1. Lecture 3 Gas exchange O 2 transport CO 2 transport

2. Gas exchange It takes place at a respiratory surface. For unicellular organisms the RS is simply the cell membrane, but for a large organisms it is the respiratory system. In humans, respiratory GE or V E is carried out by mechanisms of the lungs. The matching of V E and perfusion is the critical determinant of GE, and a deficiency of excess of V E relative to the amount of BF → either inadequate or wasteful respiration.

3. Alv are designed for rapid GE. Alv are found at the end of the branching bronchioles and so they have a good air supply. The alv walls are very thin and have a moist surface. They are covered by a network of capillaries which transport the gases. Blood takes about 1 sec to pass through the lung capillaries. In this time the blood becomes nearly 100% saturated with O 2 and loses its excess of CO 2. When you breath in the first 150 ml fills the tubes which are outside the alv (anatomic VD). There is also a functional VD (air in these alv doesn’t exchange with the blood and is part of the VD). The amount of air reaching the alv with each breath is equal to VT – VD.

4. Inspired air contains about 21% O 2 and 78% N 2, almost no CO 2. Blood returning to lungs is high in CO 2 and is low in O 2. While blood leaving lungs is enriched with O 2, low in CO 2. In pulmonary capillaries, O 2 diffuses into capillary blood, while CO 2 diffuses into alveolar air. Note; No exchange of gases occurs in heart, arteries, or arterioles. The ratio of CO 2 produced / O 2 consumed is known as RQ.

8. O 2 transport O 2 is carried in the blood in 2 forms; 1) bound to Hb (approx 98.5 %) 2) dissolved in the plasma (approx 1.5 %). The amount of any gas that dissolves in blood is directly proportional to the partial pressure of the gas and the solubility of the gas. Therefore, CO 2 = SO 2 * PO 2 (Henry's law). where SO 2 is the solubility of O 2. where SO 2 is the solubility of O 2. At 37C, the solubility of O 2 is 0.003 ml O 2 / 100 ml blood / mmHg. The content of O 2 dissolved in blood = 0.003 * PO 2. If plasma PO 2 is 100 mmHg (arterial blood), the amount of O 2 dissolved is 0.3 ml. This small amount of O 2 will not sustain normal human metabolism. So another method is needed to transport O 2 to tissues in sufficient quantity to meet metabolic demands. The Hb mol meets this requirement. Each mol of Hb can carry 4 mol of O 2. Fully sat Hb can carry approx 1.36 ml O 2 / g Hb, and normal human blood contains about 15 g Hb / 100 ml blood. Multiplying these two constants yields 20.4 ml O 2 / 100 ml blood. Because blood is almost fully sat at a PO 2 of 100, there are about 20 ml O2 / 100 ml of normal arterial blood, which is considerably more than the 0.3 ml dissolved in plasma.

9. Hb is a protein in which a haem group is attached to each of 4 subunit polypeptide chain (2 alpha & 2 beta). Hb contains 4 iron atoms (4 haem group). Each one contain a Fe 2+ within a haem group. If 100 ml of plasma is exposed to an atmos with a PO 2 of 100 mmHg, only 0.3 ml of O 2 would be absorbed. However, if 100 ml of blood is exposed to the same atmos, about 19 ml of O 2 would be absorbed. WHY? The total quantity of O 2 bound with Hb in normal systemic arterial blood is about 19.4 ml /100 ml of blood. On passing through the tissue capillaries, this amount is reduced to approx 14.4 ml. Therefore, 5 ml is the quantity of O2 that are transported from the lungs to the tissues by each 100 ml of BF. During heavy exercise, there might be upto 20 times ↑ in O 2 transport to the tissues compared to normal.

10. The O 2 carrying capacity is the vol of O2 contained in a vol of O2 sat blood; the CC depends on the conc of effective Hb. The CC is reduced in various forms of anemia ( ↓ No of RBC, insufficient prod of Hb or abnormal prod of Hb). Failure of Hb prod occurs in dietary iron deficiency anemia, because iron is needed for synthesis of haem group. Dietary deficiency or failure of absorption of vit B12 causes pernicious anemia, in which formation of RBCs is impaired. In sickle cell anemia, substitution of a single AA in the β chain causes Hb to aggregate into large polymers when PCO 2 is low. People with various forms of thalassemia, an inherited defect in the DNA, have higher hematocrit levels than normal, but the RBCs contain less Hb, and the O 2 binding characteristics of Hb are abnormal. Because almost all O 2 in the blood is carried and transported by Hb, the relationship between the conc (pp) of O 2 and Hb sat (the % Hb mol carrying O 2 is very important. i.e. O 2 -Hb dissociation curve. PO 2 is a very important factor to determine the extent of O 2 binding to Hb. The relationship is shown by the curve.

