed of four polypeptide chains. - There are many types of polypeptide chains according to their amino acid sequence. e.g.,  -chain, β-chain, γ-chain, and δ-chain. -Four pigment molecules containing a single ferrous ion in the center of each molecule. Each ferrous ion can combine with one molecule of O 2. Therefore, One Hb molecule can combine with 4 molecules of O 2.

9. - According to the type of polypeptide chains forming the globin portion, Hb can be classified into:  Hb A  Hb A (formed of 2  + 2 β chains): it represent 98% of Hb in adults.  Hb A 2  Hb A 2 (formed of 2  + 2 δ chains): it represents 2% of Hb in adults.  Hb F  Hb F (formed of 2  + 2 γ chains): it represents the main Hb in fetus.

10.  The reaction is reversible and rapid.  The reaction is oxygenation not oxidation. i.e., the iron in the heme remains in the reduced form “Fe ++ or ferrous iron”.  The combination of Hb and O 2 occurs in steps and each step accelerates the next one. i.e. Hb + O 2 HbO 2 (25 % saturation) HbO2 + O 2 HbO 4 (50 % saturation) HbO4 + O 2 HBO 6 (75 % saturation) HbO6 + O 2 HBO 8 (100 % saturation) Binding of Oxygen to Hb is characterized by:

11. Oxygen content of the blood: -It is amount of O 2 present in chemical combination with Hb in 100 ml of blood. Oxygen capacity of the blood: - It is the amount of oxygen present in chemical combination with Hb in 100 ml of blood when it is fully saturated. - In normal subjects, Hb content is about 15 gm % and each gram of Hb can combine with 1.33 ml O 2. - O 2 capacity = 15 x 1.33 = 19.95 ml (about 20 ml O 2 / 100 ml.) - Oxygen capacity depends upon Hb content. So, It is decreased in anaemia. - It is the amount of oxygen present in chemical combination with Hb in 100 ml of blood when it is fully saturated. - In normal subjects, Hb content is about 15 gm % and each gram of Hb can combine with 1.33 ml O 2. - O 2 capacity = 15 x 1.33 = 19.95 ml (about 20 ml O 2 / 100 ml.) - Oxygen capacity depends upon Hb content. So, It is decreased in anaemia.

12. Percentage (%) saturation of hemoglobin with oxygen: - This equals = O 2 content / O 2 capacity x 100 - Under normal condition, the Hb of systemic arterial blood is only 97% saturated with O 2 (not fully saturated). physiological shunt - This is due to addition of venous blood from bronchial and coronary veins to the arterial blood which is called physiological shunt. - This equals = O 2 content / O 2 capacity x 100 - Under normal condition, the Hb of systemic arterial blood is only 97% saturated with O 2 (not fully saturated). physiological shunt - This is due to addition of venous blood from bronchial and coronary veins to the arterial blood which is called physiological shunt.

13. Coefficient of O 2 utilization: - Definition: It is the % of the blood that gives its oxygen as its passes through the tissue capillaries. - The total quantity of oxygen bound with Hb in normal arterial blood is approximately 19.5 ml/100 ml blood. On passing through tissue capillaries, this amount is reduced to about 14.5 ml /100 ml blood. Thus, during rest about 5 ml of O 2 is utilized by the tissues by each 100 ml of blood. The normal value for utilization coefficient is approximately 25%. -In muscular exercise, It is increased to 75%. - The total quantity of oxygen bound with Hb in normal arterial blood is approximately 19.5 ml/100 ml blood. On passing through tissue capillaries, this amount is reduced to about 14.5 ml /100 ml blood. Thus, during rest about 5 ml of O 2 is utilized by the tissues by each 100 ml of blood. The normal value for utilization coefficient is approximately 25%. -In muscular exercise, It is increased to 75%. O 2 content in arterial blood – O 2 content in venous blood O 2 content in arterial blood O 2 content in arterial blood – O 2 content in venous blood O 2 content in arterial blood It equals =

14. O 2 Dissociation Curve  It is the curve which study the factors that affect the % saturation of Hb with O 2 in relation to O 2 tension of the blood. How to obtain the curve? - Blood samples are placed in special vessels known as tonometer used for blood equilibration with gases at body temperature, and each is exposed to a certain O 2 tension. - The O 2 content in each tonometer is determined. - O 2 content is divided by the O 2 capacity to get the % saturation. - % saturation is plotted against the O 2 tension.

