CVS Physiology Part 3

In this podcast, Maddi and I discuss the basics of CVS physiology and peripheral circulation.

CARDIOVASCULAR PHYSIOLOGY

What is mean arterial pressure?

Mean arterial pressure is the average arterial pressure during a cardiac cycle and is cardiac output multiplied by total peripheral resistance MAP is thought to be important for tissue perfusion as organ blood flow autoregulation, with the exception of the left ventricle, is generally thought to depend on MAP rather than systolic or diastolic pressure. It can be estimated by diastolic pressure + pulse pressure divided by 3. It is mainly determined by peripheral resistance. It is not altered by damping of transducers and is independent of the site or technique of blood pressure measurement. The ideal MAP to target in ICU is unknown but generally a minimal MAP of 65-70 is targeted. 

What is pulse pressure?

Pulse pressure is the difference between the systolic and the diastolic blood pressure and is normally about 40-60mmHg. The systolic pressure is the maximal aortic pressure following ventricular ejection while the diastolic pressure is the lowest pressure in the aorta just prior to the ejection of blood from the ventricle into the aorta. The pulse pressure depends on aortic compliance, that is the change in volume for a given change in pressure. The aorta has the highest compliance within the arterial system, therefore can dampen the pulsatile output from the left ventricle and reduce the pulse pressure. Pulse pressure is generally proportional to stroke volume and inversely proportional to aortic compliance

Causes of widened pulse pressure include 

• Age
• Atherosclerosis
• Aortic regurgitation
• Fever
• Pregnancy
• Hyperthyroidism
• Arteriovenous fistulas
• Patent ductus arteriosus
• Thiamine deficiency

Causes of narrow pulse pressure include

• Hypovolemic shock
• Cardiogenic shock
• Aortic stenosis
• Cardiac tamponade

Pulse pressure variation is a percentage calculated by taking the maximum pulse pressure, subtracting the minimum pulse pressure, dividing this by the mean pulse pressure over a respiratory cycle and multiplying this by 100. It relies on the premise that pulse pressure is proportional to stroke volume. During mechanical ventilation, inspiration normally causes an augmentation of left ventricular stroke volume and an increase in arterial blood pressure while expiration results in decreased stroke volume. Pulse pressure is usually maimal at end inpiration and minimal at end expiration. Patients who are higher on the Frank-Starling curve will have less change in their pulse pressure with the changes in volume that occur during the respiratory cycle. Therefore, a pulse pressure variation of > 12% is thought to suggest volume responsiveness. However, to calculate pulse pressure variation patients must be in sinus rhythm, be intubated and ventilated with no spontaneous respiratory efforts, have no significant changes in their chest wall compliance such as an open chest and have adequate tidal volumes.  

Outline the role of the vasomotor centre and the autonomic nervous system in the regulation of blood pressure

The vasomotor centre is located in the reticular substance of the medulla and the lower third of the pons. It transmits parasympathetic impulses through the vagus nerves to the heart and sympathetic impulses via the spinal cord and peripheral sympathetic nerves to the vasculature. There are three important areas that have been identified in the vasomotor centre

• A vasoconstrictor area in the anterolateral upper medulla which excites preganglionic vasoconstrictor neurons in the sympathetic nervous system
• A vasodilator area located in the anterolateral lower medulla. These neurons project to the vasoconstrictor area and inhibit this area thus resulting in vasodilatation
• Sensory area in the tractus solitarius in the posterolateral medulla and lower pons which receive sensory input mainly through the vagus and glossopharyngeal nerves and then help provide reflex control of both the vasoconstrictor and vasodilator areas.

As blood pressure is dependent on cardiac output and total peripheral resistance, the vasomotor centre and autonomic nervous system can regulate blood pressure via effects on the vessels and effects on the heart. 

Normally there is ongoing impulses from the vasoconstrictor area of the vasomotor centre which maintains baseline sympathetic tone of the vessels, helping to maintain normal blood pressure. All blood vessels except capillaries and venules receive motor nerve fibres from the sympathetic nervous system. The fibres to the arterial vessels change the resistance and the fibres from the veins change the capacitance and thus the volume of blood in the veins. The arterial vasculature is densely innervated whilst the veins, with the exception of splanchnic veins, are less innervated. Sympathetic stimulation results in arterial and venoconstriction. Arterial constriction increases total peripheral resistance thus increasing blood pressure. Constriction of the veins displaces blood out of large peripheral blood vessels and back towards the heart thus increasing contractility via the Frank Starling mechanism and thus increasing blood pressure. 

