Gallstone disease differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]

Overview

Gallstone disease must be differentiated from other diseases that cause epigastric and left and right hypochondriac pain such as: Abdominal pain, esophageal chest pain,gastroesophageal reflux disorder, peptic ulcer disease, non-ulcer dyspepsia,hepatitis, functional gallbladder disorder, sphincter of Oddi dysfunction,Chronic pancreatitis, Irritable bowel syndrome, ischemic heart disease, Pyelonephritis, ureteral calculi and complications of gallstone disease include: acute cholecystitis, choledocholithiasis, acute pancreatitis, and acute cholangitis

Differentiating Gallstone disease from other Diseases

• As Gallstone disease manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. The presence of biliary colic is an important diagnostic feature to distinguish between gallstones and non-biliary disorders. It has been shown that this feature is predictive of finding stones on imaging.

However, it is important to note that biliary colic concomitant in patients with other biliary disorders such as acute cholecystitis, choledocholithiasis, sphincter of Oddi dysfunction, and functional gallbladder disorder. 

Laboratory studies can be helpful, along side clinical presentation in making a preliminary diagnosis:

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin

Classification of pain in the abdomen based on etiology Disease Clinical manifestations Diagnosis Comments Symptoms Signs Fever Rigors and chills Abdominal Pain Jaundice Diarrhea GI Bleed Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Abdominal causes Inflammatory causes Pancreato-biliary disorders Acute suppurative cholangitis + + RUQ + − − + + + N Abnormal LFT WBC >10,000 Ultrasound shows biliary dilatation/stents/tumor Septic shock occurs with features of SIRS Acute cholangitis + − RUQ + − − − − − N Abnormal LFT Ultrasound shows biliary dilatation/stents/tumor Biliary drainage (ERCP) + IV antibiotics Acute cholecystitis + − RUQ + − − − − − Hypoactive Hyperbilirubinemia Leukocytosis Ultrasound shows gallstone and evidence of inflammation Murphy’s sign Acute pancreatitis + − Epigastric ± − − ± − − N Increased amylase / lipase Ultrasound shows evidence of inflammation Pain radiation to back Primary biliary cirrhosis − − RUQ/Epigastric + − − − − − N Increased AMA level, abnormal LFTs Primary sclerosing cholangitis + − RUQ + − − − − − N Increased liver enzymes Increased IgM, IgG4 Anti-neutrophil cytoplasmic antibody (p-ANCA) Anti-nuclear antibody (ANA) Anti-smooth muscle antibody (Anti-Sm) Anti-endothelial antibody Anti-cardiolipin antibody ERCP and MRCP shows Multiple segmental strictures Mural irregularities Biliary dilatation and diverticula Distortion of biliary tree The risk of cholangiocarcinoma in patients with primary sclerosing cholangitis is 400 times higher than the risk in the general population. Cholelithiasis ± − RUQ/Epigastric ± − − − + + N to hyperactive for dislodged stone Leukocytosis Ultrasound shows gallstone Murphy’s sign Gastric causes Peptic ulcer disease ± − Diffuse − − Gastric ulcer- melena and hematemesis Duodenal ulcer- melena and hematochezia + in perforated + + N Ascitic fluid LDH > serum LDH Glucose < 50mg/dl Total protein > 1g/dl Air under diaphragm in upright CXR Upper GI endoscopy for diagnosis Gastritis ± − Epigastric − + in chronic gastritis − Gastroesophageal reflux disease − − Epigastric − − − − − − Gastric outlet obstruction − − Epigastric − − − ± Hyperactive Gastrointestinal perforation + ± Diffuse ± − +, depends on site + + ± WBC> 10,000 Air under diaphragm in upright CXR Dumping syndrome − − Lower and then diffuse Intestinal causes Acute appendicitis + +in pyogenic appendicitis Starts in epigastrium, migrates to RLQ − − − + in perforated appendicitis + + Hypoactive Leukocytosis Ultrasound shows evidence of inflammation Nausea & vomiting, decreased appetite Acute diverticulitis + ± LLQ − − Hematochezia − + − Hypoactive Leukocytosis CT scan and ultrasound shows evidence of inflammation Inflammatory bowel disease ± − Diffuse ± Hematochezia Irritable bowel syndrome ± − Diffuse − + − − − − N Tests done to exclude other diseases as it diagnosis of exclusion Tests done to exclude other diseases as it diagnosis of exclusion Symptomatic treatment High dietary fiber Osmotic laxatives Antispasmodic drugs Whipple's disease ± − Diffuse ± − − ± − − N Thrombocytopenia Hypoalbuminemia Small intestinal biopsy for Tropheryma whipplei *Endoscopy is used to confirm diagnosis. Images used to find complications Chest and