Kidney Stones Diseases

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 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

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 -  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 -  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,

Tigerstedt and Bergman, in 1898, found that extracts of rabbit kidney raised the blood pressure of anaesthetized rabbits and they gave the name renin to the pressor substance involved. Between 1925 and 1932 the three types of cells that are found in relation to the vascular pole of the glomerulus were described and the name ‘juxtaglomerular apparatus’ was applied to the complex by Goormaghtigh. The association between the two discoveries and the final localization of renin in the granules of the epithelioid cells of the juxtaglomerular apparatus makes a fascinating story of research which has been reviewed by Cook (1971) and F aarup (1971). The role played by the renin-angiotensin system in the functioning of the kidney has grown, from being merely the production of the most potent pressor substance known, to being a system which is probably deeply involved in the regulation of the glomerular filtration rate and the renal circulation in general. The juxtaglomerular appara

The basement membrane - The endothelium of the capillaries rests on a prominent basement membrane to which, on its outer aspect, the foot processes are applied (Fig. 1.20/Read: The epithelial cells ). It is difficult to give a figure for the thickness of the basement membrane since it varies according to the species. It also increases in thickness with age. Jorgensen (1967) estimated the thickness in the human kidney to be 257-418 nm but Latta et al. (1975) give a figure of between 100 and 150 nm. The basement membrane consists of a central dense layer with inner and outer more translucent zones. With certain staining methods several systems of fibres can be Visualized (Latta 1970, Latta et al. 1975), but no ‘pores’ can be seen even in experimental animals in which tracer particles can be seen apparently making their way through the basement membrane. On biochemical analysis, the basement membrane contains a collagen-like material containing 8-10 per cent carbohydrate, the c

The epithelial cells, or podocytes, are stellate cells which are applied closely to the outer aspect of the basement membrane of the capillary loops. The enlarged central portion of the cell contains the nucleus, numerous mitochondria, a lot of granular endoplasmic reticulum and a prominent Golgi apparatus. The endoplasmic reticulum often has dilated cisternae that are filled with a dense material resembling basement membrane (Farquhar et al. 1961) and there is some evidence to suggest that the podocytes do, in fact, produce the basement membrane, which is in a state of continuous turnover. From the central part of the cell, thick processes called trabeculae radiate out and wrap themselves round the circumference of one or, more commonly, several capillaries (Fig. 1.19). Fig. 1.19:  Scanning electron micrograph of capillary loops from a rat glomerulus. The cell body of a podocyte is seen on the right, its processes enveloping a capillary loop. Note the interdigitation of t

The term ‘glomerulus’ is here used in its original sense to mean the small knot or ball of capillaries which forms the most noticeable feature of the Malpighian body or renal corpuscle. The afferent arteriole divides at the vascular pole into a number of branches which supply the lobules of the glomerulus. These branches run fairly superficially towards the opposite pole before breaking up into a series of anastomosing capillary loops which return towards the vascular pole, becoming more deeply placed as they do so. They unite to form the efferent arteriole which usually emerges from the central region of the glomerulus (Fig. 1.18) so that the most distal part of the capillary system, where equilibrium of the filtration pressures is reached, is deeply situated (Spinelli 1974). Fig.1.18 : A juxtamedullary glomerulus (human) to show how the afferent arteriole gives rise to surface branches while the efferent arteriole emerges from the centre of the glomerulus, Microfil injec

The mucosa of the pelvis and calyces has its own profuse vascular plexus which is supplied by large branches from the interlobar and proximal arcuate arteries. As the latter vessels pass into the renal parenchyma, they are surrounded by their own connective tissue sheaths and these are continuous with the connective tissue of the submucosa of the pelvis so that the pelvic branches have a convenient pathway to their destination. The pelvic arteries anastomose freely with each other and with vessels in the hilum, by means of which they communicate with the capsular vessels. The arteries have a characteristic coiled or spiral course (Fig. 1.17) which is usually said to be necessary to allow distension of the pelvis but this is doubtful. From the network of large arteries, branches are given off which form a coarse plexus in the mucosa and from this, in turn, branches form the very dense mucosal capillary plexus. Detailed accounts of the pelvic vasculature have been given by a nu

In the past, the vascular system of the kidney has been described in great detail while the arrangement of the tubules, and their fme structure, have been equally well studied. It is only relatively recently, however, that the two major components of the kidney have been studied in relation to each other. One theory of glomerulo-tubular balance suggests that tubular reabsorption is mediated by the composition and osmolality of blood in the peritubular capillaries. If each individual nephron is to regulate its own function in this way it is essential that the tubule should be surrounded by capillaries derived from the efferent arteriole of its own glomerulus. This relationship has been studied in the kidney of the dog (Beeuwkes 1971, Beeuwkes & Bonventre 1975) and in the human kidney (Beeuwkes, personal communication). It was found that, while the relationship holds good for the subcapsular glomeruli, there is complete dissociation between the tubules derived from a juxtam

These are composed basically of the intermingled descending and ascending vasa recta but they are also, in animal kidneys, closely related to the descending limbs of the loops of Henle. The bundles are not very noticeable in normal sections of the kidney since they run parallel to the usual plane of sectioning, but in sections cut at right angles to the long axis of the bundles they are a very prominent feature of the outer medulla (Figs 1.15 and 1.16). The structure of the vascular bundles has been studied in a number of species but so far there have unfortunately been no detailed studies of the human kidney. The most comprehensive descriptions have been given by Kriz and his colleagues, who studied rodents (Kriz 1967, Kriz et a]. 1972, Kriz & Koepsell 1974). In these species, at least, each bundle consists of a central core composed of closely intermingled ascending and descending vasa recta. These vessels are in very close contact, being separated one from another only

GLOMERULAR SHUNTS -  A number of investigators have described glomeruli in which the afferent and efferent arterioles are continuous across the vascular pole, the glomerular capillaries branching off from the afferent arteriole or the connecting vessel. These afferent-efferent shunts occur almost exclusively in the juxtamedullary glomeruli. Ljungqvist (1964), in a survey of 180 normal and diseased human kidneys, showed by angiography combined with histological methods that, while in the cortical zone the glomeruli showed the normally accepted pattern in which the afferent arteriole, capillary tuft and efferent arteriole are arranged in series, in most of the juxtamedullary glomeruli there was direct continuity between afferent and efferent vessels. In fetal and neonatal kidneys, however, the juxtamedullary glomeruli showed the cortical pattern. It was suggested that the afferent-efferent shunt in the juxtamedullary glomeruli might explain the differing reaction of glomeruli t