Physiology

Neurological and humoral control of blood pressureNick Ashton

AbstractBlood must be maintained under pressure to overcome the resistance

offered by blood vessels, and thus ensure an adequate rate of flow

to metabolizing tissues. if pressure is too low, the flow of blood can-

not deliver sufficient oxygen; if it is too high, damage occurs to the

blood vessels and organs. hence, blood pressure is regulated around

a ‘set point’. Pressure in the arterial system is regulated on a minute-

to-minute basis by the autonomic nervous system and in the long

term by a number of hormones that act on the kidney. high-pressure

sensors (baroreceptors) are located in the carotid sinus and aortic

arch, which monitor pressure generated by the beating heart. Afferent

fibres of the ninth and tenth cranial nerves (glossopharyngeal and

vagus, respectively) project into the cardiovascular control centre in

the medulla oblongata. Parasympathetic vagal tone acts to slow heart

rate and thus cardiac output, whereas sympathetic tone increases

both force and rate of contraction, as well as stimulating vasoconstric-

tion of blood vessels to increase resistance. long-term regulation of

blood pressure depends on the maintenance of blood volume. This

is achieved by the combined actions of the renin–angiotensin sys-

tem, aldosterone and vasopressin (antidiuretic hormone), which act on

the kidney to promote retention of sodium and water. Blood volume

is reduced by atrial natriuretic peptide, which causes diuresis and

natriuresis. Together, the nervous and endocrine systems act to correct

fluctuations in blood pressure and ensure that it is maintained at an

appropriate level.

Keywords angiotensin ii; baroreceptor; parasympathetic fibres;

sympathetic fibres; vasopressin

One of the principal functions of blood is the transport of gases and nutrients to metabolizing tissues. To achieve this, an ad­equate supply of blood must flow through the capillary network. Blood flow is determined by pressure, generated by contraction of the heart, and resistance, which is a function of blood vessel diameter and length. Coordinated control of cardiac output and arteriole diameter ensures that blood flow in the capillaries is maintained. The relationship between flow (F), pressure (P) and resistance (R) can be derived from Darcy’s law. Originally based on experiments describing the flow of water through sand, Darcy established that flow rate is equal to the product of the

Nick Ashton, PhD, is lecturer in Physiology at the University of

Manchester, Faculty of Life Sciences. He qualified from the universities

of Manchester and Sheffield. His research interests include the

hormonal regulation of renal function and blood pressure.

ANAEsThEsiA AND iNTENsiVE CARE MEDiCiNE 8:6 22

permeability of the medium, the cross­sectional area to flow and the pressure drop, divided by the viscosity and the distance over which the pressure drop occurs. When simplified and applied to the flow of blood through a blood vessel, we get the equation: F is proportional to ∆P/R. The pressure gradient (∆P) along the vessel is more important than absolute pressure (P). However, there is a minimal pressure requirement to overcome the resis­tance to flow. If pressure is too low (hypotension), the pressure drop is too great and capillaries are not perfused adequately. If pressure is too high (hypertension) blood vessels and organs are damaged, leading to cardiovascular disease.

‘Blood pressure’ is usually understood as arterial pressure, specifically systemic arterial pressure. This is the pressure that is normally measured in the clinic, and is the pressure that is managed therapeutically to reduce the risk of cardiovascular disease. The pressure drops across the systemic arterial system from approximately 100 mm Hg at the aorta to 35 mm Hg at the start of a capillary network. Capillary hydrostatic pressure is a measure of the blood pressure within the capillaries. Typically, pressure falls from 35 mm Hg to 18 mm Hg across a capillary bed. Pressure in the venous circulation is much lower than that in the arterial branch, ranging from 18 mm Hg in the venules to 2–3 mm Hg at the right atrium.

