Cardio e Resp

Question 1

1. What is mean arterial pressure (MAP)?

Answer 1

1. Mean arterial pressure (MAP) is the time-weighted average blood pressure. On modern monitors, MAP is calculated from electronically integrating the arterial waveform over time. Automated blood pressure cuffs estimate the MAP by the point of maximum amplitude of the pressure oscillations. MAP can also be esti‐mated by adding one third of the pulse pressure to the diastolic blood pressure. (53)

Question 2

2. What is the relationship of MAP to cardiac output and systemic vascular resistance (SVR)?

Answer 2

2. MAP is the product of cardiac output (CO) and systemic vascular resistance (SVR), or MAP = CO × SVR. This relationship is similar to Ohm’s law in elec‐tricity, where voltage = current × resistance. If we were to be exactly correct, we would use the pressure drop across the systemic vascular system, or MAP – CVP (central venous pressure). (54)

Question 3

3. What is the “pulse pressure”?

Answer 3

3. Pulse pressure is the difference between systolic and diastolic blood pressures. (54)

Question 4

4. What factors affect pulse pressure?

Answer 4

4. Pulse pressure is produced from the stroke volume being pushed into the aorta on top of the diastolic blood pressure. The compliance features of the aorta therefore have a very significant effect on pulse pressure so that a stiff aorta results in a higher pulse pressure, a common feature of aging. A lower diastolic pressure can reduce pulse pressure by shifting to a more compliant part of the aortic compliance curve. A higher stroke volume generally increases pulse pres‐sure. Lower SVR can decrease pulse pressure because part of the stroke volume “runs off” rapidly during ejection. Aortic insufficiency can increase pulse pres‐sure as the diastolic pressure drops significantly during backward flow into the left ventricle. (54)

Question 5

5. What pathologic factors may decrease SVR?

Answer 5

5. Classic pathologic causes of low SVR include sepsis, anaphylactic and ana‐phylactoid reactions, liver failure, and reperfusion of ischemic organs. Many antihypertensive medications, anesthetic drugs, and neuraxial anesthetics also lower SVR. (54)

Question 6

6. How is SVR calculated?

Answer 6

6. SVR = 80 × (MAP − CVP)/CO, where MAP is mean arterial pressure, SVR is systemic vascular resistance, CVP is central venous pressure, and CO is cardiac output. The factor 80 converts the SVR to the proper units. (54)

Question 7

7. How is resistance related to the radius of the blood vessel?

Answer 7

7. Resistance is inversely proportional to the fourth power of the radius of the vessel. (54)

Question 8

8. Where is most of the resistance in the vascular system?

Answer 8

8. Most of the resistance in the vascular system is in the arterioles. Despite capil‐larys having smaller diameters than arterioles, there are large numbers of capil‐larys in parallel, resulting in overall lower resistance at this level of the vascu‐lar tree. (54)

Question 9

9. Which monitors allow calculation of cardiac output?

Answer 9

9. Cardiac output is the amount of blood (L/min) pumped by the heart. Cardiac output can be determined by thermodilution with a pulmonary artery (PA) catheter and is the dominant technique. In addition, transesophageal echocardi‐ography (TEE) may be used to estimate cardiac output. A variety of other non‐invasive monitors are available and are being developed that estimate cardiac output, including Doppler of the ascending aorta and arterial pressure wave‐form analysis. The Fick equation can also be used to calculate cardiac output from the oxygen consumption and arterial and mixed venous oxygen content. (54)

Question 10

10. How is stroke volume (SV) calculated?

Answer 10

10. Stroke volume (SV) is the cardiac output (CO) divided by heart rate (HR): SV = CO/HR. It is important to calculate stroke volume, because a high heart rate may make cardiac output appear normal despite inadequate stroke volume. (54)

Question 11

11. What is the cardiac index?

Answer 11

11. Because the appropriate cardiac output changes with body size, the cardiac index is used to normalize for body size by dividing cardiac output by body surface area. (54)

Question 12

12. How might changes in heart rate or rhythm affect stroke volume?

Answer 12

12. Both tachycardia and bradycardia can affect stroke volume. An excessively rapid heart rate might not leave sufficient time to fill the ventricle. Loss of sinus rhythm, as reflected by the lack of a p wave on the ECG, will also lead to inadequate ventricular filling from loss of atrial contraction. This is particularly true in patients with a poorly compliant ventricle. A slow heart rate may allow for enhanced ventricular filling and stroke volume, but an excessively low heart rate results in an inadequate cardiac output. (54)

Question 13

13. Define ejection fraction (EF).

Answer 13

13. Ejection fraction (EF) is the percentage of ventricular blood volume that is pumped during a single contraction, or stroke volume/end‐diastolic volume (SV/EDV). (54)

Question 14

14. What is a normal value for EF?

Answer 14

14. A normal EF is 60% to 70%. Unlike stroke volume, EF does not change with body size. Poor cardiac function is indicated by a low EF, although with dilated cardiomyopathy, the stroke volume can improve despite the lower EF. (54)

Question 15

15. Describe factors that may affect EF.

Answer 15

15. Hyperdynamic states with low SVR, such as sepsis and liver failure, are reflected by an elevated EF. Increased SVR can decrease EF, particularly in patients with poor cardiac function. (54)

Question 16

16. Define preload.

Answer 16

16. Preload refers to the amount the heart muscle is “stretched” before contraction. Preload is best defined clinically as the EDV of the heart. (54)

Question 17

17. How can preload be measured clinically?

Answer 17

17. The EDV of the heart, or preload, can be measured directly by transesophageal echocardiography (TEE). Ventricular filling pressures can be measured on the right side of the heart with central venous pressure and on the left side of the heart by pulmonary capillary wedge pressure. A complete picture of preload would still require both pressure and volume information to more fully under‐stand the compliance of the heart. Systolic pressure variation (SPV) may also be an important indicator of preload. (54)

