Capillary and interstitial transport of fluid and solutes across the peritoneal membrane

Sammanfattning: According to the three-pore model of peritoneal transport the major exchange pathway between the blood and the peritoneal cavity is represented by “small pores”, permeable to small solutes and water. Osmotically induced fluid flow, as during peritoneal dialysis (PD), is postulated to occur to a great extent through a water-only pathway, whereas proteins are predicted to reach the peritoneal cavity by unidirectional convection across “large pores”. Using an experimental rat model of PD, we were able to show the existence of aquaporins (AQP1) in mesothelial and endothelial cells and to block these aquaporins using mercuric chloride after gentle pre-fixation of the peritoneum in vivo. Data obtained from isolated perfused rat hindquarters, using N-ethylmaleimide (NEM) as a blocker of transcytosis, did not support a significant role for “non-porous” transport mechanisms in the overall transendothelial passage of proteins. The interstitial space of the peritoneum was investigated using a combination of different techniques. The increased mass-transfer area coefficients to small solutes occurring early during PD dwells are mainly attributed to initial vasodilatation and recruitment of capillaries instead of interstitial solute discharge from the spaces surrounding the peritoneal cavity. Neither interstitial edema, as during peritonitis, or during pre-incubation of the peritoneal cavity using phosphate buffered saline, nor removal of the interstitial hyaluronan seemed to markedly alter overall peritoneal transport. Furthermore, vibration of rats markedly increased the contact between dialysate and the visceral, but not the parietal, peritoneum, indicating that there are “unmixed” conditions during normal PD. In peritonitis lymph flow from the peritoneum was reduced, not increased. In conclusion the present thesis points out the capillary wall as the major transport barrier between the plasma and the peritoneum, while the interstitial compartment seems to be of less importance. The data presented support the presence of a water-only and a large pore pathway in the capillary wall, in agreement with the three-pore model of peritoneal transport.