Pancreatitis

Acute pancreatitis begins when trypsinogen is activated prematurely inside pancreatic acinar cells instead of in the duodenum. Activated trypsin starts an enzyme cascade that digests pancreatic tissue from within. Injury to acinar and ductal mitochondria depletes ATP and lowers intracellular pH, which further impairs enzyme handling and amplifies cell damage. The local injury produces oedema, inflammation, fat necrosis, and sometimes haemorrhage. Inflammatory mediators then increase systemic capillary permeability. Plasma leaves the vascular space and collects in the retroperitoneum, bowel wall, peritoneal cavity, or other third spaces. The patient can therefore become intravascularly depleted even while the total amount of fluid in the body is increasing. This explains the combination of tachycardia, concentrated blood, falling urine output, hypotension, and later pulmonary or peripheral oedema. Gallstones and alcohol are common causes. Other possibilities include marked hypertriglyceridaemia, hypercalcaemia, medication effects, abdominal trauma, and recent ERCP. Identifying the cause is not just diagnostic housekeeping: treating it is how recurrence is prevented.