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Acute Cholangitis (Clinical)

Acute cholangitis refers to acute inflammation in the bile duct system; it is a life-threatening condition characterized by fever, jaundice, and abdominal pain. This condition develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. The diagnosis is confirmed with ultrasound (or other hepatobiliary imaging studies) showing dilation of the common bile duct (CBD) or gallstones, elevated liver function tests, and leukocytosis. Treatment includes hemodynamic stabilization, broad-spectrum antibiotics, urgent biliary drainage, and addressing the underlying etiology (e.g., cholecystectomy for gallstones).

Last updated: May 15, 2023

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Epidemiology[2]

  • Relatively uncommon
  • Men and women are equally affected.
  • More common in adults
  • Peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is in the 6th and 7th decades of life.
  • Increased incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in Northern Europeans, Hispanics, and Native Americans

Etiology[1,2 5,9]

  • Obstruction of the biliary system:
    • Choledocholithiasis Choledocholithiasis Presence or formation of gallstones in the common bile duct. Cholelithiasis (responsible for 60% of cases)
    • Biliary strictures
    • Malignancy Malignancy Hemothorax
    • Extrinsic compression Compression Blunt Chest Trauma ( pancreatic pseudocyst Pancreatic pseudocyst Cyst-like space not lined by epithelium and contained within the pancreas. Pancreatic pseudocysts account for most of the cystic collections in the pancreas and are often associated with chronic pancreatitis. Acute Cholangitis or acute pancreatitis Acute pancreatitis Acute pancreatitis is an inflammatory disease of the pancreas due to autodigestion. Common etiologies include gallstones and excessive alcohol use. Patients typically present with epigastric pain radiating to the back. Acute Pancreatitis)
    • Parasites ( Ascaris Ascaris Ascaris is a genus of parasitic nematodes. The infection, ascariasis, is most often caused by A. lumbricoides. Transmission occurs primarily via ingestion of water or food contaminated with Ascaris eggs. Most patients with ascariasis are asymptomatic. Ascaris/Ascariasis lumbricoides, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy flukes such as Clonorchis sinensis
    • Postinfectious strictures (e.g., AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS cholangiopathy)
  • Iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome manipulation of the bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy tract:[8]
    • ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis ( endoscopic retrograde cholangiopancreatography Endoscopic Retrograde Cholangiopancreatography Fiberoptic endoscopy designed for duodenal observation and cannulation of Vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (Vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis
    • Sphincterotomy Sphincterotomy Surgical incision of a sphincter. Anal Fissure
    • Stent placement
  • Commonly a bacterial infection in the setting of biliary obstruction; causative organisms include:
    • Gram-negative bacteria gram-negative bacteria Bacteria which lose crystal violet stain but are stained pink when treated by gram’s method. Bacteriology (most common)
      • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli (isolated in up to 50% of cases)
      • Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella 
      • Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas
      • Serratia Serratia A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that occurs in the natural environment (soil, water, and plant surfaces) or as an opportunistic human pathogen. Acute Cholangitis
      • Proteus Proteus Proteus spp. are gram-negative, facultatively anaerobic bacilli. Different types of infection result from Proteus, but the urinary tract is the most common site. The majority of cases are caused by Proteus mirabilis (P. mirabilis). The bacteria are part of the normal intestinal flora and are also found in the environment. Proteus
      • Bacteroides Bacteroides Bacteroides is a genus of opportunistic, anaerobic, gram-negative bacilli. Bacteroides fragilis is the most common species involved in human disease and is part of the normal flora of the large intestine. Bacteroides
    • Gram-positive bacteria gram-positive bacteria Bacteria which retain the crystal violet stain when treated by gram’s method. Bacteriology
      • Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus
      • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus
      • Clostridia Clostridia Clostridia species comprise a group of spore-forming, obligate anaerobic, gram-positive bacilli. Major pathogenic species include Clostridium perfringens (C. perfringens), which is associated with gas gangrene; Clostridioides difficile, which is associated with pseudomembranous colitis; C. tetani, which causes tetanus; and C. botulinum, which causes botulism. Clostridia

Mnemonic: Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology responsible for cholangitis—KEEPS:

