PSL301 Cardiovascular System

Functions of the Circulatory System

1) transport substances to tissues, 2) remove byproducts, 3) adjust O2 and nutrient supply, 4) regulate body temp, 5) "humoral" communication

what is the pulmonary circuit

R ventricle --\> pulmonary trunk -\> pulmonary arteries (branches) -\> lungs pulmonary veins return O2 rich blood to L atrium

Systemic Circuit

L ventricle -\> Aorta (carries O2 rich blood) from L ventricle -\> branches with artery to each organ -\> arteries branch to arterioles and capillaries -\> then lead to venules

what is the heart composed of

myocardium muscle and pericardium (thin membranous sac that contains lubricant fluid)

what are the four valves of the heart

tricuspid, pulmonary, bicuspid (mitral), aortic

semilunar valves

cup-like leaflets: includes the pulmonary valve (btwn RV and aorta) and the aortic valve (btwn LV and aorta)

atrioventricular valves (AV)

fund btwn atria and ventricles and re-enforced by chordae tendinae attached to projections in the ventricles: includes the tricuspid valve (three leaflets on R AV junction) and bicuspid/mitral valve (on L AV junction)

what is the role of the chordae tendinae

hold the valves in place, preventing backflow into the atrium

why is the left ventricle more muscular

because it has to pump against high pressures in order to drive blood through the systemic circuit (against 120 mmHg)
versus the right ventricle (only against 40 mmHg)

what is the sequence of the path through the heart

Superior and inferior vena cava -\> R atrium -\> tricuspid valve -\> R ventricle -\> pulmonary valve -\> pulmonary trunk + arteries -\> pulmonary veins -\> L atrium -\> bicuspid/mitral valve -\> L ventricle -\> aortic valve -\> aorta -\> body

how is the cardiac muscle made up

syncytial network (branched connections of single nucleus myocytes) connected by intercalated disks (containing desmosomes and gap junctions), and aligned in parallel

what do desmosomes help with

force transfer (strengthening feature)

what do gap junctions help with

electrical connectivity (contain ports for specific ion transfer)

what is the role of the sarcoplasmic reticulum

storage of Ca2+ for AP -\> linked to plasma membrane by T-tubule invaginations

Cardiac muscle Excitation-contraction coupling steps

1) AP enters from adjacent cell
2) V-gated Ca2+ channels open
3) Ca2+ induces Ca2+ release through RyR
4) Local release causes Ca2+ spark
5) Summed Ca2+ sparks causes signal
6) Ca2+ ions bind troponin to shift tropomyosin off, so myosin can bind -\> initiate contraction
7) relaxation occurs when Ca2+ unbinds troponin
8) Ca2+ pumped back into SR
9) Ca2+ exchanged with Na+ by NCX antiporter
10) Na+ gradient maintained by Na+-K+ ATPase

what is the upstroke phase of a cardiac AP

the Na+ channels open and the membrane potential approaches E Na+

what is the downstroke phase of a cardiac AP

Na+ permeability decreases as Na+ channels inactivate and K+ channels open, so the membrane potential approaches E K+

propogation in the heart tissue

Na+ channels open which generates a local depolarization and activates adjacent Na+ channels to spread

What are the different durations of APs for different tissues

Nerves \= 1ms
Skeletal muscle \= 2-5ms
Cardiac muscle \= 200-400ms

Contractile AP

1. upstroke
2. Na+ channels close and fast Ka+ channels open
3. Ca2+ channels open and fast K+ channels close
4. Ca2+ channels close, slow K+ channels open (drive repolarization to RMP)
5. RMP

why is the refractory period long for cardiac muscle cells (as compared to skeletal muscle)

to prevent tetanus (summation of the APs) which would cause serious issues in the heart -\> so, the refractory period is almost as long as the muscle contraction

what is the membrane potential of myocardium stable at

-90 mV (b/c of higher number of K+ leak channels)

What are the two types of cardiac action potentials

1) Non-pacemaker (myocyte)
2) packe-maker (autorhythmic)

Myocyte cells

"fast response' APs -\> rapid depolarization response to AP
-contractile cells are "soldiers" \= await instructions
-location: make up most of the atrial and ventricular muscle wall

Autorythmic cells

unstable resting potential --\> slow depolarization causes spontaneous firing
-non-contractile cells \= provide the instructions
-location \= sinoatrial (SA) and atrioventricular (AV) nodes

what is the role of the funny current channels

cause unstable resting potential because they are permeable to both K+ and Na+
-\> Na influx \> K efflux

