Download Cardiac Physiology

Physiology Review Sheet
Cardiac Physiology
I.
II.
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
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
III.
IV.
V.
VI.
VII.
5. CO = 4500 mL/min
ii. Flow = P / R
1. CO = (Paorta – Pright atrium) / TPR
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
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
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
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)
Cardiac Muscle Cell Mechanics
VIII.
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
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
IX.
X.
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
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)
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
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)
XIII.
c. note: very high HR can decrease SV due to impaired filling without changes in contractility
XIV.
Central venous pressure (CVP)
a.
b.
c.
d.
XV.
peripheral venous pool: systemic blood (2/3)
central venous pool: in great veins and RA (1/3)
↑ in peripheral venous constriction  ↑ central venous pool  ↑ CVP  ↑ cardiac filling
VR = CO = rate at which blood enters central venous pool
i. change in VR changes CVP to adjust C.O.
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.
b.
c.
d.
CVP is always driven to value that makes C.O. = VR
norms: CO = VR = 5L/min @ CVP = 2 mm Hg
all C.O. changes result from shift in CO and/or VR curve
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.
b.
c.
d.
e.
XXI.
catheterization: LV EDV and ESV determined (used to calculate others)
forward SV = CO / HR
total LV SV = EDV – ESV
regurgitant volume = total LV SV – forward SV
regurgitant fraction = (regurgitant volume / total LV SV) x 100
***********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 >
iii.
iv.
v.
vi.
vii.
viii.
ix.
x.
xi.
xii.
atrium
sharp ↑ in LV pressure (isovolumetric contraction – shortest phase)
LV pressure > aortic pressure  open aortic valve  begin rapid ejection phase
pressure ↑ in both LV and aorta in early systole – max out at peak systolic pressure
reduced ejection phase – still contracting, but at reduced rate – aortic pressure falls (T wave
occurs)
at beginning of ejection, sharp decrease in atrial pressure due to stretching of heart; then pressure
rises with filling
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
ESV when aortic valve closes
LV pressure falls rapidly (isovolumetric relaxation)
begin new cycle
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