joint x-ray CT MRI Echocardiography Extra intestinal findings: Uveitis Endocarditis Encephalitis Dementia Hepatosplenomegaly Arthritis Ascites Toxic megacolon + − Diffuse − + − + ± − Hypoactive Anemia Leukocytosis especially in patients with Clostridium difficile infection Hypoalbuminemia Metabolic alkalosis associated with a poor prognosis Metabolic acidosis secondary to ischemic colitis CT scan shows: Dilated transverse colon Loss of colonic haustrations Segmental parietal thinning Intraluminal soft-tissue masses Ultrasound shows: Loss of haustra coli of the colon Hypoechoic and thickened bowel walls with irregular internal margins in the sigmoid and descending colon Prominent dilation of the transverse colon (>6 cm) Insignificant dilation of ileal bowel loops (diameter >18 mm) with increased intraluminal gas and fluid Tropical sprue + − Diffuse + − Celiac disease − − Diffuse ±, also dermatitis herpetiformis + − − − − Hyperactive (increased sounds) IgA endomysial antibody IgA tissue transglutaminase antibody Anti-gliadin antibody Infective colitis + Hepatic causes Viral hepatitis + − RUQ + − − − + Liver masses + + in Liver abscess RUQ ± − − + in sepsis Budd-Chiari syndrome ± − RUQ ± − + in liver failure leading to varices − − − N Elevated serum aspartate aminotransferase and alanine aminotransferase levels may be more than five times the upper limit of the normal range. Elevated serum alkaline phosphatase and bilirubin levels, decreased serum albumin level. Findings on CT scan suggestive of Budd-Chiari syndrome include: Early enhancement of the caudate lobe and central liver around the inferior vena cava Delayed enhancement of the peripheral liver with accompanying central low density (flip-flop appearance) Peripheral zones of the liver show reversed portal venous blood flow In the chronic phase, there is caudate lobe enlargement and atrophy of the peripheral liver in affected areas Ascitic fluid examination shows: Total protein more than 2.5 g per deciliter White blood cells are usually less than 500/μL. Hemochromatosis − − RUQ Dull / aching + with infections and GI involvement − + in cirrhotic patients may be in cardicmyopathy − − >60% TS >240 μg/L SF Raised LFT Hyperglycemia Ultrasound shows evidence of cirrhosis Extra intestinal findings: hyperpigmentation Diabetes mellitus Arthralgia Impotence in males Cardiomyopathy Atherosclerosis Hypopituitarism Hypothyroidism Extrahepatic cancer Prone to specific infections Cirrhosis + − RUQ + − varices − Peritoneal causes Spontaneous bacterial peritonitis + − Diffuse + in cirrhotic patients − − ± − − Hypoactive Ascitic fluid PMN>250 cells/mm³ Culture: Positive for single organism Ultrasound for evaluation of liver cirrhosis Hollow Viscous Obstruction Small intestine obstruction − − Diffuse − − − − + ± Hyperactive then absent Leukocytosis Abdominal X ray Nausea & vomiting associated with constipation, abdominal distention Volvulus − − Diffuse − − − − + − Hypoactive Leukocytosis CT scan and abdominal X ray Nausea & vomiting associated with constipation, abdominal distention Biliary colic − − RUQ + − − − − − N Increased bilirubin and alkaline phosphatase Ultrasound Nausea & vomiting Renal colic − − Flank pain − − − − − − N Hematuria CT scan and ultrasound Colicky abdominal pain associated with nausea & vomiting Vascular Disorders Ischemic causes Mesenteric ischemia ± − Periumbilical − + Hematochezia ± − − Hyperactive Leukocytosis and lactic acidosis CT scan Nausea & vomiting, normal physical examination Acute ischemic colitis ± ± Diffuse − + Massive + + Hyperactive then absent Leukocytosis CT scan Nausea & vomiting Hemorrhagic causes Ruptured abdominal aortic aneurysm − − Diffuse − − Massive + − − N Normal CT scan Unstable hemodynamics Intra-abdominal or retroperitoneal hemorrhage − − Diffuse − − Massive + − − N Anemia CT scan History of trauma Gynaecological Causes Tubal causes Torsion of the cyst − − RLQ / LLQ − − − ± ± N Increased ESR and CRP Ultrasound Sudden onset sever pain with nausea and vomiting Acute salpingitis + ± RLQ / LLQ − − − − ± ± N Leukocytosis Pelvic ultrasound Vaginal discharge Cyst rupture − − RLQ / LLQ − − − + ± ± N Increased ESR and CRP Ultrasound Sudden onset sever pain with nausea and vomiting Pregnancy Ruptured ectopic pregnancy − − RLQ / LLQ − − − + − − N Positive pregnancy test Ultrasound History of missed period and vaginal bleeding Extra-abdominal causes Pulmonary disorders Pleural empyema + ± RUQ/Epigastric − − − − − − N Cardiovascular disorders Myocardial Infarction − − Epigastric − − − + in cardiogenic shock − − N

