Lecture 22 ? Gases Gas Exchange And Transport (Slide 1) 1. Sea level versus extreme environments 2. Solubility of gases in aqueous solutions 3. Diffusion barrier and changes 4. Bound oxygen versus free in solution Influences Of Hypoxia On Respiratory And Cardiovascular Function In Man (Slide 2) 1. As altitude increases, the amount of oxygen in the air decreases. 2. It takes time for your body to get used to this lack of oxygen. 3. AMREE (American Research Expedition to Everest) is a research mission by the Americans to Mt. Everest to do research at high altitudes. 4. As a person becomes more hypoxic (lack of oxygen), there is an exponential increase in blood flow and tissue content of the vasodilatory adenosine as well as its production rate. It is only generated in high concentrations when tissues become hypoxic. Physiology Under Extreme Conditions (Slide 3) 1. Many laboratories were set up at various levels. 2. A machine was set up to measure the concentrations of various gas levels. These measurements were made at different altitudes. 3. You can breathe using either oxygen from a container or from the air. There is much less oxygen in the air as you increase your altitude. Free And Scuba Diving In The Pacific Ocean (Slide 4) 1. For each 33ft. of depth, barometric pressure increases by one atmosphere. 2. World?s records for unassisted and assisted free diving are being challenged regularly. 3. A man named Frenchman died on Wednesday, April 11, 2007 during such an attempt. 4. The partial pressure of nitrogen in our blood is about 605mmHg to 610mmHg. It is physiologically inert until you go to a very low depth, where the partial pressure of nitrogen reaches 8000mmHg to 9000mmHg. a. If you ascend too rapidly, the dissolved nitrogen can come out of solution and form air bubbles in the blood. Those air bubbles can circulate, creating microemboli, air emboli, that circulate to the brain and heart. b. These people can suffer decompression sickness, in which the nitrogen affects the elbows, knees and makes it hard to bend them (the bends). More likely is the probability of those emboli causing stroke, myocardial problems, etc. Solubility Of Gases In Water (Slide 5) 1. If partial pressures in two environments are not at equilibrium, they will come to be. At a specific pressure, you can take the concentration of O2 dissolved in water and find out how much O2 was able to dissolve. 2. At 100mmHg, there is only 0.15mmol/liter of O2. It dissolves very slightly compared to other gases, such as CO2. Its concentration is about 3.0mmol/liter. a. CO2 is much more soluble than O2 in water, plasma or whole blood. 3. Our bodies are designed more to regulate CO2 than O2. Diffusion Of Gases Across Respiratory Membrane (Slide 6) 1. The respiratory membrane between alveolar air spaces and the pulmonary artery is composed of Type I epithelial cells, an alveolar basement membrane, a capillary basement membrane and the endothelial cells in capillary walls. 2. In this pulmonary capillary, blood coming into the artery is actually deoxygenated. Functionally, it is venous blood, even though it is carried in an artery. The CO2 is released from the blood and O2 is mixed into the blood. So now, functionally it is arterial blood even though it is carried in a vein. Diffusion Of Gases Across A Barrier (Slide 7) 1. Diffusion is based on several considerations: a. If you have a barrier that separates two compartments, one with a high gas content and another with a low gas content, you have a partial pressure gradient. Even though there is a flow of gas in both directions, the net flow is from high to low. For example, the alveoli have high O2 pressure and the pulmonary capillary has low O2 pressure. So O2 diffuses from the alveoli into the capillaries. b. The barrier?s surface area has an impact. The greater the surface area for a given change in partial pressure, the higher the diffusion rate will be for that gas. The diffusion barrier can have different chemical compositions. For example, O2 and CO2 are more soluble in lipid than aqueous media. That helps their diffusion. c. The wider the aqueous barrier, the slower the diffusion. So if the distance between the alveoli and capillary is large, the diffusion rate is very slow. 2. Compare the distance along a pulmonary capillary from the arteriolar end to the venous end versus the partial pressure of oxygen. This is mixed venous blood entering the pulmonary artery and reaching the pulmonary capillary at the arteriolar end. a. Before the blood has travelled just about 1/3 the distance in the capillary, it has equilibrated with the O2 in the alveoli. b. At the same time, there is a loss of CO2 from the same capillary, and a similar story pertains. c. So it takes about 1/3 the distance of the capillary to fully equilibrate with the alveolar air. The extra distance is there just in case something goes wrong during the first 1/3. Diffusion (Exchange) Of O2 At The Summit Of Everest (Slide 8) 1. Mixed venous blood entering the capillary has about half the partial pressure of oxygen then that at sea level. By the time their pulmonary capillary blood enters the venous end, its partial pressure has only risen to about 28mmHg, 1/4th or 1/5th the rate it should be at sea level (100mmHg). 