Gas Exchange (Part II) Notes PDF

WSUSOM Medical Physiology – Respiratory Physiology Page | 1 of 16 Gas Exchange GAS EXCHANGE – PART II Learning Objectives 1. List the normal airway, alveolar, arterial, and mixed venous PO2 and PCO2 values. 2. Be able...

WSUSOM Medical Physiology – Respiratory Physiology Page | 1 of 16 Gas Exchange GAS EXCHANGE – PART II Learning Objectives 1. List the normal airway, alveolar, arterial, and mixed venous PO2 and PCO2 values. 2. Be able to calculate the alveolar to arterial PO2 difference, (A-a) DO2. Describe the normal value for (A-a) DO2 and the significance of an elevated (A-a) DO2. 3. Name the factors that affect diffusive transport of a gas between alveolar gas and pulmonary capillary blood. 4. Explain the development of pulmonary edema by a) increased hydrostatic pressure b) increased permeability c) impaired lymphatic outflow or increased central venous pressure. 5. Define right-to-left shunts, anatomic and physiological shunts, and physiologic dead space (wasted ventilation). Describe the consequences of each for pulmonary gas exchange. 6. Describe how the ventilation/perfusion (V/Q) ratio of an alveolar-capillary lung unit determines the PO2 and PCO2 of the blood emerging from that lung unit. 7. Identify the average V/Q ratio in a normal lung. Explain how V/Q is affected by the vertical distribution of ventilation and perfusion in the healthy lung. 8. Describe the regional differences in pulmonary blood flow in an upright person. Define zones I, II, and III in the lung, with respect to pulmonary vascular pressure and alveolar pressure. Lecture Outline I. Calculating the partial pressure of oxygen and carbon dioxide II. Partial pressures of oxygen and carbon dioxide at the lung, pulmonary capillaries and tissue bed III. Alveolar air equation IV. Determinants of diffusion of oxygen and carbon dioxide  Solubility  Molecular weight of gas  Cross-sectional area  Membrane thickness V. Diseases that impact diffusion  Emphysema  Fibrotic lung disease  Pulmonary edema VI. Factors that impact partial pressure of oxygen and carbon dioxide  Hyperventilation and hypoventilation  Shunts  Ventilation and perfusion interaction  Impact of gravity on ventilation and perfusion VII. Corrective mechanisms in response to local ventilation and perfusion mismatch WSUSOM Medical Physiology – Respiratory Physiology Page | 2 of 16 Gas Exchange Calculating the Partial Pressure of Oxygen and Carbon Dioxide  Pressure is proportional to the average force exerted by molecules colliding with the walls of a container. At sea level, the barometric pressure is 760 mmHg conversely at high altitude (5500 meters) the barometric pressure is 380 mmHg.  The barometric pressure in addition to the percent concentration of gas in the atmosphere must be considered when calculating the partial pressure of a gas. The concentration of oxygen, nitrogen and carbon dioxide in the atmosphere is 20.93 %, 79.04 % and 0.03 %, respectively.  Water vapor pressure must also be considered when calculating the partial pressure of a gas. When water is exposed to air, water molecules leave the liquid and become water vapor.  Vapor pressure depends on temperature and is independent of barometric pressure. Inspired air is warmed and saturated with water.  The vapor pressure of water at 37 degrees Celsius (i.e. body temperature) is 47 mmHg. Thus, although the PO2 of dry air at sea level is 159 mmHg (760 mmHg* 0.2093), the PO2 once air is inspired into the lungs is 149 mmHg ((760 - 47) * 0.2093), since the water vapor pressure of 47 mmHg is subtracted from the barometric pressure.  As shown below in the table, the PO2 in the atmosphere decreases as one travels from sea level to altitude. However, note that the decrease in PO2 occurs because the barometric pressure decreases not because of a decrease in the % concentration of oxygen. In other words, the % concentration of oxygen remains at 20.93 % independent of whether you are at sea level or at altitude. ALTITUDE (meters) PB (mmHg) PO2 (mmHg) 0 760 159.2 1,000 674 141.2 2,000 596 124.9 3,000 526 110.2 4,000 462 96.9 9,000 231 48.4 WSUSOM Medical Physiology – Respiratory Physiology Page | 3 of 16 Gas Exchange Partial Pressure of Oxygen and Carbon Dioxide at the Lung, Pulmonary Capillaries and Tissue Bed  The above diagram illustrates the partial pressure of oxygen and carbon dioxide at the level of the systemic veins/pulmonary capillaries (i.e. venous side), lung/arterial blood, and tissue bed.  