e26 SECTION XV Pediatric Critical Care Board Review Questions which eventually leads to pulmonary edema (answer C is incor rect) In this setting, the normal preload reserve has already been used to ma[.]
e26 S E C T I O N XV Pediatric Critical Care: Board Review Questions which eventually leads to pulmonary edema (answer C is incorrect) In this setting, the normal preload reserve has already been used to maintain stroke volume (answer D is incorrect) Afterload reduction in this context is useful because a small decrease in afterload results in a large increase in stroke volume and large decrease in end-diastolic volume (EDV) and end-diastolic pressure (EDP) There is a relatively flat slope of the maximal ventricular elastance line, NOT a steep slope Answer A is incorrect Pressure I V0 A D Volume The true statement concerning endothelins is: A Bosentan is an endothelin agonist B Endothelins act on ET-A receptor and cause vasodilation C Endothelins act on ET-B receptor and cause vasoconstriction D Endothelins cause either vasoconstriction or vasodilation Preferred response: D Pressure I D EDV V0 B Pressure Volume EDV EDV V0 C I II Rationale In all except young infants, the preferential source of energy for myocardial function comes from the b-oxidation of long-chain fatty acids After fatty acids enter the cell, they are activated to fatty acid (or acyl) coenzyme A (CoA) compounds by palmitoyl-CoA synthetase, then linked by carnitine palmitoyl transferase I to carnitine to form acylcarnitines, thus releasing CoA The acylcarnitines cross the mitochondrial membrane, and at the inner surface of the membrane another enzyme, carnitine palmitoyl transferase II, transfers the fatty acids back to CoA The fatty acids can now undergo b-oxidation with the production of ATP These enzymes also help transport acylcarnitine esters of CoA out of the mitochondria These esters are toxic in high concentrations Fetuses and neonates have decreased activity of carnitine palmitoyl transferase and palmitoyl-CoA synthetase, so glucose, lactate, and short-chain fatty acids are the preferred myocardial energy substrates at this age III Volume • Fig 136.1 The main difference in the fetal/neonatal myocardium compared with mature adult myocardium is: A Complete coupling of b adrenoreceptors to G-proteins B More b adrenoreceptors C More contractile components D Sparse, disorganized, and immature T-tubule and sarcoplasmic reticular system Preferred response: D Rationale The fetal/neonatal myocardium contains less b adrenoreceptors and less contractile components when compared to the adult myocardium There is incomplete uncoupling of b adrenoreceptors to G-proteins in the fetal/neonatal myocardium as well The T-tubule and sarcoplasmic reticular system of the fetal/neonatal myocardium are sparse and disorganized Except in young infants, the preferential source of energy for myocardial function comes from: A Glucose B Glycogen C Ketones D Long-chain fatty acids Preferred response: C Rationale The vascular endothelium elaborates the endothelins (ET-1, ET-2, ET-3), a family of compounds that are vasoactive, structurally related peptides ET-1 is the most potent vasoconstrictor known It also promotes mitogenesis and stimulates the renin-angiotensin-aldosterone system and the release of vasopressin and atrial natriuretic peptide These peptides act on one of two receptor subtypes: ET(A) and ET(B) ET(A) is located mainly on vascular smooth muscle cells and is responsible for mediating vasoconstriction and cell proliferation ET(B) is present predominantly on endothelial cells and mediates vasorelaxation, as well as ET-1 clearance Endothelins cause local vasoconstriction or vasodilation, depending on dose and location in the circulation Individual endothelins occur in low levels in the plasma, generally below their vasoactive thresholds This finding suggests they are primarily effective at the local site of release Even at these levels, however, they may potentiate the effects of other vasoconstrictors such as norepinephrine and serotonin Endothelin antagonists, such as bosentan, now are being used specifically in the setting of pulmonary arterial hypertension Regarding the regulation of vasomotor tone: A Adenosine causes vasoconstriction B Hypokalemia causes vasodilation C Hyperkalemia causes vasodilation D Neuropeptide Y causes vasodilation Preferred response: C Rationale Local metabolic regulation of vasomotor tone provides an ideal homeostatic mechanism whereby metabolic demand can directly influence perfusion Adenosine, which accumulates locally when tissue metabolism is high and tissue oxygenation is marginal, causes pronounced vasodilation in the coronary, striated muscle, splanchnic, and cerebral circulations Potassium is released from muscle in response to increased work, ischemia, and hypoxia Hypokalemia causes vasoconstriction Hyperkalemia, within the physiological range, causes vasodilation by stimulating KIr channels CHAPTER 136 Board Review Questions Pressure What does the