GASTROENTEROLOGY
PANCREATITIS
Pathogenesis
• Acinar injury via direct or indirect toxicity → release or impaired secretion (ie, duct obstruction) of enzymes → autodigestion → fat necrosis
• Profound acute inflammatory response
Etiologies
• Gallstones (40%): 
> 
, usually small stones (<5 mm) or microlithiasis
• Alcohol (30%): > , usually chronic, w/ acute flares
• Drugs (via hypersens, toxic metab or direct toxicity): furosemide, thiazides, sulfa, ddI, ? DPP- 4 inhib, asparaginase, estrogen, 6-MP/AZA, ACEI, dapsone, 5-ASA, valproic acid
• Obstructive: panc/ampullary tumors, mets (breast, lung), annular pancreas, divisum w/ concurrent minor papilla stenosis and ascaris
• Metabolic: hypertriglyceridemia (TG >1000 and usually ~4500; seen w/ types I, IV, & V familial hyperlipidemia), hypercalcemia
• Infections: coxsackie, mumps, EBV, CMV, HAV, HBV, mycoplasma, TB, candida/toxo/crypto
• Autoimmune: can p/w chronic disease or panc mass; ↑ IgG4, 
ANA, duct abnl
• Ischemia: vasculitis, cholesterol emboli, hypovolemic shock, cardiopulmonary bypass
• Post ERCP: ~5% w/ clinical, overt pancreatitis; 35–70% with asx ↑ amylase; prevent w/ indomethacin 100 mg PR immediately after ERCP (NEJM 2012;366:1414)
• Post trauma: blunt abd trauma, pancreatic/biliary surgery
• Familial: autosomal dominant w/ variable penetrance (PRSS1, CFTR, SPINK1 genes)
• Scorpion sting (in Trinidad): mechanism believed to be hyperstimulation of pancreas
Clinical manifestations
• Epigastric abdominal pain, radiating to back, constant, some relief w/ leaning forward
• Nausea and vomiting
• Ddx: acute cholecystitis, perforated viscus such as DU, intestinal obstruction, mesen- teric ischemia, IMI, AAA leak, distal aortic dissection, ruptured ectopic pregnancy
Physical exam
• Abdominal tenderness and guarding, ↓ bowel sounds (adynamic ileus) ± palpable abdominal mass; ± jaundice if biliary obstruction
• Signs of retroperitoneal hemorrhage (Cullen’s = periumbilical; Grey Turner’s = flank) rare
• Fever, tachycardia, hypotension ± shock
Diagnostic studies (Gastro 2007;132:2022)
• Laboratory
↑ amylase: levels >3× ULN suggestive of pancreatitis; level ≠ severity
false 
: acute on chronic (eg, alcoholic); hypertriglyceridemia (↓ amylase activity)
false : other abd or salivary gland process, acidemia, renal failure, macroamylasemia (amylase binds to other proteins in serum, cannot be filtered by kidneys)
↑ lipase: more specific than amylase
false : renal failure, other abd process, diabetic ketoacidosis, HIV, macrolipasemia
ALT >3 × ULN suggests gallstone pancreatitis (Am J Gastro 1994;89:1863); AΦ, bili not helpful
Other labs (see “Prognosis”): ↑ WBC, ↑ or ↓ Hct, ↑ BUN, ↓ Ca, ↑ glc, ↑ CRP
• Imaging studies
KUB/CXR: can see “sentinel loop” air in small bowel in LUQ, atelectasis, effusion
Abd CT: not required for dx, but test of choice to make dx. Helps exclude other dx, stage severity, & r/o complications. CT w/ IV contrast on day 3 of presenta- tion in severe cases to evaluate for pancreatic necrosis (avoid on presentation b/c theoretical concern of ↑ necrosis w/ IV contrast; defer if concomitant AKI).
Abd U/S: typically not useful to visualize pancreas (obscured by bowel gas), but helpful to investigate biliary etiology (ie, gallstones and BD dilatation); can see pseudocyst
MRI/MRCP: can detect necrosis; also used to assess for stones & ductal disruption
Endoscopic U/S (EUS): limited role acutely; useful for occult biliary disease (microlithiasis)
Treatment (Lancet 2008;371:143; AJG 2012;107:1146)
• Supportive therapy: in mild cases, bowel rest is usually sufficient
Fluid resuscitation LR may be superior to NS (↓ SIRS, CRP at 24 h; contraindicated if ↑ Ca); at least 250 mL/h, may need up to 10 L/d if severe; titrate to UOP ≥0.5 mL/kg/h
Nutrition: if mild, initiate oral nutrition when pain, nausea allow.