Note that blood returning to the lung from the tissue (i.e. venous side) is comprised of elevated levels of carbon dioxide (46 mmHg) and reduced levels of oxygen (40 mmHg).  At the level of the alveoli a partial pressure gradient is evident that promotes the diffusion of carbon dioxide from the pulmonary capillaries into the alveoli (black arrow) and movement of oxygen from the alveoli into the pulmonary capillaries (white arrow).  Once gas is exchanged at the level of the alveoli, arterial blood is rich with oxygen (100 mmHg) accompanied by a reduced level of carbon dioxide (40 mmHg).  Also note that the difference in the partial pressure of oxygen in the alveoli and the partial pressure oxygen in arterial blood is normally 5 mmHg. This difference is primarily due to the shunting of deoxygenated blood from the venous to the arterial side without passing by the alveoli.  At the level of the tissue, the partial pressure of oxygen is reduced (40 mmHg) and carbon dioxide, the by-product of metabolism, is increased (46 mmHg). Thus, a partial pressure gradient exists which promotes the diffusion of oxygen from the blood into the tissue (white arrow) and the diffusion of carbon dioxide from the tissue into the blood (black arrow).  WSUSOM Medical Physiology – Respiratory Physiology Page | 4 of 16 Gas Exchange Changes in the Partial Pressure of Oxygen and Carbon Dioxide during Inspiration and Expiration  Panel 1 in the above figure shows the partial pressure of oxygen and carbon dioxide in the atmosphere (blue shading) and at the level of the alveoli (yellow shading) prior to inspiration. Panel 1 in the figure also shows the presence of stale air in the conducting zone (gray shading) (anatomical deadspace) of the trachea-bronchial tree. The anatomical deadspace is comprised of air that remains in the airway at the end of expiration.  Panel 2 shows that on average 500 ml of atmospheric air is inspired during each breath. 350 (blue shading) of the 500 ml will move from the atmosphere to the level of the alveoli. In addition, the stale air (gray shading) (approximately 150 ml) that existed in the conducting zone of the airway at the end of expiration will also flow to the level of the alveoli.  Panel 3 shows that the air from the atmosphere and the anatomical dead space mix at the level of the alveoli (blue, gray and yellow shading).  Panel 4 shows that during expiration 500 ml of gas is expired. 350 (blue, gray and yellow shading) of the 500 ml is expired into the atmosphere along with 150 ml of air (blue shading) that was present in the conducting zone at the end of inspiration. Also note that 150 ml of the mixed gas remains in the conducting zone at the end of expiration.  As a result of the exchange of gas during inspiration and expiration, note that at the end of expiration (Panel 1) the partial pressure of carbon dioxide and oxygen at the level of the alveoli is approximately 42 mmHg and 97 mmHg, respectively. In contrast, at the end of inspiration (Panel 3) the partial pressure of carbon dioxide and oxygen at the level of the alveoli is 38 mmHg and 103 mmHg, respectively.  WSUSOM Medical Physiology – Respiratory Physiology Page | 5 of 16 Gas Exchange Pulmonary Diffusion  Movement of gases between the alveoli and capillary blood is by simple diffusion, a process requiring no metabolic energy. Gas diffusion in the lung, as elsewhere in the body, is a passive process whereby gases or other molecules move from a region of higher to lower concentration.  The design of the alveolar capillary bed is nearly ideal for optimal gas diffusion. No artificial device can approach the efficiency of the lungs for gas exchange.  