  • K: Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella
  • E: Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus
  • E: E. coli
  • P: Proteus Proteus Proteus spp. are gram-negative, facultatively anaerobic bacilli. Different types of infection result from Proteus, but the urinary tract is the most common site. The majority of cases are caused by Proteus mirabilis (P. mirabilis). The bacteria are part of the normal intestinal flora and are also found in the environment. Proteus
  • S: Serratia Serratia A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that occurs in the natural environment (soil, water, and plant surfaces) or as an opportunistic human pathogen. Acute Cholangitis

Pathophysiology[1,2]

  • Obstruction of the common bile duct common bile duct The largest bile duct. It is formed by the junction of the cystic duct and the common hepatic duct. Gallbladder and Biliary Tract: Anatomy ( CBD CBD Atypical Parkinsonian Syndromes) → biliary stasis → bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology ascend from the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy bacterial overgrowth Bacterial overgrowth Lactose Intolerance and suppuration → biliary sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock 
  • Increased intrabiliary pressure caused by obstruction also increases the permeability of bile ductules Bile ductules Gallbladder and Biliary Tract: Anatomy  → translocation of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology into the biliary tract Biliary tract Bile is secreted by hepatocytes into thin channels called canaliculi. These canaliculi lead into slightly larger interlobular bile ductules, which are part of the portal triads at the “corners” of hepatic lobules. The bile leaves the liver via the right and left hepatic ducts, which join together to form the common hepatic duct. Gallbladder and Biliary Tract: Anatomy
  • Disruption of the sphincter of Oddi can result in a loss of the mechanical barrier Mechanical barrier Innate Immunity: Barriers, Complement, and Cytokines to duodenal reflux → ascension of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology and subsequent infection
  • Procedures such as biliary stenting and endoscopic sphincterotomy Sphincterotomy Surgical incision of a sphincter. Anal Fissure also disrupt the barrier that prevents bacterial entry into the biliary tract Biliary tract Bile is secreted by hepatocytes into thin channels called canaliculi. These canaliculi lead into slightly larger interlobular bile ductules, which are part of the portal triads at the “corners” of hepatic lobules. The bile leaves the liver via the right and left hepatic ducts, which join together to form the common hepatic duct. Gallbladder and Biliary Tract: Anatomy.

Clinical Presentation

  • Charcot triad (50%–75% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will have all 3 features):[1–3,5,9]
    • Right upper quadrant Right upper quadrant Anterior Abdominal Wall: Anatomy (RUQ) abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever 
    • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
    • Note: Charcot triad has high specificity (about 95%), but low sensitivity (about 25%).[5,9]
  • Reynolds pentad (signals severe disease):[1–3, 9]
    • RUQ abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever 
    • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice 
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension 
    • Altered mental status Altered Mental Status Sepsis in Children
  • Other signs or symptoms:[2]
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Abdominal distention Abdominal distention Megacolon
    • Acholic (without bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy) stools
    • Dark urine
    • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
    • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children

Diagnosis

Clinical evaluation

  • Acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis can be life-threatening, so the condition should be suspected in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship presenting with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, and/or abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (Charcot triad). 
  • In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship > 80 years of age, presentation is more consistent with Reynolds pentad or malaise Malaise Tick-borne Encephalitis Virus.[6]

Laboratory tests

The next step in evaluation is determining presence of inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and biliary obstruction/stasis.[5,6,13]

  • Inflammatory markers: ↑ WBC count, ↑ CRP
  • Hepatic function test:
    • Alkaline phosphatase Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma ( ALP ALP An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma), bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism, and gamma-glutamyl transpeptidase Gamma-glutamyl transpeptidase An enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. Liver Function Tests ( GGT GGT An enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (gsh, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. Alcoholic Liver Disease) → cholestasis
    • AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests ( aspartate Aspartate One of the non-essential amino acids commonly occurring in the l-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. Synthesis of Nonessential Amino Acids aminotransferase) and ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests ( alanine Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. Synthesis of Nonessential Amino Acids aminotransferase)
    • Values > 1.5 the standard upper limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation of normal are suggestive of cholangitis
  • Additional laboratory tests:
    • Lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion → rule out concurrent pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis
    • Blood cultures:
      • Potentially isolate the causative organism
      • Not routinely needed for community-acquired infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease in hemodynamically stable immunocompetent patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship[10]
    • PT/INR → assesses liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function
    • Procalcitonin Procalcitonin Neutropenic Fever → elevated values (> 0.5 μg/L) associated with severe cholangitis and ↑ mortality Mortality All deaths reported in a given population. Measures of Health Status[14]
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test in women of childbearing age

Imaging and diagnostic procedures[6,7,10]

Imaging is necessary to confirm the diagnosis and to exclude other conditions. Generally, on initial presentation, ultrasonography and CT are performed 1st in evaluating cholestasis.

