Pancreatic enzymes: Secretion and luminal nutrient digestion in health anddisease

Severe pancreatic exocrine insufficiency leading to malabsorption of nutrie nts is one of the most important late features of chronic pancreatitis. In contrast to other key enzymes, pancreatic synthesis and secretion of lipase is impaired more rapidly, its intraluminal survival is shorter due to its higher susceptibility against acidic and proteolytic denaturation, and its luminal digestive action is hardly compensated by nonpancreatic mechanisms. As a consequence, steatorrhea is in general more severe and occurs several years before clinical malabsorption of protein or starch. Apart from the d etrimental effects of nutrient deficiency, profound alterations of upper ga strointestinal secretory and motor functions may be an additional and hithe rto underestimated consequence of increased nutrient delivery to distal int estinal sites. Effective reduction of nutrient malabsorption in pancreatic insufficiency requires delivery of sufficient enzymatic activity into the d uodenal lumen simultaneously with meal nutrients. Modern enteric-coated pan creatin microsphere preparations attempt to achieve this by optimizing the size of individual microspheres and chemical properties of the coating. How ever, lipid digestion cannot be completely normalized in most patients by c urrent standard therapy. In the future, acid and protease stable bacterial and fungal lipases with additional pH optima in the acidic milieu or animal or bioengineered human gastric lipase preparations may offer superior ther apeutic alternatives. This review first summarizes current knowledge about secretion and luminal fate of pancreatic enzymes and their effects on nutri ent digestion in health and chronic pancreatitis. Second, rationale, curren t standards, options, and future aspects of enzyme replacement therapy are discussed.