Describe the relationship between the systemic and pulmonary circulations.
The entire output of the right heart is directed through the pulmonary circulation which is supply driven - it must accommodate the entire cardiac output, whatever the systemic circulation determines it to be.
The systemic circulation is demand led.
Pulmonary circulation is in series with all the systemic circulations.
Systemic circulations are in parallel to each other.
Describe the dual circulation of the lungs
Bronchial circulation is part of the systemic circulation and meets metabolic requirements of most parts of the lungs (parts of the lungs that are not well-perfused by the pulmonary circulation e.g. the bronchi and bronchioles).
Pulmonary circulation: blood supply to alveoli – required for gas exchange
Describe the 2 main features of the pulmonary circulation
Low resistance due to:
Short wide vessels
Lots of capillaries (high density, high capillary surface area, connected together in parallel)
Arterioles have relatively little smooth muscle.
The pulmonary circulation works with low pressure and low resistance.
If the pressure is too high, this could lead to pulmonary oedema and rupture of fine capillaries.
State the normal pressures in the pulmonary artery, pulmonary capillaries and pulmonary veins
Pulmonary artery: mean pressure: (~12-15mmHg; changes in arterial pressure can have an effect on capillary pressure due to the low resistance)
Pulmonary capillary: mean pressure: (~9-12 mmHg; lower than in systemic circulation).
Pulmonary vein: mean pressure: (~2-5mmHg)
What are the adaptation of the pulmonary circulation to promote efficient gas exchange?
Large capillary surface area due to very high density of capillaries in alveolar wall.
Short diffusion distance due to very thin layer of tissue separating gas phase from plasma; combined endothelium and epithelium thickness is ~0.3 micrometres
Large surface area and short diffusion distance produce high O2 and CO2 transport capacity.
Movement of molecule is always down a concentration gradient.
Explain the concept of ventilation perfusion matching in the pulmonary circulation
For efficient oxygenation, the ventilation of alveoli needs to match perfusion of alveoli.
The optimal ventilation/perfusion ratio = 0.8
If there is a ventilation/perfusion mismatch, the blood leaving the lungs will contain less oxygen and hypoxia will result.
Maintaining this ratio means diverting blood from alveoli which are not well ventilated (e.g. Due to disease or mucus plug) as the blood leaving these alveoli is not well oxygenated.
What is the so-called physiological shunt?
Many cardiovascular and respiratory conditions lead to ventilation/perfusion mismatch and even in normal lungs there is a small mismatch because of the way in which gravity increases blood flow to the base of the lungs when more air is delivered to the apices.
This leads to some blood passing through the lungs without being properly oxygenated - the so-called physiological shunt.
Why is tissue fluid formation not normally formed in the lungs?
The pressure in the pulmonary capillaries is normally less than the colloid osmotic pressure.
What is the main mechanism that ensures optimal ventilation perfusion ratio?
There is no overall control of the pulmonary resistance but the pulmonary arterioles can control the distribution of the cardiac output to the lung.
Blood is generally directed away from areas where oxygen uptake is reduced by hypoxic pulmonary vasoconstriction.
Hypoxic pulmonary vasoconstriction is the most important mechanism in regulating pulmonary vascular tone.
Alveolar hypoxia results in vasoconstriction of pulmonary vessels, and the increased resistance means less flow to poorly ventilated areas and greater flow to well ventilated areas.
This mechanism ensures that perfusion matches ventilation. Poorly ventilated alveoli are less well perfused.
Helps to optimise gas exchange.
What can chronic hypoxic vasoconstriction lead to?
Chronic hypoxia can occur at altitude or as a consequence of lung disease such as emphysema.
Chronic increase in vascular resistance due to chronic vasoconstriction leads to chronic pulmonary hypertension.
High afterload (too much pressure) on right ventricle (as it has to pump against high resistance) can lead to right ventricular heart failure.
Describe how gravity influences low pressure pulmonary vessels
Gravity creates hydrostatic pressure in a column of blood (or any fluid) which therefore allows posture to influence the distribution of fluid flow through the lungs.
