1. Respiratory Physiology Division of Critical Care Medicine University of Alberta

2. Outline 1. Lung Function 2. Oxygen Transportation 3. Carbon Dioxide Transportation 4. Respiratory Failure

3. Lung Function - Ventilation Tidal volume is about 500 ml per breath. Tidal volume is about 500 ml per breath. 150 ml of the tidal volume remains in the airways (anatomical dead space). 150 ml of the tidal volume remains in the airways (anatomical dead space). Thus, (500 ml – 150 ml) X 12 bpm = 4.2 L/min of fresh gas enters the respiratory zone. Thus, (500 ml – 150 ml) X 12 bpm = 4.2 L/min of fresh gas enters the respiratory zone. This is called alveolar ventilation and represents the gas available for exchange. This is called alveolar ventilation and represents the gas available for exchange.

4. Lung Function – Dead Space This is the air in the lungs that is not available for gas exchange. This is the air in the lungs that is not available for gas exchange. Amount varies with tidal volume (increases with deep breath from traction on the bronchi by the parenchyma) and size and posture of the subject. Amount varies with tidal volume (increases with deep breath from traction on the bronchi by the parenchyma) and size and posture of the subject. Normal range is 0.2 to 0.35 Normal range is 0.2 to 0.35

5. Lung Function - Compliance During the respiratory cycle, the lungs follow the pressure-volume curve below. During the respiratory cycle, the lungs follow the pressure-volume curve below. The lung volume is greater at any given pressure during deflation than inflation (hysteresis). The lung volume is greater at any given pressure during deflation than inflation (hysteresis). Notice that the lungs still have some air even at zero pressure. Notice that the lungs still have some air even at zero pressure. There will still be air left if the pressure around lung is raised above zero due to small airway closure, trapping residual gas. There will still be air left if the pressure around lung is raised above zero due to small airway closure, trapping residual gas.

7. Lung Function - Compliance The slope of the pressure-volume curve is the compliance (volume change per unit pressure change). The slope of the pressure-volume curve is the compliance (volume change per unit pressure change). A normal lung is very compliant, normally 200 mL/cm H 2 O. A normal lung is very compliant, normally 200 mL/cm H 2 O. As distending pressure increases, the lungs become stiffer with a smaller compliance and the pressure-volume curve flattens. As distending pressure increases, the lungs become stiffer with a smaller compliance and the pressure-volume curve flattens. Lung compliance can increase or decrease with pathological states. Lung compliance can increase or decrease with pathological states.

8. Lung Function - Resistance Airflow is proportional to tube length and inversely proportional to the fourth power of the radius. Airflow is proportional to tube length and inversely proportional to the fourth power of the radius. The bronchi are supported by radial traction of the surrounding tissue. The bronchi are supported by radial traction of the surrounding tissue. Therefore, as lung volume decreases, airway resistance increases. Therefore, as lung volume decreases, airway resistance increases. At very low volumes, the small airways may close completely. At very low volumes, the small airways may close completely.

9. Lung Function – Regional Differences in Ventilation The lower lung regions ventilate better than the upper regions. The lower lung regions ventilate better than the upper regions. The base of the lungs have a lower volume because of the lower pleural pressure whereas the apex is normally at a higher volume because of a higher pleural pressure. The base of the lungs have a lower volume because of the lower pleural pressure whereas the apex is normally at a higher volume because of a higher pleural pressure. This places the base on the steep part of the pressure-volume curve. (i.e. the bases are more compliant than the apices) This places the base on the steep part of the pressure-volume curve. (i.e. the bases are more compliant than the apices) Therefore, the bases expand more with inspiration and ventilate more. Therefore, the bases expand more with inspiration and ventilate more.

11. Lung Function – Regional Differences in Blood Flow Upright, blood flow in the lungs decreases linearly from bottom to top. Upright, blood flow in the lungs decreases linearly from bottom to top. This can be explained by the hydrostatic pressure in the blood vessels. This can be explained by the hydrostatic pressure in the blood vessels. There are regions at the apex where arterial pressure falls below alveolar pressure (Zone 1). There are regions at the apex where arterial pressure falls below alveolar pressure (Zone 1). The capillaries are collapsed and there is no flow. The capillaries are collapsed and there is no flow. This region is ventilated but not perfused and contributes to alveolar dead space. This region is ventilated but not perfused and contributes to alveolar dead space.

13. Lung Function – Regional Differences in Blood Flow In Zone 2, arterial pressure exceeds alveolar but venous pressure is still lower. In Zone 2, arterial pressure exceeds alveolar but venous pressure is still lower. This causes blood flow to be dependant on the arterial-alveolar pressure. This causes blood flow to be dependant on the arterial-alveolar pressure. In Zone 3, venous pressure exceeds alveolar and flow is determined in the usual way by the arterial-venous pressure difference. In Zone 3, venous pressure exceeds alveolar and flow is determined in the usual way by the arterial-venous pressure difference.

14. Oxygen Transportation The partial pressure of oxygen in the alveoli determines the driving pressure for oxygenation of the blood. The partial pressure of oxygen in the alveoli determines the driving pressure for oxygenation of the blood. The alveolar oxygen partial pressure can be calculated from the alveolar gas equation. The alveolar oxygen partial pressure can be calculated from the alveolar gas equation. P A O 2 = P i O 2 – (P A CO 2 /R) P A O 2 = P i O 2 – (P A CO 2 /R) P i O 2 is the partial pressure of inspired, humidified oxygen ((P B - 47)X0.21) P i O 2 is the partial pressure of inspired, humidified oxygen ((P B - 47)X0.21) P A CO 2 is alveolar CO 2 partial pressure which is approximated to the arterial CO 2. P A CO 2 is alveolar CO 2 partial pressure which is approximated to the arterial CO 2. R is the respiratory quotient which is the ratio of CO 2 production over O 2 consumption in the tissues. R is the respiratory quotient which is the ratio of CO 2 production over O 2 consumption in the tissues. The difference between P A O 2 and P a O 2 can be used to determine the cause of respiratory failure. The difference between P A O 2 and P a O 2 can be used to determine the cause of respiratory failure.

15. Oxygen Transportation Oxygen binds to hemoglobin in an S shaped curve called the oxygen dissociation curve. Oxygen binds to hemoglobin in an S shaped curve called the oxygen dissociation curve. The amount of O 2 increases rapidly up to a PaO 2 of 50 then becomes flatter. The amount of O 2 increases rapidly up to a PaO 2 of 50 then becomes flatter. The flat portion allows for continued O 2 loading even if the P A O 2 falls while the steep portion allows the tissues to extract large amounts of O 2 for only a small drop in capillary P O2. The flat portion allows for continued O 2 loading even if the P A O 2 falls while the steep portion allows the tissues to extract large amounts of O 2 for only a small drop in capillary P O2.

16. Oxygen Transportation The curve is shifted to the right (O 2 affinity for hemoglobin is reduced) by an increase in PCO 2, temperature, acidity, and 2,3 DPG. The curve is shifted to the right (O 2 affinity for hemoglobin is reduced) by an increase in PCO 2, temperature, acidity, and 2,3 DPG. This allows for more unloading of O 2 at a given PO 2 in the tissue. This allows for more unloading of O 2 at a given PO 2 in the tissue.

17. Oxygen Transportation Oxygen is carried in the blood by hemoglobin and dissolved in solution. Oxygen is carried in the blood by hemoglobin and dissolved in solution. For each mmHg of PO 2, there is 0.03 mL O 2 /L of blood (obviously inadequate to meet tissue needs) For each mmHg of PO 2, there is 0.03 mL O 2 /L of blood (obviously inadequate to meet tissue needs) One gram of hemoglobin can combine with 1.39 mL O 2 and factoring the percentage saturated, the full equation is: One gram of hemoglobin can combine with 1.39 mL O 2 and factoring the percentage saturated, the full equation is: (Hgb X 1.39 X SaO 2 /100) + 0.03PaO 2 (Hgb X 1.39 X SaO 2 /100) + 0.03PaO 2 Normal value is about 200 mL O 2 /L blood. Normal value is about 200 mL O 2 /L blood. Multiply by the cardiac output and you get the oxygen delivery to the tissue (about 1000 mL O 2 /min). Multiply by the cardiac output and you get the oxygen delivery to the tissue (about 1000 mL O 2 /min).

18. Carbon Dioxide Transportation The PaCO 2 is proportional to the amount of CO 2 produced in the tissue and partial pressure of humidified gas and inversely proportional to the respiratory rate, tidal volume and dead space. The PaCO 2 is proportional to the amount of CO 2 produced in the tissue and partial pressure of humidified gas and inversely proportional to the respiratory rate, tidal volume and dead space.

19. Carbon Dioxide Transportation CO 2 is carried in three forms in the blood; dissolved, as bicarbonate, and in combination with proteins. CO 2 is carried in three forms in the blood; dissolved, as bicarbonate, and in combination with proteins. Dissolved CO 2 is 20X more soluble than O 2 and plays a significant role in its carriage. Dissolved CO 2 is 20X more soluble than O 2 and plays a significant role in its carriage. Bicarbonate is formed by the reaction of CO 2 with H 2 0 in the presence of carbonic anhydrase. Bicarbonate is formed by the reaction of CO 2 with H 2 0 in the presence of carbonic anhydrase. The bulk of the CO 2 is in the form of bicarbonate. The bulk of the CO 2 is in the form of bicarbonate. Carbamino compounds are formed by the combination of CO 2 with terminal amine groups in blood proteins. Carbamino compounds are formed by the combination of CO 2 with terminal amine groups in blood proteins. Binding CO 2 to hemoglobin facilitates O 2 unloading (Haldane effect). Binding CO 2 to hemoglobin facilitates O 2 unloading (Haldane effect).