What is normal blood pressure?Textbooks usually quote blood pressure at 120 mm Hg systolic and 80 mm Hg diastolic (written as 120/80 mm Hg). However, arterial pressure is dynamic, changing according to the state of arousal. Blood pressure usually decreases at night during sleep and increases during stressful situations (the fight­or­flight response). Furthermore, resting pressure is influenced by a num­ber of factors, including age (pressure increases with age), gender (pressure tends to be higher in men) and race (Afro­Caribbeans tend to have higher blood pressure than Caucasians). A range of environmental factors also affect blood pressure, including socio­economic status, nutrition (obesity and salt intake), alcohol con­sumption, physical inactivity and exposure to environmental stressors. Consequently, the British Hypertension Society define normal blood pressure as 130/85 mm Hg, with ‘high normal’ pressure up to 140/90 mm Hg (Table 1).

Regulation of blood pressure can be divided into short­term mechanisms, which correct changes in pressure on a minute­ to­minute basis, and long­term mechanisms, which manage pres­sure for days and weeks. Generally, short­term adaptations are regulated by neural reflexes; however, hormones can also play a part in rapid changes in blood pressure. Long­term regulation of blood pressure is achieved through the combined actions of a number of hormones, which influence the kidney and the regula­tion of extracellular fluid volume (ECFV).

Neurological regulation of blood pressureThe autonomic nervous system monitors and regulates arterial pressure on a minute­to­minute basis. This is achieved through groups of receptors that monitor blood pressure (barorecep­tors), pH and the partial pressures of carbon dioxide and oxygen (chemoreceptors). These receptors send information to a central cardiovascular control centre, which then adjusts cardiac output (and thus ‘flow’) and vascular tone (and thus ‘resistance’), and so corrects any change in arterial pressure away from the set point

1 © 2007 Elsevier ltd. All rights reserved.

Physiology

(see below). This ensures that an appropriate blood pressure is maintained to meet the metabolic demands of respiring tissues.

Afferent input: the high­pressure sensors are located in the inter­nal carotid arteries and the aortic arch, where they are in a posi­tion to detect maximal pressure generated by contraction of the heart. The carotid baroreceptors are located in the carotid sinus, a dilatation in the internal carotid artery where it joins the external carotid artery. Lamella­like receptors are found in the adventitia of the blood vessel, aligned parallel to the long axis of the vessel. These receptors are innervated by a branch of the glossopharyn­geal nerve (ninth cranial nerve), which projects into the nucleus tractus solitarius in the medulla oblongata. Receptors in the aortic arch are innervated by the vagal nerve (tenth cranial nerve). The frequency of firing of both nerves increases when blood pressure rises, and decreases when blood pressure falls. Individual fibres vary, but the average threshold at which firing begins is nor­mally not less than 50 mm Hg; maximal output occurs at about 170 mm Hg. The carotid and aortic baroreceptors are equally sen­sitive to pulsatile pressure; however, the carotid sinus barorecep­tors are much more sensitive to non­pulsatile changes in arterial pressure. The chemical composition of the blood is monitored by receptors in the carotid bodies and aortic bodies adjacent to the baroreceptors, which are innervated by branches of the ninth and

British Hypertension Society classification of blood pressure

Category Systolic blood

pressure (mm Hg)

Diastolic blood

pressure (mm Hg)

optimal blood pressure < 120 < 80

Normal blood pressure < 130 < 85

‘high normal’ blood

pressure

130–139 85–89

grade 1 hypertension

(mild)

140–159 90–99

grade 2 hypertension

(moderate)

160–179 100–109

grade 3 hypertension

(severe)

≥ 180 ≥ 110

isolated systolic

hypertension (grade 1)

140–159 < 90

isolated systolic

hypertension (grade 2)

≥ 160 < 90

This classification equates with those of the European society of hypertension and the World health organization–international society of hypertension, and is based on clinic blood pressure (not values for ambulatory blood pressure measurement). Threshold blood pressures for the diagnosis of hypertension with self/home-monitoring are greater than 135/85 mm hg. For ambulatory monitoring, 24-hour values are greater than 125/80 mm hg. if systolic blood pressure and diastolic blood pressure fall into different categories, the higher value should be taken for classification. Reproduced with permission from B Williams, Poulter NR, Brown MJ. guidelines for management of hypertension: report of the fourth working party of the British hypertension society, 2004—Bhs iV. J Hum Hypertens 2004; 18: 139–85

