General characteristics of the renal circulation

Although kidneys constitute only about 0.5 per cent of the human body mass, they receive about 20 per cent of the cardiac output. This rate of blood flow, which amounts to approximately 4 ml/min/g, is much greater than the one received by other organs ordinarily considered to be well perfused, such as heart, liver and brain. From this sizable blood flow (about 1 litre/min) only a small amount of urine is formed (less than 1 ml/min).

The blood that enters the kidney circulates through several areas with different characteristics. Thus the kidney can be divided into several microcirculatory networks, i.e. the glomerular microcirculation, the cortical peritubular microcirculation and the medullary network. It is important to be aware that there are physiological and pharmacological manoeuvres that can alter blood flow distribution between these areas without altering total renal blood flow.

Measurement of renal blood flow

Total renal blood flow is usually determined in humans by ‘clearance techniques’. This determination is based upon the application of Fick’s principle to the disappearance of an indicator substance from the blood passing through the kidney and its subsequent appearance in the urine. Assuming that this indicator substance is neither synthesized nor catabolized within the kidney, it is evident that its rate of disappearance from the plasma (DP) must be equal to the rate of urine appearance (UA). DP is equal to the difference in concentrations between the arterial (Ai) and venous (Vi) blood multiplied by the renal plasma flow (RPF):

(2.1)

UA is equal to the product of urinary concentration (Ui) by urinary flow rate (UF):

(2.2)

Thus

(2.3)

Rewriting This Equation:

(2.4)

If the fraction of indicator removed by the arterial circulation is designated as the extraction ratio (E), equation (2.4) yields

(2.5)

The indicator most frequently used to estimate RPF is para-aminohippuric acid (PAH) because its extraction rate in humans is between 0.7 and 0.9 when plasma concentrations are below the transport maximum (about 0.02 mg/ml). Plasma concentrations are maintained constant by means of a continuous infusion of PAH. In clinical practice, E is rarely measured and often assumed to be 1. Thus RPF is slightly underestimated. Formerly, it was assumed that the incomplete extraction of EPAH in the human kidney was due to perfusion of ‘inactive’ tissue and PAH clearance was often referred to as ‘effective renal plasma flow’. However, much of the flow supply to the medulla fails to perfuse pars recta segments of proximal tubules (which are the main nephron sites of PAH secretion). Furthermore, there is evidence that in experimental animals such as the dog, EPAH, that is about 0.75 in normal conditions, falls below 0.5 under conditions of high renal blood flow (Earley and Friedler, 1965). Thus, determination of actual extraction ratio during experimental manoeuvres is necessary if precise measurement of RPF is desired. Renal blood flow (RBF) can be calculated from RPF by correcting for the haematocrit (HTC).:

(2.6)

where HCT is expressed in fractional form, about 0.45 in normal humans.

Because the clearance technique requires that patients have near normal urine flow rates and because the technique requires chemical analysis, several alternative methods for measuring total RBF have been developed. Those most used in humans are direct measurements of the dilution of indicators continuously infused in the renal artery and studies of uptake, transit time or washout kinetics of radioactive tracers.

By using clearance techniques, Smith (1943) reported that RPF in young people averaged 592 ± 153 ml/min/1.73 m2 in women and 654 ± 163 in men (mean ± S.D.). In infants, RPF corrected by body weight is approximately one-half that of adults and increases progressively, reaching adult values by 3 years of age (McCrory, 1972). After the age of 30, RBF decreases progressively, and this fact will be the subject of a later section in this chapter.

Intrarenal distribution of renal blood flow

Analysis of RBF distribution into the kidney in man gives different figures depending on the technique used. As average, cortical blood flow represents 90–95 per cent of total RBF, or 6–8 ml/min/g. Distribution of renal cortical blood flow has been extensively investigated in several physiological and pathological situations, and it has been related with sodium balance. This hypothesis is based on the existence of at least two populations of nephrons with a different capacity to handle sodium. It was proposed that manoeuvres that distributed the flow towards inner nephrons, whose efferent arterioles form the medullary capillary network, the vasa recta, were associated with decreased sodium excretion due to the higher capacity of these nephrons to reabsorb sodium (Goodyear and Jaeger, 1955; Carriere et al., 1966). Inversely, volume expansion would induce an increase in superficial cortical blood flow (Stein, Osgood and Ferris, 1972). This phenomenon has been widely studied and, although structural and functional heterogeneity of nephron population is established, the relationship between blood distribution and sodium excretion remains undefined (Beeuwkees, Ichikawa and Brenner, 1981).

Autoregulation of renal blood flow

A typical characteristic of the kidney is the phenomenon of autoregulation of RBF. Many organs are able to maintain blood flow rate relatively constant in the face of major changes in perfusion pressure. This property is termed ‘autoregulation’ and all organs do not show the same efficiency in this autoregulatory process, the brain and kidney being the most efficient. Kidneys are able to maintain RBF in a range of 20 per cent if pressure changes between 50 and 150 mmHg, a range which is termed ‘autoregulatory range’. A similar phenomenon occurs with the glomerular filtration rate (Jones and Berne, 1964). Flow throughout the kidney depends on perfusion pressure and vascular resistance, and this is determined by the combined resistance due to the afferent and efferent arterioles (Thurau, 1964). However, the afferent arteriole seems to be the main locus of resistance changes (Thurau and Wober, 1962).

Since the changes in renal vascular resistance that accompany graded reductions in perfusion pressure are demonstrable in innervated, denervated and isolated kidneys, autoregulation of RBF is assumed to be mediated by mechanisms intrinsic to the kidney (Thurau, 1964) and to be independent of circulating humoral or neurogenic factors. Several theories have been proposed to account for this phenomenon. According to the myogenic theory, the capacity of arterial smooth muscle to contract depends on the vascular wall tension. Thus, an increase in arterial pressure, which initially will distend the vascular wall, will be followed by an active contraction of the resistance vessels, increase in resistance and the subsequent restoration of blood flow to levels similar to that previous to pressure increase. This theory, formulated by Bayliss (1902) has received recent experimental support (Robertson et al., 1972), but cannot explain the mechanism by which changes in renal blood flow are sensed or the fine adjustment of arterial radius.

According to the metabolic theory, changes in blood flow through a tissue would alter oxygen tension, pH and/or concentration of metabolites which would alter vascular...