Download Cardiac physiology: mechanical events and regulation of cardiac

Cardiac physiology: mechanical events and regulation of cardiac function
*italicized = audio
Learning objectives
- review functional anatomy: chambers and nerves of the heart
- review concepts in cardiac physiology
- discuss the cardiac cycle events
o phases
o pressure and volume changes
o pressure volume loop
- calculate
o stroke volume, cardiac output, ejection fraction
- discuss effects of the following on cardiac output
o intrinsic regulation: preload, afterload, inotropy; Frank-Starling’s mechanism
o extrinsic regulation: ANS effects
- predict changes in cardiac function due to changes in factors that affect cardiac cycle events
Extrinsic nerves to the heart
- PNS
o R vagus – SA node
o L vagus – AV node
o Vagal efferents – atria, few in ventricles
- SNS
o Atria (SA node), ventricles and in conduction system of heart
Functional anatomy and pressures in chambers
- Aorta – 120/80 mmHg
- Pulmonary aorta – 25/10
- Left atrium – 8-10
- Left ventricle – 120/10
- Right atrium – 0-4
- Right ventricle – 25/4
*pulmonary circulation – low pressure circuit
*papillary muscles contract to resist outward flow (flap shouldn’t reverse)
Cardiac myocytes (review)
- striated, involuntary
- single nuclei
- branching network of cells with intercalated discs (gap junctions)
o points of low resistance
o allow cell to cell electrical conduction
o functional syncytium
- thick filaments = myosin
o (300 myosin/thick filament; 2 myosin heads/myosin molecule)
o 1 thick filament surrounded by 6 thin filaments
- thin filaments = actin + associated proteins (tropomyosiin, troponin)
o actin 2 helical strands
o tropomyosin – associated with 7 actin molecules
o troponin regulatory complex = troponin T (bound to tropomyosin), troponin C and troponin
I (bound to actin)
- titin anchorsmyosin to Z line; keeps it in center of sarcomere
- role of calcium
- bundles of myofibrils with myofilaments
- sarcomere – with think and thick filaments
Excitation contraction coupling: role of calcium
- basically a cycle of contraction and relaxation
- similar mechanism in skeletal muscle
- major difference is that in heart, the trigger is the initial Ca (Ca on phase 2 triggers release of Ca)
1. Ca enters the cell during depolarization (L type channels = trigger Ca) and triggers release of Ca
by terminal cisternae (from membrane) to the cytoplasm (via ryanodine receptors of Ca-release
channels in sarcoplasmic reticulum)
2. Ca binds to TN-C, inducing a conformational change in the troponin complex.
3. Myosin heads bind to actin, leading to crossbridge movement (require ATP hydrolysis) and
reduction in sarcomere length
4. Ca is resequestered by sarcoplasmic reticulum by the SERCA (sarcoendoplasmic reticulum
calcium ATPase) pump
5. Ca is removed from TN-C, and myosin unbinds from actin (requires ATP); this allows the
sarcomere to resume its original position, relaxed length
*Cardiac glycosides inhibit Na-K pump, which results in intracellular Na accumulation
(PICTURE OF EXCITATION CONTRACTION COUPLING)
(LOTS OF AUDIO C/O BRYAN)
Factors affecting cytosolic Ca
- increased by
o catecholamines
o increased extracellular calcium
o lower Na gradient across membrane
 lower extracellular Na
 raising intracellular Na (cardiac glycosides that block Na/K ATPase)
- decreased by
o lower extracellular Ca
o increased Na gradient across membrane
o Ca channel blocker
*level of intracellular calcium = affect force of contraction
Cardiac physiology: concepts
- excitability
o resting membrane potential; fast and slow fibers
- automaticity
o K leak and slow calcium channels (slow action potential fibers); pacemaker cells – SA
node
- conductivity
o SA node > atrial muscle > AV node > bundle of His > bundle branches > Purkinje fibers :
ventricular muscles
- contractility
o fast action potential fibers
(PICTURE OF CARDIAC CYCLE)
Cardiac cycle
1. Late diastole – both sets of chambers relaxed. Passive ventricular filling.
2. Atrial systole – atrial contraction forces a small amount of additional blood into ventricles.
3. EDV = end-diastolic volume. The maximum amount of blood in ventricles occurs at the end of
ventricular relaxation. EDV approximately 135 mL.
4. Isovolumic ventricular contraction—first phase of ventricular contraction pushes AV valves closed
but does not create enough pressure to open semilunar valves.
5. Ventricular ejection—as ventricular pressure rises and exceeds pressure in the arteries, the
semilunar valves open and blood is ejected.
