Tissue Fibrinolytic Activity In Digestive Tract

II. Protein-Losing Gastroenteropathy

Abstract

Previously, the authors have reported from the experiences of three cases of protein-losing gastroenteropathy, that the fibrinolytic activity in the digestive tract, mainly tissue activator of plasminogen, plays an important role in the pathogenesis of excessive enteric loss of protein. This is a report of experimental protein-losing gastroenteropathy in which the participation of tissue fibrinolysis on the increase of permeability of mucous membrane to plasma protein is examined.
1) Activators of plasminogen, either streptokinase or rokinase, was found to produceexperimental protein-losing gastroenteropathy in rats, indicating the activation of fibrinolyticsystem have participated in the increase of mucosal permeability.
2) Whole body irradiation has already been known to produce protein-losing gastro-enteropathy in experimental animals. Tissue fibrinolysis in the small intestine of irradiatedmice was found to increase after 24 to 48 hours of irradiation, and decrease after 72 hours. Similarity of the pattern of the increase in tissue fibrinolysis with that of fecal excretion of ¹³¹I-PVP in the irradiated rats, as well as the reduction of fecal excretion of ¹³¹I-PVP by the useof t-AMCHA, a specific inhibitor of fibrinolysis, strongly indicated the correlation of tissuefibrinolysis with enteric loss of plasma protein.
3) In experimental protein-losing gastroenteropathy produced by the use of 5-fluorouracil (5FU), the increase of tisseue fibrinolysis in the digestive tract of rats was demonstratedto parallel with the increase of ¹³¹I-PVP fecal excretion, and further t-AMCHA waseffective to prevent the clearance of ¹³¹I-PVP, also supported our new concept.
4) Ligature of thoracic duct has been reported to produce protein-losing gastro-enteropathy. The evidence that the ligature of rat thoracic duct did not affect the tissuefibrinolysis suggested the mechanism of enteric loss of protein produced by the increase oflymphatic pressure is different from that shown before.
Tissue fibrinolysis in the digestive tract, whether it is increased primarily or secondary tothe underlying disorders, is thus proved to increase the permeability of mucous membraneof digestive tract and enhance the enteric loss of plasma protein when the increase is occuredin wide range. It seems reasonable to classify the protein-losing gastroenteropathy accompaniedby the increase of lymphatic pressure in the different category.