Diffusion across the lung is dependent on the solubility and molecular weight of the gas, the area and thickness of the blood-gas barrier and the partial pressure gradient. In healthy individuals, the area of the blood-gas barrier is 50-100 square meters and the thickness is only 0.3 μ in many areas of the lung. Thus, a large area and small thickness are well suited to gas diffusion.  As mixed venous blood from the pulmonary artery flows into the pulmonary capillaries, it becomes exposed to an alveolar gas tension with a higher partial pressure of oxygen and lower partial pressure of carbon dioxide. Thus, net oxygen diffusion is from the alveoli to the pulmonary capillary, whereas carbon dioxide moves in the opposite direction, as dictated by their respective concentration gradients. Normally, gas exchange between alveoli and pulmonary capillary blood is rapid by necessity because the red blood cell spends less than a second in the alveolar capillary. At rest, a red blood cell is estimated to pass through the alveolar capillary in about 0.75 seconds (see orange line in the graph below). However, only about 0.25 seconds is normally required for oxygen and carbon dioxide to completely equilibrate between alveoli and capillary blood. Therefore, oxygen is not normally diffusion limited.  However, if alveolar PO2 is low or the diffusion resistance is high, capillary PO2 may not reach equilibrium with alveolar PO2. Moreover, capillary PO2 may not reach equilibrium with alveolar PO2 if pulmonary blood flow increases to the point that blood is in contact with the alveoli for a shorter period than normal. This latter mechanism might explain the phenomenon of hypoxemia that is observed in elite athletes during severe exercise. Movement of gas may also be diffusion limited if the affinity for hemoglobin is high (e.g. carbon monoxide – see green line on graph above) or gas solubility is low.  Carbon dioxide diffuses about 24 times faster than oxygen in a liquid medium (membrane or blood) because carbon dioxide is about 24 – fold more soluble in body fluids than oxygen. As a result, carbon dioxide dissolves in fluid more rapidly than oxygen to hasten the establishment of concentration or diffusion gradient. However, the greater rate of carbon dioxide diffusion is offset to some extent by a smaller partial pressure difference for carbon dioxide (6 mmHg) than oxygen (60 mmHg) between the alveoli and blood. Overall, carbon dioxide diffuses about 20 times faster than oxygen between the alveolus and capillary. WSUSOM Medical Physiology – Respiratory Physiology Page | 6 of 16 Gas Exchange Diseases that Impact Pulmonary Diffusion  Pulmonary pathologies can affect alveolar ventilation and gas exchange.  Emphysema (top right figure) which is characterized in part by destruction of the alveoli means less surface area for gas exchange.  Fibrotic lung disease leads to a thickened alveolar membrane which could slow gas exchange (bottom left figure).  Lastly, pulmonary edema (bottom right figure) which is characterized by fluid in the interstitial space increases diffusion distance which could slow gas exchange. The amount of fluid in the interstitial space is dependent on the balance between hydrostatic and colloid osmotic pressure in the capillary and initial space. WSUSOM Medical Physiology – Respiratory Physiology Page | 7 of 16 Gas Exchange Pulmonary Hypertension & Edema  Pulmonary Hypertension is caused by increased pulmonary vascular resistance (Pulmonary arterial pressure = pulmonary vascular resistance × cardiac output).  As with airway resistance, pulmonary vascular resistance is inversely proportional to the 4th power of the radius. Thus, small changes in radius will significantly impact pulmonary resistance and ultimately pulmonary arterial pressure.  Sustained pulmonary vasoconstriction (i.e. hypoxia) and thickening of the pulmonary arterial wall are major causes of elevated pulmonary vascular resistance in patients with hypoxia induced pulmonary hypertension.  The thickness and tissue mass of the pulmonary artery wall is maintained at an optimal level by a balance between cell proliferation and apoptosis. If there is more pulmonary artery smooth muscle cell proliferation, the wall thickens, narrowing the lumen and ultimately leading to vascular obliteration.  The structural change leading to the pathological abnormality in the pulmonary artery is referred to as vascular remodeling.  Both vasoconstriction and vascular remodeling decrease vascular compliance which, via distention and recruitment, normally accommodates increases in cardiac output, and increase pulmonary vascular resistance and pulmonary arterial pressure. WSUSOM Medical Physiology – Respiratory Physiology Page | 8 of 16 Gas Exchange Pulmonary Hypertension & Edema  Net fluid out = K [(Pc-Pi) – σ (πc-πi) Pc = capillary hydrostatic pressure (15 mmHg) (left heart failure) Pi = interstitial fluid hydrostatic pressure (unknown but below atmospheric) (respiratory distress, pneumothorax) σ = effectiveness of capillary wall in preventing protein from crossing (radiation) πc = colloid osmotic pressure of blood proteins (28 mmHg) (kidney disease) πi = colloid osmotic pressure of interstitial fluid proteins (20 mmHg)  Net pressure is outward (20 ml/hr) in humans. Fluid travels from the interstitial space to perivascular and peribronchial space. The fluid is transported via the lymphatic system to hilar and lymph nodes. WSUSOM Medical Physiology – Respiratory Physiology Page | 9 of 16 Gas Exchange Factors that Impact on the Partial Pressure of Alveolar/Arterial Oxygen and Carbon Dioxide (Ventilation)  Hypoventilation or hyperventilation relative to metabolic production will impact on arterial oxygen and carbon dioxide levels.  Increases in ventilation (hyperventilation) relative to metabolic rate results in an increase in oxygen (orange line in graph above) and a reduction in carbon dioxide (green line in graph above).  Decreases in ventilation (hypoventilation) relative to metabolic rate results in a decrease in oxygen and an increase in carbon dioxide.  As shown im the equation below, modifications in carbon dioxide might also impact arterial blood pH. WSUSOM Medical Physiology – Respiratory Physiology Page | 10 of 16 Gas Exchange Relationship between Ventilation, Partial Pressure of Carbon Dioxide and pH (The Interaction between the Lung and Kidney)  In addition to ensuring that carbon dioxide and oxygen levels are maintained in arterial blood, ventilation also plays an important role in maintaining the acid-base balance in arterial blood.  More specifically, the respiratory system has a specific role in acutely altering pH in arterial blood.  Many conditions alter hydrogen ion concentration. As the figure above shows, the pH level is normally 7.4. If the hydrogen ion concentration increases pH will decrease below this value leading to the development of acidosis. Conversely, alkalosis will develop if pH increases.  Ventilation is capable of altering pH primarily via its impact on carbon dioxide. The relationship between pH (or hydrogen ion concentration) and CO2 is revealed in the formula shown below.  This equation shows that CO2 and hydrogen ion concentration are directly related. If CO2 increases hydrogen ion concentration will increase. Conversely, if CO2 decreases hydrogen ion concentration will decrease. WSUSOM Medical Physiology – Respiratory Physiology Page | 11 of 16 Gas Exchange Acid Base Balance  The above diagrams show the role of the lungs and the kidney in the control of acid-base balance.  If an alteration in the respiratory system causes an individual to ventilate below that required for metabolism (hypoventilate) then CO2 levels in arterial blood will increase (top of lower left-hand diagram). Consequently, the Kassirer-Bleich equation reveals that hydrogen ion concentration will increase, resulting in a respiratory induced acidosis. In order to compensate for the decrease in pH the kidney will reabsorb bicarbonate to provide a metabolic compensation for the respiratory acidosis.  Although decreases in CO2 may not be physiologically beneficial in some cases (i.e. hyperventilation is often associated with fever, anxiety, brain disorders) it should be recognized that our ability to control CO2 via ventilation may be beneficial in many other cases involving metabolic disorders.  