Question 18

18. When will central venous pressure (CVP) poorly reflect filling pressures in the left side of the heart?

Answer 18

18. Central venous pressure will poorly reflect filling of the left ventricle in a num‐ber of pathologic conditions. With pulmonary disease and elevated peripheral vascular resistance (PVR), right‐sided heart failure may increase CVP despite poor filling of the left ventricle. With left ventricular failure, CVP may be nor‐mal despite elevated left‐sided heart filling pressures as long as right ventricu‐lar function is preserved. Therefore, CVP correlates with filling pressures on the left side of the heart in the absence of pulmonary disease and when cardiac function is normal. (54)

Question 19

19. How does pulmonary capillary wedge pressure (PCWP) reflect left‐sided heart filling pressures?

Answer 19

19. Pulmonary capillary wedge pressure (PCWP) reflects the filling pressure of the left side of the heart, becoming nearly equivalent to left atrial pressures. By using a balloon to stop flow in a pulmonary artery, pressure equilibrates within the system. (55)

Question 20

20. What is the Frank-Starling mechanism?

Answer 20

20. The Frank-Starling mechanism describes how the heart responds to in‐creased filling by increasing contraction and stroke volume. A larger preload results in an increased contraction necessary to eject the added ven‐tricular volume, resulting in a larger SV and similar EF. Small increases in preload may have dramatic effects on SV and CO, although at higher filling pressures little benefit may be derived. This is described by cardiac function curves. (55)

Question 21

21. What are common causes of low preload?

Answer 21

21. Hypovolemia or low circulating blood volume is a key cause of low preload. Blood loss and fluid loss from other sources are commonly faced during sur‐gery. Low preload can also occur with venodilation from anesthetic agents and neuraxial anesthesia. Pathologic problems such as pericardial tamponade and tension pneumothorax may result in low preload (inadequate filling of the heart) despite normal blood volume and high CVP. Pulmonary embolus and pulmonary hypertension are examples of pathologic problems that may prevent the right side of the heart from pumping sufficient volume to fill the left side of the heart, also resulting in low preload. (55)

Question 22

22. What are systolic pressure variation (SPV) and pulse pressure variation (PPV), and how might they be useful in analyzing hypotension?

Answer 22

22. Systolic pressure variation (SPV) describes the regular changes in systolic pres‐sure that occur with ventilation. During mechanical ventilation, significant SPV reflects low preload. In cases of hypotension, high SPV may indicate low preload. Extreme SPV may indicate other important causes of hypotension, such as pericardial tamponade or tension pneumothorax. Pulse pressure vari‐ation (PPV), which is closely related to SPV, requires computer calculation. Many monitoring systems will compute both. Both SPV and PPV are the most sensitive and specific indicators of which patients will respond appropriately to fluid administration. Although cardiac filling pressures (CVP and PCWP) reflect preload, a single number may not adequately determine whether an individual patient requires more or less fluid. (55)

Question 23

23. What is contractility?

Answer 23

23. Contractility, or inotropic state, describes the force of myocardial contrac‐tion independent of preload and afterload. It is reflected in the rate of rise of pressure over time. Graphically, it is reflected in the systolic pressure‐volume relationships. (55)

Question 24

24. What are some important clinical causes of low contractility?

Answer 24

24. Important causes of poor myocardial contractility that may be associated with hypotension include myocardial ischemia, previous myocardial infarction, cardiomyopathy, and myocardial depression from a number of different drugs. In addition, when considering a differential diagnosis of hypotension, valvular heart disease can be reflected as low contractility. (55)

Question 25

25. Which monitors might best identify low contractility?

Answer 25

25. Low myocardial contractility is most easily observed with TEE, where it may be quite obvious even to the untrained observer. The rate of rise of the arterial pressure on arterial waveform, although theoretically reflective of low contrac‐tility, is not usually adequate. (55)

Question 26

26. Define afterload.

Answer 26

26. Afterload is the resistance to ejection of blood from the left ventricle with each contraction. Clinically, afterload is largely determined by the SVR. (55)

Question 27

27. What does low SVR or afterload do to EF?

Answer 27

27. Low SVR or afterload increases EF, which can approach 75% or even 80% in low SVR states. This is a classic feature of low SVR conditions such as liver failure. (56)

Question 28

28. What does low SVR or afterload do to cardiac filling pressures?

Answer 28

28. Low SVR or afterload lowers cardiac filling pressure (CVP or PCWP) via the Frank‐Starling mechanism. Vasodilation can therefore cause relative hypo‐volemia and a volume‐responsive condition. Likewise, high SVR or afterload increases cardiac filling pressure. (56)

Question 29

29. What does low SVR or afterload do to end‐systolic volume, and how might this best be detected by monitoring?

Answer 29

29. Low SVR or afterload leads to low end‐systolic left ventricular volume (which can also occur with very low preload!). This is a pathognomonic sign of low SVR on TEE. (56)␣

Question 30

30. What are the physiologic effects of the parasympathetic and sympathetic nerves on the cardiovascular system?

Answer 30

30. The parasympathetic nervous system primarily affects the cardiovascular sys‐tem by decreasing heart rate through vagal innervation of the sinoatrial node via muscarinic acetylcholine receptors. It also decreases conduction through the atrioventricular node. Mild negative effects on contractility are probably less important. The sympathetic nervous system can increase heart rate (via activa‐tion of β1‐adrenergic receptors), increase conduction through the atrioventricu‐lar node, and increase contractility. The sympathetic nervous system also causes peripheral vasoconstriction. (56)

Question 31

31. What is the normal heart rate response to hypotension or hypertension?

Answer 31

31. Although anesthetic agents and other medications may blunt autonomic reflex responses, significant hypotension will usually increase heart rate, and hyper‐tension will decrease it. (57)

