Acute pancreatitis

Acute pancreatitis is the sudden inflammation and hemorrhaging of the pancreas due to destruction by its own digestive enzymes—a process fittingly called autodigestion.

Most of the time the disease is actually relatively mild, but it can easily become severe, so it's critical to diagnose and treat it quickly.

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.

These pancreatic digestive enzymes break down macromolecules like carbohydrates, lipids and proteins found in food, but these macromolecules are also found in the cells of the pancreas.

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.

To digest a meal, these zymogens are released into the pancreatic duct, and delivered to the small intestine where they are activated by the protease trypsin.

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.

Alcohol also contributes to pancreatitis in other ways, though, for example, stimulating acinar cells to release inflammatory cytokines which attracts a strong immune reaction.

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.

With gallstones what happens is that they sometimes get lodged at the sphincter of Oddi which blocks the release of pancreatic juices, which is pretty similar to the alcohol-induced protein plug.

But the causes of acute pancreatitis are varied and most of the important ones can remembered with the mnemonic “I GET SMASHED”: where ‘I’ refers to unknown, or Idiopathic, causes; ‘G’ is obstruction by Gallstones, ‘E’ is Ethanol abuse; ‘T’ is a pancreatic Trauma, which is more likely if the trauma is the result of a puncture injury (like a knife wound not a punch); ‘S’ is the use of Steroids; ‘M’ is an infection of the Mumps virus, ‘A’ is the result of Autoimmune diseases; the second ‘S’ is the result of Scorpion sting—which is probably the most exciting item on this list and one of the more rare causes; ‘H’ is a cheat and stands for both Hypertriglyceridemia and for Hypercalcemia; ‘E’ is trauma from a procedure called an Endoscopic retrograde cholangiopancreatography or ERCP which is a technique used to diagnose and treat various biliary and pancreatic diseases; and finally ‘D’ stands for Drugs, like sulfa drugs, reverse-transcriptase inhibitors, and protease inhibitors.

So in acute pancreatitis, there is pancreatic tissue destruction that results from the proteases and inflammatory response of the body, and this can cause tiny blood vessels to become leaky and sometimes rupture.

Ultimately, all of the extra fluid or edema causes the capsule of the pancreas to swell, and unfortunately there can be some activation of lipases which go on to destroy the fat around the pancreas, or peripancreatic fat.

All of the digestion and bleeding can actually liquify the pancreatic tissue, a process called liquefactive hemorrhagic necrosis.