Figure 1. Organization of the exocrine pancreas. (A) Acinar cell organization. Pancreatic digestive enzymes are synthesized in the rough endoplasmic reticulum (RER) and transported to the perinuclear Golgi region, in which they are sorted from other proteins and directed into condensing vesicles. The contents are compacted to make mature zymogen granules that are transported to the apical end of the cell near to the duct lumen. The apical pole of the cell is protected from intracellular hypercalcemia by calcium pumps on the luminal membrane, the endoplasmic reticulum and the mitochondria, which may form a protective barrier between the apical and basolateral poles of the cell. (B) Duct cells seen in the cross-section of a small pancreatic duct. The cystic fibrosis transmembrane conductance regulator (CFTR) molecule is located on the apical membrane of the duct cell. The relatively small volume of the duct lumen compared with the duct cell may allow for rapid changes in the concentration and ionic concentration of fluid in the duct after opening of the CFTR. A high concentration of ions causes water to enter the lumen by osmosis, and the addition of water flushes the contents of the duct lumen (including zymogens) out of the pancreas and into the intestine.
Figure 2. Research models of chronic pancreatitis. The problem of understanding how the normal pancreas (A) progresses to chronic pancreatitis (B) is illustrated with an arrow and question mark. The molecular comparison of normal and abnormal pancreata from patients with chronic pancreatitis identifies numerous differences (e.g. by analysis of gene expression arrays), which confirms that chronic pancreatitis represents the loss of normal tissue and the addition of chronic inflammatory cells and fibrosis. Newer models of complex disease (C) consider the interaction of multiple risk factors that can be divided into three domains, which are represented by three overlapping circles. Subjects who have inadequate injury protection (e.g. they have PRSS1, SPINK1 or CFTR mutations) and who are challenged by metabolic or environmental stressors (e.g. pancreatic hyperstimulation) develop recurrent acute pancreatitis (RAP). A subset of these subjects seem to have an altered immune response that leads to prolonged episodes of acute pancreatitis (smoldering pancreatitis) or accelerated fibrosis and chronic pancreatitis (CP). Chronic pancreatitis may be similar to other chronic inflammatory diseases such as inflammatory bowel disease (IBD) or idiopathic pulmonary fibrosis (IPF), except that the pancreas, rather than the bowel or lung, is susceptible to metabolism- or environment-associated injury.