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A 40-year-old man comes to the office because of bloating, diarrhea, and abdominal pain for the past few weeks. He says that his stool has been pale and bulky recently. He has a history of chronic pancreatitis. Which of the following tests will most directly confirm the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
While a history of acute pancreatitis might lead to chronic pancreatitis these diseases have distinct histopathologies.
Acute pancreatitis is inflammation caused by destruction of the pancreas by its own digestive enzymes—a process called autodigestion, and is generally reversible.
Chronic pancreatitis is inflammation due to irreversible changes to the pancreatic structure, like fibrosis, atrophy and calcification.
The pancreas is a long, skinny gland the length of a dollar bill and is located in the upper abdomen, or the epigastric region, behind the stomach. It plays endocrine roles—for example, alpha and beta cells make hormones like insulin and glucagon that are secreted into the bloodstream, but it also plays exocrine roles— for example, acinar cells make digestive enzymes that are secreted into the duodenum to help digest food.
To protect the pancreas, the acinar cells manufacture inactive forms of the enzymes called proenzymes, or zymogens.
These zymogens are normally activated by proteases which cleave off a polypeptide chain, which is kind of like pulling the pin on a grenade.
For additional security, the zymogens are kept away from sensitive tissues in storage vesicles called zymogen granules, and are packaged with protease inhibitors that prevent enzymes from doing damage if they become prematurely active.
Trypsin is a pancreatic digestive enzyme that is produced as the zymogen trypsinogen.
Normally, trypsinogen isn’t activated until it is cleaved by protease enteropeptidase which is found in the duodenum.
But if trypsinogen and these zymogens become activated too early, then it can cause acute pancreatitis, and this might happen as a result of any injury to the acinar cells, or anything that prevents the normal secretion of the proenzymes into the duodenum.
The two leading causes of acute pancreatitis are alcohol abuse and gallstones.
With alcohol abuse it goes like this: alcohol increases zymogen secretion from acinar cells while decreasing fluid and bicarbonate production from the ductal epithelial cells. As a result, the pancreatic juices become really thick and viscous, potentially forming a plug that can block the duct.
A blocked duct is bad news because pancreatic juices start backing up, increasing the pressure, and leading to distention of the duct itself.
At the cellular level, one consequence of this is that membrane trafficking becomes chaotic.
Zymogen granules might fuse with lysosomes bringing trypsinogen into contact with lysosomal digestive enzymes.
Trypsinogen might then be turned into activated trypsin which begins the cascade of digestive enzyme activation and autodigestion of the pancreas—which is acute pancreatitis.
Neutrophils arrive quickly at the scene, and often release superoxide and their own proteases, which contribute to the problem.
Finally, it’s thought that high consumption and subsequent oxidative metabolism of alcohol may produce enough reactive oxygen species to overwhelm cellular defenses and damage the cells.
In addition to alcohol abuse, other known causes of acute pancreatitis that frequently turn into chronic pancreatitis include tumors, trauma to the pancreas, and cystic fibrosis.
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