A 21-year-old college student comes to the emergency department because of a two-day history of vomiting and epigastric pain that radiates to the back. He has a history of atopic dermatitis and Hashimoto thyroiditis. His only medication is levothyroxine. He has not received any routine vaccinations. He drinks 1–2 beers on the weekends and occasionally smokes marijuana. The patient appears distressed and is diaphoretic. His temperature is 37.9°C (100.3°F), pulse is 105/min, respirations are 16/min, and blood pressure is 130/78 mm Hg. Physical examination shows abdominal distention with tenderness to palpation in the epigastrium. There is no guarding or rebound tenderness. Skin examination shows several clusters of yellow plaques over the trunk and extensor surfaces of the extremities. Hemoglobin concentration is 15.2 g/dL and serum calcium concentration is 7.9 mg/dL. Which of the following is the most appropriate next step in evaluation?

Obtain an upright x-ray of the abdomen

Perform a pilocarpine-induced sweat test

A 46-year-old man is brought to the emergency department because of severe epigastric pain and vomiting for the past 4 hours. The pain is constant, radiates to his back, and is worse on lying down. He has had 3–4 episodes of greenish-colored vomit. He was treated for H. pylori infection around 2 months ago with triple-regimen therapy. He has atrial fibrillation and hypertension. He owns a distillery on the outskirts of a town. The patient drinks 4–5 alcoholic beverages daily. Current medications include dabigatran and metoprolol. He appears uncomfortable. His temperature is 37.8°C (100°F), pulse is 102/min, and blood pressure is 138/86 mm Hg. Examination shows severe epigastric tenderness to palpation with guarding but no rebound. Bowel sounds are hypoactive. Rectal examination shows no abnormalities. Laboratory studies show: Hematocrit 53% Leukocyte count 11,300/mm3 Serum Na+ 133 mEq/L Cl- 98 mEq/L K+ 3.1 mEq/L Calcium 7.8 mg/dL Urea nitrogen 43 mg/dL Glucose 271 mg/dL Creatinine 2.0 mg/dL Total bilirubin 0.7 mg/dL Alkaline phosphatase 61 U/L AST 19 U/L ALT 17 U/L γ-glutamyl transferase (GGT) 88 u/L (N=5–50 U/L) Lipase 900 U/L (N=14–280 U/L) Which of the following is the most appropriate next step in management?

Endoscopic retrograde cholangio-pancreatography

A 72-year-old woman comes to the emergency department because of upper abdominal pain and nausea for the past hour. The patient rates the pain as an 8 to 9 on a 10-point scale. She has had an episode of nonbloody vomiting since the pain started. She has a history of type 2 diabetes mellitus, hypertension, and osteoporosis. The patient has smoked 2 packs of cigarettes daily for 40 years. She drinks 5–6 alcoholic beverages daily. Current medications include glyburide, lisinopril, and oral vitamin D supplements. Her temperature is 38.5°C (101.3°F), pulse is 110/min, and blood pressure is 138/86 mm Hg. Examination shows severe epigastric tenderness to palpation with guarding but no rebound. Ultrasonography of the abdomen shows diffuse enlargement of the pancreas; no gallstones are visualized. The patient is admitted to the hospital for pain control and intravenous hydration. Which of the following is the most appropriate next step in the management of this patient’s pain?

Patient-controlled intravenous hydromorphone

Transdermal fentanyl every 72 hours

Oral acetaminophen every 6 hours

Transdermal bupivacaine on request

A 54-year-old man presents to the emergency department for fatigue and weight loss. He reports feeling increasingly tired over the last several weeks and has lost seven pounds over the last month. His wife has also noticed a yellowing of the eyes. He endorses mild nausea but denies vomiting, abdominal pain, or changes in his stools. Ten years ago, he was hospitalized for an episode of acute pancreatitis. His past medical history is otherwise significant for hyperlipidemia, diabetes mellitus, and obesity. He has two glasses of wine most nights with dinner and has a 30-pack-year smoking history. On physical exam, the patient has icteric sclera and his abdomen is soft, non-distended, and without tenderness to palpation. Bowel sounds are present. Laboratory studies reveal the following: Alanine aminotransferase (ALT): 67 U/L Aspartate aminotransferase (AST): 54 U/L Alkaline phosphatase: 771 U/L Total bilirubin: 12.1 mg/dL Direct bilirubin: 9.4 mg/dL Which of the following would most likely be seen on abdominal imaging?

Multifocal dilation and stricturing of intra- and extrahepatic ducts

Surface nodularity of the liver

Acute pancreatitis etiology for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

Top Causes - Stones & Spirits

The two most common causes account for ~80% of acute pancreatitis cases in the U.S.

Feature	Gallstones (Cholelithiasis)	Alcohol
Pathophysiology	Ampullary obstruction by a stone → reflux of bile and/or duodenal contents into the pancreatic duct → premature enzyme activation.	Direct toxic effect on pancreatic acinar cells + sensitization to other injuries. Chronic use leads to protein plug formation.
Patient Profile	Classically, female, overweight, and >40 years old ("fat, female, forty"). Presents with acute, severe epigastric pain.	History of chronic, heavy alcohol use (typically >5-7 years). Often presents as an acute-on-chronic episode.

⭐ An Alanine Aminotransferase (ALT) level >150 U/L has a >95% positive predictive value for gallstone pancreatitis.

Other Causes - The Usual Suspects

📌 Mnemonic: I GET SMASHED

Idiopathic: No cause found after initial workup.
Gallstones: (Covered previously)
Ethanol (Alcohol): (Covered previously)
Trauma: Blunt or penetrating abdominal injury; iatrogenic (e.g., post-operative).
Steroids: High-dose corticosteroid therapy.
Mumps: And other viruses (Coxsackie B, HIV).
Autoimmune: IgG4-related disease, SLE, IBD.
Scorpion sting: Venom from species like Tityus trinitatis.
Hyperlipidemia/Hypercalcemia:
- Triglycerides > 1000 mg/dL.
- Calcium > 12 mg/dL (e.g., from hyperparathyroidism).
ERCP: Post-procedure inflammation (5-10% of cases).
Drugs: Thiazides, furosemide, azathioprine, valproic acid, sulfonamides.

⭐ Exam Favorite: Drug-induced pancreatitis is often idiosyncratic and dose-independent. Always review the patient's medication list for common offenders like diuretics (thiazides, furosemide) and immunosuppressants (azathioprine).

Pathophysiology - The Cascade Crash

Core Defect: Premature activation of trypsinogen to trypsin within acinar cells, instead of the duodenal lumen.
Mechanism: An initial insult (e.g., obstruction, toxins) disrupts normal acinar cell secretion and protective mechanisms.

Autodigestion: Activated trypsin triggers a cascade, activating other zymogens:
- Elastase → vascular damage & hemorrhage.
- Phospholipase A2 → membrane destruction & coagulative necrosis.

Histopathology of Acute Pancreatitis

⭐ Trypsin is the key trigger. It not only digests pancreatic tissue but also activates the complement and kinin systems, amplifying inflammation and vascular permeability, leading to systemic complications.

High‑Yield Points - ⚡ Biggest Takeaways

Gallstones and chronic alcohol abuse are overwhelmingly the most common causes of acute pancreatitis.

Post-ERCP pancreatitis is the most frequent iatrogenic cause.

Severe hypertriglyceridemia (TGs >1000 mg/dL) is a key metabolic trigger.

Important drug-induced causes include diuretics, valproic acid, and azathioprine.

Mumps virus is a classic infectious cause, especially in children.

Autoimmune (IgG4-related) and idiopathic causes are considered after ruling out common etiologies.

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