segment “A” denote in the Pressure-Volume loop depicted in Figure 136.2 below? A Ejection fraction B End diastolic pressure C Ejection time D Stroke volume Preferred response: D A Volume • Fig 136.2 Rationale The figure depicts the pressure-volume relationship for a single cardiac cycle During diastolic filling, volume increases and diastolic pressure rises slightly because of the increase in passive tension At the end of diastole, isovolumic systole occurs, and ventricular pressure rises with no change in volume When ventricular pressure exceeds aortic pressure, the aortic valve opens, blood is ejected, and ventricular volume decreases Ejection ends, and pressure falls to diastolic levels as isovolumic relaxation occurs The pressure and volume reached at the end of systole are those that would have been attained by the isolated ventricle at that same end-systolic volume In other words, at a given volume, no higher pressure can be generated The decrease in volume during ejection is the stroke volume which, divided by the end-diastolic volume, gives the ejection fraction; normally, ejection fraction is greater than 65% 10 In what situation would the left ventricular (LV) pressurevolume relationship in a previously healthy 12-year-old be expected to change from loop abcd to loop abcd in Figure 136.3, below? A Blood transfusion B Hemorrhage C Myocardial contusion D Use of low-dose epinephrine Preferred response: C LV pressure (mm Hg) 200 dʹ cʹ d c 100 b bʹ aʹ a 50 100 LV volume (mL) • Fig 136.3 Rationale Loop abcd represents the pressure-volume relationship in an intact heart Contraction begins at the end-diastolic pressure and volume of point a Line ab represents isovolumetric contraction At point b, the aortic valve opens, since left ventricular (LV) pressure exceeds that in the aorta Ejection begins at point b and ends at point c At this point, the aortic pressure is equal to the maximal force produced by the ventricular wall for that specific endsystolic fiber length Isovolumetric relaxation starts at point c and the aortic valve closes The ventricular pressure drops (line cd) The mitral valve will open when LV pressure falls below left atrial pressure and blood will flow into the LV The difference between lines ab and cd is the stroke volume Point a represents preload and point b represents afterload Loop abcd reflects a decrease in contractility, which could be the result of myocardial contusion There is a decrease in stroke volume despite a larger end-diastolic volume at a similar level of LV pressure Afterload reduction and increase in inotropy (low-dose epinephrine or milrinone) would shift the PV curve to the left and upward A blood transfusion increases preload, resulting in an increase in stroke volume (see Figure 136.4 below, loop 2) The contractility has not changed (both end-systolic points are on the same line) 200 LV pressure (mm Hg) In all organs, sensory and efferent nerve endings contain nonadrenergic, noncholinergic (NANC) peptides, for example, neuropeptide Y, VIP, calcitonin gene-related peptide (CGRP), and substance P Neuropeptide Y is colocalized and released with norepinephrine, and VIP is colocalized with acetylcholine and released upon stimulation of vagal nerve endings Most of these peptides except neuropeptide Y are vasodilatory, and they help modulate blood pressure and regional flows e27 100 50 100 LV volume (mL) • Fig 136.4 11 At this same level of contractility, what strategies would restore the stroke volume for the patient with myocardial contusion and decreased contractility to his baseline? A Increase in preload and inotropic support B Increase in preload and vasoconstrictor therapy C Increase in preload and vasodilator therapy D Use of diuretics and inotropic support Preferred response: C e28 S E C T I O N XV Pediatric Critical Care: Board Review Questions Rationale In patients with decreased myocardial contractility, stroke volume can be restored with either an increase in preload (loop 4) or a decrease in afterload (loop 3) (see Figure 136.5, below) LV pressure (mm Hg) 200 100 50 100 LV volume (mL) • Fig 136.5 12 Loop in Figure 136.6, below, represents the pressure-volume loop in an intact heart The correct statement regarding the other loops (2 and 3) is: A Loop is reflective of a decrease in preload, as would occur with diuretics B Loop is reflective of a decrease in preload, as would occur with diuretics C Loop demonstrates the effect of increasing afterload D Loop demonstrates the effect of decreasing afterload Preferred response: C LV pressure (mm Hg) LV volume (mL) • Fig 136.6 Rationale The figure above represents the response of a normal heart to an increase in afterload Loop represents the normal physiologic pressure-volume loop Stroke volume is diminished in loop due to an increase in afterload Loop represents a compensatory response to the increase in afterload Contraction begins at a higher end-diastolic volume The heart ejects the same stroke volume at a higher afterload Even though the stroke