Table 1

ANAEsThEsiA AND iNTENsiVE CARE MEDiCiNE 8:6 22

tenth cranial nerves, respectively. Although primarily involved in the regulation of respiration, changes in blood gas composi­tion (low partial pressure of oxygen (PO2) and high partial pres­sure of carbon dioxide (PCO2)) can also lead to vasoconstriction. Low­pressure mechano­ and chemoreceptors are found on the venous side of the circuit at the junction of the venae cavae and pulmonary veins with the atria; receptors are also located in the lungs, the atria and ventricles.

Efferent output: the heart receives both sympathetic and para­sympathetic (vagal) fibres, which control the force and rate of contraction. Cholinergic parasympathetic tone predominates at rest, acting to slow depolarization of both the sinoatrial (SA) and atrioventricular (AV) nodes. Hence vagal tone slows heart rate. The adrenergic sympathetic fibres innervate the myocardium as well as the SA and AV nodes, hence they can increase both the rate and the force of contraction. The predominant adreno­ceptors in the heart are β­receptors.

Blood vessels are innervated predominantly by sympath­etic fibres; there is a limited parasympathetic supply to cereb­ral vessels, the tongue, salivary glands and external genitalia. While all vessels, with the exception of true capillaries, receive sympathetic fibres, neural influence on the large blood vessels is of far less importance than that on small arteries and arteri­oles. These are the ‘resistance vessels’ whose diameter has the most pronounced effect on total peripheral resistance and hence blood pressure. The resistance vessels possess both α­ and β­adrenoceptors, whereas the capacitance vessels (veins) have only α­adrenoceptors. Norepinephrine (noradrenaline) released by sympathetic fibres causes vasoconstriction in all vascular beds via α­adrenoceptors. Epinephrine (adrenaline), which is secreted by the adrenal medulla along with norepinephrine, dilates resistance vessels at low concentrations, via β­adrenoceptors, and at high concentrations produces vasoconstriction, via the α­adrenoceptors. However, under normal physiological conditions, noradrenaline release from sympathetic fibres predominates.

Central integration and regulation: signals from the sensory afferent fibres are integrated and modulated centrally (Figure 1). The complex control processes are not fully understood, but it is apparent that cardiovascular control is much more complicated than a series of simple reflex arcs. There is good evidence to suggest that afferent signals are modulated at several levels in the brain, and that efferent output may also interact en route from the cortex to the spinal cord. A number of regions of the central nervous system play a role in circulatory control, includ­ing the spinal cord, medulla oblongata, hypothalamus, cerebel­lum and cerebral cortex. Of these, the medulla is probably the most important: section of the brainstem above the medulla does not affect blood pressure. This suggests that, while upper brain levels can modify medulla activity, they do not dominate its actions. Within the medulla a functional, if not anatomical, cardiovascular control centre regulates blood pressure. Stimula­tion of the dorsal lateral medulla causes vasoconstriction, cardiac acceleration and increased myocardial contractility, suggesting that this area acts as a pressor region. Caudal and ventromedial to the pressor region is an area that lowers blood pressure. This depressor region inhibits spinal sympathetic activity and inhibits the medullary pressor region.

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Physiology

Reflex control of blood pressureShort­term changes in blood pressure are corrected by the auto­nomic system. This mechanism is most effective around the nor­mal mean arterial pressure (defined as diastolic pressure plus one­third of pulse pressure) of about 100 mm Hg (Figure 2). The slope or gain of the relation between nerve impulse frequency and blood pressure is maximal at normal mean arterial pressure: this is referred to as the set point. Pressures below 50 mm Hg are not sensed by the baroreceptors and so cannot be corrected by this mechanism. At pressures greater than 170 mm Hg the gain is very low, so changes in blood pressure will have little effect on sympathetic nerve activity. If blood pressure falls below

Neural input and output from the cardiovascular control centre in the medulla oblongata

Changes in blood pressure and partial pressure of oxygen and carbon

dioxide (PO2/PCO

2) are monitored in the carotid artery and aortic arch.

