Pancreatitis

Acinar cells normally store digestive enzymes as inactive zymogens (trypsinogen, chymotrypsinogen, proelastase) in zymogen granules, separated from lysosomes. In pancreatitis, intracellular calcium rises pathologically (from ductal obstruction, alcohol toxicity, or hypertriglyceridemia), zymogen granules fuse with lysosomes, and lysosomal cathepsin B prematurely converts trypsinogen to trypsin inside the cell. Active trypsin then activates the entire zymogen cascade — phospholipase, elastase, kallikrein — autodigesting acinar cells, peripancreatic fat, and blood vessels. SPINK1 (pancreatic secretory trypsin inhibitor) is overwhelmed once trypsin levels exceed ~10% of its capacity.

Lipase greater than three times the upper limit of normal (typically >180 U/L if ULN is 60) supports the diagnosis when combined with characteristic pain. Lipase rises within 4-8 hours of onset, peaks at 24 hours, and remains elevated 8-14 days. It is more specific than amylase, which also rises in salivary gland disease, intestinal perforation, ectopic pregnancy, and renal failure. The magnitude of enzyme elevation does NOT predict severity — a fivefold lipase can be mild while a threefold lipase can be necrotizing. Use clinical scoring (BISAP, APACHE II) and CT for severity grading.

Gallstone pancreatitis (~40%): a stone migrates from the gallbladder, lodges at the ampulla of Vater, and obstructs the pancreatic duct. Backed-up pancreatic juice raises ductal pressure, ruptures small ducts, and triggers acinar cell injury. Female predominance, often after a fatty meal, ALT >150 highly predictive. Treatment includes ERCP within 24-72 hours if cholangitis or persistent obstruction. Alcoholic pancreatitis (~30%): chronic alcohol sensitizes acinar cells via direct toxicity, increased ductal protein plugs, and altered calcium signaling. Male predominance, typically requires 5+ years of heavy use. Acute episodes often progress to chronic pancreatitis if drinking continues.

The revised Atlanta classification grades severity by organ failure and local complications. Mild (~80%): no organ failure, no local complications, resolves in days. Moderately severe: transient organ failure (<48 hours) or local complications (peripancreatic fluid, walled-off necrosis). Severe (~10-15%): persistent organ failure beyond 48 hours, often multi-organ. Necrotizing pancreatitis carries 15-25% mortality, climbing to 30%+ if infected necrosis develops. The early phase (week 1) is dominated by systemic inflammatory response; the late phase (weeks 2-4) by local complications and infection. Pancreatic abscess, pseudocyst, splenic vein thrombosis, and chronic disease are downstream sequelae.

Aggressive crystalloid resuscitation is the cornerstone — lactated Ringer at 5-10 mL/kg/hour for the first 24 hours, targeting urine output >0.5 mL/kg/hour. Pain control with IV opioids (hydromorphone, fentanyl); morphine historically avoided over sphincter of Oddi concerns but evidence is weak. Early oral or enteral nutrition (within 24-72 hours) is now standard — bowel rest worsens outcomes. Prophylactic antibiotics are not indicated; reserve for documented infected necrosis (ceftriaxone, metronidazole, carbapenems). ERCP within 24 hours for gallstone pancreatitis with cholangitis. Surgical or endoscopic drainage of infected walled-off necrosis after weeks of conservative management.

BISAP score (BUN >25, impaired mental status, SIRS, age >60, pleural effusion) — one point each; score ≥3 predicts severe disease. Ranson criteria (11 variables at 0 and 48 hours, including WBC, glucose, LDH, AST, calcium, BUN rise, hematocrit drop, base deficit, fluid sequestration) — score ≥3 indicates severe disease. APACHE II ≥8 within 24 hours similarly predicts severity. CT severity index (CTSI) at 72-96 hours combines necrosis extent with fluid collections. Hematocrit >44 and BUN rising despite hydration are simple bedside red flags. Most clinicians now favor BISAP for initial triage given simplicity.

Chronic pancreatitis is irreversible fibrosis and loss of acinar and islet tissue from repeated injury. Roughly 10% of patients with a single acute episode and 30-40% with recurrent attacks progress to chronic disease. Causes mirror acute (alcohol dominates), plus smoking, hereditary mutations (PRSS1, SPINK1, CFTR, CTRC), autoimmune. Features: chronic abdominal pain, calcifications on CT, pancreatic duct dilation or strictures, exocrine insufficiency (steatorrhea, fecal elastase <100), endocrine insufficiency (type 3c diabetes). Treatment: smoking and alcohol cessation, pancrelipase enzyme replacement, pain control, endoscopic or surgical drainage of obstructed ducts, total pancreatectomy with islet autotransplant in selected refractory cases.