volumes for loops and are the same, the ejection fraction is lower for loop 3, since the end-diastolic volume is increased Chapter 24: Regional and Peripheral Circulation The difference between autoregulated and maximal coronary flow is termed coronary flow reserve What does the coronary flow reserve indicate? A Maximal coronary artery vasoconstriction to meet increased demands for oxygen B Maximal cardiac oxygen consumption C Maximal ventricular contraction at any given coronary flow D The amount of myocardial blood flow that can increase at any given pressure in order to meet increased oxygen demands Preferred response: D Rationale At any given pressure, the difference between autoregulated and maximal flows is termed coronary flow reserve 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 Coronary flow reserve is normally lower in the subendocardium than in the subepicardium, and decreases in coronary flow reserve are always more profound in the subendocardium than in the subepicardium If autoregulated flow is normal but maximal flow is decreased, then coronary flow reserve will be reduced Coronary flow reserve also can be reduced if maximal flows are normal but autoregulated flows increase Nitric oxide (NO) is a labile humoral factor produced by nitric oxide synthase from l-arginine in the vascular endothelial cell Which of the following is true of nitric oxide? A Decreases significantly in the pulmonary vasculature immediately after birth B Is important in basal vascular tone, but less so for dynamic changes in vascular tone C Is increased in response to increases in shear/flow across endothelial cells D Produces vascular smooth muscle cell contraction by increasing the concentration of cGMP via the activation of soluble guanylate cyclase Preferred response: C Rationale NO is a labile humoral factor produced by NO synthase from L-arginine in the vascular endothelial cell NO diffuses into the smooth muscle cell and produces vascular relaxation by increasing concentrations of cGMP via the activation of soluble guanylate cyclase NO is released in response to a variety of factors, including shear stress (flow) and the binding of certain endothelium-dependent vasodilators (such as acetylcholine, adenosine triphosphate [ATP], and bradykinin) to receptors on the endothelial cell Basal NO release is an important mediator of both resting pulmonary and systemic vascular tone in the fetus, newborn, and adult, as well as a mediator of the fall in pulmonary vascular resistance normally occurring at the time of birth Dynamic changes in NO release are fundamental to the regulation of all vascular beds CHAPTER 136 Board Review Questions e29 Of the following agents, which has the most potent vasoconstricting properties? A Angiotensin II B Aldosterone C Endothelin-1 D Thromboxane A2 Preferred response: C pulmonary artery pressure These units are perfused in proportion to the driving pressure across them, which is approximately pulmonary artery pressure less vertical height (or critical closing pressure, whichever is higher) Zone III vessels lie at a vertical height less than outflow pressure Driving pressure across these units is independent of height because inflow and outflow pressures are comparably influenced by gravity Rationale Endothelin-1 (ET-1) is produced by vascular endothelial cells It has complex vasoactive properties, the most striking of which is its sustained hypertensive action ET-1 is the most potent vasoconstricting agent discovered, with a potency 10 times that of angiotensin II Humoral regulators of vascular tone include angiotensin, arginine vasopressin, bradykinin, histamine, and serotonin Of less importance are thyroxine, aldosterone, and antinatriuretic peptide Angiotensin plays a special role in the homeostasis of blood pressure and is produced in persons with hemorrhagic or hypovolemic shock It causes generalized vasoconstriction in both systemic and pulmonary circulations, but locally it stimulates the release of vasodilating prostaglandins in lung and kidney Bradykinin is a potent pulmonary and systemic vasodilator released locally by the action of the proteolytic enzymes on kallikrein after tissue injury Breakdown of phospholipids within vascular endothelial cells results in production of important byproducts of arachidonic acid, including prostacyclin (PGI2) and thromboxane (TXA2) PGI2 activates adenylate cyclase, resulting in increased cyclic adenosine monophosphate (cAMP) production and subsequent vasodilation, whereas TXA2 results in vasoconstriction via phospholipase C signaling 5 In which of the following vascular beds neural stimuli exert little effect on basal blood flow under physiologic conditions? A Cerebral B Coronary C Muscular D Pulmonary Preferred response: A Which of the West zones of the lung are effectively perfused in proportion to their height above the left atrium? A Zones I and II B Zone II only C Zones I and III D Zone III only Preferred response: B Rationale The inflow pressure of the pulmonary