Extrahepatic Biliary Tract Pathology - Cholidolithiasis, Cholidocholithiasis, Cholecystitis And Cholangitis 3b682n

EXTRAHEPATIC BILIARY TRACT PATHOLOGY CHOLELITHIASIS, CHOLEDOCHOLITHIASIS CHOLECYSTITIS AND CHOLANGITIS

Prepared by

Darien Liew Daojuin 12 May 2017

CHOLELITHIASIS (GALLSTONES)

Prepared by Darien Liew Daojuin 12 May 2017

DEFINITION OF CHOLELITHIASIS Cholelithiasis involves the presence of gallstones, which are concretions that form in the biliary tract, usually in the gallbladder. Characteristics •

Develop insidiously

•

May remain asymptomatic for decades

•

Biliary colic – increase gallbladder wall tension due to bile outflow obstruction

Cystic duct obstruction persisting for > a few hours can result in acute cholecystitis.

PATHOGENESIS Risk Factor

PATHOGENESIS OF CHOLESTEROL STONES 1. Supersaturation ­ Increased biliary secretion of cholesterol ­ Associated with risk factors, e.g. obesity, metabolic syndrome, high caloric/cholesterolrich diets and genetic risk factors etc. ­ Genetic factors ­ Mutation in CYP7A1 results in deficiency of the enzyme cholesterol 7-hydroxylase, which catalyzes the initial step in cholesterol catabolism and bile acid synthesis. ­ Mutations in the MDR3 (ABCB4) gene, which encodes the phospholipid export pump in the canalicular membrane of the hepatocyte, may cause defective phospholipid secretion into bile, resulting in cholesterol supersaturation of bile and formation of cholesterol gallstones

­ While supersaturation of bile with cholesterol is an important prerequisite for gallstone formation, it is generally not sufficient by itself to produce cholesterol precipitation in vivo. Most individuals with supersaturated bile do not develop stones because the time required for cholesterol crystals to nucleate and grow is longer than the time bile remains in the gallbladder.

PATHOGENESIS OF CHOLESTEROL STONES 2. Nucleation ­ Accelerated nucleation of cholesterol monohydrate in bile may be due to either an excess of pronucleating factors or a deficiency of antinucleating factors. ­ Cholesterol monohydrate crystal nucleation and crystal growth probably occur within the mucin gel layer. ­ Mucus hypersecretion resulting in trapping of the crystals and enhancing their aggregation into stones.

3. Gallbladder hypomobility ­ If the gallbladder emptied all supersaturated or crystal-containing bile completely, stones would not be able to grow. A high percentage of patients with gallstones exhibit abnormalities of gallbladder emptying.

4. Biliary sludge ­ The presence of biliary sludge implies two abnormalities: (1) the normal balance between gallbladder mucin secretion and elimination has become deranged, and (2) nucleation of biliary solutes has occurred.

PATHOGENESIS (SUMMARY) Cholesterol gallstone disease occurs because of several defects, which include 1.

bile supersaturation with cholesterol,

2.

nucleation of cholesterol monohydrate with subsequent crystal retention and stone growth, and

3.

hypomobility – abnormal gallbladder motor function with delayed emptying and stasis.

TYPES OF GALLSTONES Gallstones are formed because of abnormal bile composition. They are divided into two major types: 1.

Cholesterol stones ­ for >90% of all gallstones in Western industrialized countries. ­ Cholesterol gallstones usually contain >50% cholesterol monohydrate plus an ixture of calcium salts, bile pigments, proteins, and fatty acids.

2.

Pigment stones ­ Composed primarily of calcium bilirubinate; they contain <20% cholesterol and are classified into “black” and “brown” types, the latter forming secondary to chronic biliary infection.

TYPES OF GALLSTONES 1. CHOLESTEROL STONE

• Cholesterol stones arise exclusively in the gallbladder • Consist of 50% to 100% cholesterol. • Pure cholesterol stones are pale yellow; increasing proportions of calcium carbonate, phosphates, and bilirubin impart gray-white to black discoloration. • They are ovoid and firm; they can occur singly, but most often there are several, with faceted surfaces resulting from their apposition. • Most cholesterol stones are radiolucent, although as many as 20% may have sufficient calcium carbonate to be radiopaque.

TYPES OF GALLSTONES 2. PIGMENT STONE

• May arise anywhere in the biliary tree and are classified into black and brown stones. • Black pigment stones are found in sterile gallbladder bile. • Black stones are usually small in size, fragile to the touch, and numerous • Because of calcium carbonates and phosphates, 50% to 75% of black stones are radiopaque.

