Unit 4 - Review of Heart Physiology Flashcards
what are properties of excitable tissues?
- membrane potential difference (Em, Vm)
- -inside negative resting membrane potential difference
- transmembrane electrochemical gradient
- -combo if chemical and electrical potential differences
- equilibrium potential (Nernst equation)
- conductance (ionic, inverse of resistance)
- ionic driving force (Vm - Eion) and current
what is the definition of conductance?
ability of ion to flow across cell membrane
what is the definition of current?
ionic charge carried by ion movement across membrane
what autonomically controls the heart?
GPCR (indirect ligand-gated channels)
what are the most important ion channels for the heart?
voltage gated (by membrane voltage of cell), because they are excitable tissues -activity dependent on membrane potential (Vm)
what are the major targets of cardiovascular drugs?
- anti-arrhythmic
- anti-hypertensive, anti-angina
what are major voltage-gated ion channel types? what class of drugs do you treat these with?
Na+: class I anti-arrhythmic K+: class III anti-arrhythmic Ca++: class IV anti-arrhythmic
what happens if there is faulty inactivation of voltage-gated ion channels in the heart?
cardiac arrythmias
how do the kinetics of voltage-gated ion channels differ?
different VG ion channels have different activation and inactivation kinetics
-do so during different phases of cardiac AP
explain the cardiac action potentials in “fast-response APs”, where they occur, what channels are active at each time, and whether they are inward (depolarize) or outward (hyperpolarize)
working myocardium: atrium, ventricle, and His-Purkinje (major active ionic current)
- Phase 0: depolarization; Na and CaT (both depolarize)
- Phase 1: early repolarization; To (fast and slow, hyperpolarize)
- Phase 2: plateau; CaL (depolarize), Kur (hyperpolarize)
- Phase 3: repolarization; Ks/r (slow and rapid, hyperpolarize)
- Phase 4 resting (diastole); K1 (not voltage-gated, but in background, hyperpolarize)
explain cardiac AP in “slow response APs”
pacemaker AP in sino-atrial and atrio-ventricular nodes -Phase 0: Ca++ dependent upstroke (CaL) -Peak: K (no phase 1 or 2) -Phase 3: downstroke -Phase 4: depolarization (f) no K1 or Na
why are there no IK1s in the pacemaker AP?
IK1 suppresses pacemaker ability
what is the membrane voltage in pacemakers?
not stable
what are the regional cardiac APs?
primary pacemaker (SAN): 60-90 bpm --> activate atria secondary pacemaker (AVN): 40-60 bpm --> activates His-purkinje Purkinje /tertiary pacemaker: 30 bpm --> activates ventricles
explain autonomic control of HR?
SAN > AVN > atrium > ventricle
- sympathetic (NE, E) –> increase If,CaL –> positive chronotropy (increased slope of phase 4)
- parasympathetic (ACh) –> increase IK,ACh, decrease If,CaL –> negative chronotrophy (suppress pacemaker, decrease slope of phase 4)
what is the excitation threshold for myocardial cells VS nodal cells?
MC: -65 mV
NC: -35 mV
what is the threshold potential (Vth) dependent on?
- resting membrane potential (Vm)
- -hypokalemia –> hyperpolarize –> increase threshold
- -hyperkalemia –> depolarize –> decrease threshold
- Na+ current availability (gNa)
- cell size (hypertrophic heart failure)
how does resting membrane potential affect cardiac excitability?
directly, via Na+ current availability and K+ conductances
-at most negative potential, one has the most Na channels
what is the resting membrane potential determined by?
dynamic balance of inward Na+ and outward K+ ionic currents
- this makes phase 4 constant
- RM membrane is 20x more permeable to K+ than Na+ ions
- thus, while it cannot be determined by Nernst equation (which only applies to one ion at a time), Vm normally follows Ek (Nernst potential for K+) with 95% accuracy
why are both hyperkalemia and hypokalemia arrhythmogenic?
net effect is increased excitability (if moderate hyper)
what occurs during hypokalemia? incidence?
increases threshold that should decrease excitability
- -but low [K]o causes low IK1 –> decreased conductance
- net effect is increased excitability
what occurs during hyperkalemia? incidence?
