Peritoneal Transport Physiology: Insights from Basic Research1

Clinical uses of the peritoneal cavity, such as i.p. chemotherapy or peritoneal dialysis, depend on underlying physiological mechanisms of transport between the blood and the peritoneal cavity. Clinical models of peritoneal transport have focused on an idealized TMperitoneal membrane.” However, such a membrane does not physically exist. Transport actually occurs between the peritoneal cavity and blood which is contained in discrete capillaries distributed in the tissue interstitium surrounding the cayity. To integrate the properties of the capillaries and the interstitium, the “distributed model” approach couples pore theory, which simulates transendothehal transport, with diffusion and convection within the tissue space. The distributed theory can explain why the peritoneal membrane, when compared with the artificial kidney, appears tight to urea but leaky to protein. The additional resistance to urea transport has been attributed to TMunstirred layers” adjacent to the peritoneal membrane. These can now be defined physiologically by examining diffusion in the tissue space. Absolute rates of convection into and out of the cavity cannot yet be accurately predicted, but the physiological forces can be specified. Net “ultrafiltration” during dialysis results from not only high osmotic pressure in the peritoneal dialysate but also from a small but significant hydrostatic pressure which drives convection in the opposite direction. Recent implications from protein absorption studies that lymphatics are the cause of the decrease in net ultrafiltration are only partly true. Analysis of data from the tissue space has shown that ‘Received December 13. 1990. Accepted May 16, 1991. 2co espondence to Dr. M.F. Fiessner, Building 10, Room 6N-307, National institutes of Health. Bethesda, MD 20892. 1046-6673/0202-0122$03.00/0 Journal of the American Society of Nephrology Copyright © 1991 by the American Society of Nephrology U nder normal conditions, the peritoneal cavity is a potential space which surrounds the viscera of the abdomen. Because of its large surface area (2 m2 in the adult human) (1) and the large total blood flow which courses through the tissues which surround it, the cavity provides an excellent portal of entry for drugs or other solutes to the general circulation. Oncobogists use the peritoneal cavity in regional chemotherapy for ovarian and coborectal carcinomas, and interest has increased in the penetration of both small-molecular-weight drugs (2,3) and monocbonal antibodies (4) into the tissue which surrounds the cavity. Transport of water and solutes also occurs from the blood to the cavity during pentoneal dialysis. NephrobogIsts commonly use the cayity of patients with renal failure to remove uremic metabolites and water from the circulation as well as to treat peritonitis with i.p. antibiotics. The underlying physiological mechanisms which govern peritoneal transport of water and small sobutes are the same for either direction: blood-to-pentoneal cavity or penitoneal cavity-to-blood. The physiological forces which drive the mechanisms, however, do depend on the direction of transport. There is also asymmetry In the directional transport of macromolecules between the blood and the cavity. The mechanisms and the driving forces which determine the seemingly disparate medical uses of the peritoneal cavity, i.e., drug delivery and dialysis, will be the subject of this review.