The pancreas is really two organs packaged into one. The islets of Langerhans scattered in the pancreas serve critical endocrine functions, and the exocrine portion that makes up the bulk of this organ is a major source of enzymes that are essential for digestion. Diseases affecting the pancreas can be the source of significant morbidity and mortality. Unfortunately, the retroperitoneal location of the pancreas and the generally vague nature of signs and symptoms associated with its injury or with dysfunction of the exocrine portion allow many pancreatic diseases to progress undiagnosed for extended periods of time; thus, recognition of pancreatic disorders requires a high degree of suspicion.
The pancreas gets its name from the Greek pankreas, meaning “all flesh,” and is a complex lobulated organ. The endocrine portion constitutes only 1% to 2% of the pancreas and is composed of about 1 million cell clusters, the islets of Langerhans; these cells secrete insulin, glucagon, and somatostatin. The most significant disorders of the endocrine pancreas are diabetes mellitus and neoplasms; these are discussed in detail in Chapter 20 and are not discussed further here.
The exocrine pancreas is composed of acinar cells and the ductules and ducts that convey their secretions to the duodenum. The acinar cells are responsible for the synthesis of digestive enzymes, which are mostly made as inactive pro-enzymes that are stored in zymogen granules. When
The contributions of those who authored this chapter in previous editions of this book are gratefully acknowledged.
acinar cells are stimulated to secrete, the granules fuse with the apical plasma membrane and release their contents into the central acinar lumen. These secretions are transported to the duodenum through a series of anastomosing ducts.
The epithelial cells lining the ducts also are active participants in pancreatic secretion: The cuboidal cells that line the smaller ductules secrete bicarbonate-rich fluid, while the columnar cells lining the larger ducts produce mucin. The epithelial cells of the ducts also express the cystic fibrosis transmembrane conductance regulator (CFTR); aberrant function of this membrane protein affects the biochemical content and viscosity of pancreatic secretions. CFTR has a fundamental role in the pathophysiology of pancreatic disease in individuals with cystic fibrosis (Chapter 7).
As discussed later, autodigestion of the pancreas (e.g., in pancreatitis) can be a catastrophic event. A number of “fail-safe” mechanisms have evolved to minimize the risk for occurrence of this phenomenon:
A majority of pancreatic enzymes are synthesized as inactive pro-enzymes and sequestered in membrane-bound zymogen granules, as mentioned earlier.
Activation of pro-enzymes requires conversion of trypsinogen to trypsin by duodenal enteropeptidase (also called enterokinase).
Trypsin inhibitors (e.g., SPINK1, also known as pancreatic secretory trypsin inhibitor) also are secreted by acinar and ductal cells.
Trypsin cleaves and inactivates itself, a negative feedback mechanism that normally puts a limit on local levels of activated trypsin.
Acinar cells are remarkably resistant to the action of activated enzymes such as trypsin, chymotrypsin, and phospholipase A2.
Diseases of the exocrine pancreas include cystic fibrosis, congenital anomalies, acute and chronic pancreatitis, and neoplasms. Cystic fibrosis is discussed in detail in Chapter 7; the other pathologic processes are discussed in this chapter.
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