Normal and Structure and Function


To understand the clinical manifestations of pancreatic diseases a brief review of the development and macroscopic and microscopic anatomy of the pancreas is in order.

The exocrine pancreas drains into the duodenum.

The pancreas is a mixed exocrine-endocrine gland that has three parts: head, body, and tail (Fig. 9-3). The digestive juices produced by the exocrine part of the pancreas drain into the duodenum through a system of ducts. Minor interlobular ducts originating from the intercalated ducts at the center of the acini fuse and ultimately form a major pancreatic duct (duct of Wirsung). Prior to entering into the duodenum, the duct of Wirsung fuses with the common bile duct forming an ampulla of Vater in 60% of cases. In the remaining 40% such a fusion does not occur, and many anatomic variants are present instead. Most people also have a separate accessory duct (the duct of Santorini), which branches from the main duct, entering the duodenum separately at its own ampulla. In many people such an ampulla does not exist, and the accessory duct ends blindly.


Anatomy and Physiology

Acinus Secretory unit of the exocrine pancreas. It is composed of several serous cells surrounding a lumen into which these cells secrete various digestive proenzymes.

Cholecystokinin Polypeptide stimulating the secretion of enzyme from the pancreatic acinar cells. It is produced, like secretin, by the endocrine cells of the duodenum.

Ductal cells Cuboidal cells lining the ducts of the pancreas. Serous cells secrete bicarbonates, whereas the mucous cells secrete mucus into the pancreatic juice.

Endopeptidases Group of pancreatic hydrolytic enzymes comprising trypsin, chymotrypsin, and elastase. These enzymes cleave polypeptides into smaller units (oligopeptides) composed of two to six amino acids. Approximately 70% of proteins in food are broken down by endopeptidases.

Intercalated duct Small duct that drains the acinar cell secretions into the larger pancreatic ducts.

Pancreas Major exocrine gland that also contains endocrine elements in the form of the islets of Langerhans. It is located retroperitoneally and extends from the duodenum to the spleen.

Pancreatic ducts The main pancreatic duct (duct of Wirsung) extends from the tail to the head of the pancreas. It joins the common bile duct prior to entering into the duodenum at the greater duodenal papilla (papilla of Vater). The accessory pancreatic duct (duct of Santorini) may be found in some people, bifurcating from the main duct and entering the duodenum at the lesser duodenal papilla.

Pancreatic enzymes Several digestive enzymes produced by the acinar cells of the pancreas. These enzymes act on lipids (lipase and phospholipase), proteins (trypsin, chymotrypsin, carboxypeptidase), carbohydrates (amylase), nucleic acids (deoxyribonuclease, ribonuclease), and elastic tissue (elastase), just to mention the most important ones.

Secretin Polypeptide hormone that stimulates pancreatic secretion of fluid rich in bicarbonate. It is produced by the endocrine cells in the duodenum.

Trypsin Pancreatic endopeptidase that cleaves proteins into oligopeptides composed of several amino acids. It is secreted by pancreatic acinar cells as trypsinogen, an inactive proenzyme that is activated in the intestine into trypsin through the action of enterokinases located in the intestinal brush border.

Zymogen granules Cytoplasmic granules containing proenzymes in acinar cells. These enzymes are excreted into the intercalated ducts and from there through the main pancreatic duct into the intestine.

Signs, Symptoms, and Laboratory Findings

Amylase test Normal serum levels of amylase are less than 140 IU/dL. Serum amylase is a sensitive marker of pancreatic diseases, especially if amylase is present in high concentration (>700 IU/dL). However, amylase is also produced by salivary glands and may be elevated in the serum in a number of other diseases, such as liver and intestinal diseases or renal failure. Amylase is excreted in the urine and may be detected in the urine in patients who have elevated serum amylase.

Cholecystokinin test Test used to detect chronic pancreatitis. Intravenous administration of cholecystokinin and secretin increases the volume of pancreatic secretion, which may be assessed by measuring the volume of juice in the duodenum and the concentration of bicarbonate and amylase. The test is technically difficult to perform. A peak bicarbonate concentration of less than 80 mEq/L is highly specific and suggestive of pancreatic insufficiency.

Endoscopic retrograde cholangiopancreatography (ERCP) Noninvasive radiologic technique based on the injection of contrast medium into the pancreatic and biliary ducts through a catheter introduced into the duodenal papilla of Vater. It is used to visualize the ductal abnormalities of the pancreas, including ductal fibrosis, obstruction, pancreatic stones, and tumors. The catheter introduced into the pancreatic duct may be used to obtain cytologic samples for microscopic diagnosis of cancer. Approximately 5% of all patients develop acute pancreatitis after this procedure.