circulation is low, thus creating a vertical gradation to the distribution of blood flow in the lung Hydrostatic pressure must be adjusted for vertical height above the left atrium, both at the inflow and at the outflow of every alveolar capillary unit For example, given a pulmonary artery mean pressure of 20 cm H2O (zeroed at the level of the left atrium), an alveolar capillary unit 12 cm above the left atrium faces an inflow pressure of only cm H2O A left atrial pressure of cm H2O generates no opposing outflow pressure to an alveolar capillary unit more than cm above the left atrium Critical closing pressure of postcapillary vessels therefore sets outflow pressure for a unit 10 cm above the left atrium If intrinsic vascular resistance were identical throughout the lung, flow at any vertical height would be determined by hydrostatic driving pressure (inflow-outflow) and would be greatest at the base and least at the apex of the lung This phenomenon partitions the lung into three vertical regions, named West zones Zone I vessels are higher above the left atrium than pulmonary artery pressure and are not perfused by the pulmonary artery Zone II vessels lie above the height defined by the hydrostatic left atrial pressure but below the height of the Rationale In marked contrast to other vascular beds, neural stimuli have relatively little effect on basal cerebral blood flow (CBF) Cerebral vessels display extensive perivascular innervations, especially the sympathetic nerves arising from the superior cervical sympathetic ganglia, but the brain is well protected from circulating catecholamines by the blood-brain barrier Thus many of the vasoactive agents used in the critical care setting (a- and b-adrenergic agonists) have minimal effects on resting cerebral vascular tone Mild to moderate electrical stimulation, as well as surgical resection of both the sympathetic and parasympathetic nervous system, does not alter cerebral vascular tone under resting conditions However, vigorous sympathetic stimulation, as occurs with strenuous exercise or hypertension, does result in vasoconstriction of largeand medium-size cerebral vessels Thus a neurogenic mechanism may not mediate cerebral vascular resistance under normal conditions, but it does provide protection at times of stress Which of the following substrates can the brain use during periods of starvation? A Arginine B Glutamine C Glycogen D Ketones Preferred response: D Rationale At rest, cerebral blood flow is approximately 50 mL/100 g tissue/ Cerebral oxygen consumption is surprisingly high, averaging 3.2 mL/100 g tissue/min Glucose is the primary energy substrate, although ketones can be utilized during periods of starvation The brain has no functional capacity to store energy and thus is completely dependent on a steady supply of O2 because up to 92% of its adenosine triphosphate (ATP) production results from the oxidative metabolism of glucose Which of the following drugs should be used with caution in patients with increased intracranial pressure due to a risk of precipitating herniation? A Esmolol B Lorazepam C Nitroprusside D Pentobarbital Preferred response: C e30 S E C T I O N XV Pediatric Critical Care: Board Review Questions Rationale Nitroprusside and other nitric oxide donor compounds can dilate cerebral vessels This process greatly complicates the management of hypertension in patients with increased intracranial pressure In such patients, nitroprusside may reduce arterial pressure but raise cerebral blood flow and blood volume, thereby causing herniation Which of the following mediators has been implicated in the vasospasm following subarachnoid hemorrhage? A Adenosine B Carbon dioxide C Cyclic AMP (cAMP) D Endothelin-1 (ET-1) Preferred response: D Rationale Substance P, acetylcholine, oxytocin, ET-1, adenosine diphosphate, ATP, and prostaglandin cause nitric oxide (NO)-dependent cerebral vasodilation Impaired NO signaling is important in the pathophysiology of subarachnoid hemorrhage in which endothelial dysfunction has been well documented, leading to the important clinical problem of vasospasm ET-1 is an important mediator of cerebrovascular tone Both ETA and ETB receptors have been identified in the cerebral vasculature ET-1 given in high concentrations constricts cerebral vessels, probably via ETA receptor activation However, ET-1 given in low concentrations relaxes cerebral vessels via endothelial cell ETB receptor activation, a response that is NO dependent ET-1 has been identified as an important mediator of vasospasm following subarachnoid hemorrhage ET-1 levels are increased following subarachnoid hemorrhage In association with the increase in ET-1 levels are increases in ETA receptor levels, smooth muscle cell ETB receptor levels (which mediate vasoconstriction), and endothelin-converting enzyme activity Adenosine leads to cerebral vasodilation through an increase in cAMP and increases more than fivefold with hypoxia Adenosine is critical in CBF autoregulation Carbon dioxide