15. Shape of the curve: - The oxygen dissociation curve has a Characteristic sigmoid or S shape. - This is because the combination of O 2 with the haem groups of the Hb occurs in steps as the affinity of haem to O 2 is increased after the haem group is oxygenated.

17. Physiological significance of the curve: The curve has 3 parts: 1)Upper flat part (plateau). 2)Middle curved part (slope). 3)Lower vertical part (steep). Physiological significance of the curve: The curve has 3 parts: 1)Upper flat part (plateau). 2)Middle curved part (slope). 3)Lower vertical part (steep).

18. 1) The upper flat part (plateau):  At O 2 tension (100 mmHg.), % Hb saturation is 100%. (note that inside the body, % saturation will be 97% only due the physiological shunt).  At O 2 tension (80 mmHg), % Hb saturation is 93 %.  At O 2 tension (60 mmHg), % Hb saturation is 90%.  So, decrease O 2 tension from 100 to 60 mmHg., causes decrease of % Hb saturation from 100% to 90% (i.e., only 10%).  The functional significance of the flat part of the curve is that the arterial O 2 saturation does not change much until PO 2 has decreased to about 60 mmHg. This enables persons living at high altitudes or with lung disease to get enough O 2 from this blood.

19. 2) Middle curved part (slope):  This part shows that: At O 2 tension (40 mm Hg), the % Hb saturation is 70%.  So, decrease O 2 tension from 100 to 40 mmHg, causes decrease of % Hb saturation from 100% to 70% (i.e., 30% decrease of % O2 saturation which are given to the tissues during rest).  This satisfies the tissues needs during rest & maintains an oxygen reserve in the blood for emergency condition.

20. Lower vertical part (steep): This part shows that: With further decrease of O 2 tension (below 40 mmHg), there is marked decrease in the % Hb saturation (i.e., more O2 supply to the tissues). This enables peripheral tissues to withdraw large amount of oxygen for only a small drop in capillary PO2 as occurring in muscular exercise.

21. Factors affecting O 2 dissociation curve: A number of factors can influence the affinity of HB to oxygen. These factors may cause shift of the curve either to right or to left. Shift to right: Hb gives more O 2 to tissues even under high O 2 tension. Shift to left: Hb gives less O 2 to the tissue even under low O 2 tension.

23. Factors that shift the curve to right: Factors that shift the curve to left: 1) Increased H + concentration. 2) Increased Partial pressure of CO 2. 3) Increased temperature. 4) Increased 2,3 DPG Function. 1) Decreased H + concentration. 2) Decreased partial pressure of CO 2. 3) Decreased temperature. 4) Decreased 2,3 DPG function. 5) Carbon monoxide poisoning.

24.  It is a chemical substance produced by the mature RBCs to increase the release of O 2 from Hb.  Formation: Mature RBCs lack mitochondria. Therefore, they obtain energy through the anaerobic glycolysis. During the course of glycolysis, 1,3 DPG is formed where it can be converted to 2,3 DPG by a side reaction using 1,3 DPG mutase enzyme.  Function: 2,3 DPG combine with β-chain of Hb causing release of O 2 to the tissue. 2,3diphosphoglycerate (2,3 DPG)

25. 2,3 DPG is increased in :2,3 DPG is decreased in: 1) All conditions of hypoxia as in: High altitudes. 2) Muscular exercise. 3) Certain hormones such as: testosterone. 1) Fetal hemoglobin. 2) Stored blood.