When standing upright, transmural pressure within the blood vessels at the base of the lungs is elevated by the increase in hydrostatic pressure.
This may lead to some filtration of tissue but will also distend the vessels and increase flow to those areas.
In the upright position (orthostasis), there is greater hydrostatic pressure on vessels in the lower part of the lung.
Above the heart, the vessels collapse during diastole.
At the same level as the heart, the vessels are continously patent.
At a lower level to the heart, the vessels are distended (due to the hydrostatic pressure). It is more difficult to maintain the ventilation perfusion ratio.
What is the effect of exercise on pulmonary blood flow?
Increased cardiac output
Small increase in pulmonary artery pressure
Opens apical capillaries
Increased O2 uptake by lungs
As blood flow increases capillary transit time is reduced
At rest transit time is ~1s. Can fall to ~0.3s without compromising gas exchange because gas exchange is so efficient.
Describe the forces which are involved in the movement of fluid
Starling forces determine tissue fluid formation.
Hydrostatic pressure of blood within the capillary pushes fluid out of the capillary.
Oncotic pressure (colloid osmotic pressure) within the capillary is the pressure exerted by large molecules such as plasma proteins, draws fluid back into the capillary.
Capillary hydrostatic pressure is influenced more by venous pressure in the systemic circulation; fluid moves out at arterial end (higher hydrostatic pressure) and in at venous end (lower hydrostatic pressure).
Balance between hydrostatic and plasma oncotic pressure determines amount of fluid that moves out.
Venous pressure has the greatest effect in capillary hydrostatic pressure so in the low pressure pulmonary system, what happens?
Low capillary pressure minimises the formation of lung lymph - only a small amount of fluid leaves the capillaries.
Filtration approximately equals reabsorption (Some tissue fluid is formed but the lungs can cope with this without fluid build up.)
Increased capillary pressure causes more fluid to filter out (filtration > reabsorption) --> Oedema (which is normally prevented by low capillary pressure).
Increased venous pressure --> increased hydrostatic pressure.
Why might capillary pressure increase?
If the left atrial pressure rises to 20-25mmHg e.g. Due mitral valve stenosis or left ventricular failure.
What is the effect of Pulmonary Oedema?
Impairs gas exchange.
Affected by posture (changes in hydrostatic pressure due to gravity).
The fluid is mainly at the base of the lungs when upright
redistribution occurs when lying down - increased hydrostatic pressure at the top of the lungs --> increased pulmonary oedema throughout the lung,
Use diuretics to relieve symptoms.
Treat underlying cause.
Describe the O2 demand of the cerebral circulation
The brain has a high O2 demand - needs constant supply of O2.
Receives 15% of cardiac output but only accounts for 2% of body mass.
O2 consumption of grey matter accounts for ~20% of total body consumption at rest.
Must produce a secure O2 supply (neurones cannot last long without a supply of oxygen).
How is the Cerebral Circulation able to meet the high demand for O2?
High capillary density with a large surface area for gas exchange and reduced diffusion distance (<10 micrometres between neurone and capillary).
High basal rate flow - 10x faster than body average
High O2 extraction - 35% above average.
Why is a secure O2 supply to the brain vital?
Neurones are very sensitive to hypoxia.
Loss of consciousness after a few seconds of cerebral ischaemia.
Begin to get irreversible damage to neurones in ~4 minutes.
An interruption to the blood supply e.g. A stroke, causes neuronal death.
How is a secure cerebral blood supply ensured?
How is a secure cerebral blood supply ensured structurally?
Anastomoses between basilar and internal carotid arteries - 'Circle of Willis': if one part of the circle becomes blocked or narrowed (stenosis) or one of the arteries supplying the circle is blocked or narrowed, blood flow from the other blood vessels can often preserve the cerebral perfusion well enough to avoid the symptoms of ischaemia.
How is a secure cerebral blood supply ensured functionally?
Brainstem regulates other circulations.
Myogenic Autoregulation maintains perfusion during hypotension
Metabolic factors control blood supply.
How does Myogenic Autoregulation help ensure secure blood supply to the brain?