• Brown stones are found in infected intrahepatic or extrahepatic ducts. • Brown stones tend to be single or few in number and to have a soft, greasy, soaplike consistency that results from the presence of retained fatty acid salts released by the action of bacterial phospholipases on biliary lecithins. • Brown stones, which contain calcium soaps, are radiolucent.

• The stones contain calcium salts of unconjugated bilirubin and lesser amounts of other calcium salts, mucin glycoproteins, and cholesterol.

TYPES OF GALLSTONES Cholesterol Gallstones

Pigmented Gallstones

TYPES OF GALLSTONES 3. MIXED STONE

Cholesterol gallstones may become colonized with bacteria and can elicit gallbladder mucosal inflammation. Lytic enzymes from the bacteria and leukocytes hydrolyze bilirubin conjugates and fatty acids. As a result, over time, cholesterol stones may accumulate a substantial proportion of calcium bilirubinate and other calcium salts, producing mixed gallstones.

CLINICAL MANIFESTATION Only 10% of individuals with gallstones develop clinical evidence. Symptomatic gallbladder stones will manifest as biliary pain of cholecystitis. ­ Sudden onset and persists for 2 hours, if it continues for >6 hours, a complication such as cholecystitis or pancreatitis may be present. ­ Often excruciating, which typically localizes to the right upper quadrant or epigastric region and can be constant or, less commonly, spasmodic. ­ Such “biliary” pain is caused by gallbladder or biliary tree obstruction, or by inflammation of the gallbladder itself. ­ The pain is constant in nature and is not relieved by emesis, antacids, defecation, flatus, or positional changes. It may be accompanied by diaphoresis, nausea, and vomiting.

BILIARY COLIC Characteristics of Biliary Colic ­ Sporadic and unpredictable episodes ­ Pain that is localized to the epigastrium or right upper quadrant, sometimes radiating to the right scapular tip ­ Pain that begins postprandially, is often described as intense and dull, typically lasts 1-5 hours, increases steadily over 10-20 minutes, and then gradually wanes ­ Pain that is constant; not relieved by emesis, antacids, defecation, flatus, or positional changes; and sometimes accompanied by diaphoresis, nausea, and vomiting ­ Nonspecific symptoms (eg, indigestion, dyspepsia, belching, or bloating)

HISTORY Gallstone disease may be thought of as having the following 4 stages: 1.

The lithogenic state, in which conditions favor gallstone formation

2.

Asymptomatic gallstones

3.

Symptomatic gallstones, characterized by episodes of biliary colic

4.

Complicated cholelithiasis

HISTORY Distinguishing uncomplicated biliary colic from acute cholecystitis or other complications is important. Key findings that may be noted include the following: Uncomplicated biliary colic – Pain that is poorly localized and visceral; an essentially benign abdominal examination without rebound or guarding; absence of fever

Acute cholecystitis – Welllocalized pain in the right upper quadrant, usually with rebound and guarding; positive Murphy sign (nonspecific); frequent presence of fever; absence of peritoneal signs; frequent presence of tachycardia and diaphoresis; in severe cases, absent or hypoactive bowel sounds

INVESTIGATION Ultrasound – investigation of choice CT and MR – for detecting complications of gallstones

TREATMENT SURGICAL

Once gallstones become symptomatic, definitive surgical intervention with cholecystectomy is usually indicated (typically, laparoscopic cholecystectomy is first-line therapy at centers with experience in this procedure). Careful selection of patients is warranted and should fulfill the following criteria: ­ Small stone size (<0.5 to 1 cm) ­ Good gallbladder function (e.g, normal filling and emptying) ­ Minimal or no calcification

REFERENCES 1.

http://emedicine.medscape.com/article/175667-overview

2.

Harrison’s Principles of Internal Medicine, 19th Edition

3.

Davidson’s Principles and Practice of Medicine, 22nd Edition

4.

Robbin’s Basic Pathology, 9th Edition

CHOLEDOCHOLITHIASIS

Prepared by Darien Liew Daojuin 12 May 2017

DEFINITION Choledocholithiasis refers to the presence of 1 or more gallstones in the common bile duct (CBD). This occurs when a gallstone es from the gallbladder into the CBD. A gallstone in the common bile duct may impact distally in the ampulla of Vater, causing abdominal pain and jaundice. Stagnant bile often becomes infected, and bacteria can spread rapidly back up the ductal system into the liver to produce a lifethreatening infection called ascending cholangitis. Obstruction of the pancreatic duct by a gallstone in the ampulla of Vater can trigger activation of pancreatic digestive enzymes within the pancreas itself, leading to acute pancreatitis.

