Section Three Gas transport Lecture 6: Oxygen transport in blood. Carbon dioxide in blood. Objectives: i. To describe the carriage of O2 in blood. ii. iii. iv. To explain the oxyhemoglobin dissociation curve and factors that may alter it. To define Bohr effect. To describe the carbon dioxide carriage in blood. v. To relate the effect of CO2 on O2 transport (Haldane effect).
Transport of gases in the blood and body fluids: O 2 is transported principally in combination with hemoglobin (Hb). Hb combination increases O 2 transport 30 to 100 times as much as O 2 as could be transported simply in the dissolved form in the blood. In the tissue cells, O 2 react with various foodstuffs to form CO 2. CO 2 also combines with chemical substances in the blood that increase CO 2 transport 15 to 20 fold. * 98% of left atrial blood becomes oxygenated up to a PO 2 of about 104 mmhg. * 2% of blood has passed directly from the aorta through the bronchial circulation. It represents shunt flow i.e., bypassed gas exchange areas. This blood on leaving the lungs has PO 2 of normal venous blood i.e., 40 mmhg.this 2% blood combines in the pulmonary veins with oxygenated blood from alveolar capillaries; this mixing called venous admixture of blood and it causes the PO 2 of blood pumped from left ventricle into aorta to fall to about 95 mmhg.
Oxygen-Hemoglobin Dissociation Curve at Rest
Reversible combination of oxygen with hemoglobin: O 2 molecule combines loosely and reversibly with heme portion of the Hb. When PO 2 is high (in pulmonary capillaries), O 2 binds with Hb. When PO 2 is low (in tissue capillaries), O 2 is released from Hb. Oxygen-hemoglobin dissociation curve: This curve shows the relationship between the blood PO 2 (O 2 pressure or tension) and the amount of O 2 that bound to Hb (the % saturation of Hb with O 2 ). It demonstrates a progressive increase in the percentage of the Hb that is bound with O 2 (% saturation of Hb) as the blood PO 2 increases. The curve is normally sigmoid in shape i.e., S-shaped, this is due to sequential binding of the four O 2 molecules, one to each of the four heme groups where each combination facilitates the next (heme-heme interaction) until the Hb molecule becomes saturated with O 2.
Hemoglobin and Oxygen Transport Oxygen is transported by hemoglobin (97%) and is dissolved in plasma (3%) Oxygen-hemoglobin dissociation curve shows that hemoglobin is almost completely saturated when P02 is 80 mm Hg or above. At lower partial pressures, the hemoglobin releases oxygen. A shift of the curve to the left because of an increase in ph, a decrease in carbon dioxide, or a decrease in temperature results in an increase in the ability of hemoglobin to hold oxygen(means more O2 will be attached to Hb (increased affinity) for a given PO2.Thus, less O2 is available to the tissues or is freed from Hb at a given PO2.
Hemoglobin and Oxygen Transport A shift of the curve to the right because of (1)a decrease in ph, (2)an increase in carbon dioxide, or(3) an increase in temperature results in a decrease in the ability of hemoglobin to hold oxygen(the affinity of Hb for O2 is reduced, so that for a given plasma PO2, more O2 is freed from Hb). 1. The substance 2.3-bisphosphoglycerate increases the ability of hemoglobin to release oxygen (2,3-DPG; a phosphate compound normally present in the blood but in different concentration under different condition. It is a metabolite of RBCs). Fetal hemoglobin has a higher affinity for oxygen than does maternal(causes increase O 2 released to the fetal tissue under hypoxic condition in which the fetus exists).
The upper portion of the curve, between a PO2 of 70 to 100 Torr, is nearly flat. This portion of the curve is often referred to as the association part of the curve because it is important in the loading of O2 (association of O2 with Hb) in the lung capillary. The association part of the curve insures oxygenation of most of the Hb even when alveolar PO2 is decreased due to High altitude or pulmonary disease. The SbO2 decreases from 97.5% at a PO2 of 100 Torr to 92% at a PO2 of 70 Torr with only a change of 1.0 vol% in blood O2 content. Thus, this flat portion of the oxy-hb dissociation curve insures nearly normal loading of Hb with O2 even when the alveolar PO2 is reduced from normal.
the steep sloping part of the curve, between a PO2 of 50 and 20 Torr is termed the dissociation portion of the curve. The dissociation portion of the curve is important in the tissue capillaries where a large amount of O2 can be unloaded for a relatively small Change in the PO2. For example, a decrease in the PO2 from 50 to 20 Torr reduces the blood O2 content by over 10 vol% or by nearly 50%. Thus, a sizable portion of the O2 carried by Hb is available for use by the tissues for a relatively small change in the PO2.
