Montemayor's DSA

Question 1

2 types of cardiac cells

Answer 1

contractile and autorhytmic

Question 2

contractile cells

Answer 2

perform mechanical work (99%)

Question 3

autorhythmic cells

Answer 3

initiate action potentials (1%)

Question 4

atuomaticity

Answer 4

Self-stimulating: Heart’s ability to initiate its own beat Cyclic depolarization of autorhythmic cells initiates electrical activity independent of neural input

Question 5

Order and timing of electrical events

Answer 5

a. SA node
b. Inter-atrial pathway
c. AV node
d. Common AV bundle (Bundle of His)
e. R & L Bundle branches
f. Purkinje fibers

Question 6

functional syncytium

Answer 6

Myocytes can conduct APs cell-to-cell and thus contract as a single unit: due to gap junctions (electrical synapses)

Question 7

average beats per minute for parts of conduction system

Answer 7

SA node- 60-100 bpm
Bundle of His- 40-60 bpm
purkinje fibers- 20-40 bpm

Question 8

Sinoatrial Node

Answer 8

Normal pacemaker of the heart. Spontaneously depolarizing SA nodal cells: origin of normal electrical impulse.
Cells in right atrium: junction between SVC and RA

Question 9

Interatrial tracts

Answer 9

atrial muscle conducts impulse radially from SA node through the RA.
Internodal pathway (SA node--> AV node
Anterior interatrial myocardial band (Bachmann's bundle): SA node --> left atrium.

Question 10

Internodal pathway

Answer 10

anterior, middle, posterior

SA node–> AV node

Question 11

Anterior interatrial myocardial band

Answer 11

Bachmann’s bundle

SA node –> left atrium

Question 12

AV Node

Answer 12

Atrioventricular node: connects atria to ventricular conducting system
Located posteriorly on right side of interatrial septum (near ostium of the coronary sinus)

Question 13

Bundle of His

Answer 13

Passes down right side of interventricular septum. Divides into R&L bundle branches

Question 14

Right bundle branch

Answer 14

Direct continuation of bundle of His–> down right side of IV septum

Question 15

Left bundle branch

Answer 15

Thicker than RBB, perforates IV septum.

Splits –> thin anterior division & thick posterior division

Question 16

Purkinje fibers

Answer 16

Arise from RBB and Anterior & Posterior LBB
Complex network of conducting fibers spread out over subendocardial surfaces of R and L ventricles
Linearly arranged sarcomeres (like myocytes)
Typically lack T-tubule system
Largest diameter cardiac cells
Fastest conduction velocity in the heart
Rapid activation of Endocardium –> Epicardium, Apex –> Base

Question 17

Pacemaker cells

Answer 17

SA node, AV node, Bundle of His and Purkinje fibers
action potentials per minute: 
SA node- 70-80
AV node- 40-60
Bundle of His and Purkinje fibers- 20-40

Question 18

what determines the pace?

Answer 18

autorhythmic cells which reach threshold first will drive the pace of the heart. If SA node is out, then AV node next at 40-60 bpm

Question 19

What is the result of SA nodal failure?

Answer 19

bradycardia

Question 20

how bradycardia results from SA node failure

Answer 20

SA nodal failure unmasks slower, latent pacemakers in the AV node or ventricular conduction system (escape beats or rhythms) → bradycardia
Example: Junctional rhythm (ectopic focus at the AV junction becomes pacemaker)

Question 21

fastest conduction done by?

Answer 21

purkinje fibers (larger diamter –> decreased resistance). Bundle branches.

Question 22

Slowest conduction by?

Answer 22

AV node: small diameter, increased resistance.
AV nodal delay: normal delay to allow time for optimal ventricular filling.
SA node
Ventricular myocytes

Question 23

AV block or prolonged nodal delay may cause?

Answer 23

ventricular bradycardia
Result in distal pacemaker sites generating the ventricular rhythm
Secondary pacemaker sites have a lower intrinsic rate than the SA node
(e.g., Purkinje fibers ~ 20 – 40 bpm: very slow)

Question 24

Normal order of ventricular depolarization

Answer 24

Step 1: AV node–> bundle branches
Step 2: IV septum depolarizes L–>R
Step 3: anteroseptal region depolarizes –> apex
Step 4: myocardium depolarizes from endocardium –> epicardium
Step 5: depolarization spreads from apex –> base via purkinje fibers
Step 6: ventricles are fully depolarized

repolarization occurs in the opposite order, and more slowly than depolarization phase

Question 25

significance of order of events in ventricular depolarization

Answer 25

Early contraction of the IV septum: Rigid anchor point for ventricular contraction Early contraction of the papillary muscles: Prevents prolapse of atrioventricular (AV) valves during ventricular systole Final depolarization from apex to base: Allows efficient emptying of ventricles into aorta and pulmonary trunk at the base

Question 26

describe cardiac muscle

Answer 26

sarcomeres: z line to z line striated- filaments (thick myosin and thin actin, troponin, tropomyosin) mononucleated intercalated disks: gap junctions (low resistance) many mitochondria t tubules & SR- calcium stores in ECF and SR Calcium regulation of contraction: binds troponin relatively slow speed of contraction

Question 27

Biomarkers of myocardial injury

Answer 27

troponin (cTnT, cTnI)- commonly used iomarker for cardiac damage. CK-MB- creatine kinase isoform specific to cardiac muscle.