20. Shunt Shunt occurs when blood passes to the pulmonary venous system without going through gas exchanging areas. Shunt occurs when blood passes to the pulmonary venous system without going through gas exchanging areas. A shunt can occur through congenital defects in the heart or blood vessels or through areas of atelectasis or consolidation in the lungs. A shunt can occur through congenital defects in the heart or blood vessels or through areas of atelectasis or consolidation in the lungs.

21. As can be seen above, if there is a 50% shunt, the oxygen content returning to the heart will be lower. As can be seen above, if there is a 50% shunt, the oxygen content returning to the heart will be lower. If we give 100% oxygen, the P A O 2 will increase to 670 but this will only cause a small increase in the total oxygen content. If we give 100% oxygen, the P A O 2 will increase to 670 but this will only cause a small increase in the total oxygen content.

22. Shunt Hemoglobin is fully saturated above a PaO 2 of 150 so all additional oxygen content is due to dissolved oxygen. Hemoglobin is fully saturated above a PaO 2 of 150 so all additional oxygen content is due to dissolved oxygen. If the mixed venous oxygen content is directly measured (with a Swan-Ganz catheter) then the shunt fraction can be calculated from the shunt equation. If the mixed venous oxygen content is directly measured (with a Swan-Ganz catheter) then the shunt fraction can be calculated from the shunt equation.

23. V/Q Mismatch The average V/Q is about 0.8 ((4 L/min)/(5 L/min)). The average V/Q is about 0.8 ((4 L/min)/(5 L/min)). In the normal lung, blood flow is the greatest at the bottom of the lung. In the normal lung, blood flow is the greatest at the bottom of the lung. Ventilation also greater at the bottom. Ventilation also greater at the bottom. The differences in perfusion from bottom to top are greater than the differences in ventilation so the ratio of ventilation to perfusion is low in the bottom of the lung and high at the top. The differences in perfusion from bottom to top are greater than the differences in ventilation so the ratio of ventilation to perfusion is low in the bottom of the lung and high at the top.

24. V/Q Mismatch Shunt (discussed above) represents an extreme form of V/Q mismatch with no ventilation and normal blood flow such that the ratio is 0. Shunt (discussed above) represents an extreme form of V/Q mismatch with no ventilation and normal blood flow such that the ratio is 0. If an alveolus is unperfused, the blood flow is zero and the V/Q ratio increases until it approaches infinity. This is called dead space. If an alveolus is unperfused, the blood flow is zero and the V/Q ratio increases until it approaches infinity. This is called dead space. The gas in the alveolus also approach inspired gas (P O2 = 150 and P CO2 = 0). The gas in the alveolus also approach inspired gas (P O2 = 150 and P CO2 = 0).

26. V/Q Mismatch CO 2 excretion is higher in areas of higher V/Q mismatch but because the blood flow is small, this only has a modest effect on P a CO 2. CO 2 excretion is higher in areas of higher V/Q mismatch but because the blood flow is small, this only has a modest effect on P a CO 2. From the standpoint of total ventilation, this is inefficient gas exchange since the ventilation going to the high V/Q units carries away less CO 2. From the standpoint of total ventilation, this is inefficient gas exchange since the ventilation going to the high V/Q units carries away less CO 2.

27. V/Q Mismatch If PCO 2 production is constant, then the P a CO 2 will rise in the face of high V/Q ratio due to inefficient CO 2 elimination. If PCO 2 production is constant, then the P a CO 2 will rise in the face of high V/Q ratio due to inefficient CO 2 elimination. The response to this is to increase tidal volume or respiratory rate if the respiratory system is able. The response to this is to increase tidal volume or respiratory rate if the respiratory system is able. If hypoxia is present, it is usually easily corrected with a small amount of supplemental oxygen to raise the P A O 2 in the rest of the alveoli. If hypoxia is present, it is usually easily corrected with a small amount of supplemental oxygen to raise the P A O 2 in the rest of the alveoli.

28. Summary 1. There are regional differences in ventilation and perfusion, both decreasing from the base to the apex. 2. Shunt occurs in areas of ventilation but no perfusion. Causes hypoxia that is not responsive to supplemental oxygen. 3. Dead space ventilation occurs in areas of ventilation but no perfusion. 4. Dead space ventilation causes easily corrected hypoxia and elevated CO 2 due to inefficient ventilation.