Question 32

32. Where are the baroreceptors located, and what is their response to increased blood pressure?

Answer 32

32. Baroreceptors are present in the carotid sinus and aortic arch. Increased blood pressure will stimulate stretch receptors, leading to parasympathetic stimulation via the vagus and glossopharyngeal nerves and a decrease in heart rate. Sym‐pathetic nervous system activity is also decreased, resulting in a decrease in myocardial contractility and reflex vasodilation. (57)

Question 33

33. What is the effect of chemoreceptors in the carotid sinus?

Answer 33

33. Chemoreceptors in the carotid sinus respond to arterial hypoxemia with respira‐tory and cardiovascular effects. Sympathetic nervous system is stimulated by arterial hypoxemia, although more profound and prolonged arterial hypoxemia can result in bradycardia, possibly through central mechanisms. (57)

Question 34

34. What are the Bainbridge, oculocardiac, and Cushing reflexes?

Answer 34

34. The Bainbridge reflex describes the increase in heart rate from atrial stretch. This helps increase cardiac output in response to increased venous return. The oculocardiac reflex describes bradycardia in response to ocular pressure. The Cushing reflex describes bradycardia in response to increased intracranial pres‐sure. (57)

Question 35

35. What effects do anesthetic agents have on cardiac reflexes?

Answer 35

35. Anesthetic agents blunt cardiac reflexes in a dose‐dependent manner. This in‐creases the likelihood of hypotension under anesthesia. (57)

Question 36

36. What is the usual myocardial oxygen extraction, and how does this compare to whole‐body oxygen extraction?

Answer 36

36. The myocardium extracts a higher percentage of oxygen than other tissues in the body, up to 60% to 70%. Normal whole‐body oxygen extraction is approxi‐mately 25%. (57)

Question 37

37. What is the physiologic coronary response to increased oxygen demand?

Answer 37

37. The physiologic coronary response to increased oxygen demand is by coronary vasodilation and increased coronary blood flow, because increased oxygen extraction is not possible. (57)

Question 38

38. What are some endogenous regulators of coronary blood flow?

Answer 38

38. Endogenous regulators of coronary blood flow include adenosine, nitric oxide, and adrenergic stimulation. (57)

Question 39

39. When is the myocardial subendocardium perfused?

Answer 39

39. Intramural pressure of the myocardium during systole stops blood flow to the subendocardium. Therefore, blood flow to the subendocardium occurs predomi‐nantly during diastole. (57)

Question 40

40. What is the perfusion pressure of the left ventricle?

Answer 40

40. The perfusion pressure of the left ventricle is DBP – LVEDP, where DBP is dias‐tolic blood pressure and LVEDP is left ventricular end‐diastolic pressure. LVEDP may exceed CVP and is therefore used as the downstream pressure. (57)␣

Question 41

41. What is the function of the bronchial circulation?

Answer 41

41. The bronchial circulation supplies nutrients to lung tissue and empties into the pulmonary veins and left atrium. (57)

Question 42

42. How does the pulmonary artery (PA) pressure compare to systemic blood pressure?

Answer 42

42. The pulmonary circulation has much lower pressures than the systemic cir‐culation. This is due to lower pulmonary vascular resistance compared to the systemic vascular resistance, because both systems accept the entire cardiac output. Because these pressures are reported for right‐sided heart catheteriza‐tion, and can be measured clinically with a PA catheter, the anesthesiologist should be familiar with normal and pathologic values. (57)

Question 43

43. How is pulmonary vascular resistance (PVR) calculated?

Answer 43

43. Similar to SVR, PVR is calculated as 80 × (mean PA pressure − PCWP)/CO. (57)

Question 44

44. How does PVR respond to increased cardiac output?

Answer 44

44. PA pressure stays remarkably constant over a wide range of cardiac output. PVR accommodates to increased cardiac output by distention and recruitment of capillaries, so that resistance decreases as cardiac output increases. (57)

Question 45

45. How does lung volume affect PVR?

Answer 45

45. Both high and low lung volumes increase PVR. At high lung volumes, intra‐alveolar vessels are compressed. At low lung volumes, extra‐alveolar vessels are compressed. Increased PVR at low lung volumes may be physiologically helpful in diverting blood flow from a collapsed lung, thereby improving gas exchange. (58)

Question 46

46. What drugs modify PVR?

Answer 46

46. Elevated PVR can be very difficult to treat. Inhaled nitric oxide, prostaglandins, and phosphodiesterase inhibitors may lower PVR, but cannot always completely reverse elevated PA pressure. (58)

Question 47

47. What is the effect of hypoxia on PVR?

Answer 47

47. Hypoxia increases PVR through hypoxic pulmonary vasoconstriction (HPV). This process may significantly improve gas exchange by lowering blood flow to areas of poor ventilation. However, global hypoxia, such as occurs at high altitude, can result in increased PA pressure through HPV. (58)

Question 48

48. What are some pathologic causes of elevated PVR?

Answer 48

48. Pathologic elevation in PVR may occur with pulmonary emboli (blood clots, air, amniotic fluid, carbon dioxide, fat). In addition, arteriolar hyperplasia may occur with certain congenital cardiac diseases (Eisenmenger syndrome), idi‐opathically (primary pulmonary hypertension), and associated with cirrhosis (portopulmonary hypertension). Intrinsic lung disease from a variety of causes can also increase PVR. (58)

