PHSL 3051 cardiovascular

cardiovascular equations

the cardiovascular system - roles in homeostasis

• main transport system for delivering nutrients, removing wastes, distributing hormones and other signaling molecules

• temperature regulation

*to be biologically viable most cells in the body are within 10um of a capillary

components of the cardiovascular system

• heart: the biological pump; generates force to move the blood

  • 2 events for each beat: electrical (action potential) followed by mechanical (contraction)

• blood: the medium thigh through which O2 and nutrients are transported

• vasculature: the vessels through which the blood flows; they are not

blood

• total volume of blood, on average, is 5.5 liters

• plasma averages 55-58% of total blood volume, and is part of the ECF

• buffy coat: contains leukocytes (immune cells) and platelets (clotting

• erythrocyte (red blood cells) volume averages 42-45% called the hematocrit (mainly for gas transport)

overview of heart and vasculature

• 2 pumps (right ventricle RV and left ventricle LV) and 2 circulatory systems (pulmonary and systematic)

• parallel vascular beds vs vascular beds in series

• pressure differences between pulmonary and systemic circuits

• perfusion

• ischemia

perfusion

passage of blood flow through a vascular bed

ischemia

lack of oxygen/blood flow - typically due to an occlusion

size difference of the heart and vasculature

• wall of the LV (the myocardium - the muscle) is much thicker than the right. this allows the LV to generate greater pressure 

• the pressure in the systematic circulation is much higher than the pressure in the pulmonary circulation. the ventricles must generate enough pressure to create a gradient so that blood can flow (from high to low pressure)

parallel vs series arrangement of vascular beds

the pulmonary circuit is arranged in series, systemic is in parallel

• same quality of blood to all tissues

• allows for better regulation of blood flow

• takes less pressure than if arranged in series 

*total resistance across a system arranged in parallel is less than if the same system was arranged in series

receptors of the CV system

• muscarinic acetylcholine receptor (mAChR)

• nicotinic acetylcholine receptor (nAChR)

• alpha (a)

• beta (B)

pressure, flow, resistance

F (or Q) = flow (L/min)

ΔP = pressure difference between two points (mmHg) - its the gradient that matters, not the absolute pressures

R = resistance to flow (mmHg*min/L)

resistance

as resistance goes up, flow goes down

L = vessel length

n = viscosity of the blood

r = radius of vessel (to the 4th power)

purpose of heart valves

to promote one way direction of blood flow

2 types of heart valves (4 total)

1. atrioventricular valves (AV)

2. semilunar valves (SL)

*pressure gradients induce opening and closing of valves - a passive process

atrioventricular valves and function

1. right AV (tricuspid)

2. left AV (bicuspid; mitral)

prevent backflow from the ventricles into atria

semilunar valves

1. pulmonary semilunar valve

2. aortic semilunar valve

walls of the heart (inner to outermost)

1. endocardium

2. myocardium

3. pericardium

endocardium

• innermost layer of the heart

• separates chambers from the heart muscle (myocardium)

myocardium

thick layer of cardiac muscle

pericardium

• fluid filled sac that surrounds the heart, protecting it and providing lubrication

• epicardium separates the myocardium from the pericardial fluid

electrical connections between cardiac muscle cells (coordination of the heart beat)

• connected via gap junctions → provides rapid communication

• desosome

gap junctions

electrical synapse

desmosome

adhesive that holds neighboring cells together

functional syncytium

heart muscle cells are synchronized in health

cardiac myocytes

• striated 

• mostly mononucleated

• branched ends

cardiac vs. skeletal vs. smooth muscle similarities

• sliding filaments and cross bridges

• ATP powers the force generation

• elevated Ca2+ triggers contraction

cardiac vs. skeletal muscle similarities

• has sarcomeres

• striated

• has troponin

• T-tubules

cardiac vs. smooth muscle similarities

• pacemaker cells

• gap junctions (syncytium)

• Ca2+ entry from ECF

• autonomic/hormones modulate activity

• involuntary

sequence of blood vessels in the systemic circulation

arteries → arterioles → capillaries → venules → veins

conduction pathway

1. SA node (true pacemaker of the heart - these cells are the first to generate an action potential, beginning the electrical events of the cardiac cycle)

2. atrial contractile cells (atrial kick)

3. AV node (propagation is slow)

4. bundle of His (conducting cells)

5. bundle branches (conducting cells)

6. purkinje fibers (conducting cells)

7. ventricular contractile cells

timing of activation of the myocardium

• rapid conduction through the atria allows the atria to contract at essentially the same time

• AV Node delay gives the atria time to contract before ventricular excitation occurs

