Murphy sign is a classic physical examination maneuver used to elicit localized tenderness and gallbladder inflammation, serving as a hallmark clinical indicator of acute cholecystitis^1,2. The sign is performed by placing the examiner's hand gently beneath the right costal margin at the midclavicular line—corresponding to the anatomical position of the gallbladder fossa—while instructing the patient to take a deep inhalation. As the diaphragm descends during inspiration, the inflamed, edematous gallbladder moves inferiorly, making direct contact with the examining fingers. If the patient experiences a sudden, sharp halt in inspiration accompanied by localized wincing or tenderness due to peritoneal irritation, the test is deemed positive^2,3. Although traditionally elicited via manual abdominal palpation, modern clinical practice relies heavily on the sonographic Murphy sign, wherein direct pressure applied via an ultrasound transducer over the gallbladder yields superior diagnostic accuracy^4,5. Understanding the physiological basis, examination technique, and diagnostic limitations of the Murphy sign is vital for clinicians managing acute right upper quadrant abdominal emergencies^6,7.

Etiology & Risk Factors

• Calculous Cholecystitis (~90% of cases): Mechanical obstruction of the cystic duct or gallbladder neck by impacted cholesterol, pigment, or mixed gallstones, leading to increased intraluminal pressure, venous congestion, and secondary chemical or bacterial inflammation^3,4.
• Acalculous Cholecystitis (~10% of cases): Acute inflammation occurring in the absence of gallstones, typically affecting critically ill, hospitalized, or traumatized patients experiencing prolonged fasting, total parenteral nutrition, hemodynamic instability, or severe ischemia^4,6.
• Demographic & Non-Modifiable Risk Factors: Female biological sex, increasing age (particularly individuals over 40 years), genetic predispositions involving hepatic cholesterol transporter polymorphisms, and Native American or Hispanic ancestry^1,2,3.
• Metabolic & Systemic Conditions: Obesity, rapid weight loss regimens, type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), Crohn disease, terminal ileal resection, and chronic hemolytic anemias (e.g., sickle cell disease, hereditary spherocytosis) predisposing to pigment stones^1,2.
• Pharmacological Triggers: Prolonged administration of somatostatin analogues (e.g., octreotide), estrogen therapy, oral contraceptives, ceftriaxone therapy (due to calcium-ceftriaxone precipitation in bile), and fibrates¹.

Pathophysiology

The pathophysiological cascade precipitating a positive Murphy sign begins with the mechanical or functional obstruction of biliary outflow at the level of the cystic duct or infundibulum (Hartmann pouch)⁴. Obstruction halts the normal evacuation of hepatic bile, causing progressive distention and elevated intraluminal pressure within the gallbladder. This sustained stretch compromises mucosal microvascular perfusion, resulting in localized tissue ischemia and hypoxia. Simultaneously, epithelial trauma triggers the release of intracellular enzymes and phospholipase A, which converts lecithin in bile into toxic lysolecithin, inciting a severe chemical cholecystitis^3,4. As mucosal integrity fails, the protective mucosal barrier is breached, allowing secondary bacterial proliferation (predominantly Escherichia coli, Klebsiella species, Enterococcus species, and Enterobacter species) to establish an invasive infection. The inflammatory process extends transmurally through the muscularis propria to involve the overlying visceral peritoneum. Because the peritoneum lining the anterior abdominal wall and inferior hepatic surface is densely innervated by somatic afferent fibers, direct contact between the inflamed, swollen gallbladder serosa and the parietal peritoneum during diaphragmatic excursion provokes sharp, localized somatic pain. This somatic irritation forces the patient to abruptly arrest their inspiratory effort—the pathognomonic physiological mechanism underlying the Murphy sign^2,4,7.

