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The Medullary Circulation

Black (1965) provided an historical overview on the development of current concepts of medullary function: ‘Kuhn and Ryffel had suggested that the arrangement of tubes in the renal medulla qualified it to act as a single “countercurrent multiplier”; but it was some years until the patient advocacy of Wirz brought the suggestion to the effective notice of English-speaking nephrophiles. It was the German nephrophiles, however, Kramer, Thurau and Deetjen who recognized the implications of the blood supply for the countercurrent mechanism, who developed the first methodology required to provide a quantitative assessment of medullary perfusion and who applied these methods to assessing medullary perfusion directly. The low medullary blood flow, which is required for effective countercurrent function, is not due to poorly developed vasculature, but rather is accounted for by the very high resistance to flow created by the length of the vasa recta. A low flow is critical; the osmolar co

Peritubular Capillary Circulation

In normal man approximately 120 ml/min are filtered, but only 1 ml/min is excreted as urine. Thus over 99 percent must be reabsorbed, removed from the kidney and returned to the systemic circulation. There has been considerable recent interest in the role played by the peritubular environment, especially as it is influenced by renal haemodynamics, in the control of net reabsorption of salt and water from the proximal tubule. The concept that has evolved reflects the possibility that changes in colloid osmotic pressure and hydrostatic pressure in tubular capillaries can influence proximal tubular reabsorption. Peritubular capillary pressure is among the lowest in the body: for example, Wunderlich and Schnermann (1969) and Falchuk and Berliner ( 1971) applied a new, remarkably sensitive pressure measuring device to assess peritubular capillary pressure in the rat kidney, and found a pressure of 65 i 0-5 mmHg, about 20-25 per cent of the value in typical systemic capillaries. Simila

Glomerular Permeability to Macromolecules

The composition of the fluid which passes the glomerular membrane conforms closely to that of an ideal ultrafiltrate of plasma. A large number of micropuncture experiments agree that the concentration of sodium, chloride, phosphate, urea, glucose, hydrogen ion and uric acid in fluid collected from Bowman’s capsule exceeds by 2-4 per cent the concentration in plasma (Renkin & Gilmore 1973). After correction for the influence of Donnan effects of the non-filtered protein on charged particles, the concentrations show remarkable conformity with that predicted for a passive, freely permeable membrane. Dextrans and inulin with a molecular weight of 5,000 or less also appear in the filtrate in concentrations which indicate that the membrane is freely permeable to molecules of this size. Conversely, normal plasma proteins are present in the filtrate only in concentrations at the level of the threshold sensitivity for detection. Bayliss et al. (1933) found in the cat, rabbit and dog t

The Glomerular Regional Intrarenal Circulations

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The extremely high flow rate which characterizes renal perfusion is confined to the renal cortex. The results of a number of representative studies performed with a variety of techniques in the dog under barbiturate anaesthesia are summarized in Figure 2.1. In these studies cortical blood flow ranged from 4-5 to 5-9 ml/g/min. Blood flow in the renal papilla was in the neighbourhood of 0-3 ml/g/min, considerably less than that in most metabolically active organs. Outer medullary flow was intermediate, and close to that which characterizes flow in most metabolically active tissues. A gradient of blood flow from the outer to the inner cortex has been demonstrated with a number of techniques, including microsphere delivery to the kidney (McNay & Abe 1970, Slotkoffet al. 1971, Stein et al. 1973b), and rubidium delivery (Steiner & King 1970). Microsphere delivery, perhaps the most widely used method to date for assessing regional cortical perfusion, has been criticized because

The Anatomy of the Renal Circulation

In the kidney, as in the lung, only a relatively small proportion of the enormous volume of blood flowing through the organ (about 1,300 ml/min) is concerned with the nutrition of the tissues themselves, the greater part having to pass through complicated pathways so that its pH, osmolality and composition may be regulated. The anatomy and physiology of the renal circulation is therefore of the greatest importance but, for reasons which will become apparent, the subject presents many problems and a great deal of work remains to be done before the full contribution of the circulation to renal function may be understood. In particular it must be mentioned that a great deal of investigation has been carried out on the kidneys of various laboratory animals rather than on human kidneys. This applies particularly to ultrastructural studies since adequate fixation for electron microscopy can only be carried out on absolutely fresh material, preferably fixed by intravascular perfusio

The localization of renin in the juxtaglomerular apparatus and The nerve supply of the renal vessels

The localization of renin in the juxtaglomerular apparatus -  Tigerstedt and Bergman found that pressor activity was confined almost entirely to cortical extracts, but it could not be found in the most superficial layers which contain no glomeruli. Later, it was found that renin could be extracted from collections of glomeruli, from individual glomeruli isolated by microdissection and finally, from the vascular poles of isolated glomeruli. Renin activity in the granular epithelioid cells was identified by immunofluorescent methods and a correlation was found between the granulation index (a method of quantifying the granulation of the epithelioid cells) and the renin content of the kidney under different experimental conditions. The source of renin was narrowed down still further by microdissection until finally Cook was able to remove granules from individual epithelioid cells and found that they contained renin. Thurau et al. (1970) found that all the factors necessary to p

The macula densa, The afferent arteriole, and The lacis cells

The macula densa -  As the distal tubule approaches its own glomerulus, the cells on the side facing the vascular pole of the glomerulus become modified to form the macula densa. The cells are taller and narrower than normal distal tubule cells, although this feature is less well marked in the human kidney than in other species. The infoldings of cell membrane near the base of the cell become less deep and the mitochondria diminish in size and number. The intercellular spaces may he dilated, an appearance which in other situations is known to indicate transepithelial transport of salt and water. Experimental evidence suggests that the macula densa is the receptor through which changes in the composition of distal tubular fluid can affect the activities of the juxtaglomerular apparatus and it is presumed that this involves the transepithelial transport of ions. However, Beeuwkcs et al. (1975) have found that while normal distal tubule cells show high Na-K-ATP-ase activity,