Ii. Open and Close Passively in Response to Pressure Changes

Physiology Review Sheet Cardiac Physiology

I. Cardiac Anatomy a. Valves i. unidirectional ii. open and close passively in response to pressure changes iii. atrioventricular valves 1. R= tricuspid 2. L = mitral 3. thin, require very little backflow to close 4. soft closure 5. larger opening iv. semilunar valves 1. R = pulmonic 2. L = aortic 3. massive, requires stronger backflow 4. snap shut 5. smaller opening increases flow velocity 6. subject to mechanical abrasion v. abnormalities 1. murmur – abnormal heart sound, usu resulting from left valve defect (can be right) 2. stenosis - failure of valves to fully open (narrowing) 3. insufficiency/regurgitant - failure to seal upon closure resulting in regurgitation of blood back into chamber b. Autonomic Nervous System in the heart i. all parts of heart innervated by adrenergic sympathetic fibers 1. inputs release NE 2. NE binds to β adrenergic receptors on cardiac muscle cells a. β1 b. sensitive to both epi and NE (more so than α) c. activates adenylate cyclase and produces cAMP 3. ↑ heart rate, AP velocity, and contractility ii. cholinergic parasympathetic fibers innervate SA node, AV node, and atrial muscle via the vagus nerve 1. release Ach 2. Ach binds muscarinic receptors on myocardium 3. ↓ heart rate at SA node 4. ↓ AP velocity at AV node 5. ↓ contractility of atrial contractions II. Pump Cycle overview (more detail later) a. Diastole i. ventricular filling ii. volume at end = EDV iii. pressure at end = EDP (develops in ventricles as walls are stretched) b. Systole i. ventricular contraction ii. entire volume not ejected – remaining volume = ESV iii. volume of blood ejected with each beat of the heart = SV iv. SV = EDV – ESV c. CO (ml/min) = HR (bpm) x SV (ml/beat) i. norms: 1. HR = 60 bpm 2. EDV = 150 ml 3. ESV = 75 ml 4. SV = 75 ml 5. CO = 4500 mL/min ii. Flow = P / R 1. CO = (Paorta – Pright atrium) / TPR III. Venous Return a. flow of blood entering heart b. highly variable c. autoregulation – heart will pump out volume received during diastole . . . CO=VR d. Frank-Starling Mechanism of the heart i. CO = VR ii. ↑ in diastolic fiber length due to increase in VR allows greater contraction to expel extra fluid iii. also balances output between two ventricles IV. Electromechanical Coupling a. electrical activity precedes mechanical contraction b. conduction velocities vary in different areas: Purkinje > atria > ventricle > AV node c. intrinsic rates differ: i. SA node = 70-80 bpm ii. AV node = 40-60 bpm iii. Purkinje fibers = 15-40 bpm d. contraction same as skeletal e. Ca2+ regulation i. ↑ [Ca2+]i will ↑ force development*** 1. catecholamines ↑ influx of extracellular Ca2+ via cAMP dependent phosphorylation of Ca2+ channels 2. cardiac glycosides poison Na+/K+ pump – accumulation of Na+ inside cell reverses Na+/Ca2+ exchanger so that less Ca2+ is removed from cell ii. ↓ [Ca2+]i will ↓ force development*** 1. ↓ extracellular Ca2+ 2. ↑ Na+ gradient across PM 3. Ca2+ channel blockers f. Other regulators i. Phospholamban 1. chronically ↓ SERCA pump 2. inhibited by phosphorylation by PKA (as a result of stimulation by catecholamines)  removes inhibition of SERCA ii. phosphorylation of troponin I 1. inhibits Ca2+ binding to troponin C 2. occurs via PKA iii. Na+/Ca2+ exchanger 1. removes Ca2+ from cell V. Control of HR a. ANS inputs i. sympathetic ↑ (NE ↑ Ca2+ conductance) ii. parasympathetic ↓ (↓ Ca2+ conductance) iii. alter rate of rise of pacemaker potential iv. conduction velocity through AV node influenced 1. sympathetic – ↑ velocity (positive dromotropic effect) 2. parasympathetic – ↓ velocity (negative dromotropic effect) b. other factors: extracellular ion concentration, hormones, physical influences (e.g. temp) c. factors ↑ HR = positive chronotropic factors d. factors ↓ HR = negative chronotropic factors VI. Control of SV a. ventricular EDV (preload - load delivered to the heart that sets the resting fiber length) i. ↑ preload causes ↑ in peak systolic pressure developed by LV b. afterload – load the ventricles must overcome to shorten and propel blood – MAP c. contractility (as it ↑, so does SV) VII. Cardiac Muscle Cell Mechanics a. Isometric contractions i. aka