• rapid conduction through the interventricular septum

• depolarization of the ventricular contractile cells is almost simultaneous

action potential of a cardiac ventricular contractile cell

phase 0

depolarization

• fast Na+ channels open

phase 1

initial repolarization

• fast Na+ channels close

• transient (fast) K+ channels open

phase 2

plateau

• L type Ca2+ channels open (L for long) (same as DHP channels)

• transient K+ channels close

phase 3

rapid repolarization

• L type Ca2+ channels close

• slow K+ channels open

phase 4

resting membrane potential

• -80 to -90 mV in ventricular contractile cells 

• this phase is the pacemaker potential in some cell types

cardiac action potentials

• ventricle  

• atrium

• sinoatrial node

ventricle AP

atrium AP

SA Node AP

cardiac ion channels

the - indicates minimal/insignificant

describing excitation in the heart

• automaticity

• sinus rhythm

• latent pacemaker

• ectopic pacemaker

automaticity

• capable of generating spontaneous action potentials (pacemaker potential)

• Sa node, AV node, conducting cells

sinus rhythm

normal cardiac excitation sequence beginning at the SA node

latent pacemaker

• not actively driving

• includes AV node and conducting cells (cells that have pacemaker potential)

ectopic pacemaker

• abnormal

• any site/group of cells driving heart rhythm that is not the SA node

intrinsic firing rate

action potentials per minute

intrinsic firing rate - SA node

100-110

intrinsic firing rate - AV node

60-80

intrinsic firing rate - conducting cells

bundle of His - 40

Purkinje fibers - 15-20

cardiac muscle excitation-contraction coupling

• calcium induced calcium release (CICR)

• similar to smooth muscle

  • Ca2+ from the ECF entering the cell and causing additional Ca2+ release from the SR

cardiac muscle excitation-contraction coupling STEP 1

the membrane is depolarized by Na+ entry as an action potential begins

cardiac muscle excitation-contraction coupling STEP 2

depolarization opens L-type Ca2+ channels in the T-tubules

cardiac muscle excitation-contraction coupling STEP 3

• a small amount of “trigger” Ca2+ enters the cytosol, contributing to cell depolarization

• this trigger Ca2+ binds to and opens ryanodine receptors (RyR) located in the SR membrane (calcium-induced calcium release)

cardiac muscle excitation-contraction coupling STEP 4

• Ca2+ flows out of the SR into the cytosol, raising the Ca2+ concentration

• (for every 1 Ca2+ that enters cell through L-type channel, 10 Ca2+ are released from SR through RyR)

cardiac muscle excitation-contraction coupling STEP 5

binding of Ca2+ to troponin exposes cross bridge binding sites on thin filaments (actin)

cardiac muscle excitation-contraction coupling STEP 6

cross bridge cycling causes force generation and sliding of thick and thin filaments

cardiac muscle excitation-contraction coupling STEP 7

Ca2+ ATPase pumps return Ca2+ to the SR

cardiac muscle excitation-contraction coupling STEP 8

Ca2+ ATPase pumps (and also Na+/Ca2+ exchangers) remove Ca2+ from the cell into the ECF

cardiac muscle excitation-contraction coupling STEP 9

membrane is repolarized when K+ exits to end the action potential

refractory periods of cardiac muscle

1. absolute refractory period (ARP)

2. relative refractory period (RRP)

absolute refractory period

• the ventricular cell is completely refractory to fire another action potential, regardless of stimulus size

• fast Na+ channels are inactive and unavailable to carry inward, positive current

relative refractory period

• begins at the end of ARP and continues until the cell membrane has almost fully repolarized

• some amount of fast Na+ channels have recovered and are available to open (and carry inward current) again

the cardiac cycle - diastole

relaxation of the ventricles

• longer; 2/3 of time

the cardiac cycle - systole

contraction of the ventricles

• shorter; 1/3 of time

4 phases of the cardiac cycle (in reference to the LV by default)

• one cardiac cycle 

  • ventricular filling → diastole

  • isovolumetric contraction → systole

  • ejection → systole

  • isovolumetric relaxation → diastole

end product of each cardiac cycle

stroke volume (SV) - the volume of blood ejected from each ventricle per beat (mLs/beat)

• SV = End-Diastolic Volume - End-Systolic Volume

• SV = EDV - ESV

ventricular filling (diastole)

AV valves - open

aortic and pulmonary valves - closed

• ventricles fill with blood during diastole

• the initial period of ventricular filling is passive; blood passively moving from atria to ventricles

• followed by “atrial kick” (atrial contract). this contributes to an additional 10-20% of blood to the ventricles

• the end of this phase is EDV

  • EDV = final volume of blood in the ventricle after filling (~135mLs at rest)

isovolumetric contraction (systole)

