HEMOSTATIC AND IMMUNOLOGICAL SEQUELAE OF PORTACAVAL-SHUNT IN RATS

We have evaluated the link between haemostatic abnormalities and immun e dysfunction in liver disease by evaluating parameters of cellular an d humoral immunity in conjunction with coagulation profiles in rats fo llowing portacaval anastomosis, induction of portal hypertension by po rtal vein stenosis or by sham surgical procedures. Twelve weeks follow ing surgery, portacaval shunted rats were markedly anaemic (8.9+/-0.6 g/dl; controls 12.3+/-1.4 g/dl, p<0.05), had low plasma fibrinogen lev els (0.6+/-0.3 g/l, controls 2.5+/-0.2 g/l p<0.05) and markedly elevat ed fibrin(ogen) degradation products (FDP) titres (1/40-1/80; controls <1/10. p<0.05). Portal vein stenosed rats were less anaemic (11.5+/-0 .8 g/dl), had near normal fibrinogen levels (2.1+/-0.3 g/l but elevate d FDP levels (1/40-1/80). Both portacaval shunted and portal vein sten osed rats had elevated serum IgG levels (35.1+/-4.1 g/l; 29.2+/-13.9 g /l respectively; control values 20+/-5.9 g/l p<0.05 for comparison wit h both experimental groups). Intrinsic lymphocyte proliferation to T a nd B cell mitogens was markedly depressed in the portacaval anastamose d rats when compared to controls. Serum factors inhibitory to control lymphocyte proliferation were noted in the shunted rats. Phagocytosis of complement and immunoglobulin sensitised sheep RBC by Kupffer cells purified from rats that had undergone portacaval shunting was markedl y reduced (p<0.05). The increased degree of phagocytosis following exp osure to LPS-endotoxin (50 mu g/ml) was proportionate in degree to the control group. Spontaneous release of bioactive lymphocyte activating factors (IL-L and IL-6) by purified rat sinusoidal cell populations w as decreased in the portacaval shunted group, and decreased still furt her following stimulation with LPS (50 mu g/ml) in vitro. The observat ion that many of the haemostatic and immunological abnormalities assoc iated with chronic liver disease are present in rats with surgically c reated portacaval shunts or with induced portal hypertension, lends cr edence to the hypothesis that shunting of portal blood is, at least in part, responsible for many of the systemic manifestations associated with chronic liver disease.