  • Abdominal ultrasound (US): 
    • Possible findings:
      • Biliary duct dilation (most common finding) 
      • Gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis
      • Evidence of underlying etiology
    • A normal US does not rule out acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis.
    • Advantages of US:[1, 5]
      • Noninvasive
      • No radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma
      • Widely available
      • Can be performed at bedside in those who are critically ill 
  • Computed tomography (CT):
    • Performed if ultrasound is unremarkable but acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis is still suspected
    • Higher specificity with helical Helical Computed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures. Computed Tomography (CT) (compared to conventional) CT[5]
    • Possible findings:
      • Dilated intrahepatic and extrahepatic ducts 
      • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the biliary tree Biliary tree The bile ducts and the gallbladder. Gallbladder and Biliary Tract: Anatomy/ bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct wall thickening
      • Malignancy Malignancy Hemothorax
      • Abscesses 
    • Gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis are poorly visualized (dependent on the amount of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes carbonate or calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes in the stones).[5]
  • Magnetic resonance cholangiopancreatography Magnetic resonance cholangiopancreatography Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis ( MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis):[5] 
  • Endoscopic retrograde cholangiopancreatography Endoscopic Retrograde Cholangiopancreatography Fiberoptic endoscopy designed for duodenal observation and cannulation of Vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (Vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis ( ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis):
    • Gold standard for diagnosing cholangitis[4]
    • Diagnostic and therapeutic
    • May skip the above imaging and proceed directly to ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with Charcot triad and elevated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy tests
    • Complications:[4]
      • Pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis
      • Bleeding
      • Trauma/ perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis
      • Cardiopulmonary problems
  • Endoscopic US (EUS):[4] 
    • An option for those unable to undergo MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis
    • Both diagnostic and therapeutic (biliary drainage)
    • Detects small stones and biliary duct dilatation
  • Biliary scintigraphy Scintigraphy Sjögren’s Syndrome (hepatobiliary iminodiacetic acid [HIDA)]:
    • Detects biliary obstruction
    • Takes time; therefore, it is not recommended for critical or unstable patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.

Diagnostic criteria (Tokyo guidelines 2018)

  • After review of clinical findings, laboratory tests, and imaging, a diagnosis of cholangitis can be made (see table of diagnostic criteria).
  • Note: Normal LFTs essentially rule out a diagnosis of acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis.[6]
Table: Diagnostic criteria for acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis (Tokyo guidelines 2018)[4–6,9]
Suspected diagnosis:1 item from A + 1 item from either B or C
Definite diagnosis:1 item from A + 1 item from B + 1 item from C
A.Systemic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever (temperature > 38 °C) and/or shaking chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever
Laboratory evidence of inflammatory response:
  • Abnormal WBC count: < 4000 or > 10,000 cells/µL
  • ↑ CRP: ≥ 1 mg/dL
  • B. Cholestasis Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice (total bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism ≥ 2 mg/dL)
    Abnormal liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy tests > 1.5 the standard upper limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation of normal:
  • ALP ALP An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma
  • GGT GGT An enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (gsh, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. Alcoholic Liver Disease
  • ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests
  • AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests
  • C.Imaging findings Biliary dilatation
    Evidence of the etiology (e.g., common bile duct common bile duct The largest bile duct. It is formed by the junction of the cystic duct and the common hepatic duct. Gallbladder and Biliary Tract: Anatomy stone(s), stricture Stricture Primary Sclerosing Cholangitis)

