The Heart As A Pump - physiological processes involved in cardiac pump function

Question 1

How many chambers does the mammalian heart have?

Colours?

Answer 1

4
RA (blood from body)
RV (pumps the o2-poor blood to the lungs)

LA (blood from the lungs)
LV (pumps the o2-rich blood to the body)

Right = blue
Left = red

The heart has a thick muscular wall, particularly in the LV

Question 2

The structure of Heart muscle?

Answer 2

Vena cava
RA > Tricuspid valve > RV > Pulmonary valve >
Pulmonary Artery

Pulmonary vein
LA > mitral valve > LV > aortic valve >
Aorta

Question 3

Cardiac cycle graph..
Reasoning for the dichortic notches in aortic pressure and atrial pressure

Why LAP continues dropping for a while even after the mitral valve has opened.

Answer 3

Aortic pressure
Atrial pressure
Ventricular pressure

Ventricular volume

ECG…

Systole: increase ventricular pressure, decrease in ventricular volume

Diastole: heart relaxing

Question 4

What is the muscular myocardium mainly made up of?

Answer 4

Mainly made up of cardiomyocytes. - has a v.limited capacity to regenerate (‘terminally differentiated’)

Question 5

Describe the process of regulating excitation-contraction coupling.

Answer 5

Depolarization of muscle cells activates the L-type Ca channel…
That Inflow of Ca activates another Ca channel (ryr-receptor)…
>Calcium-induced Calcium-release

This amount of Ca that’s available for contraction can be regulated in both directions: increase Ca = stronger contractile force

Note: This Ca oscillates bw the SR and cytosol on a beat-to-beat basis.
Back into SR thru protein SERCA2 - a key regulator of cardiac diastolic function

Question 6

How can the Excitation-Contraction coupling process be regulated?

(B-adrenergic stimulation = increase HR, increase in the strength of contraction, and increase in the rate of myocyte contraction + relaxation).
PKA - the common modulator - targets the proteins that are key regulators of each of these processes.

Answer 6

PLN inhibits the cardiac muscle SR Ca ATPase = decrease contractility and the rate of muscle relaxation.
However, when phosphorylated (by PKA), the protein is disinhibited = faster Ca uptake into the SR.
PKA activators: beta-adrenergic agonist Epinephrine. May enhance the rate of cardiac myocyte relaxation. In addition, since the protein is more active, increased contractility

> Adrenaline: increase HR + force of contraction via B1-receptors - due to phosphorylation, by PKA
Epinephrine: increase HR + force of contraction via B1-receptors (results in increase in cardiac output)
ACh: decrease HR + cardiac output etc via cholinergic (M2) receptors.

Question 7

3 ways how Heart rate & force of contraction can be regulated

Answer 7

> Adrenaline (hormone)
Sympathetic neural activation
ACh (parasympathetic)

Question 8

How can Excitation-contraction mechanism go wrong in diseases?

Answer 8

Eg: Ischemia. Decrease in ATP = Ca overload = cell death

Ischemia happens during heart attack or myocardial infarction (supply to myocardium is interrupted)

Cardiac diastolic function reduced, weak/ prevent next AP for next contractility

Question 9

Length-tension relationship

Answer 9

Because of the structure of the myofilaments of the muscle (where you have the thick + thin filaments sliding over each other) there’s a relationship bw the development of contractile force and the length of the sarcomere - and the repeating units of the thick + thin filaments where they overlap.
There’s an optimal sarcomere length in order to generate force of contraction, where you have maximum overlap of thick + thin filaments (myosin heads interacting w actin myosin in thin filament)

Question 10

What is the optimal sarcomere length in cardiac muscle?

Answer 10

~2.2 micrometer

Each sarcomere = contractile unit.
It is repeated many times in muscle cells

Question 11

The filament overlap explanation is unlikely to be the full story. What are the Other possible explanations?

