Blood Pressure Regulation
The human body is an incredibly complex machine, consisting of numerous organ systems that interact continuously with both the internal and external environment.The internal environment is that inside the body itself and is dynamic, i.e. constantly changing, but within well defined limits.These limits are defined by set points in the various body systems, such as core temperature, which is set at around 37oC in thermoregulatory centres of the hypothalamus (Cabanac 1975).
Maintaining important physiological parameters, such as temperature, blood pressure, pH, blood sugar levels and oxygen saturation of the blood, in narrow ranges is crucial for biological health and is referred to as homeostasis (literally translated as ‘unchanging’). Biological health occurs when the body systems are functioning adequately to keep these parameters in their normal range.Disease occurs when one or more of these extends outside the range.There are numerous homeostatic mechanisms in the body, all of which consist of three basic components: a receptor that is able to detect a stimulus in the internal body environment and convey this along an afferent pathway to a control centre, where inputs from many receptors are integrated and where the set point is determined.From here an efferent pathway runs to the third component; the effector, which produces a controlled response to either decrease or enhance the stimulus (see figure 1). Most homeostatic mechanisms work to decrease the stimulus, i.e. form a negative feedback system (except blood clotting, which has a positive feedback system).So if an increase in, for example, blood pressure is detected, homeostasis will act to reduce this back to within the normal range.
Communication between the 3 components occurs via the nervous system (most commonly the autonomic system, with input from higher centres), but may also occur by hormones travelling in the blood (Marieb 2004).
Figure 1: Basic outline of homeostatic control systems
- Stimulus produces a change in the variable, away from the baseline value
- Receptor detects change
- Receptor sends signal along afferent pathway to control centre
- Control centre integrates inputs and compares to set-point
- Efferent signal sent out to effector
- Effector produces controlled response, which usually opposes the stimulus to return the variable to within its homeostatic range (negative feedback).
(Redrawn from Marieb 2004)
HOMEOSTATIC REGULATION OF BLOOD PRESSURE
An important parameter that must be kept within the normal range for biological health is blood pressure.Every cell in our body requires a constant supply of nutrients, such as glucose and oxygen, as well as removal of waste products, such as carbon dioxide, to prevent a toxic build up.To maintain this constant exchange of material, we rely on blood to circulate in the transport network of blood vessels and interact with cells in organs and tissues.If this does not occur at a sufficient rate cells suffer hypoxia, lack of energy substrates and the toxic effects of metabolic waste build up, which leads to poor function and eventually cell death.Therefore, it is obviously crucial to maintain blood flow at a sufficient rate through the systemic tissues and lungs.This is achieved by the heart, which pumps the blood around the vessels and maintains blood pressure, which drives the blood through the arterial system to the capillary beds within the tissues.To ensure that blood flows fast enough to perfuse the tissues, it needs to flow down a pressure gradient.This gradient is created by the muscular pumping of the heart ventricle and is greatest nearest the heart.The walls of the large arteries that receive this blood are elastic and recoil when blood is pumped into them under pressure.The heart pumps to produce a systolic blood pressure of 120mmHg, followed by recoil of the arteries, which produces a second pump of around 80mmHg, called diastolic pressure.As the semilunar valves are closed, this ensures the blood flows distally, down the pressure gradient and towards the arterioles, then capillaries and tissue beds of cells.By the time blood reaches the arterioles, blood pressure has dropped to much lower levels than that in the arteries and is lower still in the venous system, falling to zero in the vena cavae (Martini & Ober 2005).It is also important to prevent blood pressure from becoming too high (hypertension), as it puts extra strain on the heart and can damage delicate capillaries and predispose to strokes (Levy et al. 1996).
The general term ‘blood pressure’ usually refers to the mean arterial pressure (MAP), which is an average of systolic and diastolic pressures.The time in each phase is taken into account and MAP is worked out according to the formula:
MAP = diastolic pressure + 0.33 (systolic-diastolic).
Meaney and colleagues (2000) have more recently suggested that 0.412 is a more accurate factor to multiply pulse pressure by (i.e. systolic-diastolic pressures), rather than the traditional 0.33.
Maintaining blood pressure is dependent upon several variables: cardiac output, blood volume and the peripheral resistance of the blood vessels.If one of these variables changes, compensatory mechanisms are triggered in the other variables to maintain homeostasis.Control of blood pressure is achieved by several mechanisms:
• ¬NEURAL MECHANISMS
The vasomotor centre of the medulla in the brain acts with other regions of the cardiovascular centre in the medulla to integrate the control of cardiac output and blood vessel diameter in the regulation of blood pressure.The vasomotor centre contains sympathetic neurons and connects to the smooth muscle of blood vessels via efferent motor fibres, which release noradrenaline (NA; also known as norepinephrine); a potent vasoconstrictor.In this way vasomotor tone of the blood vessels is maintained, under sympathetic control.An increase in sympathetic activity causes increased vasoconstriction. This increases the peripheral resistance to blood flow that the heart needs to pump against, thereby increasing blood pressure.Vasomotor activity can be modified by inputs from baroreceptors and chemoreceptors, higher brain centres (hypothalamus and cerebrum) as well as some hormones, to alter blood pressure.
Baroreceptors are located in the large arteries of the neck and thorax, the aortic arch and the carotid sinus and detect changes in arterial blood pressure by the amount the vessel wall is stretched when blood is pumped across them.