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• Liver biochemical tests (serum aminotransferases, total bilirubin, alkaline phosphatase), which may be abnormal in patients with hepatitis, biliary tract obstruction, or (less commonly) acute cholecystitis
• Serum amylase and lipase, which are elevated in acute pancreatitis
• Complete blood count, which may show an elevated white blood cell count in patients with acute cholecystitis or acute cholangitis
• Urine analysis, which may show indicate a urinary tract infection or ureteral calculi

Other tests that may be indicated depending upon the patient's symptoms and history including:

• Upper endoscopy to look for peptic ulcer disease
• Endoscopic ultrasonography to look for chronic pancreatitis
• Endoscopic retrograde cholangiopancreatography (ERCP) with sphincter of Oddi manometry to look for sphincter of Oddi dysfunction
• Cholescintigraphy with or without cholecystokinin (CCK)-stimulation to look for acute cholecystitis and functional gallbladder disorder, respectively
• Testing for ischemic heart disease
• Esophageal manometry to look for esophageal sources of chest pain, such as esophageal spasm

Classification of acute abdomen based on etiology Presentation Clinical findings Diagnosis Comments Fever Rigors and Chills Abdominal Pain Jaundice Hypotension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Common causes of Peritonitis Spontaneous bacterial peritonitis + Diffuse − − − − Hypoactive Ascitic fluid PMN>250 cells/mm³ Culture: Positive for single organism Ultrasound for evaluation of liver cirrhosis - Perforated gastric and duodenal ulcer + Diffuse − + + + N Ascitic fluid LDH > serum LDH Glucose < 50mg/dl Total protein > 1g/dl Air under diaphragm in upright CXR Upper GI endoscopy for diagnosis Acute suppurative cholangitis + + RUQ + + + + ± Acute cholangitis + − RUQ + − − − N Abnormal LFT Ultrasound shows biliary dilatation Biliary drainage (ERCP) + IV antibiotics Acute cholecystitis + RUQ + − − Hypoactive Hyperbilirubinemia Leukocytosis Ultrasound shows gallstone and evidence of inflammation Murphy’s sign Acute pancreatitis + Epigastric ± − − N Increased amylase / lipase Ultrasound shows evidence of inflammation Pain radiation to back Acute appendicitis + RLQ − + + Hypoactive Leukocytosis Ultrasound shows evidence of inflammation Nausea & vomiting, decreased appetite Acute diverticulitis + LLQ ± + − Hypoactive Leukocytosis CT scan and ultrasound shows evidence of inflammation Hollow Viscous Obstruction Small intestine obstruction − Diffuse − + ± Hyperactive then absent Leukocytosis Abdominal X ray Nausea & vomiting associated with constipation, abdominal distention Gall stone disease/Cholelithiasis ± − Volvulus - Diffuse - + - Hypoactive Leukocytosis CT scan and abdominal X ray Nausea & vomiting associated with constipation, abdominal distention Biliary colic - RUQ + - - N Increased bilirubin and alkaline phosphatase Ultrasound Nausea & vomiting Renal colic - Flank pain - - - N Hematuria CT scan and ultrasound Colicky abdominal pain associated with nausea & vomiting Vascular Disorders Ischemic causes Mesenteric ischemia ± Periumbilical - - - Hyperactive Leukocytosis and lactic acidosis CT scan Nausea & vomiting, normal physical examination Acute ischemic colitis ± Diffuse - + + Hyperactive then absent Leukocytosis CT scan Nausea & vomiting Hemorrhagic causes Ruptured abdominal aortic aneurysm - Diffuse - - - N Normal CT scan Unstable hemodynamics Intra-abdominal or retroperitoneal hemorrhage - Diffuse - - - N Anemia CT scan History of trauma Gynaecological Causes Fallopian tube Acute salpingitis + LLQ/ RLQ − ± ± N Leukocytosis Pelvic ultrasound Vaginal discharge Ovarian cyst complications and endometrial disease Torsion of the cyst - RLQ / LLQ - ± ± N Increased ESR and CRP Ultrasound Sudden onset sever pain with nausea and vomiting Endometriosis - RLQ/LLQ - +/- +/- N Normal Laproscopy Menstrual-associated symptoms, pelvic symptoms Cyst rupture - RLQ / LLQ - +/- +/- N Increased ESR and CRP Ultrasound Sudden onset sever pain with nausea and vomiting Pregnancy Ruptured ectopic pregnancy - RLQ / LLQ - - - N Positive pregnancy test Ultrasound History of missed period and vaginal bleeding Functional Irritable Bowel Syndrome - Diffuse - - - - N Clinical diagnosis ROME III/IV criteria Pharmacologic studies based criteria - High dietary fiber Osmotic laxatives Antispasmodicdrugs References