Afferent signals are carried by the ninth cranial (glossopharyngeal) nerve

and tenth cranial (vagus) nerve. Sympathetic (solid line) and

parasympathetic outflow (broken line) modify heart rate

and vasoconstriction

Cerebral cortex

Hypothalamus

Medulla

Spinal

cord

Tenth

Ninth

Carotidbody

↑PCO2

↓PO2

↑PCO2

↓PO2

SA node

Heart

Splanchnic viscera

Bloodvessels

Kidney

Adrenal

Figure 1

ANAEsThEsiA AND iNTENsiVE CARE MEDiCiNE 8:6 22

the set point, the baroreceptor discharge rate decreases, stimula­ting the medullary pressor region. After a typical lag time of 10–15 seconds, sympathetic activity increases, leading to an increase in heart rate and force of contraction, and thus a rise in cardiac output. The change in heart rate precedes the increase in blood pressure by 1–2 seconds. The tachycardia and hyperten­sion are not sustained because the increase in pressure is sub­sequently detected by the baroreceptors, which in turn reduce the response of the medullary neurones. This causes a secondary fall in heart rate and blood pressure, correcting any overshoot in pressure caused by the initial burst of sympathetic activity.

Relation between the carotid sinus pressure and activity of the carotid sinus (glossopharyngeal) nerve (top) and sympathetic nerve (bottom)

Note that at pressures below 50 mm Hg, carotid sinus nerve activity does

not alter, so sympathetic activity is unchanged. Sensitivity (slope of the

curve or gain) of the carotid sinus nerve is greatest around the normal mean

arterial pressure of 100 mm Hg

200150100500

Carotid sinus pressure (mm Hg)

Sym

pa

the

tic

ne

rve

act

ivit

yC

aro

tid

sin

us

ne

rve

act

ivit

y

Figure 2

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Physiology

The set point around which the baroreceptors maintain blood pressure can change in both physiological and pathophysiologi­cal circumstances. Nerve endings in the carotid sinus normally adapt to a prolonged stimulus by decreasing their firing rate, despite continued exposure to high pressure. This adaptation begins within a matter of minutes and is complete within a few days. Gain is unaffected, but the threshold is shifted to a higher pressure. The relation between pressure and reflex baroreceptor discharge may also be altered in disease states. In chronic hyper­tension, the walls of blood vessels become stiffer, which reduces distensibility. Consequently, there is less distortion of the baro­receptor at a given pressure, leading to a reduction in the gain of the system. Furthermore, the set point is increased. In congestive heart failure, the gain is reduced without affecting the threshold for nerve discharge.

Hormonal regulation of blood pressureMaintenance of blood pressure in the long term is achieved through regulation of ECFV, and thus blood volume. This regula­tion is in turn achieved through the integrated actions of several hormones acting on the kidneys. The key hormones involved in the regulation of ECFV are the renin–angiotensin–aldosterone system, vasopressin (antidiuretic hormone) and atrial natriuretic peptide. Erythropoietin, secreted by the kidney in response to a fall in the PO2 in the blood, also affects blood pressure by stimu­lating RBC production. This leads to an increase in the volume and viscosity of the blood.

The renin–angiotensin–aldosterone system plays a major role in the regulation of blood volume and pressure by stimulating the kidney to retain sodium and by vasoconstricting resistance blood vessels. The biologically active component of the system is the octapeptide angiotensin II. It is produced when angioten­sinogen, synthesized in the liver, is cleaved by the enzyme renin into angiotensin I. Angiotensin­converting enzyme then cleaves angiotensin I to form angiotensin II. Other smaller peptides (angiotensin III and angiotensin IV) may also be produced, which have less affinity but nonetheless make a significant contribu­tion to blood pressure regulation. Angiotensin II has four main characteristics: it is a potent vasoconstrictor; it stimulates renal sodium reabsorption, directly through increased Na+:H+ anti­porter activity in the proximal tubule, and indirectly, by stimulat­ing aldosterone secretion from the adrenal cortex; it stimulates vasopressin secretion, which increases the water permeability of the collecting ducts, so increasing water reabsorption; and it stimulates thirst. These effects are mediated by the type 1 angio­tensin II receptor (AT1). A second receptor, the type 2 angioten­sin II receptor (AT2), is found in the fetal kidney, but its role in adults remains controversial.