The lateral portions of the vasomotor centre transmit impulses through sympathetic nerves to increase heart rate and contractility whilst the medial portion of the vasomotor centre send signals to the dorsal motor nuclei of the vagus nerves which transmits these impulses via the vagus nerve to the heart to decrease heart rate and contractility. There is normally a baseline amount of vagal input to the heart which maintains vagal tone.

The vasomotor centre also receives input from other areas of the brain including the reticular substance of the mesencephalon and diencephalon, the hypothalamus and the cerebral cortex including the motor cortex, the temporal lobe, the amygdala and the hippocampus. These areas can either stimulate or inhibit the vasomotor centre and thus affect blood pressure. The vasomotor centre also receives input from baroreceptors and from are affected directly by changes in carbon dioxide and oxygen levels. Nervous control of blood pressure is rapid, being able to act within seconds. 

Explain the role of baroreceptors in the control of blood pressure

Baroreceptors are spray-type nerve endings that lie in the carotid sinus and in the aortic arch. They are important for the acute and rapid control of blood pressure and achieve this via a negative feedback loop. A rise in arterial pressure stretches these receptors thus increasing their firing rate. These signals are then transmitted to the medulla and vasomotor centre which feedbacks via the autonomic nervous system to reduce blood pressure due to a decrease in peripheral resistance and cardiac output. The carotid baroreceptors signal is transmitted through Hering’s nerve which is a branch of the glossopharyngeal nerve which then synapses in the nucleus tractus solitarius in the medulla while the aortic baroreceptors signal is transmitted via the vagus nerve to the nucleus tractus solitarius. The carotid sinus is quantitatively more important than the aortic baroreceptors in regulating arterial blood pressure as they are more sensitive and respond to systolic pressures between 60 – 180mmHg whereas aortic baroreceptors operate at threshold pressures approximately 30mmHg higher. The baroreceptors are more sensitive to a rapidly changing pressure and to a sudden decrease in blood pressure, so are important in maintaining relatively stable blood pressures during changes in posture. They also are sensitive to changes in the mean arterial pressure.  Under normal conditions baroreceptors exert a constant inhibitory influence on sympathetic outflow from the medulla. When the blood pressure drops this inhibitory influence is released and there is an increase in sympathetic activity resulting in vasoconstriction, increased heart rate and positive inotropy leading to an increase in blood pressure. Baroreceptors adapt to sustained changes in blood pressure so in chronic hypertension their threshold resets to maintain this elevated rather than normal blood pressure. Therefore, they do not have an important role in long term blood pressure control but are crucial for the acute control and rapid adjustments in blood pressure that occur during the day.

Describe total peripheral vascular resistance and the factors that affect it.

Resistance is equal to the change in pressure divided by the flow and can be mathematically expressed by the Hagen Poiseuille equation which states that resistance equals 8 times the viscosity of the fluid times the length of the tube divided by pi x radius to the power of 4. Consequently, any small changes in vessel diameter result in large changes to resistance in vessel resistance as a halving of the radius will increase the resistance 16 times. The Hagen Poiseuille equation does not apply perfectly to the vasculature as it assumes long straight blood vessels, a Newtonian fluid which blood is not, and laminar flow. Laminar flow is characterised by concentric layers of blood moving in parallel down the blood vessel with the highest velocity being the blood in the centre of the vessel and the lowest velocity along the vessel wall. 

However, the Hagen-Poiseuille equation does outline the main factors affecting resistance, with resistance being directly proportional to vessel length (which does not change significantly), directly proportional to blood viscosity and inversely proportional to the vessel radius to the power of 4. 