Effect of DPG: The normal DPG in the blood keeps the O 2 -Hb dissociation curve shifted slightly to the right all the time. In hypoxic condition that last longer than a few hours, the quantity of DPG in the blood increase, thus is shifting the curve further to the right. This causes O 2 to be released to the tissue. Therefore this can be an important mechanism for adaptation to hypoxia, especially to chronic hypoxia of people living at high altitude and hypoxia caused by poor tissue blood flow (ischemic hypoxia), as in heart failure, and shock. Shift of the curve during exercise: In exercise, several factors shift the curve of the muscle capillary blood to the right. The exercising muscles release large quantities of CO 2 ; this, plus several acids released by exercising muscle, increases the H + ion concentration in the muscle blood capillaries. In addition, the temperature of the muscle raises 2-3 C. All these factors act together to shift the curve of the muscle capillary blood to the right. The right shift of the curve allows O 2 to be released to the muscle at PO 2 between 15-40 mmhg. Then, in the lungs, the shift occurs in the opposite direction, thus allowing pickup of extra amount of O 2 from the alveoli.
The Bohr effect: (CO 2 & H + ion) Shift of the curve in response to changes in the blood CO 2 and H + ion has the following significant effects: Oxygenation of the blood in the lung (left shift). Releases of O 2 from the blood in the tissue (right shift). As the blood passes through the lungs, CO 2 diffuses from the blood into the alveoli. This reduces the blood PCO 2 and decreases H + ion concentration because of the resulting decrease in the blood carbonic acid. CO 2 + H 2 O H 2 CO 3 H + + HCO 3 - Both these effects ( PCO 2 & H + ion) shifts the curve to the left, therefore the quantity of O 2 that bind with the Hb at any given alveolar PO 2 becomes increased, thus allowing greater O 2 transport to the tissues. When the blood reaches the tissue capillaries, the opposite effects occur. CO 2 entering the blood shifts the curve to the right, which displaces O 2 from Hb and therefore delivers O 2 to the tissues.
Temperature effects:
Shifting the Curve
Transport of Carbon Dioxide Carbon dioxide is transported as bicarbonate ions (70%), in combination with blood proteins (23%), and in solution with plasma (7%) Hemoglobin that has released oxygen binds more readily to carbon dioxide than hemoglobin that has oxygen bound to it (Haldane effect) In tissue capillaries, carbon dioxide combines with water inside RBCs to form carbonic acid which dissociates to form bicarbonate ions and hydrogen ions
Transport of Carbon Dioxide In lung capillaries, bicarbonate ions and hydrogen ions move into RBCs and chloride ions move out. Bicarbonate ions combine with hydrogen ions to form carbonic acid. The carbonic acid is converted to carbon dioxide and water. The carbon dioxide diffuses out of the RBCs. Increased plasma carbon dioxide lowers blood ph. The respiratory system regulates blood ph by regulating plasma carbon dioxide levels
CO 2 Transport and Cl - Movement
Haldane effect It was pointed out that an increase in carbon dioxide in the blood causes oxygen to be displaced from the hemoglobin (the Bohr effect), which is an important factor in increasing oxygen transport. The reverse is also true: binding of oxygen with hemoglobin tends to displace carbon dioxide from the blood. The Haldane effect approximately doubles the amount of CO2 released from blood in the lungs and doubles the pickup of CO2 in the tissues. The Haldane effect results from the simple fact that the combination of oxygen with hemoglobin in the lungs causes the hemoglobin to become a stronger acid.
This displaces carbon dioxide from the blood and into the alveoli in two ways: (1) The more highly acidic hemoglobin has less tendency to combine with carbon dioxide to form carbaminohemoglobin, thus displacing much of the carbon dioxide that is present in the carbamino form from the blood. (2) The increased acidity of the hemoglobin also causes it to release an excess of hydrogen ions, and these bind with bicarbonate ions to form carbonic acid; this then dissociates into water and carbon dioxide, and the carbon dioxide is released from the blood into the alveoli and, finally, into the air.
Ventilation-perfusion coupling: