Regulation of Cardiac Output

[1ST ORDER] What is cardiac output (CO)?

The volume of blood pumped by a ventricle per minute

[HIGH-YIELD][1ST ORDER] What is the equation for cardiac output?

CO = heart rate × stroke volume

[1ST ORDER] What two variables can be adjusted to regulate cardiac output?

Heart rate and stroke volume

[1ST ORDER] What factors influence an individual's cardiac output?

Age, body size, metabolic rate, and physical activity

[2ND ORDER] How does cardiac output change as oxygen consumption increases during exercise?

It increases to support greater metabolic demand

[2ND ORDER] How does cardiac index account for differences in body size?

It expresses cardiac output relative to body surface area

[2ND ORDER] At what stage of life does cardiac index tend to be highest?

Early in life, when metabolic demands are especially high

[2ND ORDER] How can cardiac output in elite endurance athletes compare with resting cardiac output?

It may increase dramatically, reaching approximately 25–30 L/min during intense exercise

[CALCULATION][2ND ORDER] HR is 80 beats/min and SV is 75 mL/beat. Calculate CO.

80 × 75 = 6000 mL/min = 6 L/min

[CALCULATION][3RD ORDER] CO increases from 5 to 8 L/min while HR remains 100 beats/min. What is the new SV?

8000/100 = 80 mL/beat

[1ST ORDER] What is chronotropy?

Regulation of heart rate

[1ST ORDER] What is dromotropy?

Regulation of cardiac impulse conduction velocity

[1ST ORDER] What is inotropy?

Regulation of myocardial contractile force independent of loading state

[1ST ORDER] What is lusitropy?

Regulation of the rate of myocardial relaxation

[DRAW/MAP] Match the four cardiac regulatory terms to their functions.

Chronotropy → heart rate

dromotropy → conduction velocity

inotropy → contractile force

lusitropy → relaxation rate

[1ST ORDER] Which cells primarily determine intrinsic heart rate?

SA nodal pacemaker cells

[1ST ORDER] Which ion current produces phase 0 depolarization in pacemaker cells?

Calcium influx

[1ST ORDER] Which ion current produces phase 3 repolarization in pacemaker cells?

Potassium efflux

[1ST ORDER] What is phase 4 of the pacemaker action potential?

Spontaneous slow diastolic depolarization toward threshold

[HIGH-YIELD][1ST ORDER] What three ionic changes contribute to pacemaker phase 4?

Funny current, decreasing potassium efflux, and increasing calcium influx

[2ND ORDER] Which ion predominantly enters through the funny current during pacemaker depolarization?

Sodium

[2ND ORDER] Why does reduced potassium efflux promote phase 4 depolarization?

It decreases the outward hyperpolarizing current

[2ND ORDER] Why does increasing calcium influx during phase 4 promote the next heartbeat?

It helps the membrane reach threshold sooner

[DRAW/MAP] Map the pacemaker action potential.

Phase 4 → funny current with net sodium entry + reduced potassium efflux + calcium entry → threshold → phase 0 calcium influx → phase 3 potassium efflux → repeat

[HIGH-YIELD][2ND ORDER] What three membrane properties determine how quickly a pacemaker cell reaches threshold?

Phase 4 slope, maximum diastolic potential, and threshold potential

[2ND ORDER] What happens to HR if phase 4 depolarization becomes steeper?

Heart rate increases because threshold is reached sooner

[2ND ORDER] What happens to HR if phase 4 depolarization becomes shallower?

Heart rate decreases because threshold is reached later

[2ND ORDER] What happens if the maximum diastolic potential becomes more negative?

More depolarization is required to reach threshold, slowing heart rate

[2ND ORDER] What happens if threshold potential becomes more negative?

Threshold is reached sooner, increasing heart rate

[2ND ORDER] What happens if threshold potential becomes less negative?

Threshold is reached later, decreasing heart rate

[3RD ORDER] A drug increases the slope of SA nodal phase 4 without changing threshold. What happens to HR?

Heart rate increases

[3RD ORDER] A drug hyperpolarizes the SA node without changing phase 4 slope. What happens to HR?

Heart rate decreases

[3RD ORDER] The SA nodal threshold shifts closer to resting membrane potential. What happens to firing frequency?

It increases

[DRAW/MAP] Map the three mechanisms of increased pacemaker firing.

