e31CHAPTER 136 Board Review Questions At any given pressure, the difference between autoregulated and maximal flows is termed coronary flow reserve (Coronary flow re serve can be measured in units of[.]
CHAPTER 136 Board Review Questions e31 at the same low perfusion pressure (as will occur if the ventricle becomes dilated), the requisite increase in flow will not occur These two conditions cause subendocardial ischemia At any given pressure, the difference between autoregulated and maximal flows is termed coronary flow reserve (Coronary flow reserve can be measured in units of mL/min but also can be assessed by a dimensionless flow reserve ratio derived by dividing maximal flow by resting flow.) Flow reserve depends on perfusion pressure because of the steepness of the pressure-flow relation in maximally dilated vessels Coronary flow reserve indicates how much extra flow the myocardium can get at a given pressure to meet increased demands for oxygen; if reserve is much reduced, then flow cannot increase sufficiently to meet demands and myocardial ischemia will occur What the figure does not show is that coronary flow reserve is normally lower in the subendocardium than in the subepicardium and that decreases in coronary flow reserve are always more profound in the subendocardium than in the subepicardium • Fig 136.7 flow are coupled, increasing aortic blood pressure will increase coronary flow not only by increasing perfusion pressure but also by increasing myocardial oxygen demand Under normal conditions coronary blood flow is autoregulated, such that if perfusion pressure is raised or lowered from its normal value, there is a range over which almost no change in flow occurs; a rise in pressure has caused vasoconstriction, and a fall in pressure has caused vasodilation At perfusion pressures above some upper limit, flow increases, probably because the pressure overcomes the constriction More important, at pressures below about 40 mm Hg (but varying, as discussed later), flow decreases predominantly in the deep subendocardial muscle (Figure 136.8), indicating that some vessels have reached maximal vasodilation and can no longer decrease resistance to compensate for the decreased perfusion pressure In these vessels, flow and pressure are directly related If this pressure dependency occurs, then a further decrease in perfusion pressure decreases local blood flow below the required amount, or if myocardial oxygen demands increase Rationale Coronary flow reserve also can be reduced if maximal flows are normal but autoregulated flows increase (Figure 136.9) Increased myocardial flows above normal values can occur with exercise, tachycardia, anemia, carbon monoxide poisoning, leftward shift of the hemoglobin oxygen dissociation curve (as in infants with a high proportion of fetal hemoglobin), hypoxemia, thyrotoxicosis, acute ventricular dilation (because of increased wall stress), inotropic stimulation by catecholamines, and acquired ventricular hypertrophy If autoregulated flow is normal but maximal flow is decreased, as indicated by the decreased slope of the pressure-flow relation during maximal dilation (Figure 136.10), then coronary flow reserve will be reduced Such a change can occur with marked tachycardia; a decrease in the number of coronary vessels due to Normal maximal flow 600 500 500 400 400 300 R1 200 R2 Normal autoregulated flow 100 0 40 80 120 160 Perfusion pressure (mm Hg) • Fig 136.8 Normal maximal flow 600 Flow (mL/min) Flow (mL/min) 11 Regarding coronary artery perfusion, a shift from normal autoregulated flow to increased autoregulated flow may be seen in which of the following conditions? A Myocardial ischemia B Coronary spasm C Increased blood viscosity D Carbon monoxide poisoning Preferred response: D 300 Increased autoregulated flow R2 200 R1 Normal autoregulated flow 100 0 40 80 120 160 Perfusion pressure (mm Hg) • Fig 136.9 e32 S E C T I O N XV Pediatric Critical Care: Board Review Questions small vessel disease, as in some collagen vascular diseases, especially systemic lupus erythematosus; increased resistance to flow in one or more large coronary vessels because of embolism, thrombosis, atheroma, or spasm; impaired myocardial relaxation due to ischemia; myocardial edema; a marked increase in left ventricular diastolic pressure; marked increase in left ventricular systolic pressure if coronary perfusion pressure is not also increased, as in aortic stenosis or incompetence; and an increase in blood viscosity, most