Question 49

49. How does gravity affect pulmonary blood flow in West’s zones 1, 2, and 3 of the lung?

Answer 49

49. Because the PA pressure is low, hydrostatic changes due to gravity can have significant effects on pulmonary blood flow. For every 20‐cm change of height there is a 15‐mm Hg pressure difference. This has minimal effect for systemic pressure but can be significant in the lung. Notable effects are in West’s zone 1 of the lung, where airway pressure is higher than PA pressure, leading to no perfusion and therefore dead space. This zone normally does not exist, but with positive‐pressure ventilation or low PA pressures zone 1 develops. In zone 2, airway pressure is more than pulmonary venous pressure but not more than PA pressure. Therefore, blood flow is proportional to the difference between PA pressure and airway pressure. In zone 3, PA pressure and venous pressure exceed airway pressure, and blood flow is proportional to their difference. This can be useful clinically, by positioning the patient such that areas of poor gas exchange are in an elevated position where there is also lower perfusion, improving gas exchange. In lung surgery, the lower PA pressure in the nonde‐pendent collapsed lung helps gas exchange. (58)

Question 50

50. What are the two main types of pulmonary edema?

Answer 50

50. Pulmonary edema can be due to hydrostatic leak or capillary leak. Hydrostatic leak can occur in the lung when pulmonary capillary pressure is elevated. Pul‐monary edema results when lymphatic system removal of fluid is overwhelmed by the degree of hydrostatic leak. The risk of pulmonary edema increases as PCWP exceeds 20 mm Hg. Pulmonary edema due to capillary leak can also oc‐cur with pulmonary injury from a variety of causes, such as aspiration, sepsis, or blood transfusion (transfusion‐related acute lung injury). The acute respira‐tory distress syndrome (ARDS) represents very significant lung injury with a high risk of mortality. (59)␣

Question 51

51. How does arterial hypoxemia differ from hypoxia?

Answer 51

51. Arterial hypoxemia, which reflects pulmonary gas exchange, is defined as a low partial pressure of oxygen in the blood. Mild and even moderate arterial hy‐poxemia (e.g., high altitude) can be tolerated and may not result in substantial injury or adverse outcomes. Hypoxia is a more general term including tissue hypoxia, which also reflects circulatory factors. Anoxia is a nearly complete lack of oxygen. (59)

Question 52

52. How is blood oxygen measured?

Answer 52

52. Three measurements of blood oxygen are used clinically: the partial pressure (PaO2 in mm Hg), oxyhemoglobin saturation (SaO2 in %), and arterial oxygen content (CaO2 in mL O2/dL). (59)

Question 53

53. How is arterial oxygen content calculated?

Answer 53

53. Arterial oxygen content (CaO2) is really a concentration and is the sum of the amount of oxygen bound to hemoglobin (1.39 mL O2/dL/g hemoglobin fully saturated) and dissolved in the plasma (0.003 mL O2/mm Hg/dL). The contribu‐tion of dissolved oxygen to the CaO2 can be clinically important at high FIO2 levels and with hyperbaric oxygen therapy. (59)

Question 54

54. Why is PaO2/FIO2 (P/F ratio) useful for measuring oxygenation?

Answer 54

54. PaO2/FIO2 ratio (P/F ratio) is a common clinical index of arterial oxygenation that is less affected by variations in the FIO2 than is PaO2 or A-a gradient. (59)

Question 55

55. What is the P50? What is a normal value?

Answer 55

55. The oxyhemoglobin dissociation curve relates PaO2 and SaO2, or oxygen par‐tial pressure and oxyhemoglobin saturation. The P50 is the partial pressure of oxygen (PO2) at which hemoglobin is 50% saturated, normally 26.8 mm Hg. Sigmoidal curves are defined by such midpoints. (59)

Question 56

56. What are common clinical factors that shift the oxyhemoglobin dissociation curve left and right?

Answer 56

56. The most important factors shifting the oxyhemoglobin dissociation curve to the right are metabolic acidosis and hypercapnia. Metabolic alkalosis and hypocapnia shift the curve to the left. Lower 2,3‐DPG in stored blood and the presence of fetal hemoglobin lead to a significant left shift. (59)

Question 57

57. What are the benefits of a rightward shift in the oxyhemoglobin dissociation curve?

Answer 57

57. Rightward shifts of the oxyhemoglobin dissociation curve improve unloading of oxygen in the tissues. For the same tissue PO2 more oxygen will be unloaded because of a rightward shift, improving tissue oxygenation. Because of the sig‐moidal shape of the curve, little change in loading of oxygen in the lungs will occur because of the rightward shift. (59)

Question 58

58. What is the equation describing the effect of ventilation on oxygenation?

Answer 58

58. The alveolar gas equation is used most commonly to determine the effect of ventilation on oxygenation. The equation describes the transfer of oxygen from the environment to the alveoli and therefore contains all the determinants of alveolar oxygen: barometric pressure (PB), FIO2, and ventilation in respiratory quotient (RQ). The respiratory quotient is the ratio of carbon dioxide production to oxygen consumption and is assumed to be 0.8 on a normal diet. The alveolar gas equation is PAO2 = FIO2 × (PB − PH2O) − PaCO2/RQ. (60)

Question 59

59. How does increased FIO2 improve oxygenation during hypercapnia?

Answer 59

59. FIO2 is a determinant of alveolar oxygen, and it can overcome the effect of higher CO2 on alveolar oxygen as can occur during hypoventilation. The al‐veolar gas equation can be used to describe this effect of supplemental oxygen improving arterial oxygenation. (60)

Question 60

60. Is it possible to deliver hypoxic gas mixtures with a modern anesthesia machine?

Answer 60

60. Modern anesthesia machines can effectively prevent delivery of hypoxic gas mixtures. Multiple features are necessary, including pin indexing of tanks and gas hoses, shut‐off valves for nitrous oxide, and use of oxygen to drive the bellows. These safety mechanisms might be overcome if a gas other than oxygen were delivered through the oxygen piping, which has occurred because of construction mishaps. A monitor measuring FIO2 is therefore still critical. Hypoxemia still occurs because of unintentional delivery of room air in patients requiring supplemental oxygen, such as might occur with an exhausted oxygen transport cylinder. (60)