12. Factors which affect the O 2 -Hb dissociation curve: These factors may shift the curve to the right, indicating lower affinity of Hb to O 2, or shift the curve to the left, indicating an increased affinity of Hb to O 2. These factors includes; 1) PCO 2 : ↑ PCO 2 → ↓ affinity of Hb to O 2 → shift the curve to the right (this is called Bohr effect). 2) PH: ↓ PH (or ↑ [H + ]) → ↓ affinity of Hb to O 2 → shift the curve to the right. 3) Temp : ↑ Temp → shift the curve to the right. 4) 2,3- diphosphoglycerate (2,3-DPG): : ↑ 2,3-DPG → ↓ affinity of Hb to O 2 → shift the curve to the right. P50 is the pp of O 2 required to achieve 50% Hb sat.

15. Dissociation curve of myoglobin Myo is a heme-containing protein found in energetic tissues such as cardiac & skeletal muscle. Myo differs from Hb in that it consist of a single chain and can bind only a single O 2 mol. So it resembles Hb but binds one rather than 4 mol of O 2 per mole. However, Myo binds to O2 more strongly than Hb. Myo dissociation curve is a rectangular hyperbola rather than a sigmoid curve. Because its curve is to the left of Hb curve, it takes up O 2 from Hb in the blood. Myo has 2 roles; 1) it represents an intracellular reserve of O 2, 2) when the PO 2 in the muscle cell has fallen very low, the presence of Myo ↑ the rate of O 2 diffusion from the cell surface to interior.

16. Hb in the fetus The blood of the human fetus normally contains fetal Hb (HbF). Its structure is similar to that of HbA except that the beta chains are replaced by gamma chains. The gamma chains also contain 146 AA residues but have 37 that differ from those in the beta chain. HbF is normally replaced by HbA soon after birth. In the body, its O 2 content at a given PO 2 is greater than that of HbA because it binds 2,3-DPG less avidly. HbF is adapted to function at lower pp than those that will be typical after birth. Fetal-placental BF is affected by 2 hormone system best known in adults for their role in ECF volume regulation; ADH system & renin-angiotensin system. A ↓ in PO 2 of fetal arterial blood stimulates the release of ADH, whereas ↑ in PO 2 or a ↓ in PH stimulates the release of renin and ↑ in angiotensin II.

18. CO 2 transport CO 2 transported from the body cells back to the lungs in 3 forms; (1) Dissolved in the plasma (approx 7-10%). (2) Reacts with the amino group of plasma proteins to form carbamino proteins (carbaminohemoglobin) (approx 23-30%). (3) Reacts with H2O to form H2CO3 (approx 60-70%) CO 2 + H 2 O ↔ H 2 CO 3 ↔ HCO 3 - + H +

20. CO 2 dissociation curve The volume of CO 2 carried in the blood is determined by PCO 2. The dissolved form is directly proportionate to PCO 2 (0.06 ml dissolved in 100 ml of blood/1 mmHg PCO 2 ). The relationship of CO 2 content of blood to PCO 2 is known as CO 2 dissociation curve. The curve is affected by the saturation of Hb with O 2 (Haldane effect). Oxyhemoglobin shifts the curve to the right, i.e. in the lungs CO 2 is released from the blood. Reduced Hb shifts the curve to the left, i.e. more CO 2 is taken up by the blood in the tissues. Thus, PCO 2 influences O 2 sat of Hb (Bohr effect) and PO 2 influences the CO 2 dissociation curve (Haldane effect). However, the Bohr effect is much more potent and more important than the Haldane effect.

22. Directional movement of CO 2 All movement across membrane is by diffusion. Note that most of CO 2 entering the blood in the tissues ultimately is converted to HCO 3 -. This occurs almost entirely in the erythrocytes because the CA enzyme is located there, but most of the HCO 3 - then moves out of the erythrocyte into the plasma in exchange for chloride ions “ the chloride shift”.

24. Chloride shift The rise in the HCO 3 - content of red cell is much greater than that in plasma as the blood passes through the capillaries. The excess of HCO 3 - leaves the red cell in exchange for cl -. This change is called the chloride shift. The chloride shift occurs rapidly and essentially complete in 1 second. The cl - content of the red cells in venous blood is therefore significantly greater than in arterial blood. In pulmonary capillaries; cl - leaves the red cell and move into the plasma in exchange for HCO 3 - ; in systemic capillaries, the reverse occurs.

26. The Haldane effect It results from the simple fact that the combination of O 2 with Hb in the lung causes the Hb to become a stronger acid.This displaces CO 2 from the blood and into the alveoli in 2 ways; (1) The more highly acidic Hb has less tendency to combine with CO 2 to form carbaminohemoglobin, thus displacing much of the CO 2 that is present in the carbamino form from the blood. (2) The ↑ acidity of Hb also causes it to release an excess of H +, and these bind with HCO 3 - to form H 2 CO 3 ; this then dissociate into H 2 O and CO 2, and the CO 2 is released from the blood into the alveoli and, finally, into the air.