If severe and NPO >7 d expected, early (w/in 48 h) enteral nutrition indicated and preferred over TPN; ↓ infectious complications & disease severity, & trend toward ↓ mortality (BMJ 2004;328:1407). Ideally NJ tube, but NG okay.
Analgesia: IV meperidine, morphine, hydromorphone (theoretical risk of sphincter of Oddi spasm by opiates, but has not been shown to adversely affect outcome)
• Prophylactic systemic abx (eg, imipenem) to ↓ mortality & prevent conversion of sterile to infected necrosis controversial (Am J Surg 2009;197:806; Gastro 2007;132:2022); ? reserve for severe pancreatitis w/ >30% necrosis by CT, & no >14 d
• Debridement: infected necrosis usually requires percut, endoscopic or surgical debridement. Improved outcomes by delaying surgery ≥2 wk if possible to allow organization of necrosis. CCY if gallstones (w/in 48 h if mild, o/w w/in 14 d; Surg 2009;145:260; Ann Surg 2010;251:615)
• ERCP + sphincterotomy: in acute setting, reserved for severe cholangitis/sepsis and T bili >5 (ie, presumptive obstructive BD stone). Otherwise, early ERCP does not reduce risk of local or systemic pancreatitis complications (Ann Surg 2007;245:10).
Complications
• Systemic: shock, ARDS, renal failure, GI hemorrhage, DIC
• Metabolic: hypocalcemia, hyperglycemia, hypertriglyceridemia
• Acute fluid collection (30–50%): seen early, no capsule, no Rx required
• Pseudocyst (10–20%): fluid collection, persists for 4–6 wk, encapsulated suggested by persistent pain & elevation of amylase or lipase, or mass on exam most resolve spont.; if >6 cm or persists >6 wk + pain → endo/perc/surg drainage
• Sterile pancreatic necrosis (20%): area of nonviable pancreatic tissue ? prophylactic abx (see above); supportive measures, surgery if Pt unstable
• Infection (5% of all cases, 30% of severe): usually 2° enteric GNR
infected pancreatic necrosis: new SIRS after 7 d typical; perc drainage followed by min invasive surg debridement or endoscopic necrosectomy superior to open necrosectomy; FNA no longer routinely recommended (Pancreas 2012;41:1176)
pancreatic abscess: circumscribed collection of pus (usually w/o pancreatic tissue) treat with abx + drainage (CT-guided if possible), usually seen ≥4 wk into course
• Ascites or pleural effusion: occurs due to disrupted pancreatic duct; consider early ERCP w/ stent across duct; can also occur from draining pseudocyst
Prognosis (Gastro 2007;132:2022)
• Severe pancreatitis (20%) = organ failure or local complications (necrosis, pseudocyst)
• Scoring systems: HAPS, BISAP, APACHE II, Ranson’s criteria, CT Severity Index
HAPS: no abd tenderness or rebound on exam plus nl Hct and Cr on admission predicts non-severe course w/ 98% accuracy (Clin Gas Hep 2009;6:702)
BISAP: 5-point scoring system on admission (BUN >25, GCS <15, SIRS, age >60, and pleural effusion) identifies Pts at risk for ↑’d mortality (Am J Gastro 2009;104:966)
APACHE II (www.mdcalc.com/apache-ii-score-for-icu-mortality): severe if score ≥8
Chronic pancreatitis (Lancet 2011;377:1184)
• 70–80% due to EtOH, also consider autoimmune pancreatitis. Smoking major risk factor.
• Often, but not always, recurrent acute attacks → inflammatory infiltrate → fibrosis → exocrine then endocrine insufficiency (eg, diabetes)
• Sxs include epigastric pain, N/V; over time will be painless and p/w steatorrhea and wt loss
• Amylase/lipase ↑ early, but may be nl later. fecal fat, ↓’d stool elastase & chymotrypsin, Ca2+ in pancreas on KUB/CT.
• ERCP/MRCP/EUS high Se for dx: stricture, dilated ducts, honeycombing of parenchyma
• Treatment is low-fat diet and enzyme replacement. Avoid EtOH & tobacco. Analgesia w/ NSAID ± mild opioid (eg, tramadol). Surgery in selected cases.