Question 28

Electrical syncytium of the heart

Answer 28

If one cardiac cell depolarizes, all will eventually depolarize via: Gap junctions electrical connection (low resistance) allowing AP propagation cell-to-cell Normally, cardiac APs are conducted via the conduction system to the ventricles and then spread cell-to-cell Cell-to-cell conduction of APs is by ventricular myocytes is much slower than via Purkinje fibers

Question 29

clinical correlate of ventricular depolarization that spreads only cell-to-cell via Gap Junctions:

Answer 29

slower than following the normal pathway of the conduction system. This slower process of spreading a depolarizing current through the ventricles results in the widening of the QRS complex on an ECG Examples of arrhythmias where a widened QRS complex is commonly seen: Premature Ventricular Conductions (PVCs) Ventricular Tachycardia Atria and ventricles EACH form a functional syncytium--> contract as separate units

Question 30

All-or-None Law for the Heart:

Answer 30

Normally, either all cardiac cells contract or none do There is NO variation in force production via motor unit recruitment as in skeletal muscle Due to functional syncytium

Question 31

sources of calcium for cardiac contraction

Answer 31

Influx of extracellular Ca2+ is required for additional Ca2+ release from the SR (This is different from skeletal muscle) 2 Sources of Ca2+ in for Cardiac Contraction Ca2+ influx from ECF via voltage-gated L-type Ca2+ channels (DHPR) during long plateau phase (phase 2) of cardiac m. AP 2. Ca2+-induced (Ca2+-dependent) Ca2+ release from the SR via Ca2+- release channels (RYR) Release of Ca2+ from the SR also required Amount of Ca2+ from the ECF alone is too small to promote actin-myosin binding Ca2+ influx from the ECF triggers Ca2+ release from the SR

Question 32

Relaxation (diastole): removal of calcium by 3 pumps

Answer 32

Removal of Ca2+ to the ECF 1. 3Na+- 1Ca2+ antiporter [sarcolemma] Ca2+ removal against large gradient [Na+] higher in ECF, Na+ gradient powers Ca2+ removal 2. Ca2+ pump [sarcolemma] ATP used to extrude Ca2+ from cell against gradient Sequestering Ca2+ into the SR 3. SR Ca2+ pump (SERCA); Regulated by phospholamban (β-adrenergic mediation of phosphorylation increases SERCA activity)

Question 33

No Tetanus in Cardiac Muscle

Answer 33

Cardiac tetanus would be fatal because a sustained contraction would inhibit effective pumping of blood Long AP in cardiac muscle results in a long refractory period (Primarily due to L-type Ca2+ channels and slow, delayed K+ channel opening) Thus, relaxation of myocytes occurs prior to complete repolarization of AP such that ‘twitches’ cannot be summed like they can in skeletal muscle

Question 34

Resting membrane potential of cardiac cells

Answer 34

Pacemaker cells No true RMP “Maximum Diastolic Potential” Spontaneous slow depolarization phase (phase 4) Non-pacemaker cells True resting potential (~ - 80 to - 90 mV) (phase 4)

Question 35

Ion distribution

Answer 35

Membrane potential: Determined by ion concentration gradients and conductance (membrane permeability) Time-dependent changes in membrane permeability and ion conductance result in depolarization and repolarization Primary ions: Ca2+, K+ and Na+

Question 36

K+ contribution to RMP

Answer 36

Resting cell membrane is relatively permeable to K+ (Much more permeable vs. Na+ and Ca2+) Conductance to K+ (gK) is ~ 100x > conductance to Na+ (gNa)

Question 37

Na+ contribution to the RMP

Answer 37

RMP: Because gNa is so small in the resting cell, changes in ECF [Na+] do not significantly affect resting membrane potential (Vm)

Question 38

General properties of cardiac action potentials

Answer 38

Initiation time, shape, & duration of APs are distinct for cardiac cells of varied function within different cardiac regions AP propagation requires careful timing to synchronize ventricular contraction to optimize ejection of blood

Question 39

Main types of cardiac action potentials

Answer 39

Characterized by rate of depolarizing upstroke (phase 0) 1. Slow response: SA & AV nodes 2. Fast response: Atrial, ventricular myocytes & Purkinje fibers