6. ESV = end-systolic volume, or minimum amount of blood in ventricles. ESV approximately 65 mL.
7. Isovolumic ventricular relaxation—as ventricles relax, pressure in ventricles drops, blood flows
back into cups of semilunar valves and snaps them closed.
Cardiac cycle
1- atrial systole
2- isovolumetric contraction
3- rapid ejection
4- reduced ejection
5- isovolumetric relaxation
6- rapid filling
7- reduced filling
2-4 – ventricular systole
5-7 – ventricular diastole
Phase 1
- P wave > contraction
- AV valves open
o Atrial pressure >> ventricular pressure
- atrial contraction
o 10% of ventricular filling at rest; 40% at high HR because of inc atrial force even at dec
filling time
o May produce 54 (vibration of ventricle wall due to atrial contraction especially if ventricle
is stiff or not compliant [hypertrophy])
- “a” wave of jugular pulse (rise) – due to contraction of atrium
- “x descent” fall in atrial pressure – because valve opens
- end of phase 1 – LEDV = 120-140 mL
Phase 2
- initiated by QRS complex > ventricular contraction begins
- pressure in ventricles >> atria > AV valves close = S1 (pressures equalize, first heart sound)
- no change in volume but rapid rise in pressure
- semilunar valves closed
- “c” wave in jugular pulse (c = cusp)
o bulging of tricuspid valve leaflets back into RA
Phase 3
- semilunar valves open
o normally silent
o ejection murmurs = valve disease
- AV valves closed
- blood ejected from RV to pulmonary artery; LV to aorta; volume in ventricles decrease
- atria are in diastole—filling with blood from respective venous inflow tracts
Phase 4
- T wave > repolarization
o = relaxation begins
- ventricular pressure starts to decline
- semilunar valves still open because of kinetic energy of blood
- AV valves closed
- atrial pressure gradually rise due to venous blood return to atrial chambers
Phase 5
- ventricles continue to relax
o pressure in ventricles becomes much less than outflow tract pressures >
o semilunar valves close = S2
o S2 normally split – aortic before pulmonic
- LESV = 40-70 ml
o Volume in LV at end of systole
- LEDV-LESV = SV
o 70 to 80 ml/beat
- AV valves closed
o no change in volume; pressure rapidly declines
- ejection fraction = SV/EDV
o 60-70%
*patients asked to take deep breaths – pressure is low, more blood will return to vena cava
Phase 6
- pressure in ventricles << pressure in atria
o > AV valves open
o passive filling of ventricles due to opening of AV valves and rapid active relaxation of
ventricles
o “v” wave of jugular phase
o S3 – ventricular filling; normal in children; pathologic in adults (due to volume overload,
overload is hitting the heart, ventricular dilatation)
- semilunar valves closed
Phase 7
- passive ventricular filling nears its end >
o ventricles continue to fill with blood and expand > less compliant
o low HR – diastole is long = inc reduced filling; high HR > dec cycle length > dec diastole
than systole period
- AV valves open; semilunar valves closed
*cardiac endurance
Summary: cardiac cycle events
- atrial contraction or systole
o inc atrial pressure due to atrial contraction
 “a” wave in jugular vein
o opening of AV valves when atrial pressure exceeds ventricular pressure
 ventricular pressures:
 < 12mmHg in left ventricle;
 < 5mmHg in right ventricle; indicated in level of blood in jugular vein;
o upright individual, normal venous pressure is 6-7cm H2O; vein
distends in horizontal position
o AV valves close when atrial pressure is lower than ventricular pressure => S1
- ventricular systole
o contraction of ventricles with closed valves rapid rise in pressure
 > semilunar valves open
 > ejection of blood to outflow tract
o ventricular end diastolic volume VEDV = 120 to 140 ml
o ventricular end systolic volume = 40 to 70 ml
o stroke volume = 70 to 80 ml/beat
o ejection fraction = SV/EDV x 100 = 60-70%
- ventricular diastole
o ejection of blood during systole causes decreased volume
o repolarization of ventricles initiate relaxation > decline of pressure > closure of semilunar
valves
o contraction of atria together with ventricular relaxation lead to pressure difference
between atria and ventricles
o > opening of AV valves > filling of ventricles
Ventricular pressure-volume relationship: PV loop
*how much cardiac work is involved
(PICTURE OF TABLE)
Caption to table:
Line A – ventricle filling: increase in volume but minimal
Line B – isovolumetric contraction: no change in volume, rapid change in pressure
Line C – rapid ejection of ventricle
Line D – isovolumetric relaxation
Point 1 – mitral valve closes
Point 2 – aortic valve opens
Point 3 – aortic valve closes
Point 4 – mitral valve opens
Lines 3, 4, 1 - diastole
Lines 1, 2, 3 – systole
Regulation of cardiac function
- cardiac function = propel blood into circulation
o CO = SV x HR