If arterial pH decreases because of lactic acidosis, diabetes or diarrhea our system is capable of compensating for this change immediately by altering ventilation. Thus, an increase in ventilation that leads to reductions in CO2 ultimately increases pH, thereby compensating for metabolically induced increases in pH wholly or in part. WSUSOM Medical Physiology – Respiratory Physiology Page | 12 of 16 Gas Exchange Acid Base Balance  The above graph shows the relationship between pH, PCO2 and bicarbonate. Point A on the graph represents the point of blood gas equilibrium. At this point the pH is 7.4, the PCO2 is 40 mmHg and the bicarbonate concentration is approximately 24 mEq/l.  The graph shows the potential blood gas changes that occur coincident with a respiratory or metabolic disturbance and the subsequent compensation to re-establish homeostatic pH levels.  For example, a ventilation/perfusion mismatch < 1 will result in an increase in PCO2. As a result, on the graph the location of the point representing blood gas measures would shift from point A to point B. In other words, the PCO2 in this example would increase from 40 mmHg to 60 mmHg and as a consequence of the respiratory acidosis the pH would decrease from 7.4 to 7.25.  In response to the modification in pH the kidney would reabsorb bicarbonate leading to an increase in bicarbonate levels (Point B to Point D). The increase in bicarbonate would buffer the excess hydrogen ions and provide metabolic compensation for the metabolic acidosis re-establishing pH at the homeostatic level of 7.4. WSUSOM Medical Physiology – Respiratory Physiology Page | 13 of 16 Gas Exchange Shunts  In an ideal lung, PaO2 and PaCO2 = PAO2 and PACO2 where a = the PO2 and PCO2 in arterial blood and A = the PO2 and PCO2 in the alveoli.  In normal healthy people, these values are close but not identical. In disease conditions, the numbers can vary greatly.  The word “shunt” refers to blood that has not undergone gas exchange. This blood is typically mixed with blood that has undergone gas exchange.  Thesbian circulation and bronchial circulation are two natural sources of shunts. Thesbian circulation perfuses the left ventricle and immediately dumps the blood into the left ventricle. Additionally, bronchial circulation perfuses lung tissue and empties into the pulmonary vein. In healthy individuals, these shunts account for approximately 2 - 4% of total blood flow. Perfusing collapsed alveoli or having a hole in the wall of the atria or ventricles will produce a right to left shunt. Gas Exchange – Ventilation (V)/Perfusion (Q) mismatch The alveolar oxygen and carbon dioxide levels are dependent on the V/Q ratio. The above figures provide The alveolar examples of the PO2 and PCO2 in the alveoli at extreme ends of the V/Q ratio spectrum.  In one case, the airways are completely obstructed (left-hand diagram – venous admixture) but the alveolus is adequately perfused with blood. Consequently, gas exchange does not occur between the alveoli and atmosphere. Thus, the PO2 in the alveoli decreases and the PCO2 increases compared to normal (Panel B - right-hand diagram).  In the other case, the airways are unobstructed, but the alveoli are perfused inadequately with blood (left- hand diagram – wasted ventilation). Thus, carbon dioxide does not diffuse into the alveoli and as a result, the value of PCO2 approaches zero. Additionally, alveolar PO2 increases because gas in the alveoli equilibrates with gas in the atmosphere (Panel C - right-hand diagram). WSUSOM Medical Physiology – Respiratory Physiology Page | 14 of 16 Gas Exchange Ventilation (V)/Perfusion (Q) mismatch  There are variations in perfusion and ventilation at different levels of the lung under normal conditions, thus the extreme examples outlined on the previous page may exist at various levels in the lung.  These variations affect the V/Q ratio (orange line) and consequently PO2 and PCO2. In the upright human, the lung is approximately 30 cm from the apex to the base, thus, gravity has an effect on blood flow distribution. The distribution of blood flow is heterogeneous across the lung as measured using dissolved xenon.  The highest blood flow is found near the base of the lung while the lowest flow is at the apex of the lung (left-hand figure).  