    Assessing severity of illness

    • Severity assessments help direct the plan of care.
    • Severity is affected by different factors, including:[9] 
      • Response to initial treatment
      • Presence of organ dysfunction 
    • Grading Grading Methods which attempt to express in replicable terms the level of cell differentiation in neoplasms as increasing anaplasia correlates with the aggressiveness of the neoplasm. Grading, Staging, and Metastasis (see table) based on Tokyo guidelines 2018 (calculator):[9, 11–13]
      • Grade I (mild): no organ dysfunction or specific abnormal findings
      • Grade II (moderate): no organ dysfunction but with specific abnormal findings
      • Grade III (severe): organ dysfunction
    Table: Severity assessment of acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis (Tokyo guidelines 2018)[5,9]
    Category Description Findings
    Grade I Mild
  • No organ dysfunction
  • Does not meet criteria for grade II
  • Grade II Moderate Any 2 of the following:
  • Abnormal WBC count: < 4000 or > 12,000 cells/µL
  • High fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever: ≥ 39°C (102.2°F)
  • Age ≥ 75 years
  • Hyperbilirubinemia Hyperbilirubinemia A condition characterized by an abnormal increase of bilirubin in the blood, which may result in jaundice. Bilirubin, a breakdown product of heme, is normally excreted in the bile or further catabolized before excretion in the urine. Jaundice: total bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism ≥ 5 mg/dL
  • Hypoalbuminemia Hypoalbuminemia A condition in which albumin level in blood (serum albumin) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (albuminuria). Nephrotic Syndrome in Children: < 0.7 × lower limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation of normal
  • Grade III Severe Associated with organ dysfunction (any 1 of the following):
  • Cardiovascular: hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension requiring dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS ≥ 5 µg/kg/min or norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS (any dose)
  • Neurologic: altered level of consciousness Altered Level of Consciousness Intracerebral Hemorrhage
  • Renal: oliguria Oliguria Decreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age. Renal Potassium Regulation, creatinine > 2.0 mg/dL
  • Respiratory: partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of oxygen (PaO2)/fraction of inspired oxygen ( FiO2 FiO2 percentage of oxygen delivered directly to the patient Invasive Mechanical Ventilation) ratio < 300
  • Hepatic: INR > 1.5
  • Hematologic: platelet count < 100,000/mm3
  • Gallbladder wall thickening acute cholangitis

    Acute cholangitis: Abdominal ultrasound showing gallbladder wall thickening, pericholecystic fluid and cholelithiasis (a). The common bile duct is dilated (b).

    Image: “Abdominal ultrasound” by Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Avenida Professor Egas Moniz, Lisboa, 1649-035, Portugal. License: CC BY 4.0

    Management

    Management guidelines may vary depending on practice location, and should be guided by specialist consultation (e.g., gastroenterology). The following information is based on the current literature and guidelines. 

    Overview of the management approach[9,11,13]

    • Initial steps:
      • Admit patient with cholangitis to the hospital.
      • Give supportive therapy.
      • Start antibiotics.
      • Decide on the need to perform urgent or emergent biliary drainage based on clinical severity.
    • Grade I cholangitis:
      • Initial supportive treatment and antibiotics are often sufficient.
      • If there is no response to initial treatment in 24 hours, proceed with biliary drainage/decompression.
    • Grade II cholangitis:
      • Initial supportive treatment and antibiotics
      • Urgent biliary drainage 
    • Grade III cholangitis:
      • Initial supportive treatment and antibiotics
      • Emergent biliary drainage
    • Additional recommendations:
      • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship requiring biliary drainage: transfer if the procedure cannot be performed in the current facility
      • In grades II (moderate) and III (severe) cholangitis, biliary culture is obtained (along with blood culture) to determine causative organism(s).
      • Antibiotics should eventually be tailored to the culture and susceptibility results.
      • Address the etiology after acute management/disease resolution (e.g., gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis requiring cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy, duct stricture Stricture Primary Sclerosing Cholangitis, or stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) requiring biliary stent).
    Acute cholangitis options

    A simplified management algorithm for acute cholangitis based on the hemodynamic stability of the patient: Definitive treatment requires source control with biliary drainage. Therefore, this treatment is performed emergently in patients who are hemodynamically unstable.

    Image by Lecturio.

