Drawing from diverse sources including epidemiological and clinical data, surgical observations, histopathology, serosal healing responses to fibrin and fibrinolysis, tissue reaction to chronic exposure, and to exo and endotoxins, new information on mesothelial stem cells, autocrine and paracrine influences on their proliferation and collagen synthesis, and the effect of glucose on fibroconnective tissue, we have begun to piece together the pathogenetic jigsaw of fibrosis in continuous ambulatory peritoneal dialysis (CAPD). The reaction of peritoneal mesothelium and stroma to the stress of continual dialysis results in a spectrum of alterations ranging from opacification through a tanned peritoneum syndrome to sclerosing encapsulating peritonitis (SEP). Any agent that causes irritation of the mesothelial layer and induces serositis, or single severe or multiple episodes of peritonitis resulting in mesothelial loss, predisposes the peritoneum to fibroneogenesis. An accurate definition of the histopathological changes of peritoneal thickening is a prerequisite for defining pathogenesis. This paper is the first attempt to create such a framework. It is evident from many areas of study that fibrin deposition and fibrinolysis, hyalinization of the superficial stromal collagen possibly tanned through nonenzymatic glycosylation by dialysate glucose and the proliferative potential of mesothelial stem cells play an important and possibly interdependent role in excessive fibroneogenesis in certain patients on CAPD. Many of the pieces of the jigsaw are obviously still missing, and the picture is most surely incomplete. Nevertheless, the outline of the pathologic and etiologic landscape should now be discernible.
SUMMARY
The internal anatomy, particularly the vasculature, of the human adrenal was investigated with the help of three-dimensional reconstruction models supplemented by stereo-angiography. A definite pattern of positional relationship was shown to exist between the cortex, medulla and venous drainage, and on this basis the adrenal should be considered as a tripartite structure consisting of a head, a body and a tail region. The disposition of the longitudinal muscle bundles in the adrenal veins follows a definite pattern in each region of the gland. The muscular veins lie almost entirely within sleeves of cortical tissue. The selective gathering of the muscle bundles into the medulla-facing segment of the veins in certain regions of the gland is described. The effect of this muscular arrangement on the venous sinuses which pass between the muscle bundles was investigated and considered to be one of closure. Elastic tissue was demonstrated in the medullary venous sinuses; it is suggested that together with the muscle bundles both constitute a musculo-elastic organ capable of intermittent explosive release of hormones from the venous sinuses into the central vein. The hitherto neglected effect of the unique venous sytem on the function of the cortex was examined. Its possible role in the morphological changes of the adult cortex in response to stress, adrenocorticotrophic hormone, and in adrenal pathology is considered.
Stimulated by the development of continuous ambulatory peritoneal dialysis (CAPD), it was only in the last decade that normal and dialysate-exposed peritoneum were examined by electron microscopy. Biopsies of parietal peritoneum from patients on CAPD show ultrastructural alterations in the mesothelium consisting of an increased development of the rough endoplasmic reticulum but a decrease in surface microvilli and micropinocytotic vesicles as compared to tissue from normal controls or uremic individuals. Alterations in amount and consistency of submesothelial ground substance, and number and disposition of collagen fibers combined with mesothelial changes together constitute the ‘reactive’ peritoneum of peritoneal dialysis.
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