Acute Pancreatitis Pathogenesis

By Dr Ananya Mandal, MD

Acute pancreatitis is generally considered to occur in three phases.

First phase

This phase involves a premature activation of the powerful enzyme called trypsin. Normally the pancreas contains trypsin in an inactive form within the acinar cells. Once it is released in the gut this enzyme breaks down proteins present in the food.

The pancreatic cells are protected from this enzyme by its presence as an inactive form within the pancreas. In the first phase of pancreatitis there is premature activation of this enzyme called trypsin.

There are several mechanisms by which this premature activation may take place. There may be a disruption of calcium signaling in acinar cells or breakdown of trypsinogen to trypsin by the enzyme lysosomal hydrolase cathepsin-B or decreased activity of the intracellular pancreatic trypsin inhibitor.

Once activated trypsin in turn activates several pancreatic digestive enzymes. These enzymes bring in the process of self digestion of the pancreatic cells.

Second phase

In this phase the activated trypsin causes inflammation within the pancreas.

Third phase

In this phase the inflammation within the pancreas spreads to other organs for example acute respiratory syndrome (ARDS).

Both the second and third phase of inflammation is medicated by cytokines and other inflammatory mediators. These mediators lead to activation of inflammatory cells and this set in a chain of events. The other inflammatory cells are activated and these bind to the cells lining the blood vessels.

There is activation blood coagulation or clotting factors. These spread to other organs as well via blood. The blood vessel walls become leaky and begin to release the inflammatory cells. In addition to inflammatory cells, free radicals are also released along with other chemical mediators of inflammation like cytokines (tumor necrosis factor (TNF), interleukins, arachidonic acid metabolites, platelet activator factor, leukotrines, prostaglandins, substance P, mitogen-activated protein kinase, P-selectin or E-selectin, heat shock proteins etc.

In most patients acute pancreatitis is mild. In around 10 to 20% patients there may be severe inflammation. This may lead to systemic inflammatory response syndrome (SIRS). Gall bladder stone and alcohol consumption are linked to acute pancreatitis.

Reviewed by April Cashin-Garbutt, BA Hons (Cantab)

Sources

  1. http://www.nhs.uk/Conditions/Pancreatitis/Pages/Causes.aspx
  2. http://s3.gi.org/physicians/guidelines/AcutePancreatitis.pdf
  3. http://www.bsg.org.uk/pdf_word_docs/pancreatic.pdf
  4. http://gastro.ucsd.edu/fellowship/materials/Documents/Acute%20Pancreatitis/Acute%20Pancreatitis-Annals%20In%20the%20Clinic.pdf
  5. http://cicm.org.au/journal/2004/march/Pancreatitis2.pdf
  6. http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Pancreatitis_explained

Further Reading

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