Steeper phase 4 slope OR less-negative maximum diastolic potential OR more-negative threshold → shorter time to threshold → increased SA nodal firing → increased HR

[1ST ORDER] Which autonomic division increases heart rate?

Sympathetic nervous system

[1ST ORDER] Which autonomic division decreases heart rate?

Parasympathetic nervous system

[HIGH-YIELD][1ST ORDER] What receptor mediates sympathetic increases in heart rate?

Beta-1 adrenergic receptor

[HIGH-YIELD][1ST ORDER] What receptor mediates parasympathetic decreases in heart rate?

M2 muscarinic receptor

[1ST ORDER] What neurotransmitter activates cardiac beta-1 receptors during sympathetic stimulation?

Norepinephrine

[1ST ORDER] What neurotransmitter activates cardiac M2 receptors?

Acetylcholine

[2ND ORDER] What is a positive chronotropic effect?

An increase in heart rate

[2ND ORDER] What is a negative chronotropic effect?

A decrease in heart rate

[HIGH-YIELD][2ND ORDER] How does beta-1 stimulation affect the funny current?

It increases the current, accelerating phase 4 depolarization

[HIGH-YIELD][2ND ORDER] How does beta-1 stimulation affect calcium current in pacemaker cells?

It increases calcium influx, helping threshold be reached sooner

[2ND ORDER] How does a more-negative calcium channel activation threshold affect pacemaker firing?

It allows threshold to be reached sooner, increasing firing rate

[2ND ORDER] Does the lecturer require the molecular explanation for the beta-1-induced threshold shift?

No. Understand that a more-negative threshold is reached sooner

[HIGH-YIELD][2ND ORDER] How does M2 activation affect the funny current?

It decreases the funny current, slowing phase 4 depolarization

[HIGH-YIELD][2ND ORDER] How does M2 activation affect calcium current?

It decreases calcium influx, slowing depolarization toward threshold

[HIGH-YIELD][2ND ORDER] How does parasympathetic activation affect potassium current?

It increases potassium efflux, making the maximum diastolic potential more negative

[2ND ORDER] How does increased potassium efflux slow SA nodal firing?

It hyperpolarizes the cell, increasing the time required to reach threshold

[2ND ORDER] How can parasympathetic activity alter the calcium channel threshold?

It can shift threshold to a less-negative value, delaying activation

[DRAW/MAP] Map sympathetic positive chronotropy.

Norepinephrine → beta-1 activation → increased funny current and calcium current → faster phase 4 depolarization and earlier threshold → increased SA nodal firing → increased HR

[DRAW/MAP] Map parasympathetic negative chronotropy.

Acetylcholine → M2 activation → decreased funny current + decreased calcium current + increased potassium efflux → slower phase 4 and greater hyperpolarization → delayed threshold → decreased HR

[3RD ORDER] A beta-1 agonist causes the SA node to reach threshold more quickly. What happens to HR?

It increases due to positive chronotropy

[3RD ORDER] A patient receives a drug that increases SA nodal potassium efflux. What happens to HR?

It decreases because pacemaker cells become more hyperpolarized

[3RD ORDER] A drug reduces SA nodal calcium current and funny current. Which autonomic effect does it resemble?

Parasympathetic M2 activation

[4TH ORDER] A medication decreases phase 4 slope, increases potassium efflux, and delays threshold. Which receptor pathway does it mimic?

Cholinergic M2 muscarinic signaling

[4TH ORDER] During intense exercise, SA nodal phase 4 becomes steeper and threshold is reached earlier. Which receptor is primarily responsible?

Beta-1 adrenergic receptor

[1ST ORDER] What is the intrinsic heart rate without normal autonomic influence according to the lecture?

Approximately 100–110 beats/min

[2ND ORDER] Why is normal resting HR commonly below the intrinsic SA nodal rate?

Resting vagal tone suppresses SA nodal firing

[3RD ORDER] Why can withdrawal of vagal tone increase HR even before additional sympathetic stimulation occurs?

Removing parasympathetic inhibition allows the SA node to fire closer to its intrinsic rate

[1ST ORDER] What is a positive dromotropic effect?

Increased cardiac conduction velocity

[1ST ORDER] What is a negative dromotropic effect?

Decreased cardiac conduction velocity

[HIGH-YIELD][2ND ORDER] Which action potential characteristics influence conduction velocity?

The rate of depolarization and action potential amplitude

[2ND ORDER] How does beta-1 stimulation affect cardiac conduction velocity?