AV valves - closed

aortic and pulmonary valves - closed

• ventricles contract (corresponds to ECG event - QRS complex)

• 1st heart sound at the start of this phase (S1): “lub” caused by AV valves closing

• volume constant at EDV

• pressure in ventricles < pressure in aorta and pulmonary artery

• pressure in ventricles > pressure in atria 

ejection (systole)

AV valves - closed

aortic and pulmonary valves - open

• pressure in ventricles > pressure in aorta and pulmonary artery

• stroke volume: volume of blood ejected from each ventricle per beat (~70 mLs at rest)

• reach ESV

  • ESV = volume of blood remaining in the ventricle after ejection

• ESV = EDV - SV

isovolumetric relaxation (diastole)

AV valves - closed

aortic and pulmonary valves - closed

• 2nd heart sound at the start of this phase (S2): “dup” caused by semilunar valves closing

• volume constant at ESV

• pressure in ventricles < pressure in aorta and pulmonary artery

• pressure in ventricles > pressure in atria

ejection fraction and heart failure

• measure of the efficiency of the heart. typically measured in the LV

normal EF values

55-70% - values below can be indicative of heart failure

heart failure with reduced ejection fraction (HFrEF)

• traditional marker of heart failure

• could be indicative of systolic dysfunction

heart failure with preserved ejection fraction (HFpEF)

• the ventricle is stiff and has difficulty relaxing

• could be indicative of diastolic dysfunction

wiggers diagram

• chart includes

  • pressures

  • volumes

  • ECG

  • phases of cardiac cycle

• when pressure lines cross, important events occur (and valves open/close)

• LUB (AV valves close) and DUB (semilunar valves close) heart sounds are due to valves closing

diagram *memorize

cardiac output

• cardiac output (CO) is the volume of blood ejected from each ventricle per unit time

• it is the product of heart rate (HR) and stroke volume (SV), and is typically expressed as liters/min

• CO is flow! - volume of blood per unit time

1. autonomic innervation of the heart

majority (75-80%) of beta-adrenergic receptors in the heart are B1

effects of parasympathetic

• slower HR

• weaker atrial kick

• slower AV conduction

effects of sympathetic

• faster HR

• stronger contraction = increased CO

timing

• NE is immediate

• Epi supports NE effects and helps direct blood flow

2. control of heart rate

control of heart rate - resting individual

parasympathetic input = on

sympathetic = mostly off

control of heart rate - increased physical activity

decreased parasympathetic input

increased sympathetic input

3. control of stroke volume

a. due to changes in EDV (aka load)

b. due to sympathetic stimulation (increased contractility)

c. due to MAP (afterload)

3. control of stroke volume

a. due to changes in EDV (aka load)

length tension relationship

1. increase in EDV

2. causes stroke volume to increase

HOW?

• change filament overlap and spacing

• increase Ca2+ release from SR

• increase sensitivity of troponin to Ca2+

frank starling relationship

hearts stroke volume increases in response to a greater volume of blood entering the ventricles before contraction

• increased EDV leads to a stronger contraction

implications of the frank starling relationship

• control of ESV 

  • prevents ESV from increasing (thus preventing clots)

• matching of CO from LV and RV

  • outflow from right and left sides of the heart remain equal

• prevention of rise in venous pressure (venous return determines EDV)

  • prevents blood from backing up into veins/capillaries

  • helps regulate the size of the heart

importance of matching output between RV and LV

any mismatch can lead to circulatory failure

3. control of stroke volume

b. due to sympathetic stimulation (increased contractility)

• sympathetic stimulation results in increased SV without a change in EDV

*parasympathetic input does not directly impact the contractility of the ventricles (no/few m-ACh receptors on the ventricles)

increased sympathetic stimulation results in

• increased L-Ca2+ current (bigger trigger)

• more Ca2+ into cytosol

• more troponin saturation

• faster Ca2+ removal (via SR pump)

END result of increased sympathetic stimulation

a stronger, faster (briefer) contraction

autonomic nervous system - impact on the function of the heart

3. control of stroke volume

c. due to MAP (afterload)

• high mean arterial blood pressure (MABP) decreases stroke volume (assuming equal contractility and EDV)

• INCREASED AFTERLOAD = DECREASES SV

• increased pressure in arteries decreases the ability of ventricles to shorten

• similar concept to placing a heavier load on skeletal muscle

• for a healthy heart, afterload plays a minor role compared to other factors affecting CO

  • dilated cadiomyopathy

dilated cadiomyopathy

thinner wall results in increased afterload

wall stress (afterload)

control of stroke volume review

EDV (preload) - increases SV

contractility (sympathetic stimulation) - increases SV

afterload (~MAP) - decreases SV