commonly seen with hematocrit levels higher than 65% Normal maximal flow 600 Flow (mL/min) 500 400 300 Reduced maximal flow R1 200 R2 100 Normal autoregulated flow 0 40 80 120 160 Perfusion pressure (mm Hg) • Fig 136.10 12 Pulmonary embolism and subsequent right ventricular failure develops in a previously normal 17-year-old patient Which of the following drugs would help restore right ventricular function to normal? A Dobutamine B Esmolol C Milrinone D Norepinephrine Preferred response: D Rationale Right ventricular myocardial blood flow is affected by the low right ventricular systolic pressure and the fact that changes in aortic pressure alter coronary perfusion pressure without altering right ventricular pressure work If the normal right ventricle is acutely distended—for example, by pulmonary embolism— eventually right ventricular failure occurs The increased wall stress increases oxygen consumption but the raised systolic pressure reduces coronary flow, so when supply cannot match demand, right ventricular myocardial ischemia occurs Raising aortic perfusing pressure mechanically or with a-adrenergic agonists increases right ventricular myocardial blood flow, relieves ischemia, and restores right ventricular function to normal Improved coronary flow is not the only mechanism of this improvement; increased left ventricular afterload moves the ventricular septum toward the right ventricle and improves left ventricular performance Chapter 25: Endothelium and Endotheliopathy The endothelium plays an important role in controlling the vascular tone Which of the following endothelium-derived factors is least likely to cause vasodilation? A Acetylcholine B Endothelin C Endothelium-derived hyperpolarizing factor D Nitric oxide (NO) Preferred response: B Rationale Endothelin is an endothelium-derived vasoconstrictor All other choices are endothelium vasodilators The vasodilatory action of acetylcholine is derived through NO Both NO and prostacyclin can be used clinically Binding of thrombin to cell surface thrombomodulin facilitates activation of which of the following? A Antithrombin III B Platelets C Protein C D Protein S Preferred response: C Rationale Thrombin activity is also modulated by endothelial cell synthesis of thrombomodulin The binding of thrombin to thrombomodulin facilitates the enzyme’s activation of the anticoagulant protein C Activated protein C (APC) activity is enhanced by cofactor C, also called protein S, which is synthesized by endothelial cells as well as other cells (Figure 136.11) APC inhibits factor Va and factor VIIIa Tissue factor Tissue factor inhibitor Factor VIIa ; TF Factor VII Factor VIIIa Factor X Factor Xa Prothrombin Thrombin Fibrinogen Antithrombin Fibrin Thrombomodulin Endothelium Factor VIII Factor Va Activated protein C Protein C • Fig 136.11 APC has a variety of antiinflammatory activities It suppresses inflammatory cytokine during sepsis, inhibits leukocyte adhesion, decreases leukocyte chemotaxis, reduces endothelial cell apoptosis, helps maintain endothelial cell barrier function through activation of the sphingosine-1 phosphate receptor, and minimizes the decrease in blood pressure associated with severe sepsis Another interesting effect of APC is its plasminogen activator inhibitor (PAI-1) neutralizing effect PAI-1 is a glycoprotein that acts as an acute-phase protein during acute inflammation Its primary role in vivo is the inhibition of both tissue- and urokinase-type plasminogen activators PAI-1 is the most efficient inhibitor of APC and thrombin in the absence of heparin PAI-1 CHAPTER 136 Board Review Questions competes with thrombomodulin for binding with thrombin, which, in combination with its inhibition of APC, makes it a strong local procoagulant by a combined action of displacing and inactivating anticoagulant thrombin from thrombomodulin In this way PAI-1 has important pathophysiologic effects in acute and chronic diseases Protein C acts by inhibiting the activities of which of the following? A Factors II and V B Factors II and Xa C Factors Va and VIIIa D Factors VIIa and Xa Preferred response: C Rationale See Fig 136.11 Exposure and binding of endothelial tissue factor to which of the following factors initiates the coagulation cascade, resulting in the formation of fibrin? A Factor II B Factor Va C Factor VIIa D Factor VIII Preferred response: C Rationale The expression and release of tissue factor is the pivotal step in transforming the endothelium from an anticoagulant