It increases conduction velocity, especially through calcium-dependent nodal tissue

[2ND ORDER] How does muscarinic stimulation affect conduction velocity?

It decreases conduction velocity

[2ND ORDER] Why do sodium channel blockers reduce conduction velocity in fast-response cardiac cells?

They reduce the phase 0 sodium-dependent upstroke

[2ND ORDER] How can ischemia or hypoxia decrease cardiac conduction velocity?

They can alter membrane potential and ion channel availability, reducing effective depolarization

[2ND ORDER] How can ischemia-associated hyperkalemia impair conduction?

Persistent depolarization inactivates voltage-gated channels and reduces effective action potential propagation

[3RD ORDER] A sodium channel blocker slows ventricular impulse conduction. Which action potential phase is most directly affected?

Phase 0 of fast-response action potentials

[3RD ORDER] A patient develops myocardial ischemia and slowed conduction. What ionic disturbance may contribute?

Local hyperkalemia causing membrane depolarization and channel inactivation

[DRAW/MAP] Map causes of negative dromotropy.

M2 activation → slower nodal depolarization

sodium channel blockade → reduced fast-response phase 0

ischemia/hypoxia → altered membrane potential and channel availability → slower conduction

[1ST ORDER] What are the three principal determinants of stroke volume?

Preload, afterload, and contractility

[HIGH-YIELD][1ST ORDER] What is preload?

Initial ventricular myocardial fiber stretch before contraction, commonly related to EDV

[HIGH-YIELD][1ST ORDER] What is afterload?

The pressure or load opposing ventricular ejection

[HIGH-YIELD][1ST ORDER] What is contractility?

The ability to develop force independent of initial fiber stretch or loading state

[2ND ORDER] How does increased preload affect SV in a normally functioning heart?

It increases SV through the Frank-Starling mechanism

[2ND ORDER] How does increased afterload affect SV when other variables are constant?

It decreases SV

[2ND ORDER] How does increased contractility affect SV when other variables are constant?

It increases SV

[DRAW/MAP] Compare increased preload, afterload, and contractility.

Increased preload → increased EDV → increased SV. Increased afterload → increased ESV → decreased SV. Increased contractility → decreased ESV → increased SV

[HIGH-YIELD][2ND ORDER] How does venoconstriction increase preload?

It decreases venous compliance and mobilizes stored venous blood toward the thorax

[2ND ORDER] How does increasing total blood volume affect preload?

It increases central filling pressure, venous return, and ventricular EDV

[2ND ORDER] How does decreasing HR potentially increase preload?

It allows more time for diastolic ventricular filling

[2ND ORDER] How does increased ventricular compliance affect filling?

More blood can enter the ventricle for a given filling pressure

[2ND ORDER] How can increased atrial contractility affect ventricular preload?

It enhances atrial contribution to ventricular filling

[2ND ORDER] How can increased lusitropy support ventricular filling?

Faster relaxation improves diastolic filling, especially at higher heart rates

[2ND ORDER] Why can increased afterload secondarily increase EDV on a later beat?

Increased ESV leaves more residual blood that contributes to the next filling volume

[2ND ORDER] Why can systolic heart failure produce high EDV despite poor pumping?

Impaired ejection and volume accumulation increase ventricular filling volume

[3RD ORDER] A patient receives a blood transfusion. What happens to preload, assuming other variables are unchanged?

Preload increases because circulating volume and venous return increase

[3RD ORDER] Sympathetic venoconstriction occurs without increasing total blood volume. How can preload still rise?

Stored venous blood is redistributed centrally, increasing venous return

[3RD ORDER] A patient's HR decreases, allowing longer diastolic filling. Which SV determinant may increase?

Preload

[4TH ORDER] A patient with systolic failure has elevated EDV but low SV. Why does this not contradict Frank-Starling physiology?

Severely impaired contractility limits the ability to convert increased filling into effective ejection

[DRAW/MAP] Map physiological mechanisms increasing preload.

Venoconstriction or increased blood volume → increased central venous filling → increased venous return → increased ventricular EDV. Slower HR, greater compliance, and stronger atrial contraction can also enhance filling

[HIGH-YIELD][2ND ORDER] Why does increased afterload reduce ventricular ejection?

The ventricle must generate greater pressure before opening the semilunar valve, leaving less effective ejection

[2ND ORDER] What happens to ESV when afterload increases?

ESV increases