o Intrinsic regulation – affects force of contraction and affects stroke volume
- preload (ventricular filling) > end diastolic volume > stoke volume
- afterload (aortic pressure), ionotropy (force of contraction) > end systolic volume > stroke volume
Preload
- length of sarcomere prior to contraction represents preload
- interplay between: end diastolic pressure, end diastolic volume, compliance
(PICTURE: INDEPENDENT EFFECT OF PRELOAD)
Factors affecting preload: ventricular compliance
- compliance = ratio of change in volume per unit change in pressure
- determined by physical properties of wall tissue
o thick wall (hypertrophy) > dec compliance; higher ventricular end diastolic pressure for
any given ventricular end diastolic volume
- relationship is nonlinear – compliance decreases with increasing pressure or volume
- ventricular compliance – determines end diastolic volume
- heart rate – affects filling time
- atrial contraction – at rest minimal; in exercise higher effect because of sympathetic effect on
atrial contraction force
- inflow resistance (valvular stenosis – tricuspid or mitral) – less blood transported from ventricle to
atrium
- ventricular contraction force – if dec > inc end systolic volume (ESV) > blood backs up in ventricle
Frank-Starling’s mechanism
- “increasing VR and ventricular preload leads to an increase in stroke volume”
- each curve is defined by afterload imposed on heart and inotropic state of heart
- inc afterload and dec inotropy > shift downward
- dec afterload & inc inotropy > shift upward
Importance of Frank-Starling’s mechanism
- balances output of right side of heart (pulmonary circulation) and left side of the heart (systemic
circulation)
-
inc venous return to RA > inc output of RV > pulmonary circulation > input to LA > inc output of
LV
Basis of Frank-Starling’s mechanism: effect of preload on length-tension relationship
- increase preload stretch > inc passive tension prior to stimulation; also inc development of active
tension and inc rate of tension development
- as preload increases, there is an increase in active tension up to a maximal limit == length of
sarcomere (2.2 micrometers); stiffness of cardiac muscles prevents stretch beyond 2.2
Afterload: outflow resistance
- the load against which heart must contract to eject blood = LV > aortic pressure
- increased afterload > dec stroke volume
o due to impaired emptying of ventricles
- effect of afterload on Frank-Starling’s mechanism
o increased afterload – shifts curve downward and to the right
o decreased afterload – shifts curve up and to the left
- effect of afterload on force-velocity relationship
o increased afterload slows down the velocity of muscle shortening
Inotropy
- inotropy = contractility > force of contraction
- changes in inotropy are due to intrinsic cellular mechanisms that regulate interaction between
actin and myosin independent of changes in sarcomere length
- usually associated with changes in available calcium for muscle contraction
Factors affecting inotropic state
- activity of autonomic nerves
- Anrep effect – abrupt increase in afterload can cause modest increase in inotropy; mechanism
unknown
- Bowditch effect, Treppe or frequency dependent activation – increase in heart rate can cause
small increase in force of contraction due to inability of the Na/K ATPase to keep up with the Na
influx at high frequency of action potentials leading to accumulation of intracellular calcium (in the
cardiac myocyte)
Factors regulating inotropy
- inotropic state
o (+) sympathetic activation
o (-) parasympathetic activation
o (+) afterload (Anrep effect)
o (-) systolic failure
o (+) heart rate (Bowditch effect)
o (+) catecholamines
Regulation of cardiac function
- extrinsic regulation: mainly affects HR; nerves to the heart thru ANS
o ANS: PNS – dec (Ach), SNS (NE) inc
o cardiac centers in medulla: CIC (-); CAC (+)
o higher centers: cerebral cortex, limbic system
o cardiac reflexes:
 baroreceptors – upright > decrease HR
 chemoreceptors – dec pO2 > increase HR
 Bainbdridge reflex (volume stretch RA > increase HR)
Factors: oxygen consumption
- heart rate
- inotropy
-
afterload
preload
-
Basal conditions: 8-10 ml oxygen/min/100 gm heart tissue
Oxygen content of cardiac venous blood 5ml/dL, increased cardiac oxygen demand is met by
increasing coronary blood flow
Increased cardiac work means increased oxygen demand
-
Energy source of cardiac work
- 35-40% of total cardiac O2 consumption for oxidation of carbohydrates
- major part of energy from oxidation of non-carbohydrate sources: esterified and non-esterified
fatty acids
Websites:
http://library.med.utah.edu/kw/pharm/hyper_heart1.html
cardiac cycle movie – msjensen.cehd.umn.edu/1135/Links/Animations/Flash/0028-swf_the_cardiac
human systems explorer (documentary). athome.harvard.edu/programs/hse/video/hse1_6.html