Question 61

61. How is the A-a gradient useful clinically with respect to a problem in oxygenation?

Answer 61

61. Calculation of an A-a gradient (PAO2 − PaO2) divides the potential causes of hypoxemia into two groups of causes. The first group of causes includes all the factors that determine alveolar oxygen: FIO2, barometric pressure (altitude), and ventilation. Hypoxemia in the presence of a normal A-a gradient (5 to 10 mm Hg) would indicate that this first group is the problem. An abnormal A-a gradient indicates a gas exchange issue, usually V̇ ˙ (ventilation-perfusion) mismatch or shunt. A-a gradients are simple to calculate but are clinically most useful at room air. The P/F ratio is more consistent and clinically useful at higher FIO2. (61)

Question 62

62. What is intrapulmonary shunt?

Answer 62

62. Intrapulmonary shunt describes the passage of mixed venous blood through the lung, unexposed to alveolar gas. This commonly occurs because alveoli are collapsed (atelectasis) or filled with fluid such as in pneumonia or pulmonary edema. Mixed venous blood combines with blood passing through normal lung, lowering the PaO2, which is the end result of the mixture. An intracardiac shunt can occur in various congenital types of heart diseases and sometimes in adults with blood flow through a patent foramen ovale. (62)

Question 63

63. What does the shunt equation describe?

Answer 63

63. The shunt equation quantitatively describes the physiologic effect of shunt on oxygenation. The equation calculates the shunt fraction, or shunt flow relative to total flow. Because V̇ ˙ mismatch may also be present, the shunt equation really describes a simple two‐compartment model analyzing oxygenation as if it were all pure shunt. (62)

Question 64

64. What does V̇ ˙ (ventilation-perfusion) mismatch describe?

Answer 64

64. Ventilation-perfusion mismatch describes the disparity between the ventilation and perfusion in various alveoli. Well-ventilated alveoli are described as having a high V̇ ˙ , whereas a low V̇ ˙ describes alveoli that are poorly ventilated and, if this reflects a significant portion of the lungs, may result in a low PaO2 and arterial hypoxemia. (62)

Question 65

65. Is diffusion impairment a significant clinical cause of hypoxemia?

Answer 65

65. Diffusion impairment is not a major clinical cause of hypoxemia. However, dif‐fusion impairment is often misunderstood and is not equivalent to a low diffus‐ing capacity. Diffusion impairment occurs when a partial pressure gradient still exists between the alveolus and the capillary blood after the blood has passed through. Diffusion impairment is rare because there is usually sufficient time for diffusion, with equilibration occurring early in the process. If an alveolus is filled with fluid, such that no diffusion of oxygen occurs, this is shunt, not diffusion impairment. Even alveolar thickening, which may slow diffusion, does not usually result in diffusion impairment because equilibration of PO2 between the alveolus and capillary blood does occur. Diffusion impairment may be a clinically significant physiologic problem at extreme altitude during exercise because of both a smaller driving oxygen partial pressure and the limited time for equilibrium due to the rapid transit of blood through the pulmonary capil‐larys. (62)

Question 66

66. Which causes of hypoxemia are very responsive to supplemental oxygen and therefore easily treated with higher FIO2?

Answer 66

66. Hypoventilation, diffusion impairment, and V̇ ˙ mismatch are all very respon‐sive to supplemental oxygen. High FIO2 can effectively eliminate hypoxemia from these causes. Shunt is much more resistant to supplemental oxygen. At shunt fractions over 30%, hypoxemia may remain despite administration of 100% oxygen. Higher FIO2 does improve oxygenation with intrapulmonary shunt by adding more dissolved oxygen in the normally perfused alveoli. Arte‐rial hypoxemia remaining despite administration of 100% oxygen is always caused by the presence of an intrapulmonary shunt. (62)

Question 67

67. How does low mixed venous oxygen saturation affect arterial oxygenation?

Answer 67

67. Low mixed venous oxygen levels may affect PaO2 but only in the presence of shunt. For the same shunt, lower mixed venous oxygen results in a lower PaO2. (62)

Question 68

68. What are the three forms in which carbon dioxide is carried in the blood?

Answer 68

68. In the blood, carbon dioxide is carried as dissolved gas, as bicarbonate, and bound to hemoglobin as carbaminohemoglobin. The greatest total quantity of CO2 is as bicarbonate, which is in fairly rapid equilibrium with CO2. Equilib‐rium occurs because of the enzyme carbonic anhydrase, through carbonic acid. Despite being the smallest total, the CO2 from carbaminohemoglobin represents about one third of the venous to arterial CO2 movement. (63)

Question 69

69. Why is hypercapnia a problem clinically?

Answer 69

69. Hypercapnia can be well tolerated, although at higher levels, probably ap‐proaching 80 mm Hg or greater, hypercapnia can cause CO2 narcosis. The most significant problem is what hypercapnia represents. A major cause of hypercap‐nia is oversedation or narcotization. This could progress to apnea and anoxia. Hypercapnia may also represent impending respiratory failure from a variety of causes. (63)

Question 70

70. What are some physiologic effects of hypercapnia on the lungs, kidneys, central nervous system, and heart?

Answer 70

70. Hypercapnia affects the lungs (pulmonary vasoconstriction, right shift of the hemoglobin‐oxygen dissociation curve), kidneys (renal bicarbonate resorption), central nervous system (somnolence, cerebral vasodilation), and heart (coronary artery vasodilation, decreased cardiac contractility). (63)

