Physiology for MRCEM Primary

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Cardiovascular physiology

Local control of blood flow

[box type=”download”] Local control of blood flow  Range of pressures within which autoregulation occurs  Basis of the myogenic regulatory response and the effects of local vasodilatory factors  Role of potassium, carbon dioxide and adenosine in metabolic hyperaemia  Effects of inflammatory mediators in altering microcirculatory dynamics (dilation). Pulmonary flow  Special arteriolar response to hypoxia (constriction) and its basis. Cutaneous flow  Role of arteriovenous anastomoses in thermoregulation  Contributory factors to enhanced local blood flow. Coronary flow  Coronary metabolic hyperaemia as the basis of high oxygen extraction. Brain circulation  Main components of blood-brain barrier  Key roles of CO2 and potassium in determination of cerebral autoregulation. Skeletal muscle flow  Capillary recruitment via metabolic hyperaemia  Role of skeletal muscle beds in generating total peripheral resistance [/box]

Local control of blood flow


The ability to maintain a constant flow during arterial pressure variations (between ∼50 and 170 mmHg).
It is particularly important in the brain, kidney and heart.
Two mechanisms contribute to autoregulation.
The myogenic response involves arteriolar constriction in response to increased pressure and/or distention of the vessel wall. This probably involves activation of transmembrane integrins in smooth muscle cells, with subsequent opening of voltage-activated L-type Ca2+ channels, but stretch-activated channels permeable to Ca2+ and Na+ also contribute by causing depolarization, further activation of L-type channels and Ca2+ entry.
The second mechanism is via locally produced vasodilating factors. An increase in blood flow dilutes these factors, causing vasoconstriction, whereas decreased blood flow allows accumulation, causing vasodilatation.

Metabolic factors.

Many factors may contribute to metabolic hyperaemia (increased blood flow).
The most important are K+, CO2 and adenosine, and in some tissues hypoxia.
K+ is released from active tissues and in ischaemia; local concentrations can increase to >10 mM.
It causes relaxation, partly by stimulating the Na+ pump, thus both increasing Ca2+ removal by the Na+–Ca2+ exchanger and hyperpolarizing the cell.
The vasodilatory effects of increased CO2 (hypercapnia) and acidosis are mediated largely through increased nitric oxide production and inhibition of smooth muscle Ca2+ entry.
Adenosine is a potent vasodilator released from heart, skeletal muscle and brain during increased metabolism and hypoxia.
It is produced from adenosine monophosphate (AMP), a breakdown product of adenosine triphosphate (ATP), and acts by stimulating the production of cyclic AMP (cAMP) in smooth muscle.
Hypoxia may reduce ATP sufficiently for KATP channels (which are inhibited by ATP) to activate, causing hyperpolarization.

Autocoids are mostly important in special circumstances; examples: In inflammation, infection and tissue damage initiate release of the vasodilators histamine, bradykinin and prostaglandin E2, which increase blood flow but also the permeability of exchange vessels, leading to swelling but facilitating access by leucocytes and antibodies to damaged tissues. The activation of platelets during clotting releases the vasoconstrictors serotonin and thromboxane A2, so reducing blood loss.

Specific circulations

Skeletal muscle.

Takes 15–20% of cardiac output at rest; this can rise to >80% during exercise.
A major contribution to the total peripheral resistance.
At rest, most capillaries are not perfused, as their arterioles are constricted.
Arterioles dilate due to local release of K+, CO2 and adenosine by working muscle (metabolic hyperaemia), which overrides sympathetic vasoconstriction.
Muscular contraction compresses blood vessels and inhibits flow; metabolic hyperaemia compensates by vastly increasing flow during the relaxation phase.
In isometric (static) contractions, continuously reduced flow can cause muscle fatigue; when contraction ceases there is reactive hyperaemia(large flow).


The brain receives ∼15% of cardiac output, and has a high capillary density.
The endothelial cells of these capillaries have very tight junctions and membrane transporters control the movement of substances, such as ions, glucose and amino acids, and tightly regulate the composition of the
cerebrospinal fluid.
This is the blood–brain barrier, and is continuous except where substances need to be absorbed or released from the blood (e.g. pituitary gland, choroid plexus).
The autoregulation maintains a constant flow between 50 and 170 mmHg blood pressures.
CO2 and K+, when increased cause a functional hyperaemia linking blood flow to activity.
Hyperventilation reduces blood PCO2, and can cause fainting due to cerebral vasoconstriction.
Astrocytes surrounding cerebral blood vessels may also release vasodilators including K+ and PGE2.

Coronary circulation.

The heart has a high metabolic demand.
It extract an unusually high proportion of oxygen from the blood (∼70%).
Majority of flow occurs during diastole. In exercise, the diastole is reduced.
A greatly increased blood flow is achieved under the influence of adenosine, K+ and hypoxia.
The heart therefore controls its own blood flow by a well-developed metabolic hyperaemia.
This overrides vasoconstriction mediated by sympathetic nerves, and is assisted by circulating adrenaline (epinephrine) which causes vasodilatation via β2-adrenergic receptors.

Pulmonary circulation.

This is not controlled by either autonomic nerves or metabolic products, and the most important mechanism regulating flow is hypoxic pulmonary vasoconstriction, in which small arteries constrict to hypoxia.
This diverts blood away from poorly ventilated areas of the lung, maintaining optimal ventilation–perfusion matching; conversely, global hypoxia due to lung disease or altitude can increase the pulmonary artery pressure (pulmonary hypertension).
In health the pulmonary capillary pressure is low (∼7 mmHg) compared to systemic capillaries, but fluid filtration still occurs because the interstitial hydrostatic pressure is also low (negative) (about −4 mmHg) whereas the interstitial oncotic pressure is high (18 mmHg).


The skin contains venous plexuses which facilitate heat transfer from blood to the surface.
In glabrous (hair-less) skin of hands, feet and areas of the face, coiled, thick-walled arteriovenous anastomoses (AVAs) directly link arterial and venous vessels, bypassing capillaries and enabling high blood flows through the venous plexus and increased radiation of heat.
Cooler temperatures increase sympathetic vasoconstrictor activity, AVAs being particularly strongly affected, and skin blood flow can fall as much as 90% (pale skin).
Sympathetic stimulation also causes piloerection to trap an insulating layer of air.
Skin temperature can also directly affect blood flow, probably via local sensory reflexes and/or altered sensitivity to noradrenaline.
Prolonged cold causes transient paradoxical vasodilatations in hands and feet, maintaining manual dexterity at the cost of some heat loss.
An elevated TC(Core temp) reduces sympathetic-mediated vasoconstriction and increases blood flow, particularly through AVAs, and heat loss.
If TC exceeds the sweating threshold, sympathetic cholinergic (acetylcholine-releasing) nerves activate sweat glands, causing sweating and release of bradykinin, a powerful vasodilator.
Neural co-transmitters (nitric oxide, substance P) contribute to the consequent increase in blood flow.
In very hot conditions skin blood flow can increase 30-fold.
At low sweat rates most salt and water is subsequently reabsorbed in the duct, leaving a sweat rich in urea, lactate and K+.
At high sweat rates more salt than water is reabsorbed, creating a hypotonic sweat. Sweating greatly increases evaporative cooling, the only way heat can be lost to an environment hotter than TC, but is highly dependent on humidity.
We can tolerate 45 °C in a dry environment indefinitely after acclimatization, but with a humidity >40% we would be in extreme danger of heat stroke.