plays a critical role in regulation of CBF A linear increase in CBF is seen with increasing Paco2, making CO2 one of the most potent known cerebral vasodilators Carbon dioxide exerts its effect via reduction in perivascular pH Arterial H1 cannot cross the blood-brain barrier, but CO2 can easily diffuse into the brain Perivascular acidosis dilates the cerebral vasculature, whereas alkalosis leads to vasoconstriction In the normal heart, which of the following regions is more prone to ischemia because of low perfusion pressure? A Right ventricle subepicardial regions B Right ventricle subendocardial regions C Left ventricle subepicardial regions D Left ventricle subendocardial regions Preferred response: D Rationale Myocardial perfusion over a cardiac cycle is normally approximately the same per gram of tissue in the outer (subepicardial), mid, and inner (subendocardial) layers of the left ventricle, but the dynamics during the cardiac cycle are complicated At the end of diastole, when the ventricle is relaxed and tissue pressures are probably less than 10 mm Hg in any layer of the left ventricle, pressures in the intramural arteries are probably similar to each other and to aortic pressure At the beginning of systole, tissue pressure rises to equal intracavitary pressure in the subendocardium but then falls off linearly across the wall to about 10 mm Hg in the subepicardium These pressures are for an instant added to those inside the vessels because the vessels’ walls are not rigid, and as a result, intravascular pressures in subendocardial arteries exceed aortic pressures, but aortic pressures are higher than are pressures in subepicardial arteries These pressure gradients and the greater shortening of subendocardial versus subepicardial muscle fibers during systole compress the subendocardial vessels and squeeze blood out of them both forward into the coronary sinus and backward toward the epicardium In fact, narrowing of the subendocardial vessels facilitates thickening and shortening of the myocytes This backflow enters the subepicardial arteries to supply their systolic flow In systole, some forward flow into the orifices of the coronary arteries does indeed occur, but this forward flow does not perfuse the myocardium; it merely fills the extramyocardial arteries In fact, there is often reverse flow in the epicardial coronary arteries In early diastole, blood flows first into the subepicardial vessels that have not been compressed, but it takes longer to refill the narrowed subendocardial vessels Given enough time and perfusing pressure, all the myocardium will be perfused, but if diastole is too short or perfusion pressure is too low, subendocardial ischemia occurs Right ventricular myocardium, on the other hand, normally is perfused both in systole and in diastole, because of lower tissue pressures 10 Based on the graph for pressure-flow relations in the left coronary artery during normal flow and maximal vasodilation, which of the following statements is correct? A Coronary vascular reserve is independent of perfusion pressure B For normal maximal flow, flow is uncoupled from metabolism C For normal autoregulated flow, flow is uncoupled from metabolism D For normal autoregulated flow, an increase in heart rate will increase maximal flow at any perfusion pressure Preferred response: C Rationale Coronary vascular resistance has three components: a basal low resistance in the arrested heart with maximally dilated vessels, an added resistance when vessels have tone, and a phasic resistance added whenever the ventricle contracts In the beating heart with vessels maximally dilated by a pharmacologic dilator, the second of these resistances is absent Perfusion of the left ventricular myocardium then produces a steep pressure-flow relation that is linear at higher flows but usually curvilinear at low pressures and flows (Figure 136.7) Because the vessels are maximally dilated, flow is uncoupled from metabolism and depends only on driving pressure and resistance If heart rate is increased, maximal flow at any perfusion pressure decreases because the heart is in a relaxed state for a smaller proportion of each minute If tone is allowed to return to the coronary vessels, then the pressure-flow relationship can be assessed at different perfusion pressures after cannulating the left coronary artery It is necessary to this because when cardiac metabolism and blood ... the epicardium In fact, narrowing of the subendocardial vessels facilitates thickening and shortening of the myocytes This backflow enters the subepicardial arteries to supply their systolic flow... help modulate blood pressure and regional flows e27 100 50 100 LV volume (mL) • Fig 136.4 11 At this same level of contractility, what strategies would restore the stroke volume for the patient... action of the proteolytic enzymes on kallikrein after tissue injury Breakdown of phospholipids within vascular endothelial cells results in production of important byproducts of arachidonic acid,