Role of Na+ in cardiac muscle cells

rapid depolarization phase caused by opening of Na+ channels

role of Na+ in pacemaker cells

slowly depolarizing pacemaker potential (If opening results in net Na+ influx)

Role of Ca2+ in cardiac muscle cells

influx prolongs the duration of the AP and produces a characteristic plateau phase

Role of Ca2+ in pacemaker cells

involved in the inital depolarization phase of the AP (move in)

What are the components of the intrinsic conduction system (wiring)

SA node, AV node, Bundle of His, Purkinje fibers

how are electrical signals conducted in the heart

SA node -\> internodal pathways -\> AV node -\> AV bundle -\> bundle branches -\> purkinje fibers

steps of conduction through the heart

1) SA node depolarizes
2) rapidly to AV node via internodal pathways
3) Depolarization spreads more slowly --\> conduction slows through AV node
4) depolarization moves rapdily through ventricular conducting system to apex
5) wave spreads upwards from apex

what is the role of the delay for depolarization at the AV node

allows completion of the contraction of the atria before the signal is passed on to the ventricles

what does the SA node control

sets the pace of the heartbeat (70 bpm)

what does the AV node control

routes the direction of electrical signals, delays transmission of AP, and can provide a backup to the heartbeat (50 bpm) under certain conditions (but slower than SA)

what is the role of the inert fibrous tissue barrier between the atrial and ventricular myocyte syncytia

to prevent the ventricles from beating too early in the activation process (separates the two - no gap junctions between them)

pathway of parasympathetic NS for heart rate

Lower heart rate
-activates the vagus nerve that innervates the SA node, releases Ach that binds to muscarinic receptors (M2R) in the SA node cells --\> significant vagal tone on SA (towards resting)

what does atropine do

antagonist --\> leads to an increase in heart rate of 20-40 bpm

what are the effector pathways of the parasympathetic signalling

1) GIRK activation by B beta-gamma
2) Galpha-i inhibition of adenylyl cyclase (decreased cAMP)
3) decreased cAMP/PKA activation of Cav
4) decreased cAMP activation of HCN (funny channel)

Sympathetic control of heart rate

increases heart rate
-need activation of symp. nerves innervating hte SA node
-release NE that binds to beta-adrenergic receptors (betaARs) on SA node cells
-can also be stimulated by circulating catecholamines released from adrenal gland during symp response

what does sympathetic activity result in

increased cAMP, increased PKA activity and increased Cav (L-type Ca2+ channels) and HCN (funny current) channel activity

how does sympathetic NS change the heart rate APs

makes them reach threshold faster and increases the number of APs per time frame

how does the parasympathetic NS change the heart rate APs

spreads out of the APs (by hyperpolarizing) --\> to slow the heart rate

which NS can change the contraction force and why

the sympathetic NS b/c it also innervates the atria and ventricles themselves, so can increase the force of contraction

what are the waves of the electrocardiogram

P wave, QRS complex, T wave

what does the P wave correlate to in the cardiac cycle

atrial depolarization

what does the PQ or PR segment represent

conduction through the AV node and AV bundle --\> the atria contract after the P wave

what does the R wave correspond to

signal reaches the purkinje fibers

what does the S wave correspond to

the signal spreads upwards from the apex towards the base

what does the ST segment represent

the contraction of the ventricles --\> slightly delayed manner compared to QRS

what does the T wave correspond to

ventricular repolarization

why is the T wave positive

the direction of repolarization is opposite the direction of depolarization in the *ventricles*

what does a normal P wave, and wide QRS mean

a third degree block --\> complete block: alternate pacemaker in ventircle... purkinje fibers, infarcted (embolus or thrombus?)

what does no P wave and irregular QRS mean

atrial fibrillation --\> normal conduction pathways through atria are lost and disregulated

what does no P wave and no QRS mean

ventricular fibrillation --\> ventricles beating fast but not producing blood flow

what does normal P, and normal QRS, but P not triggering QRS mean?

