The kidneys receive approximately 20% of cardiac output. They are capable of increasing flow even further, although they constitute less than 0.5% of the total body weight. This marked renal blood flow is well in excess of that required to provide renal tissue with sufficient oxygen and nutrients. Therefore, renal blood flow is regulated to maintain an optimum delivery of filtrate to the nephrons and adequate reabsorption of fluid back into the vascular system. The factors that control renal circulation are divided into intrinsic factors (autoregulation and renal nerves) and extrinsic factors (hormonal and other endogenous vasoactive agents).
Regulation of the renal blood flow depends closely on changes of vascular resistance secondary to constriction or relaxation of vascular smooth muscles. Autoregulation is the intrinsic ability of the kidney to maintain a relatively constant blood flow over a range of renal perfusion pressure from 75 to 180 mm Hg. Outside this pressure range, afferent arteriolar resistance is less responsive and flow becomes pressure dependent.5 As this vascular reaction is demonstrable in isolated kidneys, autoregulation of renal blood flow is generally assumed to be mediated by factors intrinsic to the kidney. It is well accepted that blood flow to the renal cortex is autoregulated. Whether there is also blood flow autoregulation in the medulla remains controversial.
Currently, two theories are proposed to explain autoregulation. One is the myogenic theory first discussed by Bayliss in 1902.6 It has been shown that a vasoconstrictor is released from renal vessels when the transmural pressure difference increases, supporting a relationship between the endothelium and the vascular smooth muscle, which mediates the autoregulation. The second theory postulates a tubuloglomerular feedback mechanism which enables autoregulation of both renal blood flow and glomerular filtration rate. Within the autoregulatory range, there is a coupling between renal blood flow and glomerular filtration rate, which supports the postulate that the principal autoregulatory actions on renal vascular resistance occur at preglomerular arterioles.7 The tubuloglomerular feedback theory is based on a relationship between the distal tubular Na+ delivery and the intrarenal release of renin.8 Changes in distal tubular flow and/or solute can affect renal blood flow and thus modulate glomerular filtration rate. Recent data support a close interaction between the tubuloglomerular feedback and the myogenic mechanisms (Fig 8.1). Thus, the renal vascular bed is believed to consist of a rapid (myogenic
response) and a slow (tubuloglomerular feedback mechanism) component of renal autoregulation.
The renal nerves contain both afferent and efferent nerve fibres which release noradrenaline (norepinephrine).9 Both noradrenaline and adrenaline (epinephrine) released from the adrenal medulla activate ^-adrenoceptors and cause vasoconstriction, which decreases both renal blood flow and glomerular filtration rate. Renal nerves also release dopamine (DA) which activates specific dopamine receptors existing in abundance in the renal tissues. Activation of the DA^receptors causes significant increases in both cortical and medullary blood flows.10 In addition, the release of neuropeptideY and noradrenaline from sympathetic activation can stimulate Y-receptors and contribute to the modulation of renal vascular resistance.11
Renin is a proteolytic enzyme that is synthesised in the epithelial cells of the juxtaglomerular apparatus and secreted into the surrounding interstitium. It cleaves angiotensin I from angiotensinogen. Angiotensin I is converted into angiotensin II which exerts both direct and indirect adrenergic actions on renal arterioles. Angiotensin II can also act as a circulating hormone. It is a potent vasoconstrictor; however, its most important action is to stimulate aldosterone production and secretion by the adrenal cortex. Thus, an increase in renin release from the kidney will lead to an increase in Na+ reabsorption secondary to a higher blood level of aldosterone. The increased reabsorption of Na+ will facilitate water movement from the interstitial space and increase plasma volume. The renin-angiotensin system shuts off once the volume deficit is corrected.12 Although angiotensin II has potent vasoconstrictor effects on the afferent arterioles, its primary action appears to be on the efferent arterioles. Vasoconstriction of the efferent arterioles can contribute to the maintenance of the glomerular filtration, particularly when renal plasma flow is reduced. There are two main angiotensin II receptors: ATi and AT2. Activation of these receptors increases the sensitivity of the tubuloglomerular feedback mechanisms and augments autoregulation. Blockade of the renin-angiotensin system, however, has no effect on autoregulation.13
This hormone, also called vasopressin, is synthesised in the hypothalamus and released from the posterior pituitary gland. The release of antidiuretic hormone (ADH) can be stimulated by changes in the volume and osmolality of body fluids or by activation of the sympathetic nervous system. This hormone acts on the collecting tubules where it inhibits diuresis and increases water reabsorption leading to increased plasma volume. Thus, ADH modulates urinary concentration via an increase in osmotic water permeability and a decrease in medullary blood flow by constricting juxtamedullary arterioles.13 Although ADH is involved in the maintenance of the volume and osmolality of plasma, the magnitude and direction of such involvement remain controversial. The conflicting results may result from different dosages of ADH, varying states of fluid balance, and the influence of other vasoactive agents.