    Supportive therapy[911]

    • Intravenous fluid resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome
    • Electrolyte correction
    • Close vital sign monitoring
    • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control
    • Vasopressors Vasopressors Sepsis in Children for septic shock Septic shock Sepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status. Sepsis and Septic Shock (e.g., norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS, dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS)
    • Intensive care unit admission for individuals in a critical state

    Antimicrobial therapy

    Antibiotic coverage for gram negatives and anaerobes Anaerobes Lincosamides:[1012]

    • Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones +/– metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess:
    • Cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins +/– metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess:
      • Added coverage for anaerobes Anaerobes Lincosamides with is recommended in cases of biliary-enteric anastomosis.
      • Options:
        • Cefazolin Cefazolin A semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine. Cephalosporins
        • Cefuroxime
        • Ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins
        • Cefotaxime Cefotaxime Semisynthetic broad-spectrum cephalosporin. Cephalosporins
    • Piperacillin Piperacillin Semisynthetic, broad-spectrum, ampicillin derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics. Penicillins tazobactam Tazobactam A penicillanic acid and sulfone derivative and potent beta-lactamase inhibitor that enhances the activity of other anti-bacterial agents against beta-lactamase producing bacteria. Cephalosporins
    • Carbapenems Carbapenems A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. Carbapenems and Aztreonam:
      • Ertapenem Ertapenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of gram-positive and gram-negative bacterial infections including intra-abdominal infections, acute gynecological infections, complicated urinary tract infections, skin infections, and respiratory tract infections. It is also used to prevent infection in colorectal surgery. Carbapenems and Aztreonam
      • Imipenem Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. Carbapenems and Aztreonam cilastatin Cilastatin A renal dehydropeptidase-i and leukotriene d4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-i, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene d4 to leukotriene e4. Carbapenems and Aztreonam 
      • Meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam
      • Doripenem Doripenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of infections such as hospital-acquired pneumonia, and complicated intra-abdominal or urinary-tract infections, including pyelonephritis. Carbapenems and Aztreonam
    • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides should be added to cover MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with health care–associated infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease who are:
      • Known to be colonized with MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus
      • Have significant antibiotic exposure/prior treatment failure
    Table: Antibiotic dosing for acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis[10-12]
    Medication Typical dosing (adult; IV)
    Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones 400 mg every 12 hours
    Levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones 750 mg daily
    Moxifloxacin Moxifloxacin A fluoroquinolone that acts as an inhibitor of DNA topoisomerase II and is used as a broad-spectrum antibacterial agent. Fluoroquinolones 400 mg daily
    Metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess 500 mg every 8 hours
    Cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins Cefazolin Cefazolin A semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine. Cephalosporins 1–2 g every 8 hours
    Cefuroxime 1.5 g every 8 hours
    Ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins 1–2 g daily
    Cefotaxime Cefotaxime Semisynthetic broad-spectrum cephalosporin. Cephalosporins 2 g every 8 hours
    Piperacillin Piperacillin Semisynthetic, broad-spectrum, ampicillin derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics. Penicillins tazobactam Tazobactam A penicillanic acid and sulfone derivative and potent beta-lactamase inhibitor that enhances the activity of other anti-bacterial agents against beta-lactamase producing bacteria. Cephalosporins
  • General: 3.375 g every 6 hours
  • For Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas coverage: 3.375 g every 4 hours OR 4.5 g every 6 hours
  • Carbapenems Carbapenems A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. Carbapenems and Aztreonam Ertapenem Ertapenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of gram-positive and gram-negative bacterial infections including intra-abdominal infections, acute gynecological infections, complicated urinary tract infections, skin infections, and respiratory tract infections. It is also used to prevent infection in colorectal surgery. Carbapenems and Aztreonam 1 g daily
    Imipenem Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. Carbapenems and Aztreonam–cilastin 500 mg every 6 hours OR 1 g every 8 hours
    Meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam 1 g every 8 hours
    Doripenem Doripenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of infections such as hospital-acquired pneumonia, and complicated intra-abdominal or urinary-tract infections, including pyelonephritis. Carbapenems and Aztreonam 500 mg every 8 hours

    Duration of antibiotics:[10]

    Factors considered in choosing antibiotic regimens (see table):[1012]