Similar to blood flow, ventilation is also greater at the base of the lung compared to the apex of the lung.  The relationship between ventilation and blood flow (i.e. V/Q ratio) throughout the lung is also shown in the above diagram on the left-hand side (orange line). Note that the V/Q ratio is lower at the base of the lung compared to the apex of the lung.  This variation in the V/Q ratio will have a significant impact on the PO2 and PCO2 as discussed previously. Thus, as shown in the above diagram on the right-hand side, the PO2 is decreased and the PCO2 is increased closer to the base of the lung compared to measures obtained at the apex of the lung. WSUSOM Medical Physiology – Respiratory Physiology Page | 15 of 16 Gas Exchange Local Correction of Ventilation-Perfusion Mismatch  In addition to normal variations in the V/Q ratio from the top to the bottom of the lung, other pathological issues might also impact the V/Q ratio and thus disrupt homeostatic blood gas levels. Fortunately, there are local compensatory mechanisms that serve to correct pathological V/Q mismatches. These mechanisms are shown in the above figures.  On the left is an example of an obstructed lung. Because the lung is completely obstructed ventilation to that lung is zero while perfusion is unaffected. Consequently, the V/Q ratio is zero. In other words, blood is shunted passed the obstructed lung without being ventilated.  As a result of the V/Q ratio being zero, the partial pressure of oxygen and carbon dioxide approach mixed venous levels (i.e. decreased oxygen and increased carbon dioxide). In addition, because one lung is not ventilated, an increased level of ventilation occurs in the unaffected lung. The result of this increase in ventilation is that the V/Q ratio increases, resulting in alterations in the partial pressure of oxygen and carbon dioxide in the unaffected lung.  To compensate for the shunt, the pulmonary vessels that surround the alveoli of the obstructed lung constrict. Constriction of these vessels occur because of the hypoxia that was induced by the reduced V/Q ratio. The result is that blood is diverted to the lung that is ventilated. Diversion of the blood also corrects the elevated V/Q ratio at the level of the ventilated lung.  In the second example (shown on the right), both lungs are adequately ventilated. However, one lung is not perfused. As a result, the V/Q ratio will approach infinity and the partial pressure of oxygen and carbon dioxide in the unperfused lung will approach atmospheric values.  In addition, perfusion of the other lung will increase resulting in reduction in the V/Q ratio. To compensate for this pathology, ventilation of the lung which is not perfused will decrease. This decrease occurs because the bronchial smooth muscle constricts due to the changes in blood gases that occur because of the increased V/Q ratio.  In addition, because of the reduced perfusion, alveolar type II cells produce less surfactant resulting in alveoli collapse. As a result of this compensatory response, airflow is diverted to the lung that receives more than adequate perfusion. WSUSOM Medical Physiology – Respiratory Physiology Page | 16 of 16 Gas Exchange Diagnosing a V/Q Mismatch Caused by Shunt  If an individual with a V/Q imbalance caused by non-uniformity of ventilation inhales 100% oxygen the alveolar arterial difference will be reduced or eliminated. This scenario is shown in the figure above on the left.  In the example shown one lung has a reduced V/Q ratio. However, because the lung is still being ventilated and perfused the administration of 100 % oxygen ensures that oxygen content and saturation is similar in both lungs.  In contrast, the example on the right shows that one lung is completely obstructed and as a result blood is shunting by the lung without the blood being re-oxygenated.  As a result of the obstructed lung, inspiration of 100 % oxygen does not alter the partial pressure of oxygen in the unventilated lung. The end result is that deoxygenated blood is shunted into the arterial system and the overall content and oxygen saturation in the blood is reduced.