ORIGIN AND DEVELOPMENT OF EXOCRINE PANCREATIC INSUFFICIENCY IN EXPERIMENTAL RENAL-FAILURE

Chronic renal failure affects the physiological function of many organ systems. One of them is the exocrine pancreas. Although varying degre es of pancreatic insufficiency are the dominating clinical characteris tic of uraemic pancreatic disease, it remains unclear whether this dis ease should be regarded as a manifestation of chronic pancreatitis, ar ising from recurring attacks of acute pancreatitis, or represents a di stinct entity. The exocrine pancreas was studied in a model of experim ental renal failure. The pancreas was removed from each rat at selecte d time points over eight weeks after subtotal nephrectomy and from a s tandard rat model of pancreatitis for comparison. The data show that t he in vitro secretory response is considerably changed in renal failur e (increased during early acute and decreased during chronic renal fai lure). While the pancreatic content of digestive enzymes progressively declines, DNA and protein synthesis increase over time. Acinar cell d eletion is increased and accompanied by an increased rate of mitosis. This increased cellular turnover is not associated with tissue oedema, pancreatic fibrosis, inflammatory changes, autophagocytosis or subcel lular redistribution of lysosomal hydrolases, all of which are charact eristic for pancreatitis. The ultrastructural changes of uraemic pancr eatic disease bear no resemblance to the changes seen in pancreatitis. It is concluded that the morphological and biochemical changes in ear ly uraemic pancreatic disease are quite distinct, correspond with toxi c damage of the pancreas, and are dominated by functional impairment a nd an increased cellular turnover.