PATHOPHYSIOLOGY age of gallstones into the CBD occurs in ∼10–15% of patients with cholelithiasis. The incidence of common duct stones increases with increasing age of the patient, so that up to 25% of elderly patients may have calculi in the common duct at the time of cholecystectomy. Undetected duct stones are left behind in ∼1–5% of cholecystectomy patients. The overwhelming majority of bile duct stones are cholesterol stones formed in the gallbladder, which then migrate into the extrahepatic biliary tree through the cystic duct.

PATHOPHYSIOLOGY Primary calculi arising de novo in the ducts are usually brown pigment stones developing in patients with 1.

hepatobiliary parasitism or chronic, recurrent cholangitis;

2.

congenital anomalies of the bile ducts (especially Caroli’s disease);

3.

dilated, sclerosed, or strictured ducts; or

4.

an MDR3 (ABCB4) gene defect leading to impaired biliary phospholipids secretion (low phospholipid–associated cholesterol cholelithiasis).

Common duct stones may remain asymptomatic for years, may spontaneously into the duodenum, or (most often) may present with biliary colic or a complication.

PARASITISM Parasites residing in the biliary tree include 1.

Clonorchis sinensis,

2.

Opisthorchis viverrini,

3.

Opisthorchis felineus, and

4.

Fasciola hepatica.

They are willowy, leaf-like, flat flukes dwelling in the bile ducts and gallbladder. Human ascarides, Ascaris lumbricoides, dwelling in the small intestine, inadvertently migrate into the bile ducts and cause biliary obstruction.

Reference : https://www.ncbi.nlm.nih.gov/pubmed/17515382

CLINICAL FEATURES May be asymptomatic May be found incidentally by operative cholangiography at cholecystectomy May manifest as recurrent abdominal pain with or without jaundice. RUQ pain Fever, pruritus and dark urine

CHOLECYSTITIS

Prepared by Darien Liew Daojuin 12 May 2017

ACUTE CHOLECYSTITIS Acute inflammation of the gallbladder wall usually follows obstruction of the cystic duct by a stone. Inflammatory response can be evoked by three factors: 1.

mechanical inflammation produced by increased intraluminal pressure and distention with resulting ischemia of the gallbladder mucosa and wall

2.

chemical inflammation caused by the release of lysolecithin (due to the action of phospholipase on lecithin in bile) and other local tissue factors; this will disrupt the normal mucosal epithelium to the direct detergent action of bile salts. Prostaglandin released will contribute to mucosal and mural inflammation.

3.

bacterial inflammation, which may play a role in 50–85% of patients with acute cholecystitis. The organisms most frequently isolated by culture of gallbladder bile in these patients include Escherichia coli, Klebsiella spp., Streptococcus spp., and Clostridium spp.

PATHOPHYSIOLOGY Cause

Mechanism of injury

Type of Injury

Obstruction of the Distention of the outflow tract and/or gallbladder compression of the cystic artery by a gallstone

Ischemic necrosis

Mechanical and inflammatory injury to biliary cells

Formation of inflammatory mediators and chemical injury by detergents

Mucosal injury or necrosis and inflammation

Secondary bacterial infection

Inflammatory response

Mucosal injury or necrosis and inflammation

ACUTE CHOLECYSTITIS Acute calculous cholecystitis – Acute inflammation of a gallbladder that contains stones. Precipitated by obstruction of the gallbladder neck or cystic duct.

MORPHOLOGY In acute cholecystitis, the gallbladder usually is

­ enlarged and tense, ­ bright red or blotchy, violaceous color, the latter imparted by subserosal hemorrhages.

The serosa frequently is covered by a fibrinous, or in severe cases, fibrinopurulent exudate. In 90% of cases, stones are present, often obstructing the neck of the gallbladder or the cystic duct. The gallbladder lumen is filled with cloudy or turbid bile that may contain fibrin, blood, and frank pus. When the contained exudate is mostly pus, the condition is referred to as empyema of the gallbladder. In mild cases the gallbladder wall is thickened, edematous, and hyperemic. In more severe cases the gallbladder is transformed into a green-black necrotic organ—a condition termed gangrenous cholecystitis.

MORPHOLOGY On histologic examination, the inflammatory reactions are not distinctive and consist of the usual patterns of acute inflammation (i.e., edema, leukocytic infiltration, vascular congestion, frank abscess formation, or gangrenous necrosis). The morphologic changes in chronic cholecystitis are extremely variable and sometimes subtle. The gallbladder may be contracted, of normal size, or enlarged. Mucosal ulcerations are infrequent; the submucosa and subserosa often are thickened from fibrosis. In the absence of superimposed acute cholecystitis, mural lymphocytes are the only signs of inflammation.