partial disconnect \= second degree heart block: AV node (prevents normal transmission on every cycle)

two phases of cardiac cycle

systole (ventricles contract) and diastole (ventricles relaxed)

how do the pressures differ between the two sides of the heart

events are the same on both, but pressures lower on the right

Mechanical events of the cardiac cycle

1. late diastole
2. atrial systole (atrial kick)
3. isovolumic ventricular contraction (AV valve shut)
4. ventricular ejection (semilunar valve open)
5. isovolumic ventricular relaxation (semilunar valve shut)

what does the dicrotic notch on the graph represent

aortic valve shuts \= creates small pressure wiggle

what are the heart sounds caused by

The first heart sound is a vibration following the closure of the AV valves \= "lub"
The second heart sound is a vibration created by closing the semilunar valves \= "dup"

Auscultation

listening to the heart through the chest wall with a stethoscope

what does A on a pressure volume loop represent

the start of the loop/cycle

what does B represent on a pressure volume loop

the end diastolic volume (or max volume)

what does the phase from B to C represent

the isovolumetric phase

what does C represent on a pressure volume loop

aortic valve opening

what does D represent on a pressure volume loop

end systolic volume (aortic valve closes)

what does the D to A phase represent in a pressure volume loop

isovolumetric relaxation

what information can PV loops provide

stroke volume, atrial filing pressure (preload), and aortic pressure (afterload)

what are values associated with ESV and EDV

ESV \= 65 mL
EDV \= 135 mL

what is the equation for stroke volume

SV \= EDV - ESV

what does stroke volume represent

amount of blood pumped by 1 ventricle in 1 contraction

cardiac output equation

CO \= HR x SV

what does the cardiac output represent

amount of blood pumped per ventricle per unit time
5L/min

what is normal blood volume

5L

what is the cardiac reserve

difference between resting and maximal CO (reflect the amount of extra CO used for extreme circumstances

what would happen with increased preload

increased SV and increased EDV

what would happen with increased afterload

decreased SV and increased ESV

what would happen with increased ionotropy

increased SV and decreased ESV

the large veins have...

high compliance and high capacitance

the large arteries have...

low compliance and low capacitance

Frank starling law

stroke volume increases as ADV increases \==\> length-force relationships is curved

how does an increased EDV lead to an increased SV

force generation is dependent on the amount of crossbridges that can form between the myosin headgroups and the actin filaments
-stretch increases the number of crossbridges and approaches the optimal sarcomere length

what happens with it surpasses the optimal sarcomere length

LV dysfunction (heart no longer pumping normally despite the blood given to it)

what is venous return affected by?

skeletal muscle pump, respiratory pump, and sympathetic innervation

what are the extrinsic factors influencing SV

an increase in contractility -\> which comes from an increased sympathetic stimuli, certain hormones and Ca2+ and some drugs

how can catecholamines modulate cardiac contraction

NE and Epi bind to Beta receptors which use cAMP pathway to phosphorylate V-gated Ca2+ channels (which allow influx of Ca2+) and phospholamban -\> which increases the activity of the Ca2+\=ATPas on SR to increase Ca2+ stores (which leads to a more forceful contraction) and remove it from the cytosol (which leads to a shorter duration of contraction)

What is the ionotropic effect?

the effect of NE on contractility of the heart --\> (b/c NE increases the amount of Ca2+ in the cells)
-can use ionotropic agents to increase or decrease ESPVR

How does the SympNS regulate HR

uses NE -\> Beta-receptors of autrorhythmic cells -\> increase Na+ and Ca2+ influx (increased I(f)) -\> increase rate of depolarization -\> increase HR

how does the parasympathetic regulate HR

uses Ach -\> binds muscarinic receptors -\> increased K+ efflux and decreased Ca2+ influx -\> hyperpolarizes the cell and decreases the rate of depolarization -\> decrease HR

what are the three layers of the blood vessels

1. tunic intima (endothelium)
2. tunic media (smooth muscle)
3. tunic externa (fibrous connective tissue)

what type of blood vessel has the most smooth muscle

arteries

what blood vessel was no smooth muscle

venule and capillary

what blood vessels have no elastic tissue

arteriole, capillary, venule

Windkessel effect

The expansion and contraction of compliant vessels. In the aorta the vessel expands and increases the volume within it, then when the pressure is reduced, the vessel is able to contract to push the remaining blood forward. No backward flow is allowed due to valves.

types of capillary beds

1) arteriovenous shunt
2) true capillaries

arteriovenous shunts

directly connects an arteriole to a venule (aka metateriole) --\> bypass highway

true capillaries

the nutrient exchange vessels -\> oxygen and nutrients into cells, CO2 and metabolic waste into blood
-1 cell layer htick

when the sphincters on the capillaries are open

the tissue is metabolically active