The rate­limiting step in the production of angiotensin II is the secretion of renin, a glycoprotein protease. Renin is synthesized in the kidney by the juxtaglomerular cells, which are located in the wall of the afferent arteriole supplying the glomerulus. Release of renin is controlled by three distinct mech­anisms: renal baroreceptors; the macula densa; and sympathetic nerves. Similar to the baroreceptors found in the aortic arch and carotid arteries, the renal baroreceptors, located in the afferent arterioles, sense arterial pressure. If renal artery pressure falls below 80 mm Hg, the baroreceptor stimulates the release of

ANAEsThEsiA AND iNTENsiVE CARE MEDiCiNE 8:6 2

renin, leading to angiotensin II formation. This acts to constrict the efferent arteriole, raising glomerular capillary pressure and so maintaining glomerular filtration rate. This mechanism acts primarily within the kidney, to control glomerular filtration rate, but the angiotensin II generated may also have systemic effects.

Renin is also released in response to stimulation of the mac­ula densa, a specialized region of the distal tubule, which lies adjacent to the juxtaglomerular cells. The macula densa monitors sodium chloride concentration in the tubular fluid, stimulating the juxtaglomerular cells to release renin in response to a decrease in concentration. This in turn results in angiotensin II formation and aldosterone secretion, which together stimulate sodium reabsorption. This in turn leads to greater water reabsorption and, hence, expansion of ECFV.

The third trigger for renin release is sympathetic nerve activity. The juxtaglomerular cells are innervated by sympathetic fibres that can cause renin release in response to central stimuli. A decrease in blood volume leads to activation of renal sympathetic nerves, which stimulate renin release and so angiotensin II gen­eration. Angiotensin II restores blood pressure in the short term by vasoconstriction, and in the long term by promoting sodium and thus water retention.

In addition to its direct effect on tubular sodium reabsorp­tion, angiotensin II also stimulates cells in the adrenal cortex to release the mineralocorticoid hormone aldosterone. The adrenal cortex is divided into three zones. The zona glomerulosa, which synthesizes aldosterone, is the outermost zone. The middle layer is called the zona fasciculata, which secretes the glucocorticoids, primarily cortisol. The inner layer is the zona reticularis, which secretes androgens (dehydroepiandrosterone and androstene­dione). All adrenal steroids are derived from cholesterol and are produced by a series of hydroxylations. The specificity of steroid product in each zone is determined by the presence or absence of hydroxylase enzymes. Thus, cells in the zona glomerulosa, which possess 18­hydroxylase, are able to convert corticoste­rone to aldosterone. However, these cells lack 17α­hydroxylase, which is essential for the synthesis of cortisol and androgens. Angiotensin II stimulates the rate­limiting conversion of choles­terol to pregnenolone and the 18­hydroxylation of corticosterone to aldosterone. Aldosterone synthesis is also stimulated by high plasma K+ concentrations. In addition to promoting renal Na+ retention, aldosterone stimulates tubular secretion of K+.

The main target of aldosterone are the principal cells of the collecting duct. The hormone–receptor complex interacts with the cell’s DNA, leading to synthesis of epithelial sodium channels (which are inserted into the apical membrane) and stimulation of the basolateral Na+:K+ATPase pump. Together these increase the tubule’s permeability and driving force for Na+ reabsorption (Figure 3).