Prostaglandin E2 (PGE2) and prostacyclin (PGI2) are produced within the kidney during haemorrhagic hypovolaemia. The production of these substances is stimulated by sympathetic nerve activity and angiotensin II. During haemorrhage, prostaglandin synthesis occurs within the kidneys, which causes vasodilation in the afferent and efferent arterioles to prevent severe renal vasoconstriction and ischaemia. Therefore, prostaglandins appear to play a role in modulating the renal vascular effects of other vasoactive agents, including vasoconstrictor hormones and bradykinins. As prostaglandin inhibitors do not significantly alter renal blood flow autoregulation, the contribution of prostaglandins to the control of basal or resting renal blood flow is considered to be minimal.14
Atrial natriuretic peptide (ANP) is a recently discovered peptide that appears to be involved in the regulation of renal function and Na+ balance. ANP is released primarily from cardiac atria in response to atrial distension secondary to volume expansion. This peptide is a rapidly acting, potent natriuretic and diuretic substance, which can also exert direct vasodilator effects on the systemic vasculature. There are membrane receptors for ANP throughout the renal cortical and medullary vasculature, particularly at the glomerular capillaries. Infusion of ANP increases renal blood flow, glomerular filtration rate, papillary plasma flow, and sodium excretion caused by a direct vasodilator effect.15 As ANP can inhibit renin secretion and aldosterone release, and increase urinary kallikrein excretion, part of the renal effects of ANP may be indirect. Nevertheless, ANP appears to have an important role in the control of Na+ balance during conditions of altered plasma volume. The Na+ excretion may be partially mediated by the vasodilator effect of ANP which increases the glomerular filtration rate.
It has been proposed that adenosine may play a role in the regulation of renal blood flow and glomerular filtration.16 Administration of adenosine causes significant changes in renal vascular resistance, glomerular filtration rate, and renin release. Responses of renal vascular resistance to intrarenal infusion of adenosine include an initial transient vasoconstriction of the afferent arterioles, possibly by interaction with the renin-angiotensin system, and is followed by a dilatory phase that may be associated with a marked vasodilation caused by both direct and indirect mechanisms. The vasoconstriction of the afferent arterioles combined with the vasodilation of the efferent arterioles can result in sustained decreases in glomerular filtration pressure and rate. In addition, adenosine can exert a direct and powerful inhibition of renin release by the juxtaglomerular cells. In general, adenosine appears to be an important mediator in the control of renal blood flow. Further studies are, however, necessary to delineate the effects of adenosine on both the renal and the systemic vasculature.
Administration of bradykinin released from plasma kallikrein causes marked renal vasodilation. Infusion of kinin antagonist decreases papillary blood flow by 20% without changing outer cortical blood flow, indicating that kinins exert a vasodilatory influence on the papillary vessels. The role of kinin in regulating medullary haemodynamics is not, however, clear because more than 90% of the renal kallikrein is found in the cortex and a very small fraction in the medulla and papilla.
