Page created on February 12, 2019. Last updated on December 13, 2020 at 22:27
The exocrine pancreas produces digestive enzymes. They are secreted in proenzyme form inside zymogen granules, so they’re not active before they reach the duodenal lumen. Once they reach the lumen will they be activated by brush border-bound enteropeptidase (also called enterokinase).
The most important pancreatic digestive enzymes are trypsin, chymotrypsin, elastase, collagenase, lipase, phospholipase and amylase.
If the zymogens were activated before they arrived at the intestinal lumen, i.e. inside the pancreas, would they start digesting the organ itself. This is normally prevented by three mechanisms:
- The digestive enzymes are in proenzyme form
- The pressure inside the ducts is smaller than the pressure inside the parenchyme – this favours the movement of secretion from the parenchyme toward the duct
- α1-antitrypsin in the parenchyme inactivates any enzymes that are activated
In acute pancreatitis is there an abnormal and premature activation of the digestive enzymes inside the pancreas. This may occur because the zymogens and lysosomes fuse, causing the proenzymes to be activated by lysosomal enzymes. The activated enzymes start to autodigest the pancreas. It may also be due to primary damage to the acinar cells that produce and secrete the zymogens.
Inflammation of the pancreas recruits neutrophils that secrete proteolytic enzymes that may further active the proenzymes, exacerbating the problem.
It’s an acute condition with very variable symptoms. It may be life-threatening, but in most cases that aren’t life-threatening will the patient recover fully. Some cases of acute pancreatitis progress into chronic pancreatitis.
Etiology of acute pancreatitis include:
- Bile reflux into the pancreatic duct – often due to bile stone
- Alcohol abuse
- Large food intake, especially if consumed with alcohol or after starvation
- Infection (Coxsackie, mumps etc)
- Hypercalcaemia – hypercalcaemia enhances secretions
- Snake venom
- Autoimmune (SLE)
- Vascular (Polyarteritis nodosa, shock, atheroembolism)
- ERCP, iatrogenic or perioperative injury.
Gallstones and alcohol abuse are by far the most important causes and account for greater than 80% of cases of acute pancreatitis in the US.
Alcohol causes the pancreatic secretions to be thicker, which slows down the secretions and may cause congestion of the ducts. When the secretions flow more slowly will there be more opportunities for the zymogens to get into the parenchyme. Alcohol also decreases α1-antitrypsin levels and increases the muscular tone of the sphincter of Oddi. Indeed is alcohol a cofactor in many cases of acute pancreatitis. Strangely enough is alcohol-related acute pancreatitis more common in non-alcoholics than in alcoholics.
Large food-intake, especially if consumed with alcohol or after starvation may cause acute pancreatitis simply because the amount of secretion is so large.
Bile stones blocking the outflow of pancreatic juice will cause the pressure inside the pancreatic ducts to increase, which may force zymogens into the parenchyme. Bile may also activate the proenzymes themselves.
The potential consequences of acute pancreatitis are:
- Pancreatic adiponecrosis
- Fluid loss to the peritoneum -> hypovolaemic shock
- Phospholipase in the circulation -> acute respiratory distress syndrome
- Ischaemic pancreas produces MDF -> depresses the myocardium
- Kallikrein-kinin system activation -> increased permeability everywhere -> extravasation of fluid
- Activation of coagulation -> DIC
- Langerhans dysfunction -> hyperglycaemia
- Infection -> sepsis
- Retroperitoneal bleeding -> irritation of the peritoneum -> paralytic ileus
As the pancreas digests itself will pancreatic enzymes be released into the vicinity of the organ and eventually into the systemic circulation as well. The released lipase will break down peripancreatic triglycerides into fatty acids. Fatty acids will bind to Ca2+ to form soap, which is characteristic for adiponecrosis. The reduced serum levels of Ca2+ may lead to symptoms of hypocalcemia (tetany).
The self-digesting pancreas also inevitably digests some vessels, causing severe bleeding. Bleeding into the retroperitoneum may induce paralytic ileus.
The digestive enzymes also trigger inflammation, potentially even systemic inflammatory response syndrome (SIRS). It’s not uncommon that a bacterial superinfection occurs, which may cause progression into sepsis.
Released proteases activate the complement and kallikrein-kinin systems in the vessels. The latter causes bradykinin to be produced which causes vasodilation and increased vascular permeability. Both systems may contribute to the formation of distributive shock. Increased vascular permeability causes extravasation of fluid into the interstitium and body compartments like the peritoneum. This, together with severe bleedings, contribute to hypovolaemic shock.
As phospholipase is released into the circulation will it travel to the lungs. There will it break down the surfactant, causing acute respiratory distress syndrome (ARDS).
The digestive enzymes damage the endothelium of tissues, causing activation of the coagulation cascade. This may lead to DIC.
Ischaemic pancreas produce myocardial depressing factor, a protein that depresses the function of the myocardium. This contributes to cardiogenic shock.
Diagnosis is based on sudden, dull abdominal pain and serum amylase and lipase levels.
Treatment includes restricting oral feeding completely, as that would induce the production of more pancreatic secretions. Otherwise is the treatment generally supportive and includes fluid replacement, parenteral nutrition if needed, antibiotics if needed, and calcium supplement if needed. Surgical intervention may be necessary depending on the cause.
The part about restricting oral feeding is outdated; nowadays we know that oral feeding as soon as possible improves the prognosis of acute pancreatitis. Unfortunately, pathophysiology has a tendency to teach outdated stuff.
11. Obstipation, subileus, diverticulosis. GIT motility disorders
13. Pathophysiology of chronic pancreatitis