The Physiology of the Renal Circulation
Burton-Opitz and Lucas (1911) were the first to note the striking constancy of renal blood How in the face of wide variation in perfusion pressure-a phenomenon which struck them as remarkable in the light of their earlier demonstration that the renal vessels were capable of intense vasoconstriction, when the sympathetic nerves were stimulated.
Rein (1931) confirmed that observation and extended it by contrasting the responses of the kidney’s blood vessels to those of the femoral, mesenteric and carotid vascular beds, which were influenced much more by changing perfusion pressure.
The ‘autoregulation’ of renal blood flow despite changes in arterial blood pressure has had too much impact on current thinking: the concept, unfortunately, has gradually broadened so that a consensus of Opinion today might indicate the belief that the renal circulation is relatively autonomous and that renal perfusion is fixed.
In fact renal perfusion shows wide variation in response to external stimuli and changes in the internal milieu, a matter of some importance since changes in renal function clearly cannot be influenced by blood flow if blood flow does not change.
In fact renal perfusion shows wide variation in response to external stimuli and changes in the internal milieu, a matter of some importance since changes in renal function clearly cannot be influenced by blood flow if blood flow does not change.
Emphasis in the following account will be placed on the relationships between renal perfusion and renal function, and on the determinants of renal perfusion. The unequivocal fact that renal perfusion is ordinarily little influenced by perfusion pressure does not mean that perfusion is not influenced by a host of other factors: it is indeed so influenced under a wide variety of circumstances and the renal vascular response probably plays a pivotal role as a determinant of renal function.
There are a number of reasons for a continuing active interest in the renal circulation. Nephron function begins in the glomerulus, where capillary hydrostatic pressure is sufficient to create an ultrafiltrate of plasma.
In man about 180 litres of ultrafiltrate per day cross about one M2 of capillary surface area in about 1 million glomeruli. In the filtrate’s transit through the nephron all but about 1 per cent of the filtered water is reabsorbed, along with a selected portion of the salts and the biologically important organic constituents such as glucose and amino acids.
Evidence is accumulating that the kidney’s blood supply plays a role in the maintenance of the volume, tonicity and electrolyte composition of the body fluids not only through its impact on filtration, but also through more subtle influences on the reabsorptive processes. It has become apparent in the last two decades that the renal vasculature contributes to the fundamental process of converting a plasma ultrafiltrate to urine in several ways.
In man about 180 litres of ultrafiltrate per day cross about one M2 of capillary surface area in about 1 million glomeruli. In the filtrate’s transit through the nephron all but about 1 per cent of the filtered water is reabsorbed, along with a selected portion of the salts and the biologically important organic constituents such as glucose and amino acids.
Evidence is accumulating that the kidney’s blood supply plays a role in the maintenance of the volume, tonicity and electrolyte composition of the body fluids not only through its impact on filtration, but also through more subtle influences on the reabsorptive processes. It has become apparent in the last two decades that the renal vasculature contributes to the fundamental process of converting a plasma ultrafiltrate to urine in several ways.
In common with other vascular beds the blood supply provides oxygen and substrates for renal metabolism, but-especially in the renal cortex-perfusion exceeds these requirements by far. Glomerular capillary pressure is among the highest in the body, due to the very low preglomerular vascular resistance.
This accounts for the very high perfusion rate in the cortex which provides not only the hydrostatic pressure which initiates filtration but also the large volumes of plasma for ultrafiltration. Peritubular capillary hydrostatic pressure in the cortex, conversely, is substantially lower than hydrostatic pressure in other systemic capillaries. Moreover, plasma oncotic pressure in the peritubular capillaries is raised by the previous filtration of from 20 to 30 per cent of the plasma water in the glomerulus. Both factors
This accounts for the very high perfusion rate in the cortex which provides not only the hydrostatic pressure which initiates filtration but also the large volumes of plasma for ultrafiltration. Peritubular capillary hydrostatic pressure in the cortex, conversely, is substantially lower than hydrostatic pressure in other systemic capillaries. Moreover, plasma oncotic pressure in the peritubular capillaries is raised by the previous filtration of from 20 to 30 per cent of the plasma water in the glomerulus. Both factors
enhance peritubular capillary fluid reabsorption. Medullary perfusion, especially blood How in the papilla. is considerably lower than that in most vascular beds. and the low blood flow in the medullary vessels is critical for efficient function ofthe countercurrent mechanism.
Development of methodology made many of the conceptual advances possible, as was true in the case of the observations made by BurtonOpitz, which were based on the then recent development of the thermostromuhr. Developments in methodology may generate more than new concepts; they also frequently engender hot debate, especially when alternative methods provide different answers. Methodology will be discussed only when competing concepts depend directly on the method applied.
Trueta and his collaborators (1947) focused attention on the possibility of an independent circulation in the renal cortex and renal medulla in the 19403. The concept was not new. Earlier Fuchs and Popper (1938) had distinguished parallel outer and inner cortical zones and had pointed out several special features of the medullary blood supply, including a suggestion of a non-glomerular medullary circulation.
Springorum (1939) reported that epinephrine could induce anuria in the dog, associated with a sharp reduction in blood flow measured by thermostromuhr. The reduction in urine output appeared to be out of proportion to the reduction in blood flow-leading to Springorum’s postulate of an intrarenal vascular shunt. Trueta et al. used a number of techniques to assess the renal circulation in the rabbit, including arteriography and intravital staining, but they never measured blood flow directly.