fixed-length ii. muscle develops tension but doesn’t shorten iii. ↑ muscle length will ↑ preload iv. total tension = active + resting tension 1. active tension depends on resting length of muscle 2. there is an optimal length for muscle tension generation (Lmax = 2.2 micron sarcomere length) 3. overlap of thick and thin filaments v. cardiac muscle usually operates well below Lmax*** so that increasing lengths ↑ tension development (not so with skeletal) 1. heart has a reserve that allows greater contractility when stretched with increased EDV (preload) 2. cardiac has no plateau phase in length-tension curve (skeletal does) 3. cardiac muscle develops greater passive tension when stretched to same degree as skeletal b. Isotonic contractions i. muscle shortens but doesn’t develop tension because it doesn’t have anything to contract against – muscle shortens against a constant load ii. aka fixed-tension iii. there is a length at which peak isometric tension is established based on how far the muscle can shorten iv. afterload 1. muscle must generate enough tension to isometrically hold the weight first 2. then can exceed that and shorten isotonically 3. contraction stops when inability to shorten decreases muscle’s ability to produce tension to isometric levels again v. total load = preload + afterload c. Force-Velocity Relationship i. velocity of initial shortening = tangent to initial slope of shortening curve ii. cardiac cells lift light weights faster than heavy ones 1. max velocity = 0 load 2. max force = 0 velocity (isometric) iii. ↑ preload (at a given afterload) increases initial velocity of shortening, but does not change max velocity at 0 load iv. ↑ in contractility produces an increased velocity of shortening at a constant muscle length (curve shifts up and to the right) d. Contractility i. vigor or forcefulness of contraction ii. degree of Ca2+ activation of muscle iii. isometric tension that a muscle can develop at a fixed length iv. increasing factor = positive inotropic effect v. decreasing = negative inotropic effect VIII. Factors affecting contractility a. positive inotropic agents i. sympathetic NE*** 1. most important regulator of contractility 2. ↑ both HR and contractility 3. ↑ force produced at every muscle length in both preloaded and afterloaded conditions ii. pharmacological agents (e.g. digitalis) iii. ↑ HR (tachycardia) 1. more Ca2+ entering myocyte during plateau phase 2. catecholamine/sympathetic stim – inward Ca2+ current ↑ 3. SR accumulates more Ca2+ for future release (via above and via phosphorylation of phospholamban via sympathetic stim increasing activity of SERCA) 4. Positive Staircase Effect a. aka Bowditch phenomenon, aka treppe b. HR doubles – contractility increases on each beat in staircase manner until reaches a max c. results from more Ca2+ accumulation 5. Postextrasystolic Potentiation a. extrasystole (abnormal extra beat) occurs with less than normal tension b. postextrasystole is greater than normal due to additional increment in amt of Ca2+ entering during extrasystole b. negative inotropic agents i. parasympathetic Ach ii. pharmacological agents (e.g. pentobarbital) iii. diseased myocardium iv. ↓ HR IX. Law of LaPlace***** a. T = P x r (or T = P x r/h for thick-walled chambers) b. diastole: ventricular r ↑ with little change in pressure because T increases proportionately c. isovolumetric contraction: T ↑ with no change in r  ↑ P d. systole: ↑P due to ↓ r and constant T e. isovolumetric relaxation: ↓P and T with constant r f. LV pressure-volume loop***(Understand this graph & what happens at each point)

X. Changes in preload, afterload, and contractility (factors determining myocardial shortening) a. general i. preload = end diastolic pressure ii. afterload = systemic arterial pressure iii. SV depends on shortening of muscle cells (depends on length-tension and load) b. if ↑ preload i. ↑ shortening ii. ↑ SV (heterometric autoregulation) via ↑ EDV (no change in ESV) c. if ↑ afterload i. ↓ shortening ii. ↓ SV via ↑ ESV (no change in EDV) d. if ↑ contractility (inotropic state) i. ↑ peak isometric tension (force that heart can develop at a fixed length) ii. important regulator: NE from sympathetic stimulation 1. ↑ shortening by changing final