Question 71

71. What are the four physiologic causes of hypercapnia?

Answer 71

71. Hypercapnia is caused by increased production or decreased removal. Physio‐logically, hypercapnia can be caused by (1) rebreathing (elevated inspired CO2), (2) hypoventilation, (3) elevated CO2 production, and (4) elevated dead space. (63)

Question 72

72. What are significant causes of increased CO2 production under anesthesia?

Answer 72

72. The most concerning cause of significant CO2 production under general an‐esthesia is malignant hyperthermia (MH). Although fever alone will increase CO2 production, the increase is not dramatic. MH may increase CO2 produc‐tion severalfold. Thyroid storm may increase CO2 production. Absorption of CO2 introduced during laparoscopy may be quite significant for certain proce‐dures, particularly if subcutaneous CO2 emphysema develops. The CO2 removed through the lungs appears as if it is CO2 production. Other causes of increased CO2 under anesthesia include malfunctioning expiratory valves on the anesthe‐sia machine, exhausted CO2 absorbents, and, although temporary effects, the administration of sodium bicarbonate and the release of an extremity tourni‐quet. (64)

Question 73

73. Define dead space. What are the types of dead space?

Answer 73

73. Dead space is “wasted ventilation,” or areas receiving ventilation that do not participate in gas exchange. Dead space is described as anatomic, alveolar, or physiologic (total). Anatomic dead space consists of the conducting airways, which are not involved in gas exchange, plus the larynx and pharynx. Alveolar dead space consists of alveoli that are not involved in gas exchange, usually from lack of blood flow. Physiologic or total dead space consists of all dead space and is the easiest to measure. “Equipment” dead space may be produced by the addition of tubing beyond the Y‐connector of the anesthesia circuit. (64)

Question 74

74. What pathologic conditions may increase dead space?

Answer 74

74. Many forms of end‐stage lung disease, such as emphysema and cystic fibro‐sis, are characterized by elevated dead space. Pulmonary emboli of any source increase dead space. Hypovolemic shock increases dead space, because very low PA pressures result in more zone 1 of the lung, where alveoli are not perfused and therefore represent dead space. Increased airway pressure and positive end‐expiratory pressure (PEEP) can also increase dead space. (64)

Question 75

75. What is a normal value for physiologic dead space?

Answer 75

75. Normal dead space is 25% to 30% and consists almost entirely of anatomic dead space. (64)

Question 76

76. What does the Bohr equation describe?

Answer 76

76. The Bohr equation is used to calculate the amount of dead space, expressed as a ratio of the volume of dead space relative to tidal ventilation, VD/VT. It requires measuring PaCO2 and mixed‐expired CO2 by collecting exhaled gas. Because collection of exhaled gas may be difficult, devices have been developed to measure dead space from exhaled CO2 and expiratory flow and also CO2 production. (64)

Question 77

77. How can dead space be estimated under general anesthesia?

Answer 77

77. Clinically, the gradient from PaCO2 to end‐tidal PaCO2 is a reflection of alveolar dead space and is a simple way of evaluating dead space under general anes‐thesia. However, even when dead space is constant the gradient will change with hyperventilation or hypoventilation. (64)

Question 78

78. What is the effect on PaCO2 if alveolar ventilation decreases by one half?

Answer 78

78. The PaCO2 should double when alveolar ventilation decreases by one half. This change occurs over several minutes as a new steady state develops. (64)

Question 79

79. How quickly can apnea increase PaCO2?

Answer 79

79. CO2 jumps up fairly rapidly during the first 30 seconds to 1 minute of apnea. This jump is due to rapid transition to mixed venous CO2 levels, which usually means an increase of about 6 mm Hg. This occurs because the lungs do not continue to store CO2, so once equilibration of CO2 occurs across the alveoli, PaCO2 will jump to mixed venous levels. Thereafter, CO2 increases as a result of metabolism at a slower rate of about 2 to 3 mm Hg/min. (65)␣

Question 80

80. What are pulmonary mechanics?

Answer 80

80. Pulmonary mechanics describes the pressure, volume, and flow relationships of gas within the lungs and the tracheobronchial tree. (65)

Question 81

81. What factors contribute to the static pressure in the lung?

Answer 81

81. The static pressure in the lung is determined by the interplay between the elastic properties of the lung, the pressure effect of the chest wall and abdomi‐nal cavity, and alveolar surface tension, which exists at any air‐fluid interface. (65)

Question 82

82. How is surface tension reduced in the lungs?

Answer 82

82. Surfactant reduces surface tension in the lungs and makes the alveoli more compliant. Without surfactant the lungs would be much stiffer, and alveoli would be less stable and would tend to collapse. (65)

Question 83

83. Define static compliance.

Answer 83

83. Static compliance is the change in volume divided by the change in pressure. By static, this means that the pressure and volume measurements are made at a point of no gas flow, which would contribute a resistive pressure component. Low or poor compliance would indicate that more pressure is needed to inflate the lungs. True static compliance would require measurement of intrapleural pressures to isolate just the lung, whereas measurement of airway pressure reflects additional factors outside the lung. (65)

Question 84

84. What is functional residual capacity (FRC) with respect to the static mechanical properties of the lung and chest wall?

Answer 84

84. The functional residual capacity (FRC) is simply the balance point between the lungs collapsing and the chest wall expanding. Stiffer lungs will produce a lower FRC, because this balance point will occur at a lower lung volume. On the other hand, a disease such as emphysema, with loss of elastic recoil, results in a higher FRC. (65)

Question 85

85. What determines airway resistance?

Answer 85

85. Similar to the vascular system, resistance is largely determined by airway diam‐eter. However, turbulent gas flow can add a significant resistance component, which can happen at airway narrowing points. (65)

Question 86

86. How can one distinguish clinically between elevated airway pressure produced from resistance and that caused by static compliance?