to a procoagulant surface Tissue factor accelerates factor VIIa–dependent activation of factors X and IX The synthesis of tissue factor is induced by a number of agonists, including thrombin, endotoxin, several cytokines, shear stress, hypoxia, oxidized lipoproteins, and other endothelial insults Once endothelial cells expressing tissue factor are exposed to plasma, prothrombinase activity is generated and fibrin is formed on the surface of the cells Tissue factor also can be found in plasma as a soluble protein Its role there is not well understood, but it probably plays a role in the initiation of coagulation Which of the following causes the production of inducible NO synthase (iNOS)? A Bradykinin B Histamine C Insulin D Tumor necrosis factor-a Preferred response: D Rationale NO is generated from the conversion of L-arginine to NO and L-citrulline by the enzyme nitric oxide synthase (NOS) Two general forms of NOS exist: constitutive and inducible In the unstimulated state, NO is continuously produced by constitutive NOS (cNOS) The activity of cNOS is modulated by calcium that is released from endoplasmic stores in response to the activation of certain receptors Substances such as acetylcholine, bradykinin, histamine, insulin, and substance P stimulate NO production through this mechanism Similarly, shearing forces acting on the endothelium are another important mechanism regulating the release of NO The inducible form of NOS is not calcium dependent but instead is stimulated by the actions of cytokines (e.g., e33 tumor necrosis factor-a and interleukins) or bacterial endotoxins (e.g., lipopolysaccharide) Induction of iNOS occurs over several hours and results in NO production that may be more than 1000fold greater than that produced by cNOS This mechanism is important in the pathogenesis of inflammation (see Figure 136.12) Endotoxins Cytokines Shearing forces L-arg + Ca2+ + iNOS cNOS NO + Cit + Ca2+ CaM Vasoactive agents + R Endothelial cell NO + GTP GC cGMP-PK cGMP cGMP-P Smooth muscle cell • Fig 136.12 Where is NO produced? A Endothelial cell B Neutrophils C Platelets D Red blood cell Preferred response: A Rationale Furchgott and Zawadzki first postulated the existence of an endothelial relaxing factor in 1980, when they noticed that the presence of endothelium was essential for rabbit aortic rings to relax in response to acetylcholine Later, it was determined that the biological effects of endothelial relaxing factor are mediated by NO NO is generated in the endothelial cell from the conversion of L-arginine to NO and L-citrulline by the enzyme NOS NO acts by which of the following mechanisms? A Binding to cyclic adenosine monophosphate (cAMP) B Binding to cyclic guanosine monophosphate (cGMP) C Binding to adenyl cyclase D Binding to guanylyl cyclase Preferred response: D Rationale Once NO is formed by an endothelial cell, it readily diffuses out of the cell and into adjacent smooth muscle cells, where it binds to and activates the soluble form of guanylyl cyclase, resulting in the production of cGMP from guanosine triphosphate Prostacyclin acts by which of the following mechanisms? A Binding to cAMP B Binding to cGMP C Binding to guanylyl cyclase D Binding to prostacyclin receptors Preferred response: D Rationale Prostacyclin is a potent vasodilator that is active in both the pulmonary and systemic circulations In addition to its vasodilatory effects, prostacyclin also has antithrombotic and antiplatelet activity Its release may be stimulated by bradykinin and adenine nucleotides Like NO, it is chemically unstable with a short half-life However, unlike NO, prostacyclin activity in arterial beds de- S E C T I O N XV Pediatric Critical Care: Board Review Questions Which of the following statements regarding the interaction between nitric oxide (NO) and prostacyclin is correct? A NO inhibits the action of prostacyclin B NO and prostacyclin act sequentially to cause vasodilation C Prostacyclin inhibits the action of NO D Prostacyclin facilitates the cellular release of NO Preferred response: D Rationale Prostacyclin facilitates the release of NO by endothelial cells, and the action of prostacyclin in vascular smooth muscle is potentiated by NO Interestingly, NO also may potentiate the effects of prostacyclin The NO-mediated increase in cGMP in smooth muscle cells inhibits a phosphodiesterase that breaks down cAMP, therefore indirectly prolonging the half-life of the second messenger of prostacyclin Chapter 26: Principles of