    • Individual risk factors that increase mortality Mortality All deaths reported in a given population. Measures of Health Status:
      • Age > 70 years
      • Comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus (cardiovascular disease, poor nutritional status)
      • Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis state
      • Severity of illness/cholangitis
    • Increased risk of antibiotic resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing:
      • Health care–associated infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease 
      • Travel to areas with resistant organisms or intake of antibiotics prior to travel
      • Colonization Colonization Bacteriology of antibiotic-resistant organisms
    Table: Antibiotic regimens in cholecystitis Cholecystitis Cholecystitis is the inflammation of the gallbladder (GB) usually caused by the obstruction of the cystic duct (acute cholecystitis). Mechanical irritation by gallstones can also produce chronic GB inflammation. Cholecystitis is one of the most common complications of cholelithiasis but inflammation without gallstones can occur in a minority of patients. Cholecystitis[12]
    Grade Grade I Grade II Grade III or health care–associated infection
    Single agents
  • Ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins sulbactam Sulbactam A beta-lactamase inhibitor with very weak antibacterial action. The compound prevents antibiotic destruction of beta-lactam antibiotics by inhibiting beta-lactamases, thus extending their spectrum activity. Combinations of sulbactam with beta-lactam antibiotics have been used successfully for the therapy of infections caused by organisms resistant to the antibiotic alone. Cephalosporins*
  • Ertapenem Ertapenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of gram-positive and gram-negative bacterial infections including intra-abdominal infections, acute gynecological infections, complicated urinary tract infections, skin infections, and respiratory tract infections. It is also used to prevent infection in colorectal surgery. Carbapenems and Aztreonam
  • Cefoxitin
  • Moxifloxacin Moxifloxacin A fluoroquinolone that acts as an inhibitor of DNA topoisomerase II and is used as a broad-spectrum antibacterial agent. Fluoroquinolones
  • Piperacillin Piperacillin Semisynthetic, broad-spectrum, ampicillin derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics. Penicillins tazobactam Tazobactam A penicillanic acid and sulfone derivative and potent beta-lactamase inhibitor that enhances the activity of other anti-bacterial agents against beta-lactamase producing bacteria. Cephalosporins
  • Ertapenem Ertapenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of gram-positive and gram-negative bacterial infections including intra-abdominal infections, acute gynecological infections, complicated urinary tract infections, skin infections, and respiratory tract infections. It is also used to prevent infection in colorectal surgery. Carbapenems and Aztreonam
  • Moxifloxacin Moxifloxacin A fluoroquinolone that acts as an inhibitor of DNA topoisomerase II and is used as a broad-spectrum antibacterial agent. Fluoroquinolones
  • Piperacillin Piperacillin Semisynthetic, broad-spectrum, ampicillin derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics. Penicillins tazobactam Tazobactam A penicillanic acid and sulfone derivative and potent beta-lactamase inhibitor that enhances the activity of other anti-bacterial agents against beta-lactamase producing bacteria. Cephalosporins
  • Ertapenem Ertapenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of gram-positive and gram-negative bacterial infections including intra-abdominal infections, acute gynecological infections, complicated urinary tract infections, skin infections, and respiratory tract infections. It is also used to prevent infection in colorectal surgery. Carbapenems and Aztreonam
  • Imipenem Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. Carbapenems and Aztreonam cilastatin Cilastatin A renal dehydropeptidase-i and leukotriene d4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-i, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene d4 to leukotriene e4. Carbapenems and Aztreonam
  • Meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam
  • Agents that may be used alone OR in combination with metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess**
  • Cefazolin Cefazolin A semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine. Cephalosporins
  • Cefuroxime
  • Ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins
  • Cefotaxime Cefotaxime Semisynthetic broad-spectrum cephalosporin. Cephalosporins
  • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones
  • Levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones
  • Ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins
  • Cefotaxime Cefotaxime Semisynthetic broad-spectrum cephalosporin. Cephalosporins
  • Cefepime Cefepime A fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia. Cephalosporins
  • Ceftazidime Ceftazidime Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for pseudomonas and other gram-negative infections in debilitated patients. Cephalosporins
  • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones
  • Levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones
  • Cefepime Cefepime A fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia. Cephalosporins
  • Ceftazidime Ceftazidime Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for pseudomonas and other gram-negative infections in debilitated patients. Cephalosporins
  • Aztreonam Aztreonam The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam
  • * Only if resistance is < 20%
    ** Most mild-to-moderate uncomplicated biliary infections do not require metronidazole. Both the Tokyo guidelines[11] and the Infectious Diseases Society of America[6] recommend anaerobic coverage in biliary-enteric anastomosis, typically with metronidazole. Another anti-anaerobic therapy option is clindamycin (though resistance in Bacteroides spp. is significant).