Answer 86

86. Pressure from resistance only occurs during gas flow. By ceasing gas flow with an inspiratory pause (a feature of most ventilators), the pressure on the airways contributed by resistance and flow disappears, and one can determine the static or “plateau” pressure. (65)

Question 87

87. List important clinical causes of elevated airway resistance.

Answer 87

87. High airway resistance can be caused by a number of common clinical condi‐tions. A useful differential might trace the potential resistance anatomically, starting with airway equipment, including the endotracheal tube. Causes of resistance in the upper airways can include compression, foreign bodies, and secretions. In the lower airway, bronchoconstriction becomes the dominant cause. (66)␣

Question 88

88. Where are the central chemoreceptors located?

Answer 88

88. The central chemoreceptors are located on the ventral surface of the brainstem (medulla). (66)

Question 89

89. What is the main stimulus for the central chemoreceptors?

Answer 89

89. Carbon dioxide is the main stimulus for the central chemoreceptors. Carbon dioxide crosses the blood‐brain barrier and rapidly equilibrates with carbonic acid. Although the signal for the chemoreceptors is transduced by protons pro‐duced through local changes in the pH, for clinical purposes the chemoreceptors are considered responsive to CO2. (66)

Question 90

90. How would the central chemoreceptors respond to lactic acidosis?

Answer 90

90. The central chemoreceptors are protected from metabolic acid by the blood‐brain barrier. Cerebrospinal fluid pH will change in response to peripheral blood pH changes, but this may take days. An acute lactic acidosis will therefore have no effect on central chemoreceptors, except due to decreases in PaCO2 that may occur from the ventilatory response to the peripheral acidosis. (66)

Question 91

91. What are the primary peripheral chemoreceptors?

Answer 91

91. The carotid bodies are the primary peripheral chemoreceptors in humans. Aortic bodies do not appear to have a significant clinical effect (which was studied in humans who had carotid body denervation). (66)

Question 92

92. What factors stimulate the peripheral chemoreceptors?

Answer 92

92. The peripheral chemoreceptors are stimulated by low pH, high PaCO2, and low PaO2. Unlike the central chemoreceptors, the peripheral chemoreceptors are not protected from an acute metabolic acidosis, which will cause stimulation and hyperventilation (the lower PaCO2 from this hyperventilation will affect the cen‐tral chemoreceptors). (66)

Question 93

93. Why do peripheral chemoreceptors effectively sense arterial, not venous, blood values?

Answer 93

93. High blood flow relative to metabolic rate creates a tissue with hardly any arterial to venous PO2 difference. This allows the carotid bodies to effectively “sense” arterial values. (66-67)

Question 94

94. What is the hypercapnic ventilatory response?

Answer 94

94. The hypercapnic ventilatory response describes increases in ventilation in response to increases in PaCO2. Although a variety of techniques are used to obtain ventilatory data, the slope of CO2 versus minute ventilation is the primary measure of hypercapnic ventilatory responsiveness. The slope is the change in minute ventilation divided by the change in CO2 and is moderately linear except at the extremes. Minute ventilation does not tend to go to “zero” because of an “awake” drive to breathe, whereas at high PCO2 levels minute ventilation is eventually limited by maximal minute ventilation. Usually end‐tidal PCO2 is used clinically because a noninvasive measurement can be preferable. (67)

Question 95

95. What receptors drive the hypercapnic ventilatory response?

Answer 95

95. The central chemoreceptors are the major receptor system responsible for hypercapnic drive. However, in room air, approximately one third of the CO2 response is from peripheral chemoreceptor drive. Usually hypercapnic drive is measured at higher FIO2 where the majority of the response will then be from central chemoreceptors. (67)

Question 96

96. What is an apneic threshold?

Answer 96

96. Below a certain value of PaCO2, ventilation usually ceases. In an awake person, this can be difficult to measure due to an awake drive to breath. Under general anesthesia, this phenomenon is easy to observe. With mechanical ventilation, if a patient is hyperventilated, spontaneous ventilatory efforts cease at a PCO2 about approximately 5 mm Hg lower than the setpoint. As CO2 is allowed to build up again, ventilation begins slowly and will stabilize again at the set‐point. (67)

Question 97

97. How quickly does a CO2 ventilatory response develop?

Answer 97

97. CO2 ventilatory drive is a slow response, with a time constant (one time con‐stant is 63% toward equilibrium) of approximately 2 minutes. It takes 5 minutes to reach 90% of steady‐state ventilation. This is rarely appreciated, although it is easy to observe that ventilation takes noticeable time to stabilize as CO2 rises to a patient’s setpoint. (67)

Question 98

98. What is the hypoxic ventilatory response?

Answer 98

98. The hypoxic ventilatory response describes increases in ventilation in re‐sponse to decreases in PaO2 and SaO2. The hypoxic ventilatory drive can be measured from a plot of PO2 versus minute ventilation or SaO2 versus minute ventilation. Because the relationship of PO2 to minute ventilation is nonlin‐ear, more complex parameters would be needed to describe the relationship, which then are not very clinically useful. A plot of SaO2 (SpO2 is conveniently and noninvasively measured by pulse oximetry) versus minute ventilation is linear. Hypoxic responsiveness can then be measured by a simple slope (which will be negative), the change in minute ventilation divided by the change in SpO2. (67)

Question 99

99. What receptors are responsible for hypoxic stimulation of ventilation?

Answer 99

99. Hypoxic ventilatory stimulation is from the peripheral chemoreceptors in the carotid bodies. (67)

Question 100

100. How does hypoxia depress ventilation?

Answer 100

100. Central nervous effects of hypoxia lead to a slower development of ventilatory depression known as hypoxic ventilatory decline. The carotid bodies initially lead to increased minute ventilation, but if hypoxia is prolonged, ventilation drops to a level lower than peak ventilation to an intermediate plateau in about 15 to 20 minutes but still above baseline. This drop in ventilation is due to hy‐poxic ventilatory decline. This central response is a regulated response probably involving several inhibitory neurotransmitters. (67)