Vasopressin is the primary hormonal regulator of renal water reabsorption. In its absence, the collecting ducts are imper­meable to water. As a result, a large volume of dilute urine is excreted. Vasopressin acts, via the type 2 vasopressin receptor (V2), to stimulate insertion of aquaporin 2 water channels into the apical membrane of collecting duct cells. In doing so, it facili­tates the movement of water out of the tubular fluid back into the blood via the osmotic gradient generated through sodium reabsorption. This leads to the formation of a small volume of

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Physiology

concentrated urine. Consequently, under normal circumstances, urine is hyperosmotic to blood. In addition to its role in regula­ting renal water reabsorption, vasopressin also acts as a vaso­constrictor, via the type 1 vasopressin receptor (V1).

Vasopressin is synthesized in nerves fibres of the supraoptic and paraventricular nuclei of the hypothalamus. These fibres project axons down into the posterior pituitary (neurohypo­physis or pars nervosa), from which vasopressin is released into the systemic circulation. The two principal stimuli of vasopres­sin secretion are plasma osmolality and blood volume. However, angiotensin II may also cause its release. On a day­to­day basis, plasma osmolality is the major regulator of vasopressin secretion. In the absence of fluid intake, obligatory water loss – through moisturization of air in the lungs, sweat and urine (500 ml of water are required to dissolve the solutes excreted by the kidneys each day) – will result in an increase in plasma osmolality. This is detected by osmoreceptors in the hypothalamus, which stimulate vasopressin release. The set point, or osmostat, for vasopressin release is 280 mosmole/kg; maximal antidiuresis occurs when plasma osmolality exceeds 295 mosmole/kg. Changes in plasma osmolality as little as 1% can affect vasopressin secretion, and thus water retention. Blood volume can also affect vasopressin

Actions of aldosterone and vasopressin on renal collecting duct cells

Apical Basolateral

Aldosterone binds to the mineralocorticoid receptor (MR), forming a

complex which interacts with DNA to cause epithelial sodium channel (ENaC)

synthesis and insertion into the apical membrane. This facilitates Na+ entry

into the cell and transport into the blood. Vasopressin acts via the

vasopressin 2 (V2) receptor and cAMP to stimulate shuttling of aquaporin 2

(AQP2) water channels into the apical membrane, increasing water

permeability of the cell. Water then flows along the osmotic gradient created

by Na+ transport

ENaC

Na+

Na+

Aldosterone

AQP2

H2O

K+

ATP

V2

receptorVasopressincAMP

MR

MR

Figure 3

ANAEsThEsiA AND iNTENsiVE CARE MEDiCiNE 8:6 22

release; however, relatively large changes are required to trig­ger a response. Extracellular volume is monitored by volume­ or low­pressure receptors in the atria and pulmonary veins. These receptors, in concert with the carotid and aortic baroreceptors, detect changes in blood volume and pressure. A decrease in blood volume greater than 10% stimulates vasopressin secretion.

Atrial natriuretic peptide: ECFV is reduced by the combined actions of atrial natriuretic peptide (ANP). Synthesized by car­diac myocytes in the right atrium, this peptide is released in response to atrial stretch. It acts on the kidney to cause a diuresis by increasing the glomerular filtration rate. This is achieved by constriction of the efferent arteriole and dilatation of the afferent arteriole, so raising glomerular capillary pressure. ANP also acts on the tubule itself, inhibiting the effects of aldosterone and vaso­pressin on sodium and water transport, respectively. In addition to these renal actions, it acts centrally to reduce thirst and causes peripheral vasodilatation. The net effect of these actions reduces ECFV, venous return and cardiac output, and thus blood pressure is lowered. Two related peptides, brain natriuretic peptide, syn­thesized by ventricular myocytes, and C­type natriuretic peptide, have similar natriuretic and vasodilatory effects, respectively.

Haemorrhage – the response to severe blood lossIf blood loss is severe, arterial blood pressure plummets, stimulat­ing both neurological and hormonal responses, which attempt to restore pressure back to normal. Success depends on the severity of blood loss and the balance between compensatory (negative feedback) and decompensatory (positive feedback) mechanisms. Experimental evidence shows that if blood is withdrawn so that arterial pressure falls to 50 mm Hg, pressure starts to increase during the following 30 minutes (Figure 4). In some cases, blood pressure is gradually restored to normal, pre­haemorrhage levels during the following 5–6 hours, whereas in other cases, pres­sure makes an initial partial recovery before declining rapidly, resulting in death. This deterioration is known as haemorrhagic shock and after a certain point, no intervention is able to prevent death.