    Biliary decompression procedures[9,15]

    • Therapeutic ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis:
      • With sphincterotomy Sphincterotomy Surgical incision of a sphincter. Anal Fissure and stone extraction
      • Usually the treatment of choice[15]
      • Recommended within 48 hours of admission
    • Endoscopic ultrasound-guided cholangiopancreatography with biliary drainage and stent placement:
      • Alternative to ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis if ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis is not technically possible or fails to effectively drain the biliary tract Biliary tract Bile is secreted by hepatocytes into thin channels called canaliculi. These canaliculi lead into slightly larger interlobular bile ductules, which are part of the portal triads at the “corners” of hepatic lobules. The bile leaves the liver via the right and left hepatic ducts, which join together to form the common hepatic duct. Gallbladder and Biliary Tract: Anatomy (e.g., obstructing tumors)
    • Percutaneous transhepatic cholangiogram Percutaneous Transhepatic Cholangiogram Acute Cholangitis ( PTC PTC Acute Cholangitis) with catheter drainage:
      • Requires a dilated biliary system
      • Involves transhepatic insertion of a needle and injection of contrast material into the bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct, allowing drainage and stone extraction
      • Performed if ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis is not available or unsuccessful (e.g., history of a Roux-en-Y procedure)
    • Surgery:
      • Reserved for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship for whom the above interventions fail
      • Cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy can usually be performed at the same time.
    • All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis should also be evaluated for cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy to prevent recurrence.

    Complications and Prognosis

    Complications[1,2]

    • Septic shock Septic shock Sepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status. Sepsis and Septic Shock
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease or microabscesses
    • Acute renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
    • Liver failure Liver failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis
    • Procedure complications
      • Bleeding
      • Fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula formation
      • Bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy leak

    Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas[2,9]

    • May be life-threatening, especially in the elderly or immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis
    • Mortality Mortality All deaths reported in a given population. Measures of Health Status rate
      • Approximately 11% overall
      • 20%–30% in severe disease
    • Depends on:
      • Early recognition and diagnosis
      • Response to treatment
      • Patient comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus
    • Higher morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status seen with:
      • Women
      • Age > 50 years
      • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
      • Failure to respond to antibiotics
      • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
      • Acute renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome

    Management checklist

    • Check for the following:
      • Hemodynamic status
      • Abdominal/RUQ pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways or tenderness
      • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
      • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
      • Additional features: hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, altered mental status Altered Mental Status Sepsis in Children
      • Comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus
    • Laboratory tests:
      • CBC
      • Comprehensive metabolic panel Comprehensive metabolic panel Primary vs Secondary Headaches (includes renal and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function)
      • Amylase Amylase A group of amylolytic enzymes that cleave starch, glycogen, and related alpha-1, 4-glucans. Digestion and Absorption, lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion
      • PT/INR
      • CRP
      • Procalcitonin Procalcitonin Neutropenic Fever
      • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test in women
      • +/– Blood cultures (obtain prior to antibiotic administration based on severity)
    • Imaging studies:
      • Ultrasonography
      • CT if underlying abdominal conditions and/or infection are considered
      • MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis if the diagnosis is still uncertain 
      • Other studies based on individual patient factors and results of initial imaging
    • Assess severity of cholangitis (calculator)
    • Initiate supportive therapy:
      • Nothing by mouth
      • IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids
      • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control
      • Antiemetics Antiemetics Antiemetics are medications used to treat and/or prevent nausea and vomiting. These drugs act on different target receptors. The main classes include benzodiazepines, corticosteroids, atypical antipsychotics, cannabinoids, and antagonists of the following receptors: serotonin, dopamine, and muscarinic and neurokinin receptors. Antiemetics
      • Antibiotic therapy 
    • Determine appropriateness/timing of biliary drainage (most often by ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis)
      • Grade III cholangitis → emergent drainage 
      • Grade II cholangitis → urgent drainage
      • Grade I cholangitis → drainage typically needed only if not responding after 24 hours of supportive therapy and antibiotics
    • Reassess patient response to initial management (supportive therapy, antibiotics, +/– biliary drainage).
    • Specific management of suspected/identified etiology (e.g., cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis after acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis resolves)