Several manoeuvres induced an unequivocal reduction of cortical perfusion, which they attributed to the diversion of an unchanged total renal blood flow from the cortical to the medullary circulation. Their use of the terms ‘bypass’ and ‘diversion’ leaves little doubt that a shunt mechanism was postulated, a shunt that subsequent investigators were unable to find.
Later, Trueta’s collaborators clearly dissociated themselves from the shunt concept while continue ing to point out that a wide range of noxious stimuli preferentially reduced cortical perfusion (Daniel et al. 1952). It was the repeated failure to demonstrate a shunt, as summarized by Maxwell et al. (1950), that apparently accounted for the hiatus of interest in the subject which characterized the next decade. During that interval Good
Springorum (1939) reported that epinephrine could induce anuria in the dog, associated with a sharp reduction in blood flow measured by thermostromuhr. The reduction in urine output appeared to be out of proportion to the reduction in blood flow-leading to Springorum’s postulate of an intrarenal vascular shunt. Trueta et al. used a number of techniques to assess the renal circulation in the rabbit, including arteriography and intravital staining, but they never measured blood flow directly.
Several manoeuvres induced an unequivocal reduction of cortical perfusion, which they attributed to the diversion of an unchanged total renal blood flow from the cortical to the medullary circulation. Their use of the terms ‘bypass’ and ‘diversion’ leaves little doubt that a shunt mechanism was postulated, a shunt that subsequent investigators were unable to find.
Later, Trueta’s collaborators clearly dissociated themselves from the shunt concept while continue ing to point out that a wide range of noxious stimuli preferentially reduced cortical perfusion (Daniel et al. 1952). It was the repeated failure to demonstrate a shunt, as summarized by Maxwell et al. (1950), that apparently accounted for the hiatus of interest in the subject which characterized the next decade. During that interval Good
yer et al. (1958) found that mild haemorrhage rapidly reduced sodium excretion in the dog in the absence of a change in renal blood flow or filtration rate. Because the response appeared to be too rapid to be hormonal they postulated that a redistribution of intrarenal perfusion could have been responsible for the increased sodium reabsorption a suggestion which apparently engendered little interest at the time but which became the subject of considerable investigation a decade later.
As indicated in the preceding chapter, efferent vasa recta and ascending limbs of the loops of Henle as they leave the medulla lie in close apposition to the afferent vessels and tubules, forming a countercurrent system. As the functional implications for urinary concentration of that striking anatomic arrangement became apparent in the late 19505, it also became apparent that medullary perfusion must be considerably less than that in the renal cortex.
It was this conceptual development which led Kramer and his associates (1960, 1962, Thurau et al. 1960) to develop new methods for assessing local circulation times of indicators in the renal medulla and cortex, and to provide the first quantitative data on differences in regional intrarenal perfusion rates.
Because of the critical survival value of the capacity to generate a hypertonic urine and the unequivocal requirement that medullary perfusion must operate at low levels to prevent the continuous washout of the osmolal gradient created by tubular function, a resurgence of interest in regional intrarenal blood flow occurred-with a parallel development of many methods for assessing regional intrarenal perfusion rates.
Investigation was accelerated by a chance observation made by Barger (1966), as a byproduct of a longstanding interest in the mechanisms by which the kidney retains sodium in congestive heart failure. Catheters were placed in the renal artery of dogs with congestive heart failure, to localize administered sodium to the kidney.
Dye injected through the catheter to assess its position filled the renal cortex evenly in the normal dog, but in dogs with heart failure-despite a normal total renal blood flow-patchy outer cortical filling was evident. Krypton washout was then being used to measure myocardial perfusion in that laboratory, and was soon applied to the assessment of intrarenal perfusion (Thorburn et al. 1963).
It was this conceptual development which led Kramer and his associates (1960, 1962, Thurau et al. 1960) to develop new methods for assessing local circulation times of indicators in the renal medulla and cortex, and to provide the first quantitative data on differences in regional intrarenal perfusion rates.
Because of the critical survival value of the capacity to generate a hypertonic urine and the unequivocal requirement that medullary perfusion must operate at low levels to prevent the continuous washout of the osmolal gradient created by tubular function, a resurgence of interest in regional intrarenal blood flow occurred-with a parallel development of many methods for assessing regional intrarenal perfusion rates.
Investigation was accelerated by a chance observation made by Barger (1966), as a byproduct of a longstanding interest in the mechanisms by which the kidney retains sodium in congestive heart failure. Catheters were placed in the renal artery of dogs with congestive heart failure, to localize administered sodium to the kidney.
Dye injected through the catheter to assess its position filled the renal cortex evenly in the normal dog, but in dogs with heart failure-despite a normal total renal blood flow-patchy outer cortical filling was evident. Krypton washout was then being used to measure myocardial perfusion in that laboratory, and was soon applied to the assessment of intrarenal perfusion (Thorburn et al. 1963).
The stimulus of a possible relationship between patterns of intrarenal perfusion and both sodium and water handling by the kidney accelerated the development of many methods for assessing intrarenal perfusion patterns, used by as many investigators. Unfortunately an individual investigator rarely used more than one method, and the logic, limitations and precise index of perfusion provided by each method differed.
The result has been a decade of passionate advocacy and equally impassioned denial, which only now is being resolved. Zola, in his introduction to L’wuvre, pointed out ‘the creative effort . . . always locked in combat with truth, and always defeated . . .’. At present none of the methods provides information which is free of interpretative doubt.
The result has been a decade of passionate advocacy and equally impassioned denial, which only now is being resolved. Zola, in his introduction to L’wuvre, pointed out ‘the creative effort . . . always locked in combat with truth, and always defeated . . .’. At present none of the methods provides information which is free of interpretative doubt.