Pocket Medicine

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 (PRSS1CFTRSPINK1 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.