First Pass Miss

Question 1

What is the purpose of Ik1 channel? How does it’s activity change?

Answer 1

It is the inward rectifier potassium channel. It’s activity decreases during the plateau phase to prevent rapid repolarization

Question 2

Where do IKur channels exist and why?

Answer 2

Atrial myocytes. (ultra rapid) They shorten the atrial action potential so the plateau phase isn’t is long since it is a thinner wall and is not as necessary for them to contract as long

Question 3

Where is the IKach channels vs IKatp?

Answer 3

IKach - atrial myocytes + SA/AV nodes, opens to shorten action potentials in atrial myocytes only

IKatp - atrial and ventricular myocyes - opens to shorten both atrial and ventricular in response to low ATP levels. (unbinds when the ATP/ADP ratio is low)

Question 4

Why is there always a slow diastolic depolarization in slow fibers?

Answer 4

There is no Ik1 inward rectifier channel to keep the membrane hyperpolarized

Question 5

What is the sequence of events leading to a cardiac slow fiber contraction?

Answer 5

If = Ifunny, nonspecific channels respond to membrane hyperpolarization when membrane potential goes below -50 mV. This is a nonspecific channel.

Inward flux from If causes a depolarization via the voltage gated calcium channels (slower AP rise than sodium channels)

K+ outward current via Ik starts immediately and ensures no plateau phase to re-hyperpolarize the membrane to start next cycle

Question 6

What channels mediate the activity of positive and negative chronotropic effects on pacemakers?

Answer 6

Positive - Sympathetic - increased activity of If + Ica channels to produce a higher sloping and thus quicker diastolic depolarization (phase 4). Ik activity is decreased

Negative - Parasympathetic - IKach channels keep the membrane more hyperpolarized so it takes longer to reach threshold potential. Also reduces Ica and If activity.

Question 7

What causes an early afterdepolarization (triggered activity)?

Answer 7

Typically at low HRs or altered electrolyte levels.

Due to another depolarization in relative refractory period since Ca+2 is no sufficiently cleared from the cytoplasm and repolarization via Iks is not as good at slow heart rates (we are sitting much closer to Ca+2’s threshold, giving enhanced automaticity)

Question 8

What causes a delayed afterdepolarization?

Answer 8

Typically with high heart rates / sympathetic activity, may occur due to genetic mutations causing increased intracellular concentrations and RyR dysfunction.

Question 9

What is depolarization-induced automaticity?

Answer 9

Something that occurs in ventricular or atrial myocytes that can be induced by never reaching resting potential (i.e. ischemia). Membrane potential sits close enough to Na+ or Ca+2 threshold to trigger a depolarization.

Question 10

What is first degree heart block characterized by?

Answer 10

PR intervals longer than 200 msec (slowed AV conduction)

Question 11

What are the two types of second degree AV block characterized by?

Answer 11

Mobitz I - gradually lengthening PR intervals so that a ventricular beat will be dropped

Mobitz II - normal PR intervals and random dropping of a beat

Question 12

What characterizes third degree AV block?

Answer 12

Complete dissociation between PR intervals and ventricular contraction, an ectopic pacemaker distal to the block of the AV node will cause the ventricular contraction

Question 13

What is atrial fibrillation vs atrial flutter?

Answer 13

Atrial flutter - a single ectopic firing that is propagated through a re-entry circuit. May not lead to a ventricular tachycardia if physiological AV block is good

Atrial fibrillation - One or more ectopic foci are firing causing to chaotic, discoordinated atrial depolarization and random conductions to the ventricles. May lead to clotting since blood is net not moved.

Question 14

What is the most common cause of Ventricular Tachycardia?

Answer 14

Re-entry, especially due to areas of slowed conduction (ischemic tissue during myocardial infarction)

Question 15

How can ventricular tachycardia be caused by the AV node?

Answer 15

AV nodal re-entrant tachycardia:
alpha-pathway is refractory due to premature atrial contraction
beta-pathway is slow-travelling but lower refractory period, stimulated on next normal AV rhythm.

beta to alpha pathway stimulates re-entry loop and Vtach ensues

Question 16

What causes WPW syndrome and does not lead to Vtach? What is the ECG finding?

Answer 16

Bundle of Kent -> area of reduced resistance in cardiac skeleton to bypass AV node.

PR interval will be slightly shortened and a delta wave will appear

Question 17

How can long QT syndrome lead to ventricular arrythmias? How is it diagnosed?

Answer 17

Diagnosed as QT interval greater than 0.46 seconds, due to failure to repolarize properly (decreased activity of Ikr or Iks. Also the sodium channels H gates may not be closing)

Can lead to arrythmias due to failure to fully repolarize and subsequent EADs.

Question 18

What is the difference in the appearance of the T wave between subendocardial and transmural ischemia?

Answer 18

Subendocaridal 1. Peaked T wave - due to shortening of plateau phase due to activation of Katp channels in subendocardium, bringing the transmural repolarization closer together (Lasley says the opposite)

Transmural 2. Inverted T wave - due to failure of Ito1 channels, so that repolarization happens the same way as depolarization (endocardial to epicardial), normally happens epicardial to endocardial

Question 19

What causes ST depression?