If a decrease in blood pressure is detected, such as when changing posture from laying down to standing, the baroreceptors send impulses to the vasomotor centre, as the first part of the reflex arc.This sends efferent signals out to the blood vessels (particularly the arterioles), and causes them to constrict.This increases the peripheral resistance, thereby increasing blood pressure back to its normal level.The baroreceptors also send impulses to the cardiac centres, stimulating the cardioacceleratory centre to increase sympathetic activity and decrease parasympathetic activity, which increases the heart rate and force (and therefore cardiac output), until blood pressure has reached its homeostatic level.The opposite occurs when blood pressure increases; a decrease in heart rate and vasodilation of arterioles and veins.Veins can be dilated to act as reservoirs for blood, effectively reducing the circulating blood volume, and lowering blood pressure.
Chemoreceptors detect changes in oxygen, carbon dioxide and pH in the aortic and carotid bodies, which can indicate a change in blood flow and tissue perfusion due to blood pressure.When a fall in blood pressure causes oxygen to drop, carbon dioxide increase and pH decrease, the chemoreceptors send impulses to the cardioacceleratory centre, to increase heart rate and to the vasomotor centre to cause vasoconstriction.These responses occur until the blood pressure has risen back to normal.The main role of chemoreceptors is in the control of respiration.
These neural mechanisms are effective for short-term control of blood pressure, such as that resulting from postural changes.They are less effective at long term control, which may be due to resetting of the set point, for example in chronic hypertension (Berdeaux & Giudialli 1987).
• CHEMICAL MECHANISMS
Most chemical controls also act in the short term, but some are also effective at controlling long-term changes (namely the renal renin-angiotensin system).
These are summarised below in table 1.
Chemical Source Action
Adrenaline and noradrenaline (NA) Adrenal medulla Both act sympathetically to increase blood pressure, via vasoconstriction and increased cardiac output due to increased heart rate (adrenaline only).
Atrial natriuretic peptide (ANP) Atria of heart Reduces blood volume and pressure, by antagonising aldosterone at the kidney tubule cells and increasing the amount of sodium and water excreted.
Antidiuretic hormone (ADH) Hypothalamus Increases blood pressure by stimulating kidney tubule cells to conserve more water and hence increase blood volume.
Nitric oxide (NO) Endothelium Produced when blood flow increased and reduces blood pressure via vasodilation.
Angiotensin II* Liver/circulating blood Increases blood pressure by vasoconstriction.Also stimulates adrenal cortex to produce aldosterone, which increases retention of sodium and water, thus increasing blood volume.
*Angiotensin II is part of the renin-angiotensin system, and its production is stimulated by renin, an enzyme produced in the kidney when blood pressure falls.
Many of these chemical and neural mechanisms act simultaneously when blood pressure alters outside its normal range, and some chemicals are released under neural control.Inputs and the effectiveness of the responses to restore the blood pressure are monitored by the control centres in the medulla, to determine if the effector response need to be increased or can be halted due to return of normal pressure.Relays from the cerebral cortex and hypothalamus can also influence the centres in the medulla oblongata and hence affect blood pressure, for example in the fight-or-flight response, exercise or temperature fluctuations.
Maintaining a stable, consistent environment within the body is essential for the integrated functioning of the numerous tissues and organs in normal, biological health.This is the essence of homeostasis.Important parameters, such as blood pressure, are maintained within an optimum range by reflexes and hormonal responses, which are integrated at control centres in the brainstem.These direct the suitable response, via an effector, which may be neural or chemical.The response is monitored and negative feedback ensures that the blood pressure is returned to normal levels.Maintaining blood pressure is crucial to ensure that all tissues are adequately perfused.Blood pressure is driven by the heart, with elastic arteries aiding blood flow down the pressure gradient.Baroreceptors, and to a lesser extent chemoreceptors, detect alterations in mean arterial pressure and inform the vasomotor centre and cardiac centres in the medulla, via a reflex arc.The brain centres integrate inputs and send out impulses to the blood vessels and the heart to produce changes in peripheral resistance and cardiac output, which will lead to changes in the blood pressure.These changes oppose the detected alteration to restore the blood pressure to normal, thus forming a negative feedback loop. There are also numerous chemicals which aid regulation of blood pressure in the short term, plus the renin-angiotensin system of the kidney which can help to counter long-term changes.
When these systems fail, or are overwhelmed, the delicate balance of homeostasis is lost, and disease and pathological changes occur in association with hypo or hypertension.
• Berdeaux, A., and Giudicelli, J. F. (1987). Antihypertensive drugs and baroreceptor reflex control of heart rate and blood pressure. Fundam Clin Pharmacol 1, 257-282.
• Cabanac, M. (1975). Temperature regulation. Annu Rev Physiol 37, 415-439.
• Levy, D., Larson, M. G., Vasan, R. S., Kannel, W. B., and Ho, K. K. (1996). The progression from hypertension to congestive heart failure. Jama 275, 1557-1562.
• Marieb, E. N. (2004). Human Anatomy and Physiology, 6th edn (San Fransisco, London, Pearson/Benjamin Cummings).
• Martini, F., Ober, W.C. (2005). Fundamentals of Anatomy and Physiology, 7th edn (San Fransisco, CA, Benjamin Cummings).
• Meaney, E., Alva, F., Moguel, R., Meaney, A., Alva, J., and Webel, R. (2000). Formula and nomogram for the sphygmomanometric calculation of the mean arterial pressure. Heart 84, 64.
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