Question 101

101. How quickly does the hypoxic ventilatory response develop?

Answer 101

101. Hypoxic drive from the peripheral chemoreceptors develops extremely rapidly. The time constant is 10 to 20 seconds. Peak ventilation will therefore usually occur within 1 minute. The response is rapid enough that carotid body output will actually vary in response to the small oscillations of PO2 and PCO2 that oc‐cur with tidal breathing. (67)

Question 102

102. What is the effect of PCO2 on hypoxic drive?

Answer 102

102. The hypoxic drive is significantly higher with a higher PaCO2. This synergistic response between PO2 and PCO2 is a prominent feature of apnea. The hypoxic drive is dramatically decreased by low PaCO2 levels. (67)

Question 103

103. Do opioids, sedative-hypnotics, and volatile anesthetics depress hypercapnic ventilatory drive, hypoxic ventilatory drive, or both?

Answer 103

103. Opioids, sedative-hypnotics, and volatile anesthetics work on neurons in the integratory area of the brainstem. They do not affect detection of hypoxia or hypercapnia per se. The clinically observed respiratory depression therefore affects both hypercapnic and hypoxic ventilatory drive equally in a dose‐dependent fashion. (67)

Question 104

104. What ventilatory problems are neonates of low postconceptual age at risk for?

Answer 104

104. Neonates less than 60 weeks of postconceptual age can be at risk of apnea fol‐lowing general anesthesia. (68)

Question 105

105. What is Ondine’s curse?

Answer 105

105. Originally described following surgery near the high cervical spinal cord, Ondine’s curse describes patients with a nearly absent drive to breath. While awake, they may breathe fairly normally. But asleep, or under general anes‐thesia, breathing can be significantly depressed. This is due to abnormalities in the central integratory system that seem to blunt the hypoxic and hypercapnic ventilatory responses. Idiopathic forms of Ondine’s curse, which present in childhood, are usually referred to as primary central alveolar hypoventilation syndrome. (68)

Question 106

106. When is periodic breathing most likely to occur?

Answer 106

106. Periodic breathing occurs frequently when some degree of hypoxia is present, such as can occur during drug‐induced sedation. This is most likely caused by the peripheral chemoreceptors responding to mild arterial hypoxemia leading to overcorrection and undercorrection of the PaO2. Oscillations of the PaCO2 and SaO2 result. This is a major cause of sleep disturbance at high altitudes. Some patients with central sleep apnea have problems primarily with periodic breath‐ing. Periodic breathing will not usually be observed in patients who are awake. (68)␣

Question 107

107. Write the Fick equation.

Answer 107

107. The Fick equation describes the relationship between cardiac output, oxygen consumption (VO2), and arterial to venous oxygen content difference: VO2 = CO× (CaO2 – CvO2). This value reflects oxygen needs at the tissue level. (68)

Question 108

108. Define oxygen delivery.

Answer 108

108. Oxygen delivery (DO2) is the total amount of oxygen supplied to the tissues. It is defined as the product of cardiac output (CO) and arterial oxygen content (CaO2), DO2 = CO × CaO2. Decreased cardiac output or arterial oxygen content (anemia, hypoxemia) can result in decreased oxygen delivery. (68)

Question 109

109. Why is examining oxygen extraction clinically useful?

Answer 109

109. Examining oxygen extraction provides a better global indication of whether cardiac output is matched to the body’s oxygen needs. Oxygen extraction may provide clinically and diagnostically useful clues as to disease state. In cardio‐genic shock, oxygen extraction is high because cardiac output is insufficient for oxygen consumption. In sepsis and liver failure, oxygen extraction may be very low. (68)

Question 110

110. What is normal mixed venous oxygen saturation?

Answer 110

110. Normal whole‐body mixed venous oxygen saturation is about 75%. Individual organs and tissues can differ significantly. (68)

Question 111

111. How does the normal mixed venous oxygen saturation value change with hemoglobin level?

Answer 111

111. Cardiac output increases in response to anemia so that oxygen delivery is maintained. Therefore, the mixed venous oxygen saturation remains relatively constant. But this means that arterial to venous oxygen content difference necessarily decreases with anemia. At some level of hemoglobin, cardiac output does not completely compensate and increased oxygen extraction occurs. Under anesthesia, with a blunted heart rate response, increased extraction may occur earlier. (68)

Question 112

112. How would the arterial to venous oxygen content difference change with higher FIO2?

Answer 112

112. Arterial to venous oxygen content difference (CaO2 – CvO2) is independent of FIO2, whereas the mixed venous oxygen saturation (S O2) can increase signifi‐cantly with higher PaO2. Arterial to venous oxygen content difference decreases with anemia, because not as much oxygen can be extracted without excessively desaturating mixed venous blood. (68)

Question 113

113. Why is the oxygen extraction ratio useful?

Answer 113

113. The oxygen extraction ratio is probably the most reliable index of oxygen ex‐traction. It is the oxygen extraction value most independent of FIO2 and hemo‐globin level. (68)

Question 114

114. How can the body respond physiologically to anemia or increased metabolic demand (oxygen consumption)?

Answer 114

114. The two major compensatory mechanisms for increased demand or less avail‐ability of oxygen are (1) increased cardiac output and (2) increased extraction. This is readily apparent by examining the Fick equation. In anemia without general anesthesia, the primary compensation is increased cardiac output. Increased extraction occurs with more severe anemia. Under anesthesia, the cardiac output compensation may be blunted, and oxygen extraction is more important. In exercise, for the increased metabolic demand and oxygen con‐sumption both increased cardiac output and increased extraction are utilized. (68)