Question 40

Fast response action potentials

Answer 40

``` Fast depolarizing upstroke (phase 0) Early, partial repolarization (phase 1) Plateau (phase 2) Final repolarization (phase 3) Resting potential (phase 4) ```

Question 41

slow response action potentials

Answer 41

Slow depolarizing upstroke (phase 0) Absent: early repolarization (phase 1) Absent: Plateau is less prolonged or absent (phase 2) Repolarization (phase 3) No true resting potential (phase 4)

Question 42

compare fast vs slow AP

Answer 42

Resting membrane potential (phase 4): More negative in fast- response APs vs. slow response (no true) Threshold potential: Slow-response threshold potential: ~ −40 mV Fast-response threshold potential: ~ −70 mV Greater slope of upstroke (phase 0), AP amplitude, and extent of overshoot in fast-response vs. slow response Conduction velocities: Slow-response (SA & AV nodes)

Question 43

major time-dependent & voltage-gated currents of cardiac APs

Answer 43

Na+ current (INa): Primarily responsible for the rapid depolarizing phase in atrial m., ventricular m., and Purkinje fibers Ca2+ current (ICa): Responsible for the “rapid” depolarizing phase in SA node and AV node Primarily responsible for plateau phase of fast-response APs Triggers contraction in all contractile cardiomyocytes K+ current (IK): Responsible for the repolarizing phase in all cardiomyocytes Pacemaker (“funny”) current (If): Responsible, in part, for pacemaker activity (slow depolarization phase) in SA and AV nodal cells and sometimes Purkinje fibers Funny channel = non-specific cation channel; primarily Na+ current

Question 44

Phase O

Answer 44

Upstroke Slow: if upstroke is only due to ICa Fast: if upstroke is due to both INa and Ica

Question 45

Phase 1

Answer 45

Early, rapid (partial) repolarization | Activation of minor K+ current (Ito = transient outward) Inactivation of INa or ICa (likely T-type Ca2+ channels)

Question 46

Phase 2

Answer 46

Plateau phase Continued influx of Ca2+ countered by small K+ current (Small, remaining Na+ current possible and a minor membrane current due to the Na-Ca exchanger)

Question 47

Phase 3

Answer 47

Final Repolarization | IK in all cells

Question 48

Phase 4

Answer 48

Electrical diastolic phase Changes in IK, ICa, and If produce pacemaker activity in SA and AV nodal cells Atrial and ventricular muscle have no time-dependent currents during phase 4

Question 49

parts that use many voltage-gated sodium channels and a large Na current

Answer 49

ventricular m., atrial m., and purkinje fibers

Question 50

Voltage-gated sodium channels

Answer 50

Closed at negative resting potentials Rapidly activate when membrane depolarizes to threshold Na+ influx mainly responsible for rapid upstroke of AP (phase 0) Inactivation gates close when membrane depolarizes Partial role in the early repolarization of the AP (phase 1) Within the range of positive voltages, a very small INa remains: prolongs plateau phase (phase 2) Magnitude of INa: impacts regenerative conduction of APs

Question 51

Sodium at the SA and AV nodes

Answer 51

If = “funny” or “pacemaker” current Activated on hyperpolarization Non-specific channel: ↑ Na+ and K+ currents Increased Na+ influx is primarily responsible for initiation of slow depolarization phase (phase 4)

Question 52

Calcium

Answer 52

ICa: all cardiac myocytes Majority: L-type Ca2+ channel (Long-lived, DHPR) Fewer T-type Ca2+ channels (Transient)

Question 53

Calcium at SA and AV nodes

Answer 53

ICa contributes to pacemaker activity (phase 4) ICa (influx) contributes to upstroke (phase 0) ICa is smaller than INa Nodal cells: slower upstroke vs. atrial & ventricular m.m. APs in nodal cells: slower conduction velocity because the smaller ICa depolarizes adjacent cells more slowly

Question 54

Calcium at the Ventricular m. Atrial m. and purkinje fibers

Answer 54

Smaller ICa adds to INa during the upstroke (phase 0) Ca2+ channels are closed at negative RMP Activate at more positive voltages (near upstroke peak, ∼1 ms) Inactivate (slower than Na+ channels, ~ 10 to 20 ms, time-dependent) Small ICa prolongs plateau (phase 2) 1° via L-type Ca2+ channels Ca2+ entering through L-type Ca2+ channels activates release of Ca2+ from SR via calcium-induced Ca2+ release in atrial & ventricular m.m.

Question 55

Potassium

Answer 55

All cardiac myocytes: Slow, delayed IK also contributes, in part, to relatively long cardiac APs IK: contributes to repolarization in all cardiac myocytes (phase 3) 2 major IK contribute to repolarization (there are other K+ currents): IKR : relatively rapid IKS : relatively slow IK: very small at negative voltages Slowly activates with depolarization (~ 20 to 100 ms), does not inactivate

Question 56

Potassium at SA and AV node

Answer 56

IK decreases at the end of phase 4, contributing to pacemaker activity (decreasing K+ efflux promotes depolarization)