    Differential Diagnosis

    The following table outlines common biliary diagnoses and how they may be differentiated from acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis:

    Condition Pathology Clinical presentation Diagnosis Management
    Cholelithiasis Cholelithiasis Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis Presence of gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis in the gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy Asymptomatic or biliary colic (constant, dull RUQ pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways lasting < 6 hours)
    • US
    • Normal blood tests
    • None, if asymptomatic
    • Cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy if symptomatic
    Cholecystitis Cholecystitis Cholecystitis is the inflammation of the gallbladder (GB) usually caused by the obstruction of the cystic duct (acute cholecystitis). Mechanical irritation by gallstones can also produce chronic GB inflammation. Cholecystitis is one of the most common complications of cholelithiasis but inflammation without gallstones can occur in a minority of patients. Cholecystitis Cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis obstruction with inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy Constant RUQ pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (> 6 hours), fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, Murphy’s sign
    • US
    • HIDA (if US is equivocal)
    • Blood tests: ↑ WBC
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy tests may be normal or mild ↑
    • Urgent cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy
    • Antibiotics
    Choledocholithiasis Choledocholithiasis Presence or formation of gallstones in the common bile duct. Cholelithiasis CBD CBD Atypical Parkinsonian Syndromes obstruction due to a stone Postprandial colicky RUQ pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways > 6 h, jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
    • US
    • MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis (if US is equivocal)
    • Blood tests: ↑ ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests, ↑ AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests, ↑ ALP ALP An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma, ↑ bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism
    ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis and cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy
    Acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis Bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct infection RUQ pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
    • US
    • ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis
    • Blood tests: ↑ ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests, ↑ AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests, ↑ ALP ALP An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma, ↑ bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism, ↑ WBC
    • ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis and cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy
    • Antibiotics
    • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock management

    Other potential diagnoses to consider:

    • Acute appendicitis Appendicitis Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. Appendicitis: an infection of the appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with right lower quadrant Right lower quadrant Anterior Abdominal Wall: Anatomy or periumbilical pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, guarding, and tenderness at McBurney’s point. Diagnosis is based on history and exam, and is supplemented by imaging showing appendiceal thickening and fat stranding. The location of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and imaging differentiate this condition from acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis. Treatment involves antibiotics and surgical removal of the appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy
    • Acute pancreatitis Acute pancreatitis Acute pancreatitis is an inflammatory disease of the pancreas due to autodigestion. Common etiologies include gallstones and excessive alcohol use. Patients typically present with epigastric pain radiating to the back. Acute Pancreatitis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with a sudden onset of severe epigastric pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways that is typically sharp and radiates to the back. Acute pancreatitis Acute pancreatitis Acute pancreatitis is an inflammatory disease of the pancreas due to autodigestion. Common etiologies include gallstones and excessive alcohol use. Patients typically present with epigastric pain radiating to the back. Acute Pancreatitis is associated with alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder and gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis. Characteristic abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion elevation, or imaging revealing pancreatic edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema will give the diagnosis and differentiate the condition from acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis. Treatment includes bowel rest, pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control, and intravenous fluid hydration.
    • Nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis: also known as kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis, which can irritate or obstruct the ureters Ureters One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the urinary bladder. Urinary Tract: Anatomy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with sudden onset of severe, colicky flank pain Flank pain Pain emanating from below the ribs and above the ilium. Renal Cell Carcinoma; nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics; vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia; and hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma. Imaging will show stones in the kidney, ureter, or bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess. The history, exam, and imaging will differentiate this condition from acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis. Nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis can be treated with supportive care, pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control, ureteral stents, lithotripsy, or surgery. 
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease: an abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease located in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, usually due to a bacterial infection. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will present with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, RUQ abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, and jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice. Abdominal exam may reveal guarding and rebound tenderness Rebound Tenderness Acute Abdomen. Laboratory tests will show leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus and increased liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes. Ultrasound or CT will reveal the diagnosis and differentiate this condition from acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis. Antibiotics are given, and the abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease needs to be drained with CT guidance, ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis, or surgery.

    References

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