Fecal fat content Test is based on collection of fecal material over 72 hours. Steatorrhea is defined as fecal fat content in excess of 7 g per 24 hours. The test is insensitive and becomes positive only if more than 90% of pancreatic acini are lost.

Lipase test Normal serum contains less than 130 IU/L lipase. Serum lipase is a sensitive marker of pancreatic disease. It is more sensitive and more specific for acute pancreatitis than amylase, especially after the first day of the onset of disease.

Magnetic resonance cholangiopancreatography Noninvasive radiologic technique used to visualize the pancreas and bile ducts, similar to ERCP.

Sweat test Test is based on measuring the concentration of sodium (Na+) and chloride (Cl) in sweat. The test is used to diagnose cystic fibrosis. On injection of pilocarpine the sweat of homozygous patients contains an increased concentration of Na+ and Cl (>60 mEq/L). Sweat Cl is a more sensitive test for cystic fibrosis than sweat Na+.

Trypsin test Normal serum contains 20 to 80 μg/L of trypsin. Serum trypsin elevation is a very sensitive test of pancreatic disease. It has, however, low specificity since trypsin may be elevated in serum in hepatobiliary, intestinal, and renal diseases. The serum trypsin is measured by a radioimmune assay, which makes it impractical for routine usage.

Pancreatic ducts are best visualized by endoscopic retrograde cholangiopancreatography (ERCP). This noninvasive radiologic technique is based on the injection of contrast medium into the pancreatic and biliary ducts through a catheter introduced into the duodenal papilla of the ampulla of Vater or the variant forms of the common bile duct and pancreatic ducts.

Histologically the exocrine pancreas consists of acini and ducts.

The secretory unit of the exocrine pancreas consists of acinar cells and excretory ducts (Fig. 9-4). The acinar cells are specialized protein-secreting cells arranged coronally around a centrally located intercalated duct. They are cuboidal and have abundant cytoplasm filled with zymogen granules. Zymogen granules contain proenzymes (zymogens) that are excreted into the ducts. The ductal cells are polarized and specialized for fluid and electron transport. These cells contribute bicarbonates, minerals, and water to the pancreatic juices. The ducts also contain scattered mucus-producing cells.


The pancreas produces approximately 1500 mL of digestive juices per day. This pancreatic juice consists of (1) water, (2) minerals, (3) enzymes, (4) nonenzymatic proteins, and (5) mucus.

The pancreatic secretion has three main functions: (1) to provide digestive enzymes, (2) to protect the tissues from autodigestion by its own enzyme, and (3) to neutralize the acidity of the chyme arriving in the duodenum from the stomach.

Pancreatic secretion is low during the fasting phase but increases 10-fold during the digestive phase.

The secretory activity of the pancreas is under complex neurohumoral control. Two secretory phases are recognized: the fasting state and the digestive phase.

In the fasting state (interdigestive period) the basal secretory rate of the pancreas is relatively low. It is predominantly under parasympathetic control. Acetylcholine released from the terminal branches of the vagus nerve maintains a low level of constitutional secretory activity, which is inhibited by adrenergic stimuli.

Basal pancreatic secretion oscillates depending on intestinal motility. However, even with heightened stimulation during intestinal contraction, pancreatic secretion reaches only 10% to 20% of the maximum achieved during the digestive phase.

In the digestive phase, when the food enters the gastrointestinal tract, pancreatic secretion increases approximately 10 times over the basal rate. This increase is a consequence of stimulation by the intestinal hormones cholecystokinin and secretin.

The digestive phase pancreatic secretion has three interval phases: cephalic, gastric, and intestinal.

Like other parts of the gastrointestinal tract the pancreatic digestive phase stimulated by food has three interval phases called cephalic, gastric, and intestinal (Fig. 9-5).

Clinical and Laboratory Evaluation of Pancreatic Diseases

The evaluation of suspected acute or chronic pancreatic disease includes taking a complete history and performing a physical examination, as well as conducting standard laboratory tests and specialized tests aimed at detecting pancreatic disease. Additional testing includes sampling of the ascites fluid, if present, CT and ultrasound examination, or ERCP.


Symptoms and signs of pancreatic disease are most pronounced in the epigastrium but may also be seen in other parts of the body. The most important signs and symptoms are as follows:

These symptoms may be present in both acute and chronic diseases of the pancreas, albeit in varying proportions (Table 9-3).

Epigastric pain is a feature of both acute and chronic pancreatitis and pancreatic cancer.

The pancreas has a rich innervation and contains numerous afferent nerve fibers that end in the celiac ganglia and the superior mesenteric ganglion (Fig. 9-6). Thus, many pancreatic diseases are accompanied by pain. However, the intensity, duration, and nature of the pain vary.

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