Invasive Cardiovascular Monitoring A critically ill 4-year-old child has been admitted to the pediatric ICU after endotracheal intubation, central venous catheter placement in the right internal jugular vein, and arterial catheter placement in the left radial artery Which set of findings below most reliably predict that a fluid bolus will increase cardiac output? A A central venous pressure of mm Hg while in normal sinus rhythm B A pulse pressure variation of 20% during deep sedation and paralysis C A pulmonary artery occlusion pressure of 12 mm Hg during deep sedation and paralysis D An increase of his mean arterial pressure by 10 when his liver is manually compressed Preferred response: B Rationale Due to cardiopulmonary interactions, when a patient receives a positive pressure breath their right ventricular preload will decrease, an effect accentuated by hypovolemia The result of this temporary decrease in right ventricular preload is a decrease in left ventricular preload which follows a few cardiac cycles later and manifests itself as a decrease in pulse pressure during insufflation of the lungs due to the decreased blood volume ejected A is incorrect as only central venous pressures ,5 mm Hg have been reliably shown to predict an increase in cardiac output following a fluid bolus C is incorrect because a pulmonary artery occlusion pressure of 12 mm Hg during deep sedation and paralysis is higher than normal suggesting that the left atrium or ventricle is stressed, a condition likely to be worsened by increasing its volume load D is incorrect as there is insufficient evidence for manual liver palpation as a surrogate or replacement for passive leg raising, particularly without the explicit inclusion of sedation and paralysis Liver compression may raise a child’s blood pressure due to pain, discomfort, anxiety, or increased alertness In a well calibrated, well-functioning arterial line of appropriate size, cannulation of which site will report the largest pulse pressure? A Axillary artery B Brachial artery C Common femoral artery D Radial artery Preferred response: D Rationale Since impedance increases in the circulatory system the further a measurement is taken from the heart, the blood pressure increases with distance from the heart while the flow velocity decreases The effect of this will be to raise the systolic peak while accelerating the diastolic downslope of the pressure reading Mathematically the area under this curve will remain the same, though the pulse pressure will vary depending on where it is measured, with the highest measurements being those taken most distally to the heart (Figure 136.13) Pressure (cm H2O) pends on its ability to bind to specific receptors in vascular smooth muscle Its vasodilator activity is therefore determined by the expression of such receptors Prostacyclin receptors are coupled to adenylate cyclase to elevate cAMP levels in vascular smooth muscle The increase in cAMP results in (1) stimulation of adenosine triphosphate–sensitive K1 channels, resulting in hyperpolarization of the cell membrane and inhibition of the development of contraction, and (2) increased efflux of Ca21 from the smooth muscle cell and inhibition of the contractile machinery Velocity (cm/sec) e34 260 220 180 140 90 50 Ascending Thoracic Abdominal Abdominal aorta aorta aorta aorta middle distal Flow velocity Femoral 30 • Fig 136.13 Which patient is most likely to display pulsus alternans on their arterial line tracing? A An infant newly diagnosed with anomalous left coronary artery from the pulmonary artery (ALCAPA) B A child on noninvasive positive pressure ventilation with community acquired pneumonia C A teenager with primary pulmonary arterial hypertension newly diagnosed with corona virus infection D A child who is postoperative day one from deceased donor renal transplant Preferred response: A Rationale Pulsus alternans is an arterial line tracing which alternates between weak and strong beats and is associated with left ventricular systolic impairment The systolic impairment results in an increased end-diastolic volume which leads to an increased stroke volume on the next cardiac cycle The most likely patient to have left ventricular systolic impairment is the child with ALCAPA due to the deoxygenated blood from the pulmonary artery supplying their left coronary artery CHAPTER 136 Board Review Questions Central venous pressure is most frequently used as a measure of which of the following? A Left ventricular preload