Control of CO (and blood flow)

Question 1

Describe how blood flow is regulated including the concept of autoregulation.

Question 2

Define cardiac output and describe its determinants.

Answer 2

Cardiac output is the rate of blood output of the left or right ventricle, measured in ml (or L) per minute.

Cardiac output = SV x HR

It can also be thought ot as total blood flow through the systemic or pulmonary circulation.

• Organ circulations are arranged in parallel with each other, therefore CO is the sum of all of the organ/tissue blood flows.
• Tissue blood flow (supply) is adjusted according to the tissue demands for blood.

Therefore, CO is determined by demands of the tissues.

Cardiac output can be adjusted by chainging either

• Stroke volume;_ _or
• Heart rate

Question 3

Describe the importance of the Frank-Starling mechanism.

Answer 3

The heart has a mechanism whereby if venous return increases, the stroke volume (and cardiac output) increases to match. This means that:

• The more blood returs to the heart, the more the heart fills
• The more the heart fills the more forcefully it contracts
• Therefore the more forefully it contracts the higher teh stroke volume (and therefore CO).

Preload, therefore is proportional to the volume of the ventricle at the end of diastole (EDV). High EDV means increased sarcomere stretch and increased force of contraction.

The Frank-Starling mechanism means that the heart autonomatically adjusts its own output to match flow requirements in the periphery.

A sudden increase in flow through the tissue results in a rapid increase in venous return to the heart, which responds by increasing the CO to sustain this increased flow to the tissues.

Question 4

Identify the determinants of stroke volume.

Answer 4

The stroke volume is determined by three variables:

1. Preload: the amount of blood that fills the heart before it contracts.
2. Afterload: the pressure that the heart has to work against during ejection
3. Contractility: the performance of the ventricle at a given preload and afterload.

Question 5

Describe the control of heart rate.

Answer 5

HR can be sped up by SNS (NAd and Ad) and slowed by PNS (Ach)

• The intrinsic firing rate in 100/min
• Resting HR is 60/min

Therefore, SA node is under resting PNS control (breaks are on). If you want to increase HR the first thing you can do is decrease vagal tone to SA node (take the breaks off).

To increase HR further we can increase SNS activation.

Also, physically stretching the SA node also increases HR.

• Mechanical stretching of the sino atrial node increases HR by up to 15%
• Therefore, the more venous return to the heart, the higher the HR and CO

Question 6

How is flow matched to demand?

Answer 6

1. Special receptors: skeletal muscle arterioles dilate in response to moderate levels of adrenaline.
2. Metabolic control: diffusion of metabolic waste (adenosine, ADP and AMP, K+ and H+) from active cells → vasodilation
3. Oxygen deficiency: oxygen uptake by active cells reduces local PO₂ → vasodilation
4. Nitric oxide: shear stress in arteries and arterioles causes their lining endothelial cells to release endothelium-derived relaxing factor (EDRF, mostly NO) → vasodilation
5. Longer term control: capillary density changes

Question 7

Why is flow not a passive reflection of pressure changes?

Answer 7

Metabolic mechanisms: actually this is just a restatement of the metabolic and oxygen mechanisms described.

Myogenic mechanisms: stretch-induces a reflex vascular constriction, prominent in arterioles.

Question 8

Mechanisms of the length tension relationship

Answer 8

In cardiac (and skeletal muscle) the initial length of the muscle sarcomere effects the tension generated in the subsequent contraction. Increased sarcomere length results in greater tension (and rate of contraction) of the subsequent contraction.

It was previously thought that the length-tension could be explained by more optimal overlap between actin and myosin fibres. It is now though that placing the sarcomere under more tension increases the sensitivity of troponin C to Ca2+ (ie increases excitation contraction coupling efficiency).

Question 9

Effect of filling time on stroke volume

Answer 9

When HR increases, time available for filling is reduced. This has little impact with moderate increases in HR as it is only the ‘reduced filling’ time that is affected.

CO is maintained as any reduction in SV is compensated for by an increase in rate (CO = SV x HR)

As filling time is reduced, the contribution made by atrial systole becomes of relatively greater importance.

Question 10

Define afterload

Answer 10

Afterload is the force against which the cardiac muscle works during ejection.

The force that it has to oppose when contracting is wall stress, which is related to the tension in the ventricular wall. Wall stress in a pressurised sphere is described by the law of LaPlace which states that:

Wall stress (N cm^-2) = (pressure x radius) / (2 x wall thickness)

Therefore, an increase in radius increases wall stress.

Increasing the afterload decreases the contraction velocity of cardiac muscle. Therefore, if afterload increases, less blood is able to be ejected during each systole.

Question 11

Describe the affects of afterload on the Frank-Starling curve

Answer 11

Changing afterload creates a new ventricular function curve

• Increasing afterload results in a lower SV at any given preload
• Decreasing afterload resulting in a higher SV at any given workload

Question 12

What can change afterload?

Answer 12

Anythign that changes the variables in the law of LaPlace

Wall stress (afterload) = [systolic pressure_vent x radius_vent] / [2 x wall thickness_vent]

Systolic pressure of the ventricles

• E.g. increased HTN
• E.g. increased aortic stenosis (ventricle has to generate more pressure to eject blood)

Radius of the ventricle

• E.g. dilated cardiomyopathy

Wall thickness

• Ventricular hypertrophy decreases wall stress and is a compensatory mechanism for when afterload increases

Question 13

What is the affect of ventricular hypertrophy and dilation on wall stress?

Answer 13

Ventricular hypertrophy reduces wall stress.

Ventricular dilation (as seen in dilated cardiomyopathy) increases wll stress.

This is because the law of LaPlace states that wall stress is inversely related to wall thickness.

Question 14

Contractility

Answer 14

Preload and afterload partially depend on the properties of the vasculature (blood volume, resistance, capacitance). Contractility refers to the rate and amount of force generated by cardiac muscle and is independent of either preload or afterload. Contractility is also called ‘inotropy’. It is caused by increased calcium release into the SR.

Contractility can be increased by:

• SNS
• Circulating catecholamines
• Medications (=inotropes)
• Force-frequency (faster HR produce more forceful contractions)

Question 15

The Bainbridge Reflex

Answer 15

Stretch receptors in both atria feed back to the ANS to regulate heart rate indirectly; this is the Bainbridge reflex.

The Bainbridge reflex prevents blood building up in the great veins and pulmonary circulation.

Question 16

What happens if we reach the limit of cardiac output and the tissues still want more flow?

Answer 16

This could arise because:

• Tissue demands increase to approach the normal maximal cardiac output; or
• Cardiac output may be impaired (cardiac failure)

At this point, even if the arterioles continue to dilate, all that happens is BP falls and flow won’t increase. The question becomes one of priorities:

• Which organ’s function are you more willing to underperfuse for a while? (heart/brain/kidney/GIT).

If CO is limited local controlof flow will try to increase flow to meet demand via arteriolar vasodilation; and the SNS will try to cause arterial and arteriolar vasoconstriction if BP starts to fall.

• In critical tissues (brain, heart, active skeletal muscle) local flow wins out.
• Kidney, skin and gut lose this tug-of-war.