Clinical Presentation & Classic Clinical Signs

• History & Cardinal Symptoms: Patients typically present with a sudden onset of severe, steady, aching right upper quadrant (RUQ) or epigastric abdominal pain that persists for greater than 6 hours and frequently radiates to the right scapula, right shoulder, or interscapular region due to diaphragmatic irritation mediated via the phrenic nerve (C3-C5)^2,3,7. Associated symptoms include anorexia, nausea, protracted vomiting, and low-grade fevers or rigors^3,7.
• Physical Examination & Named Clinical Signs:
  • Manual Murphy Sign: The examiner gently hooks fingers under the right costal margin at the intersection of the lateral border of the rectus abdominis muscle and the costal margin; a positive response is marked by abrupt inspiratory arrest due to sharp pain^2,3.
  • Sonographic Murphy Sign: Maximal focal tenderness elicited specifically by compressing the gallbladder directly with an ultrasound transducer; this sign remains positive even when the manual examination is equivocal due to guarding or obesity^4,5.
  • Boas Sign: Hyperesthesia or an area of increased cutaneous sensitivity located posteriorly in the region between the 10th and 12th ribs on the right side.
  • Abdominal Guarding & Rigidity: Localized involuntary muscle spasm in the RUQ suggesting localized peritonitis, whereas generalized rigidity indicates potential gallbladder perforation and diffuse peritonitis^3,7.

Diagnostic Workup & Interpretation (Laboratory, Imaging & ECG/Pathology)

Staging, Classification & Clinical Scoring Systems

Differential Diagnosis

Management & Treatment Protocol

• Initial Stabilization & Resuscitation: Immediate admission, strict nil-per-os (NPO) status, aggressive intravenous fluid resuscitation with crystalloids (e.g., normal saline or lactated Ringer solution), correction of electrolyte disturbances, and placement of a nasogastric tube if intractable vomiting is present^3,7.
• First-Line Medical & Pharmacological Therapy:
  • Analgesia: Prompt administration of intravenous nonsteroidal anti-inflammatory drugs (NSAIDs, such as ketorolac 15–30 mg IV every 6 hours) or opioids (e.g., morphine sulfate 2–4 mg IV PRN or hydromorphone 0.5–1 mg IV PRN) for severe biliary pain.
  • Antimicrobial Therapy: Empiric broad-spectrum intravenous antimicrobial coverage initiated immediately upon diagnosis to target enteric gram-negative bacilli and anaerobes. Regimens include:
    • Piperacillin-tazobactam: 3.375 g IV every 6 hours (or 4.5 g IV every 8 hours)³.
    • Ceftriaxone: 2 g IV every 24 hours PLUS Metronidazole: 500 mg IV every 8 hours^3,7.
    • Ampicillin-sulbactam: 3 g IV every 6 hours.
    • Ciprofloxacin: 400 mg IV every 12 hours PLUS Metronidazole: 500 mg IV every 8 hours (in penicillin-allergic patients).
• Surgical & Interventional Indications:
  • Early Laparoscopic Cholecystectomy: The gold-standard definitive treatment, ideally performed within 24 to 72 hours of symptom onset to minimize technical difficulty, conversion rates, and hospital length of stay^3,7.
  • Percutaneous Cholecystostomy: Indicated for high-surgical-risk patients (Tokyo Guidelines Grade III or severe comorbid medical conditions) who fail to improve on medical therapy or are unfit for immediate general anesthesia; involves ultrasound- or CT-guided catheter placement into the gallbladder lumen for decompression, serving as a bridge to delayed interval cholecystectomy^6,7.

Complications & Prognosis

• Gangrenous Cholecystitis: Ischemic necrosis of the gallbladder wall resulting from prolonged microvascular compromise and high intraluminal pressure; occurs in up to 20% of acute cholecystitis cases and significantly increases perforation risk^4,7.
• Gallbladder Perforation: Occurs in 2% to 10% of cases, leading to localized abscess formation, generalized biliary peritonitis, or fistulization into adjacent gastrointestinal structures (e.g., gallstone ileus)^1,4,6.
• Emphysematous Cholecystitis: A life-threatening variant caused by gas-forming organisms (e.g., Clostridium perfringens, E. coli) within the gallbladder wall and lumen, requiring emergency surgical decompression and broad-spectrum antibiotics.
• Mirizzi Syndrome: External compression of the common hepatic duct by an impacted stone in the cystic duct or infundibulum, resulting in obstructive jaundice and secondary cholangitis.
• Prognosis: Uncomplicated acute cholecystitis treated with early laparoscopic cholecystectomy carries an excellent prognosis with low mortality rates (<1%). However, delayed intervention in elderly or comorbid populations can lead to septic shock, multi-organ dysfunction syndrome, and mortality rates exceeding 15% to 25%^3,6,7.