muscle length (no change in initial) 2. ↑ SV (and C.O.) by ↓ ESV without affecting EDV – homeometric regulation of C.O. e. stroke work i. stroke work = P x SV ii. area of LV pressure-volume loop iii. ↑ with ↑ SV (volume work) or ↑ afterload (pressure work – more energy used) f. minute work (power) i. minute work = HR x SV x P ii. ↑ with ↑ BP, HR, and/or SV iii. ↑ with ↑ EDV or ↓ ESV XI. Starling Curve (Cardiac Function Curve) a. ability of heart to alter C.O. with change in EDV (preload) b. if afterload and contractility are constant, preload is major determinant of SV c. if HR is held constant, y-axis = C.O. d. reality: HR, afterload, and contractility change every few beats e. ↓ afterload or ↑ contractility shift curve to L (and vice versa) i. point on curve determined by preload

XII. Starling’s Law balancing L and R heart outputs a. over short periods of time L heart output = R heart output (not same with each beat) i. R heart output ↑ with inspiration ii. so ↑ filling of L heart iii. so ↑ LV output b. 2/3 circulating blood is systemic; 1/3 pulmonic XIII. HR and SV in ↑ C.O. a. contributions not equal b. ↑ HR has greater influence on ↑ C.O. during exercise (SV can only increase so far . . . further ↑ comes from ↑ HR) c. note: very high HR can decrease SV due to impaired filling without changes in contractility XIV. Central venous pressure (CVP) a. peripheral venous pool: systemic blood (2/3) b. central venous pool: in great veins and RA (1/3) c. ↑ in peripheral venous constriction  ↑ central venous pool  ↑ CVP  ↑ cardiac filling d. VR = CO = rate at which blood enters central venous pool i. change in VR changes CVP to adjust C.O. XV. Venous return curve *** KNOW WHY SHIFT FROM CURVE TO CURVE AND POINT TO POINT

a. Q = dP / R (pressure gradient between 2 pools / resistance in veins) b. mean circulatory pressure (MCP) = value of CVP when VR =0 c. at very low CVP (below intrathoracic prssure)  veins collapse and restrict VR d. slope determined by resistance in veins (↓ resistance  steeper curve) e. if CVP = peripheral VP, VR =0 at any resistance level XVI. Effects of peripheral venous pressure (PVP) on VR a. pressure gradient between PVP and CVP determines VR b. PVP ↑ by i. ↑ in circulating blood volume in compliant veins ii. ↑ in venous tone via sympathetic vasoconstriction c. ↑ PVP will shift VR curve up and to right (and vice versa) XVII. C.O. and VR determined by CVP a. CVP is always driven to value that makes C.O. = VR b. norms: CO = VR = 5L/min @ CVP = 2 mm Hg c. all C.O. changes result from shift in CO and/or VR curve d. response to hemorrhage (see VR/CO curve above) i. PVP falls  shift VR curve to L ii. without fluid shifts, CVP falls and C.O. shifts to new intersecting point iii. ↓ CO causes ↑ sympathetic stimulation which ↑ CO on same curve, but further ↓ CVP (no direct change in VR from symp stim of heart) iv. ↑ symp stim of veins  vasoconstriction  shifts VR to R  ↑ CO by ↑ CVP at new intersecting point XVIII. Estimates of Cardiac Function a. Fick Principle i. pulmonary arterial blood flow = O2 consumption / ([O2]pv – [O2]pa) ii. note: pulm. a. blood flow = C.O. iii. note: pv blood is arterial and pa blood is mixed venous b. indicator-dilution i. dye dilution 1. indicator injected into large vein 2. CO = (mg dye x 60s/min) / (avg [dye]/ml blood x duration of curve (s)) ii. thermodilution 1. indicator: cold saline 2. advantages a. no extrapolation b. no arterial puncture c. repeated expts can be done d. recirculation is negligible c. cardiac index i. CO depends on body size (esp body surface area) ii. index = CO / m2 surface area d. imaging i. echocardiography ii. cardiac angiography iii. radionuclide ventriculography XIX. Estimates of Contractility a. ejection fraction i. EF = SV / EDV ii. efficiency of heart at expelling blood iii. usually 55-80% (avg 65-67%) iv. ↓ with congestive heart failure of LV b. imaging as described above to calculate end systolic pressure volume: pressure-volume in ventricle XX. Estimates of Cardiac Stroke Volumes a. catheterization: LV EDV and ESV determined (used to calculate others) b. forward SV = CO / HR c. total LV SV = EDV – ESV d. regurgitant volume = total LV SV – forward SV e. regurgitant fraction = (regurgitant volume / total LV