Answer 11

> stretch-dependent sensitivity of Troponin C to Ca

> decreasing inter-filament spacing facilitating cross-bridge formation when myocytes are stretched.

Question 12

Preload?

Answer 12

If the muscle is sensitive to stretch, it means it’s responsible to these concepts…

Preload - LV wall stress/tension at End Diastole.

Therefore can apply LaPlace’s law!

Higher preload means there’s a higher diastolic volume in ventricle (so also a higher ED ventricular pressure)

Question 13

LaPlace’s law?

Apply this to Preload..

Answer 13

Wall stress (T) = (P * r) / 2w

r = r(in) + w

Pressure = mmHg
1mL = 1cm^3

V=P/Elastane (constant for a while, but goes up very quickly after a certain point

When the wall thickness of LV and Elastance are constant, people don’t need to use equation to know preload. They’ll know if it’s changed just by looking at change in pressure.

Question 14

Impact of stretching out heart cells?

Effect of (ED) preload on LV pressure during systole?

Answer 14

Increase stretching of heart cells essentially allows more myosin burning ATP and turning it into mechanical energy (how?).
>larger LV force of contraction

Via 2 mechanisms: Frank-starling & Inotropic

Force - pushing blood out against a certain area. Force/area=pressure
So larger force of contraction = large LV pressure (during systole)

Therefore a higher preload (set up the stretching of heart cells) = (as a result of 2 mechanisms) larger LV pressure during systole.

Question 15

Frank-starling mechanism

>idea of stretch relating to force.

Answer 15

Goal is to pull the Z-disks in closer to each other -myosin holding onto actin to bring Z-disks in.

Very low preload:
Titin has almost no space, myosin (crowded) almost touching the Z-disk = almost no force.
A lot of Myosin not grabbing the correct Actin (polarity). They’re blocked by the other Actin segment

High preload:
Z-disks have a lot of room
There is no actin overlap. = lots of force!

Too stretched:
No crowding issue
However, actin is out of reach. = no force

Question 16

What is Afterload

Answer 16

LV wall stress during ejection

LaPlace law not enough

Afterload (EJ) is proportional to pressure

Question 17

PV Loop analysis

Answer 17

Create a loop using EDPVR and ESPVR.
Name different stages in loop
>diastole
(Aortic valve closes) Isovolumetric relaxation + (Mitral valve opens) diastolic filling
>contraction
(Mitral valve closes) Isovolumetric contraction
>ejection
(Aortic valve open)

Question 18

Heart sounds

Answer 18

S1: closure of AV value - ‘Lub’
S2
S3: closure of Aortic valve - ‘Dub’
S4

Opening of a value doesn’t make a noise

Question 19

Cardiac output

Answer 19

Fick’s principle

Question 20

What are the 2 types of cells within the heart?

Answer 20

Cardiomyocytes - make up the atria + ventricles. These cells must be able to shorten and lengthen their fibers. Fibers must be flexible enough to stretch.
~100um long.

Pacemamaker cells - carry the impulses that are responsible for the beating of the heart, distributed throughout the heart

Question 21

What are the 2 cells types connected by?

Answer 21

All of these cells are connected by cellular bridges. Porous junctions called intercalated discs form junctions between the cells. They permit sodium, potassium and calcium to easily diffuse from cell to cell. This makes it easier for depolarization and repolarization in the myocardium. Because of these junctions and bridges the heart muscle is able to act as a single coordinated unit

Question 22

How long does a complete cardiac cycle usually take?

Pressure points at each chamber

Answer 22

~0.8 seconds

RA = 0-4 mmHg   LA = 8-10
RV = 25/4             LV = 120/10
PA = 25/10           Aorta = 120/80

Question 23

What are the 4 phases of the cardiac cycle?

‘Iso’ = same

Answer 23

Ventricular filling
Isovolumetric ventricular contraction ~0.05s
Ventricular ejection
Isovolumetric ventricular relaxation ~0.15s