Answer 19

Subendocardial ischemia - A type of systolic injury current in which the healthy tissue is the epicardium so it depolarizes more. Positive charge flows from the epicardium to endocardium in plateau phase. V5 is a positive electrode that sees positive charge moving away from it, thus causing a depression.

Question 20

What causes ST elevation?

Answer 20

Transmural ischemia - positive charges flowing towards the injured epicardium results in a positive deflection

Question 21

What does LV necrosis cause on ECG?

Answer 21

Abnormally large Q waves because RV depolarization seems more significant whenever the LV wall is dead (no electrical profile).

RS complex not really seen, often has inverted T wave as well.

Question 22

What does hyperkalemia cause on ECG? this is counterintuitive

Answer 22

Peaked T wave - Increased rate of depolarize across entire ventricular wall -> increased extracellular K+ increases the conductance of Ikr channels.

Also makes sense -> slower phase 0 membrane is already slightly depolarized. Leads to longer QRS complex and thus longer QT interval.

Question 23

What does hypokalemia cause on ECG?

Answer 23

Opposite of hyperkalemia - shallow T waves, appearance of U waves

Question 24

What does left atrial hypertrophy cause in ECG?

Answer 24

A split P wave in V1. The second part is negative due to the large depolarization of the left atrium moving away from it (V1 is next to RV).

Question 25

What are the causes of the A, C, and V peaks of the venous pulse?

Answer 25

``` A = atrial systole - right atrial contraction (increases jugular backflow) C = isovolumic Contraction - increase in RA pressure due to bulge of tricuspid valve into RA V = increased Venous return due to pressure from systole ```

Question 26

Which of the semilunar valves opens earlier and closes later and why?

Answer 26

Pulmonic valve opens earlier and closes later due to less afterload from pulmonary artery.

Question 27

When is physiological splitting of S2 heard and why?

Answer 27

During inspiration, since there is a greater volume ejected in the lungs during inspiration and the P valve must stay open even longer (long difference between aorta and pulmonic valves). Lungs want more blood because of negative intrathoracic pressure from increasing the volume of the thoracic cavity, and increased venous return from IVC and SVC during inspiration.

Question 28

What is the function of PKA in cardiac muscle contractility?

Answer 28

Stimulated by B-adrenergics, it phosphorylates: 1. L-type Ca+2 channel for greater influx 2. Phospholamban -> increases SERCA activity 3. Troponin I -> reduces affinity of TnI for TnC 2/3 decrease the time of contractions at fast HRs.

Question 29

How is stroke work defined?

Answer 29

Stroke work = stroke volume * mean arterial pressure

Question 30

How does Pulmonary Capillary Wedge Pressure approximate pre-load?

Answer 30

It is the pulmonary artery diastolic pressure, which is a good estimation for LA pressure = LV end diastolic pressure

Question 31

Why does left atrial hypertrophy often happen during aortic stenosis?

Answer 31

LV hypertrophy decreases the compliance of the ventricle, causing the same volume of blood to exert a greater pressure on the wall (greater stiffness, less give from the wall). This forces the left atrium to push harder to meet that end diastolic pressure.

Question 32

Why might mitral insufficiency not actually decrease cardiac output significantly?

Answer 32

Backflow into left atrium leads to greater volume and pressure, which allows for more diastolic filling. This increases the preload and negates most of the losses during ventricular systole

Question 33

How does aortic insufficiency affect blood pressure and size of heart?

Answer 33

More blood backflowing after ejection -> left ventricular dilation and eccentric hypertrophy This increases preload -> greater systolic blood pressure max. Backflow decreases systolic pressure. Overall, blood pressure is higher.

Question 34

What receptor is normally affected by norepinephrine but is only affected by epinephrine at high concentrations?

Answer 34

alpha-adrenergic, for vasoconstriction

Question 35

What is the sympathetic neurotransmitter causing vasodilation in the fight or flight response?

Answer 35

acetylcholine

Question 36

What neurotransmitter controls skin blood vessel dilation during hyperthermia?

Answer 36

unknown

Question 37

How does decreased inhibition of the vasomotor center by baroreceptors increase blood volume in the longterm?

Answer 37

1. Vasomotor center stimulates vasopressin release which increases thirst, kidney reuptake, and vasoconstriction 2. SANS stimulates renin release, the ratelimiting step in angiotensin conversion. Angiotensin II also stimulates thirst

Question 38

How do O2 vs CO2 chemoreceptors differ?

Answer 38

O2: SANS response does not occur unless there are large drops in PO2 CO2: very tonically activity normally, and will increase more with higher CO2 / H+ levels

Question 39

What are the skeletal muscle metaboreflex / mechanoreflex?

Answer 39

Metaboreflex - Buildup of metabolites which stimulates SANS + vasopressin release Mechanoreflex - stimulates SANS with contraction of muscles