New concepts in molecular biology and ultrastructural pathology of the peritoneum: their significance for peritoneal dialysis.
Continuous ambulatory peritoneal dialysis (CAPD) was developed into a life-maintaining therapy using a membrane whose fundamental biological characteristics were largely unknown. Recognition of this deficiency in our knowledge spurred a belated explosion of research that began with an exploration of the fine structure of the mesothelium. The monolayer of lining cells was found to be more sophisticated than previously imagined, being profusely carpeted with microvilli and bearing motile cilia, and in contrast to endothelium, was shown to possess a cytoplasm replete with organelles in which rough endoplasmic reticulum and lipid inclusions are prominent. Because these findings indicated possible secretory function, a link was sought between these observations and the discovery in effluent dialysate of phosphatidylcholine, a lubricant surfactant. Subsequently, comparison of mesothelial ultrastructure with that of type 2 pneumocytes revealed close concordance, while specialized fixation techniques developed for the preservation of lamellar bodies (the known storage vesicles of alveolar surfactant), when applied to mesothelium, for the first time revealed similar cytoplasmic inclusions. In vitro studies have shown that mesothelium, when incubated with radiolabeled precursor, is capable of synthesizing phosphatidylcholine, the principal constituent of pulmonary surfactant, in amounts similar to those produced by lung. The demonstration that the intensively studied type 2 pneumocyte and mesothelium both secrete lamellar bodies has opened up new possibilities in exploring the physiology, pharmacology, and pathology of the peritoneum. Recent work on mesothelial cell culture has shed new light on the factors involved in healing and regeneration. Recognition of the existence of subserosal multipotential cells and their importance in maintaining the integrity of the mesothelial cell layer is dawning. From the study of peritoneal biopsies in CAPD patients, evidence is accumulating that a process of nonenzymatic glycosylation of protein, similar to that which occurs in diabetes, is responsible for changes in stromal texture and the reduplication of basement membranes. Appreciation of stromal vulnerability to dialysate-induced accelerated aging following mesothelial loss may therefore require a new approach to peritoneal dialysis during peritonitis. Now that CAPD approaches clinical maturity there is increasing recognition of the need for strategies to ensure long-term preservation of the peritoneum as a dialyzing organ. Concomitantly there is a realization that these goals can only be attained through a much deeper appreciation of the molecular biology and pathology of the peritoneum itself.
Renal Division, Baxter Healthcare Corporation, William B. Graham Research Center, Round Lake, IL 60073.
J W
JW
Dobbie
D000818:Animals; D005947:Glucose / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000473:pathology / Q000502:physiology*; D010538:Peritonitis / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000378:metabolism
D011506:Proteins; D005947:Glucose