SV) x 100 XXI. ***********Integrated Cardiac Cycle************* (KNOW THIS VERY WELL!!) a. LV diastole i. begins with closing of aortic valve (aortic pressure > LV pressure) – isovolumetric relaxation ii. opening of AV valves (LV pressure < LA pressure) iii. rapid ventricular filling when mitral valve opens iv. initial drop in atrial pressure as empties into ventricles v. then pressure in atria and ventricles ↑ as both fill (slow ventricular filling = longest phase = diastasis) vi. 2/3 of cardiac cycle is diastole vii. atrial contraction near end of ventricular diastole (P wave precedes) 1. ↑ atrial pressure 2. not essential for ventricular filling except at higher HR viii. throughout, atrial and ventricular pressures are almost the same due to open AV valves b. LV systole i. preceded by QRS complex (depolarization) ii. close mitral valve (and tricuspid = S1 heart sound) due to contraction of cells  ↑ LV pressure > atrium iii. sharp ↑ in LV pressure (isovolumetric contraction – shortest phase) iv. LV pressure > aortic pressure  open aortic valve  begin rapid ejection phase v. pressure ↑ in both LV and aorta in early systole – max out at peak systolic pressure vi. reduced ejection phase – still contracting, but at reduced rate – aortic pressure falls (T wave occurs) vii. at beginning of ejection, sharp decrease in atrial pressure due to stretching of heart; then pressure rises with filling viii. when LV pressure < aortic pressure  aortic valve closes (and pulmonic = S2) with snap  dichrotic notch (sharp dip in aortic pressure trace) due to rapid reversal of blood flow that occurs transiently when valve closes ix. ESV when aortic valve closes x. LV pressure falls rapidly (isovolumetric relaxation) xi. begin new cycle xii. 1/3 of cardiac cycle in systole XXII. Pressures a. diastolic pressure (DBP): lowest pressure reached at end of diastole (usu 80 mm Hg) b. systolic pressure(SBP): highest pressure reached during systole (usu 120 mm Hg) c. pulse pressure(Pp): SBP – DBP (usu 40 mm Hg) i. proportional to SV ii. inversely proportional to blood vessel compliance d. mean arterial pressure (MAP) = DBP + 1/3 Pp e. heart chamber pressure values (mm Hg) (be able to tell where catheter is by pressures recorded) i. RA = 0-8 (CVP) ii. RV = 15-30 / 0-8 iii. PA = 15-30 / 4-12 iv. lungs (PCW) = 1-10 v. LA = 1-10 vi. LV = 100-140 / 3-12 (largest Pp here) vii. aorta = 100-140 / 60-90 f. PCW (pulmonary capillary wedge pressure) i. catheter in pulmonary artery occludes small pulmonary artery branch ii. approximates pressure of LA iii. determines LV preload (if ↑, leads to pulmonary edema) XXIII. Right Heart Cycle a. major difference is magnitudes of peak systolic pressures (R heart is low due to less resistance in lungs) b. pulmonary artery systolic and diastolic pressures: 24/8 mm Hg XXIV. Venous pulse trace (pressure in large veins near heart) (see graph above) a. a wave: atrial contraction b. c wave: onset of ventricular systole (impact of common carotid a. and initial bulging of tricuspid valve into RA) c. RA pressure falls with relaxation and downward displacement of tricuspid valve with systole of ventricles d. v wave: RA filling with closed tricuspid valve XXV. Coronary Blood Flow a. intro i. metabolism of heart almost entirely aerobic ii. oxygen requirements of heart are very high (increase 3-7X during exercise) iii. highly variable consumption of CO (5% at rest-20%) b. Oxygen Extraction i. O2 extraction = (O2 contentart – O2 contentvein) / O2 contentart ii. percentage of oxygen delivered that is removed and used iii. Fun facts: 1. O2 content = [Hb] x O2 carry capacity a. [Hb] = 14.7g/100mL (norm) b. O2 carrying capacity = 1.36 mL O2/g Hb (norm) c. fully saturated blood with normal [Hb] and O2 carrying capacity has O2 content of 20 mL O2 / 100 mL 2. typical oxygen extraction values a. body = ~ 25% b. resting heart = ~ 70% (extraction ratio) i. venous coronary sinus O2 content = 6 mL/100 mL ii. arterial [O2] = 20 mL / 100 mL iii. can only increase to about 80% under max extraction by decreasing venous [O2] to 4 mL / 100 mL c. Fick Principle revisited (see above for detail) i. increased demand for O2 can only be met by increased coronary flow ii. coronary blood flow increases in almost direct