Cerebral resistance vessels have a well developed Myogenic response to changes in transmural pressure (pressure across the wall).
Increased blood pressure --> vasoconstriction
Decreased blood pressure --> vasodilatation.
This serves to maintain cerebral blood flow when BP changes
Fails below 50mmHg
How do Metabolic Factors help ensure secure blood supply to the brain?
Metabolic regulation: cerebral vessels are very sensitive to changes in pCO2 (partial pressure).
Metabolic factors control blood flow.
Hypercapnia: increased pCO2 --> vasodilatation
Hypocapnia: decreased pCO2 --> vasoconstriction.
Panic hyperventilation (blowing off lots of CO2) can cause hypocapnia and cerebral vasoconstriction leading to dizziness or fainting (loss of consciousness - syncope).
As soon as this happens, panic hyperventilation resolves itself.
Explain about Regional Activity in the brain
Areas with increased neuronal activity have increased blood flow.
This is due to increased pCO2, increased CO2, increased Adenosine (from breakdown of ATP) and decreased pO2 leads to vasodilation of cerebral vessels.
Adenosine in particular is a powerful vasodilator of cerebral arterioles.
What is the Cushing's Reflex?
Demonstrated how the brain controls other systemic circulations: The rigid cranium protects the brain but does not allow for volume expansion.
Increases in intercranial pressure e.g. From a cerebral tumour or haemorrhage, impairs cerebral blood flow.
Impaired blood flow to vasomotor control regions of the brainstem increase sympathetic vasomotor activity--> increased sympathetic output to the peripheral circulation --> increases arterial BP (+ low heart rate, irregular breathing), and helping to maintain cerebral blood flow.
Increased cerebral blood pressure --> peripheral vasoconstriction --> more flow to brain.
Explain about the Blood-Brain Barrier
Cerebral capillaries form a tight blood-brain barrier.
Lipid soluble molecule such as O2 and CO2 can diffuse freely.
Lipid insoluble solutes such as K+ (high [K+] can affect neurones) and catecholamines can't diffuse freely - highly regulated because of tight junctions formed by the epithelial cells.
Small alterations in cerebral blood flow have large effects, including headache and other disturbances of cerebral function.
Describe the relationship between the mechanical work and oxygen demand of the myocardium
The coronary circulation must deliver O2 at a high basal rage, which must rise to meet increased demand as cardiac work rate can increase five fold.
Coronary blood flow increases to meet the myocardial O2 demand - extra O2 required at high work load is supplied mainly by increased blood flow.
There is an almost linear relationship until very high O2 demand, where there is a small increase in amount of O2 extracted.
What does the external work done by the heart per beat depend on?
Stroke volume and arterial pressure
If the volume is pumping stroke volume against a low pressure, then efficiency is high.
Pumping the same stroke volume against a higher pressure reduces efficiency.
Pumping the same cardiac output into a higher arterial pressure therefore requires much more blood flow.
Describe the particular features of the coronary circulation
During systole the tension in the walls of ventricles compresses coronary vessels and greatly reduced blood flow.
Coronary blood flow is therefore almost exclusively diastolic especially in the LV.
The right and left coronary arteries arise from the right and left aortic sinuses, and fill during diastole.
In systole, the contraction of the heart muscle makes the pressure in the coronary arteries too high for filling.
Cardiac muscle has a high capillary density to efficiently deliver O2, diffusion distance is shorter (
Describe the consequences of partial of total occlusion of coronary arteries
Coronary arteries are functional end arteries (so few arterio-arterial anastomoses) and are prone to atheromas.
Narrowed coronary arteries lead to angina on exercise (increased O2 demand).
Stress and cold can also cause sympathetic coronary vasoconstriction and angina.
Blood flow is mostly during diastole is reduced as heart rate increases.
Sudden obstruction by thrombus causes myocardial infarction.
How do you attain a mean blood flow appropriate to myocardial activity?
The coronary circulation must have a high blood flow in diastole to compensate for reduced blood flow in systole.
At rest this problem in minimal.
As heart rate increases diastole shortens much more than systole.