Blood viscosity

• Whole blood is 3-4 times as viscous and plasma is about 1.8 times as viscous as water
• Therefore, blood viscosity depends mainly on hematocrit
• Increased haematocrit will theoretically increase viscosity and thus peripheral resistance. However, in small vessels such as arterioles, this effect is much smaller than in large vessels. Consequently, changes in haematocrit have relatively little effect on total peripheral resistance unless the change is very dramatic.
• Viscosity is also affected by the resistance of the cells to deformation so conditions such as hereditary spherocytosis can increase resistance as the red blood cells are less malleable
• It is also affected by the composition of plasma: increased plasma proteins will increase viscosity

Vessel radius: 

• As we have emphasised, changes in vessel radius result in large changes to total peripheral resistance. The arterioles are the major site of resistance to blood flow. Vascular tone, or the degree of constriction of blood vessels is determined by the balance between vasoconstrictor and vasodilator influences. Only a generalised vasonconstriction, will increase total peripheral resistance. 
• Factors influencing vascular tone can be divided into systemic and local
  • Systemic factors
    • Neural
      • There is baseline sympathetic discharge which maintains vascular tone. Sympathetic noradrenergic stimulation results in vasoconstriction and inhibition results in vasodilatation. Sympathetic cholinergic fibres innervate blood vessels in skeletal muscle and stimulation causes vasodilatation. However, they are only activated by strong emotional stimuli and anticipation of exercise. The parasympathetic nervous system is not important for the systemic control of vascular tone.
    • Humoral
      • Vasoconstrictors include noradrenaline, adrenaline, angiotensin 2, vasopressin, dopamine and calcium. Decreased oxygen levels cause vasodilatation except in the pulmonary circulation.
      • Vasodilators include atrial natriuretic peptide, kinins, substance P, prostaglandins, vasoactive intestinal peptide, increased potassium, increased magnesium and increased hydrogen ions. Adrenaline causes vasodilatation in the liver and skeletal muscle. Increased carbon dioxide levels cause vasodilatation but this may be counteracted by sympathetic nervous stimulation caused by the effect of hypercarbia on the vasomotor centre.
  • Local factors:
    • Myogenic mechanisms hypothesised to be responsible for autoregulation. Increased blood pressure is thought to increase stretch on the vessels which causes the smooth muscle in the vessel wall to contract
    • Humoral
      • Vasoconstrictors include serotonin and thromboxane A2 from platelets, and endothelin which is released by damaged endothelial cells
      • Vasodilators include adenosine, nitric oxide, prostacyclin, histamine and lactic acid 

What is the microcirculation?

The microcirculation is composed of the smallest blood vessels in the body and include the arterioles, metarterioles, precapillary sphincters, capillaries and venules. Their principal function is the transfer of substances between the tissues and the circulation and this occurs mainly across the walls of the capillaries. 

Briefly outline the forces that result in fluid exchange across capillary membranes.

The capillary wall is a very thin semipermeable membrane composed of endothelial cells. Fluid exchange across capillary walls normally occurs via filtration which is governed by four main forces, termed Starling forces. These forces are:

• Hydrostatic pressure in the capillary which opposes the 
• Hydrostatic pressure in the interstitium
• Oncotic pressure in the capillary, largely determined by albumin, which opposes the
• Oncotic pressure in the interstitium

Net filtration pressure is the interaction between these pressures. It is equal to the difference in hydrostatic pressure between capillary and interstitium minus the difference in oncotic pressure between the capillary and the interstitium multiplied by the reflection coefficient, all multiplied by the capillary filtration coefficient. The capillary filtration coefficient is dependent on the area of the capillary walls and the permeability of the capillary wall to water. The reflection coefficient is a correction factor from 0 to 1 due to the fact that a small amount of protein leaks from the capillaries, in the glomerulus this is close to 1 due to the impermeability of the glomerulus to proteins while in the hepatic sinusoids this is closer to 0. If the net filtration pressure is positive it generally results in filtration of fluid out of the capillaries and into the interstitium with the opposite occurring if the net filtration pressure is negative. It was traditionally thought that the arterial end of the capillary has a positive net filtration pressure while the venous end of the capillary has a negative net filtration pressure, that is it favours absorption. However, it has recently been found that net filtration pressure is positive throughout the entirety of the capillary for most tissues and that the ultrafiltered fluid actually is not reabsorbed via venules but returns to the circulation as lymph.