proportion to metabolic consumption of O2 by the heart d. Functional Anatomy of Coronary Circulation i. 2 main coronary arteries (aka epicardial) arising from aorta just behind valve leaflets 1. left main coronary artery a. left circumflex a. b. left anterior descending a. c. supplies anterior and lateral parts of LV 2. right coronary artery a. branches to RA and RV b. has a branch for SA node – infarct here can cause arrhythmias 3. lots of variation in branching a. 50% of pop are right dominant b. 20% are left dominant c. 30% have balanced branching of both arteries ii. inner 75-100 micron of endocardium receives nutrients via diffusion from blood in chambers iii. epicardial arteries eventually give off small branches of intramural arteries and capillaries 1. go from epicardium to endocardium 2. capillaries assoc with each cell of myocardium 3. capillaries feed into intramural veins which drain into large epicardial collecting veins a. RV venous blood drains into RA via the anterior cardiac veins b. most of LV venous blood (~75% total coronary flow) drains into coronary sinus which empties into RA i. can catheter coronary sinus to examine LV venous effluent c. 5% of LV venous blood drains into LV from venous ends of capillaries or deep, very small coronary veins (thebesian veins) iv. coronary collaterals 1. very few preformed in humans 2. allow direct arterial connections between 2 coronary arteries 3. preformed can only supply ~ 10% of normal flow 4. gradual occlusions allow collaterals to enlarge and provide near normal flow e. Coronary Blood Flow i. Flow = (Paorta – Pcoronary sinus) / R ii. can only increase to a max of 3-4fold iii. phasic changes of LV 1. flow greatly drops during systole because vessels are compressed 2. flow is significant during diastole – driving pressure for coronary flow is aortic diastolic pressure iv. RV 1. phasic, but not as much 2. not as much compression by less muscular walls v. subendocardial plexus 1. tissue pressure gradient develops in muscle during systole 2. subendocardial pressure is = ventricle pressure, while outer myocardium is only slightly greater than intrathoracic pressure 3. intramyocardial pressure compresses subendocardial vessels even more than outer epicardial vessels during systole – cuts off all flow to endocardium 4. result: flow during diastole must be greater in this plexus than in outermost arteries 5. very susceptible to injury f. Regulation of Coronary Blood Flow i. almost entirely via local mechanisms responding to local needs for nutrition 1. oxygen consumption is coupled to vasodilation 2. decrease in oxygen in heart stimulates local release of vasodilator from smooth muscle or endothelium 3. adenosine hypothesis a. adenosine is a potent vasodilator and product of ATP hydrolysis b. as ATP is broken down during muscle contraction in heart, adenosine diffuses across membrane and causes vasodilation 4. other possibilities a. pO2 b. intracellular pH c. prostaglandin metabolic products d. endothelial cell-derived NO e. or decrease in vasoconstrictor such as endothelin ii. sympathetic nerve stimulation 1. increased coronary blood flow 2. indirect: due to increased HR and contractility via NE 3. primary action is vasoconstriction iii. parasympathetic stimulation 1. vagus nerve dilates coronary resistance vessels 2. doesn’t increase coronary flow, though iv. autoregulation 1. ability of vasculature to maintain a constant blood flow despite changes in perfusion pressure 2. works in coronary system when perfusion pressures are between 60-140 mm Hg (cannot compensate outside that range) 3. corrections made by alterations in vessel diameter 4. myogenic theory a. autoregulation is intrinsic to vascular smooth muscle b. passive stretch causes contraction 5. another theory: a. changes in R are mediated by adenosine b. decreased pressure decreases flow and decreases adenosine wash-out g. Myocardial Oxygen Consumption i. LV work determined by: HR, tension during systole, and contractility ii. sources of energy at rest: 1. 60-70% FA 2. 30-40% CHO (including lactate and exogenous glc) 3. some AA and ketones iii. sources of energy during exercise: 1. lactate is a major substrate 2. FFA oxidation is inhibited by lactate 3. CHO provide 75% ATP