Following the initial loss of blood, several negative feedback mechanisms are activated that work to restore blood pressure. These include the baroreceptor reflexes, the chemoreceptor reflexes, cerebral ischaemia, reabsorption of tissue fluid, release of vasoactive hormones and renal salt and water retention. The initial response is evoked by the baroreceptors, which initiate an increase in sympathetic tone and a reduction in vagal activ­ity. This increases the force and rate of cardiac contraction and causes a generalized vasoconstriction. Blood is transferred from ‘reservoirs’ in the liver, lungs and skin, which acts to increase the circulating volume. The cerebral and coronary circulations are exempt from the vasoconstriction to ensure that blood is re­directed to the brain and heart. The kidneys are also protected in mild­to­moderate haemorrhage. However, in prolonged or severe haemorrhage, renal blood flow is also reduced, which can result in acute renal failure. Pressures below 50–60 mm Hg are below the threshold for the baroreceptors, but further vaso­constriction may be evoked via the chemoreceptors. Slow blood flow results in hypoxia, stimulating the chemoreceptors. If pres­sure falls below 40 mm Hg, perfusion of the brain is reduced to the extent that cerebral ischaemia occurs. This causes profound

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Physiology

sympathetic stimulation to increase cardiac contractility and restore blood flow to the brain. However, if cerebral ischaemia persists, vagal centres may be activated, causing a reduction in heart rate, which exacerbates the hypotension. Blood volume is

Mean arterial pressure response to haemorrhage

Compensatory reflexes act to increase blood pressure by increasing

sympathetic tone. If negative feedback mechanisms predominate, mean

arterial pressure gradually returns to the resting level (solid line). However,

if decompensatory positive feedback mechanisms dominate, pressure falls

dramatically (broken line). At this stage, interventions cannot restore blood

pressure, resulting in death

752–1

0

–2

Time (hours)

Me

an

art

eri

al

pre

ssu

re (

mm

Hg

)

63 410

25

50

75

100

Figure 4

ANAEsThEsiA AND iNTENsiVE CARE MEDiCiNE 8:6 22

increased by redirecting extracellular and, eventually, intracellu­lar fluid into the blood. The decrease in arterial and venous pres­sure associated with haemorrhage reduces capillary hydrostatic pressure, favouring the movement of fluid from the interstitial space into the blood at a rate of up to 1 litre per hour. The reduc­tions in blood volume and pressure stimulate vasopressin and angiotensin II secretion, which, in addition to direct vasocon­striction, aid in the retention of fluid and gradual re­expansion of blood volume.

In addition to these negative feedback mechanisms, several positive feedback processes may be stimulated that counteract the efforts to restore blood volume and pressure. These include cardiac failure, depression of the central nervous system, altered blood clotting processes, and depression of the reticuloendo­thelial system. Cardiac failure arises through a reduction of coronary blood flow following the initial hypotension; this then results in a further reduction in pressure and lower coronary flow. The inadequate supply of oxygen to respiring tissue leads to acidosis, which is exacerbated by impaired renal excretion of H+. This acidosis has a depressant effect, reducing reactivity of both the heart and the blood vessels to sympathetic stimulation. Central ischaemia initially stimulates sympathetic outflow, but if severe, activity of the cardiovascular centre becomes depressed. Vasodilatation may also be enhanced through exposure to endo­toxins produced by the bacterial flora of the intestines following compromise of the reticuloendothelial system’s normal phago­cytic activity. Successful recovery from haemorrhage depends on the compensatory mechanisms having greater influence on blood pressure than the decompensatory mechanisms. ◆

FuRTHeR ReADiNg

British hypertension society. www.bhsoc.org (accessed 20 February

2007).

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