Consequently the peak flow in diastole must increase very rapidly with rising HR in order to maintain the necessary average flow.
Minor problems with the coronary circulation therefore become apparent only at higher heart rates.
What controls the flow rate through the myocardium?
The action of local vasodilator metabolites (adenosine, increased [K+], decreased pH) upon coronary arterioles - vasodilation due to metabolic hyperaemia (increased blood flow in response to metabolites).
The normal coronary circulation auto-regulates very effectively.
Describe the Skeletal muscle circulation
Circulation must increase O2 and nutrient delivery and removal of metabolites during exercise.
Important role in helping to regulate arterial blood pressure - accounts for 40% of adult body mass.
Resistance vessels have rich innervations by sympathetic vasoconstrictor fibres; baroreceptors maintain blood pressure (if BP decreases, blood flow increases and vasoconstriction occurs).
What does capillary density depend on in the skeletal muscle circulation?
Depends on muscle type - postural muscles have higher capillary density (active all the time); the metabolic activity of skeletal muscle varies over an enormous range and so does the blood flow.
Very high vascular tone permits lots of dilation and flow can increase >20 times in active muscle.
Describe the skeletal muscle capillaries at rest
At rest only ~1/2 of capillaries are perfused at any one time - allowed for increased recruitment.
So at rest most capillaries within a muscle are shut off by contraction of pre-capillary sphincters.
Increases in blood flow are brought about mainly by opening more capillaries under the influence of vasodilator nervous activity and local metabolites, which tend to reduce tonic sympathetic vasoconstrictor tone.
Increased capillary recruitment in skeletal muscle is important for increasing blood flow: opening of more capillaries increases blood flow and reduces diffusion distance.
Increased flow is due to metabolic hyperaemia.
In the skeletal circulation, explain how increased flow is due to metabolic hyperaemia
Major effect: various agents are thought to act as vasodilators: increased [K+], increased osmolarity, inorganic phosphates, adenosine, increased [H+].
Minor effect: adrenaline also acts as a vasodilator at arterioles in skeletal muscle - acts through B2 receptors.
Vasoconstrictor response via NA on A1 receptors.
Describe the Cutaneous Circulation
Most blood flow through skin is not nutritive and much of the blood flows through arterio-venous anastomoses (AVAs) rather than capillaries.
The skin is not very metabolically active so doesn't require a large blood flow.
Describe the special role of the cutaneous circulation in Temperature Regulation
Core temperature is normally maintained around 37oC.
Skin is the main heat dissipating surface which is regulated by cutaneous blood flow.
AVAs allow a rapid shunt of blood to venous plexus; increased blood flow allows increased dissipation of heat.
AVAs regulate heat loss from apical (acral) skin and is under neural control - innervated by sympathetic vasoconstrictor fibres.
Decrease in core temperature increases sympathetic tone in AVAs (vasoconstriction) - decreases blood flow to skin.
Increased core temperature opens AVAs (reduced vasomotor drive). Low resistance shunt to venous plexus, which is close to the skin, allows skin temperature to rise so dissipating heat (hear loss).
Vasodilation also occurs in non-apical skin.
Do local metabolites affect the cutaneous circulation?
Only a little bit - some mediators are released from active sweat glands which increase flow, and sometimes circulating vasodilator mediators from other sources increase skin blood flow.
What will happen to the pressure in the left atrium as a patient breathes in and out?
- The left atril pressue goes down as a subject breathes in because blood stays in the pulmonary circulation (right atrial pressure increases as the negative intra-throacic pressure draws blood in from the systemic veins)
If pulmonary arterial pressure is increased over a long period (e.g. in the case of a chronic left to right shunt as occurs with a ventricular or atrial septal defect) what effect would you expect this to have upon the resistance vessels of the pulmonary circulation?
They become permanently narrowed (vascular remodelling)
What is the Mean Arterial Pressure, Mean Capillary Pressure and Mean Venous Pressure in the systemic circulation?
Mean Arterial Pressure: 95mmHg
Mean Capillary Pressure: 30mmHg
Mean Venous Pressure: 2-5mmHg