The role of endothelium derived relaxing factor (EDRF) or nitric oxide (NO) is being extensively investigated. Recent data suggest that about 30% of renal vascular resistance may be controlled by NO. The collecting duct and vasa recta capillaries seem to be the major sites of NO synthesis.17 NO inhibitor infused into the renal medulla decreases papillary blood flow without changes in cortical blood flow, renal blood flow, or mean arterial pressure.18 Systemic inhibition of NO, however, significantly decreases renal blood flow without affecting the glomerular filtration rate.19 During NO blockade, renal autoregulation remains intact. Apparently, NO blockade shifts the myogenic response to a lower renal arterial pressure and thus modulates autoregulation. It has been speculated that NO blockade inhibits the myogenic response, but autoregulation is sustained by a strong activation of the tubuloglomerular feedback mechanism.7 In the presence of NO deficiency in the cells of the macula densa, the tubuloglomerular feedback mechanism becomes increasingly sensitive, which leads to elevated sodium and water retention and thereby hypertension. The release of NO in response to changes in vessel tension is postulated to be associated with the activation of membrane receptors or to involve a complex enzymatic pathway. Inflammation mediators such as tumour necrosis factor modify the release of NO from either endothelial or non-endothelial cells.20
Other vasoactive substances such as serotonin and histamine have been proposed as mediators involved in the control of renal haemodynamics. Current data, however, suggest that their role in regulating the renal circulation appears to be limited. Future studies should examine the possible role of endothelin in the local control of renal blood flow.
Fig 8.2 demonstrates the main contributors to renal circulatory control. Effects of anaesthetic drugs on renal blood flow
Anaesthetic drugs are associated with significant sympathetic and endocrine changes, particularly those with sympathomimetic properties such as pentobarbital (pentobarbitone), and ketamine can stimulate the release of catecholamines. An increased blood level of adrenaline causes significant renal vasoconstriction and triggers renin release from the juxtamedullary nephrons. The formation of angiotensin II from renin leads to profound vasoconstriction of the renal vessels, and associated decreases in both the renal blood flow and glomerular filtration rate. Surgical stress may also induce further release of catecholamines, ADH, and aldosterone into the circulation. Opioids generally decrease regional vascular resistance by both local and systemically mediated mechanisms, but changes in perfusion pressure are moderated by reflex increases in sympathetic activity. They also appear to have no significant effect on renal blood flow. A low concentration of propofol has no effect on blood pressure, heart rate, or renal nerve activity. At moderate to high doses, renal nerve activity decreased by 22-50%, but the effect of propofol on renal blood flow still has to be elucidated.
Of -Adrenergic receptors Angiotensin II
Fig 8.2 Factors controlling renal blood flow.
Prostaglandins ANP Adenosine + Kinins / WO
In healthy volunteers in the absence of surgical stimuli, as well as in patients undergoing surgery, inhalational anaesthetic drugs are associated with dose dependent decreases in renal blood flow, glomerular filtration rate, and urine production. These anaesthetic drugs have both direct and indirect effects on renal blood flow. The direct effects on the renal bed can be intensified in certain clinical conditions, including dehydration, pain, and loss of blood volume. They are accompanied by indirect factors such as depressed myocardial performance, altered vascular resistance, or decreased intravascular volume associated with most inhalational anaesthetic agents. Data from laboratory animals clearly demonstrate changes in active ion transport during anaesthesia. It has been suggested that an interaction with adrenaline is involved in the augmented Na+ transport, whereas the inhibition of Na+ transport is related to a direct effect of inhalational anaesthetic drugs. At concentrations of 3% or higher, halothane causes significant decreases in renal blood flow and oxygen consumption. The effects of enflurane and isoflurane on renal blood flow are considerably less than those of halothane. All inhalational anaesthetic drugs at high concentrations, however, possess potent vasodilator properties which may lead to loss of autoregulation.
Spinal or epidural anaesthesia may cause significant reductions in glomerular filtration rate and renal plasma flow when arterial blood pressure is markedly reduced. When the reduction of perfusion pressure is corrected, renal haemodynamics are normalised, suggesting that perfusion pressure is an important factor in sustaining normal circulation in the kidney. No change in plasma renin levels is observed with either spinal or epidural anaesthesia. Therefore, the decrease in renal blood flow during spinal or epidural anaesthesia is possibly caused by a reduction in venous return and decreased cardiac output.
In summary, anaesthetic drugs are associated with an increase in renal vascular resistance. It is still, however, controversial whether anaesthetic drugs alter renal autoregulation.
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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...