> 5.5 - 7 mM (moderate; 8% of clinical cases)
-depolarizes Vm –> decrease threshold –> increase excitability
> 7 mM (severe)
-depolarizes Vm even more –> increases threshold (b/c INa is inactive) –> decrease excitability
what is the functional refractory period? components?
minimum time duration after an AP for threshold stimulus to produce full response again
- divided into effective (absolute) and relative RP
- ERP: no AP may be elicited no matter how strong
- RRP: higher than normal stimulus will elicit AP with reduced amplitude and duration
what are the major determinants of conduction velocity?
- rate of phase 0 depolarization
- threshold potential (less negative Vth = slower conduction; more ICa, less INa)
- resting membrane potential (more negative Vth = faster conduction; more INa)
- gap junction conductance (2nd most important)
- -intercellular connectivity/conductance
- -site of cell-to-cell AP transfer
what does electric current require to complete circuit?
extracellular, internal, and gap junction resistances in closed loop circuit
where is an AP recorded?
between two adjacent cells
-delay = 100-200 us
explain the cardiac conduction sequence
complete w/in 1/4 of a second with every heartbeat
- AV node delay is critical to ensure atrial contraction finishes before ventricular contraction begins
- slow AV node conduction and recovery from refractoriness protects ventricles from supraventricular arrythmias –> essential life-saving function of AVN
what are the conduction velocities of:
- atria
- AV node
- His-BB
- Purkinje fibers
- ventricles
atria: 0.5 m/s AVN: 0.05 m/s His-BB: 2 m/s PF: 4 m/s vent: 0.5 ms
(fastest) PF > His-BB > atria/vent > AVN (slowest)
what happens if you block Ca,L?
blocked phase 2 = no cardiac contraction
what is active tension dependent on?
- AP duration (decrease together)
- sarcomere length (increase together)
what is AP duration dependent on?
frequency
explain excitation-contraction coupling for contraction
- Ca++ ions enter thru Ca,L channel
- Ca++ ions activate ryanodine receptor (CARC, RyR2)
- CaRC releases sarcoplasmic Ca++ into cytosol, initiates contraction
- CICR (Ca++-induced Ca++ release) involved
explain excitation-contraction coupling for relaxation
cytosolic Ca++ is reduced back to resting levels by SERCA (SR Ca++ ATPase) and NCX (sarcolemmal Na+/Ca++ exchanger)
what does increasing preload do to myocardial contractility?
increase together (w/in limits)
- stretching heart muscle increases sarcomere length and actin-myosin X-bridge sites –> increased active tension upon muscle contraction
- sarcomere length > 2.2 microns reduces crossbridge overlap
what does the Frank-Starling curve tell you about inotropy?
positive inotropy: SV increases as ventricular EDV increases
- occurs in exercise and at rest normally
- increased Ca,L and SERCA
- increased Ca++ sensitivity of contractile filaments
negative inotropy: SV decreases as VEDV increases
- occurs in heart failure and cardiogenic shock
- decreased Ca,L and SERCA
- decreased Ca++ sensitivity of contractile filaments
what does systolic dysfunction cause? chronically?
abnormal reduction in SV
- increased afterload
- decreased contractility
chronically:
- volume overload (mitral/aortic valve insufficiency; PDA, ASD, VSD)
- DCM (congenital or cardiotoxic)
what does diastolic dysfunction cause? chronically?
decreased ventricular compliance
- increased P/V relationship
- decreased Frank-Starling mechanism
chronically:
- pressure overload (HTN, aortic stenosis –> increased afterload)
- HCM (congenital or obstructive)
- RCM (increased filling pressure, reduced compliance, reduced ventricular volume)
what does the P wave represent?
atrial activation (phase 0)
what does the Q wave represent?
His, bundle branch, septum activation (phase 0)
what does the R wave represent?
ventricular (left) activation (phase 0)
what does the S wave represent?
late ventricular (right) activation (phase 0 in QRS, phase 2 in ST)
what does the T wave represent?
ventricular repolarization (direction is opposite of activation) -phase 2 in ST, phase 3 alone
what does the PR interval represent?
measure of AVN conduction
what does the QT interval represent?
ventricular AP duration
what does the U wave represent?
Purkinje repolarization
- hypokalemia (prolonged QT)
- hyperkalemia (decreased QT, sharper T wave)
what does the J wave represent?
occurs during ST segment
- hypothermia, hypocalcemia (decreased QT interval)
- hypercalcemia (increased QT interval)
what does the ST elevation represent? depression?
elevation: transmural infarct, coronary vasospasm (Prinzmetal)
depression: subendocardial ischemia, exertional (stable) angina