B Left ventricular afterload C Right ventricular preload D Right ventricular afterload Preferred response: C Rationale The central venous pressure is measured in the right atrium, super vena cava, or inferior vena cava and is the pressure at the end of diastole Thus it represents the force, or load, on the right ventricle during diastole which is also called preload Left ventricular preload cannot be measured from the central venous system, nor can the afterload of either ventricle A 7-day-old male with d-transposition of the great arteries presents hours after an arterial switch operation with a heart rate of 180 beats per minute and hypotension (mean arterial pressure of 35 mm Hg) He appears to have A-V dissociation on telemetry What would be the most likely pattern seen on the central venous pressure (CVP) monitor? A Broad, flat a waves B Enlarged a waves C Fused c and v waves D Steep abrupt x and y descent Preferred response: B Rationale Cannon a waves are enlarged a waves seen when the right atrium is ejecting against a closed tricuspid valve, and they may be seen when atrioventricular discordance occurs (in this case, during an episode of postoperative junctional ectopic tachycardia) They will resolve once the underlying illness is treated Response C occurs in tricuspid regurgitation, when the backflow of blood out of the right ventricle obliterates the x descent and the c wave becomes accentuated Response D occurs during pericardial constriction or tamponade physiology Although the patient is tachycardic and hypotensive, there are no other signs, from the stem, that the patient has this physiology Response A, or loss of a wave, occurs during atrial fibrillation because loss of atrial contraction results in missing the a wave (Figure 136.14) e35 An otherwise healthy infant has a peripheral arterial line placed in his dorsalis pedis for monitoring during an elective surgery What discrepancy is likely to be found between a cuff blood pressure on the arm and the readings assessed from the arterial line? A The mean arterial pressure (MAP) measurements will be widely different B The systolic blood pressure (SBP) measurement will be lower on the intraarterial measurement C The diastolic blood pressure (DBP) measurement will be lower on the intraarterial measurement D The MAPs will be the same, but the SBP on the cuff pressure will be higher Preferred response: C Rationale This is referred to as distal pulse amplification and occurs due to the nature of the vascular tree; the systolic blood pressure increases, and diastolic blood pressure decreases as you move peripherally, with a more exaggerated pulse pressure The MAPs remain the same between the peripheral and central sites Pressure waveform measurements from different sites of the arterial tree have varying morphologies depending on the properties of the vascular bed The changes that occur as you move peripherally have to with alterations in impedance and harmonic resonance A 10-year-old child has been admitted to the intensive care unit (ICU) in shock The child is endotracheally intubated, mechanically ventilated, and has a pulmonary artery catheter in place The following information is available: • Heart rate: 140 beats/min • Blood pressure: 90/60 mm Hg • Central venous pressure (CVP): 10 mm Hg • Mean arterial pressure (MAP): 70 mm Hg • Pulmonary arterial pressure: 45/25 mm Hg • Mean pulmonary arterial pressure: 32 mm Hg • Venous oxygen saturation: 65% • Pulmonary artery occlusion pressure: 15 mm Hg • Carbon monoxide (CO): L/min What is the calculated systemic vascular resistance (SVR)? A 1600 dynes sec/cm5 B 30 Woods units C 1200 dynes sec/cm5 D 1200 mm Hg/m2 Preferred response: A Rationale SVR is calculated by (MAP CVP)/CO (70 10)/3 60/ 20 in Woods units Woods units are converted to dynes sec/cm5 by a multiplicative factor of 80 Thus 20 80 1600 dynes sec/cm5 A V C X Y A C V X • Fig 136.14 Y ... velocity decreases The effect of this will be to raise the systolic peak while accelerating the diastolic downslope of the pressure reading Mathematically the area under this curve will remain the... a combined action of displacing and inactivating anticoagulant thrombin from thrombomodulin In this way PAI-1 has important pathophysiologic effects in acute and chronic diseases Protein C acts... acetylcholine, bradykinin, histamine, insulin, and substance P stimulate NO production through this mechanism Similarly, shearing forces acting on the endothelium are another important mechanism