2. These people are at marked respiratory hypoxia. Their respiratory rate could be between 75-100 cycles per minute. Our respiratory rate right now is about 12-15 cycles per minute. They are maximally hyperventilating. Diffusion Pathway And Problems (Alveolar Capillary Block) (Slide 9) 1. Alveolar wall thickens with fibrous connective tissue. 2. Capillary membrane may be thickened. 3. Membranes (1) and (2) might be separated by increased interstitial fluid. 4. Intra-alveolar fluid or exudates (pneumonia) 5. Thickened RBC membranes and diseases Summary (Slide 10) 1. Gas laws determine physiological behavior of gases such as oxygen and carbon dioxide. 2. Partial pressures of gases influence their movements. 3. CO2 is more soluble in aqueous media than O2. Overview Of Pulmonary Circulation And Exchange Of Respiratory Gases (Slide 11) 1. Arterial blood O2 and CO2 levels remain relatively constant. a. Oxygen moves from alveoli to blood at the same rate as it is consumed by cells. b. Carbon dioxide moves from blood to alveoli at the same rate as it is produced by cells. c. Respiratory quotient (RQ) = rate of CO2 released / rate of O2 consumed. i. E.g. ? 200ml/min / 250ml/min = 0.8 Physiology Of O2 And CO2 In The Alveoli And Blood (Slide 12) 1. The amount of O2 taken up by the alveoli is identical to that which is delivered to the tissues via systemic capillaries. The same holds true for CO2: the amount that is delivered to the alveoli is matched by the amount that is delivered to the capillaries by tissues. 2. In the figure on the right, the red bar tells you the partial pressure of O2, and the blue bar tells you the partial pressure of CO2 in different parts of the body. a. Alveolar air: the partial pressure of O2 is about 100 and that of CO2 is about 40. b. Pulmonary artery: partial pressure of CO2 is about 46. This favors loss of CO2 to the alveoli. The partial pressure of O2 is about 40. This favors an uptake of O2 to the blood. Oxygen Transport In The Blood (Slide 13) 1. Oxygen is not very soluble in plasma. 2. Thus, only 0.3ml O2 per 100ml arterial blood oxygen is dissolved in plasma. 3. Other 19.7ml O2 per 100ml arterial blood oxygen is transported by hemoglobin. The amount bound to hemoglobin reflects the blood-oxygen binding capacity. 4. The total O2 content is about 20 volumes %. Oxygen Binding To Hemoglobin (Slide 14) 1. Hb + O2 (( HbO2 a. Hb is deoxygenated hemoglobin. b. HbO2 is oxygenated hemoglobin. 2. So in the pulmonary artery, hemoglobin in RBCs combines with O2 from the alveoli to form HbO2. 3. When the blood gets to a tissue, the O2 is released and diffuses into the tissue cell while the hemoglobin remains with the RBC and returns to the alveoli in the lungs. Structure And Function of Hemoglobin A (HbA) (Slide 15) 1. Hemoglobin is made up of four globin chains, each containing a heme moiety. It has ferrous iron in its center, which actually binds the O2. 2. About 98.5% O2 is bound to Hb while 1.5% is dissolved in plasma. Conformational Changes Of Hb As It Binds O2 (Slide 16) 1. As ferrous iron binds molecular oxygen, its conformation changes. 2. The blue structure does not contain histamine, while the red structure has bound histamine. The blue is more dome-shaped while the red is more planar. 3. When O2 binds to the Fe2+, the heme changes from a dome-like to a planar conformation, pulling the Fe2+ downward. As the Fe2+ moves downward, it pulls the attached histamine as well, causing the Hb to switch from the tensed to the relaxed state.. Oxyhemoglobin Dissocation (Association) Curve (Slide 17) 1. It plots percent oxygen bound to hemoglobin versus the pressure of O2. 2. Under arterial conditions, PO2 of about 100mmHg, nearly 100% of the hemoglobin molecules are occupied by 4 molecules of O2 each. 3. When the oxygen is released, we have a partial pressure of about 40 in the arterioles, so the hemoglobin is about 75% saturated. Bottom line: there is much oxygen to spare, should the tissues need more oxygen, under normal conditions. 4. The partial pressure of oxygen at which 50% of the hemoglobin is saturated is called the P50. It is about 27mmHg PO2. Oxyhemoglobin Dissociation Curves (Slide 18) 1. In every case, the red curve represents physiological conditions. As pH is higher, the curve goes left. As the pH is lower, the curve goes right. a. So hemoglobin carries more O2 when the pH is low and less when pH is high. 2. The temperature can affect the relationship. As temperature increases, the curve shifts to the right. As temperature decreases, the curve shifts left. This means that the bound oxygen is release more easily when you are hot. a. So hemoglobin carries more O2 when the temperature is low and less when the temperature is high. Summary (Slide 19) 1. Exchange (diffusion) of gases depends on barriers and partial pressure gradients. 2. Gases are transported in the bound (e.g. Hb) and free states. 3. Only gas molecules that are unbound contribute to partial pressures. 4. Oxygen carrying capacity of blood depends on Hb concentration and oxygen bound to it.
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