CLINICAL PRESENTATION Biliary pain that progressively worsens.

­ Approximately 60–70% of patients report having experienced prior attacks that resolved spontaneously. ­ Generalized in the right upper abdomen. ­ Radiate to the interscapular area, right scapula, or shoulder.

A low-grade fever is characteristically present, RUQ – tender on palpation. ­ Murphy’s Sign - Deep inspiration or cough during subcostal palpation of the RUQ usually produces increased pain and inspiratory arrest .

Localized rebound tenderness in the RUQ is common, as are abdominal distention and hypoactive bowel sounds from paralytic ileus, but generalized peritoneal signs and abdominal rigidity are usually lacking, in the absence of perforation. The patient is anorectic and often nauseated. Vomiting is relatively common and may produce symptoms and signs of vascular and extracellular volume depletion. Jaundice is unusual early in the course of acute cholecystitis but may occur when edematous inflammatory changes involve the bile ducts and surrounding lymph nodes.

ACUTE ACALCULOUS CHOLECYSTITIS The main cause of this illness is thought to be bile stasis and increased lithogenicity of bile. Critically ill patients are more predisposed because of increased bile viscosity due to fever and dehydration and because of prolonged absence of oral feeding resulting in a decrease or absence of cholecystokinin-induced gallbladder contraction. Gallbladder wall ischemia that occurs because of a low-flow state due to fever, dehydration, or heart failure may also play a role in the pathogenesis of acalculous cholecystitis. Acute acalculous cholecystitis; predisposing factors ­ ­ ­ ­

Major nonbiliary surgery Severe trauma Severe burns Sepsis

CHRONIC CHOLECYSTITIS Chronic cholecystitis may be the sequel to repeated bouts of acute cholecystitis, but in most instances it develops without any history of acute attacks. It is almost always associated with gallstones. Symptoms and morphologic alterations are similar to acute calculous cholecystitis but milder in form. Presentation ­ Recurrent attacks of steady epigastric or RUQ pain ­ Nausea, vomiting and intolerance for fatty foods

Diagnosis is pathological, based on the examination of resected gallbladder.

PATHOPHYSIOLOGY In chronic cholecystitis, the varied appearance of the gallbladder reflects the degree of inflammation and fibrosis. The gallbladder may be distended or shrunken and appear atrophic. Fibrous serosal adhesions suggest previous episodes of acute cholecystitis. On gross examination, the wall is usually thickened, but it may be thin in some cases. The mucosa may be intact with preservation or accentuation of its folds, or it may be flattened with outflow obstruction. Mucosal erosions or ulcers are frequently associated with impacted stones

The diagnosis is based on three histologic characteristics: • A predominantly mononuclear inflammatory infiltrate in the lamina propria, with or without extension into the muscularis and pericholecystic tissues • Fibrosis • Metaplastic changes.

INVESTIGATION

ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ER) This technique remains widely used as both a diagnostic and therapeutic modality. Using a side-viewing endoscope the ampulla of Vater can be identified and cannulated. Injection of water-soluble contrast directly into the bile duct provides excellent images of the ductal anatomy and can identify causes of obstruction, such as calculi or malignant strictures. While the widespread availability of ultrasound and MR has reduced its diagnostic use, ER still has a real role in the assessment of the patient with obstructive jaundice. In this group of patients, it is especially useful in determining the cause and level of obstruction.

MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY (MR) MR is an imaging technique based on the principles of nuclear magnetic resonance used to image the gall bladder and biliary system. It is non-invasive and can provide either cross-sectional or projection images. E xcellent images can be obtained of the biliary tree demonstrating ductal obstruction, strictures or other intraductal abnormalities. Images comparable to those obtained at ER or percutaneous transhepatic cholangiography (PTC) can be achieved non-invasively without the potential complications of either technique.

MR

MANAGEMENT In acute cholecystitis, the initial treatment includes bowel rest, intravenous hydration, correction of electrolyte abnormalities, analgesia, and intravenous antibiotics. Laparoscopic cholecystectomy is the standard of care for the surgical treatment of cholecystitis. Percutaneous Drainage – For patients at high surgical risk, placement of a sonographically guided, percutaneous, transhepatic cholecystostomy drainage tube coupled with the istration of antibiotics may provide definitive therapy.

COMPLICATIONS 1.

Empyema of the gallbladder

2.

Gangrene of the gallbladder and perforation

3.

Fistula formation ­ Fistula formation into an adjacent organ adherent to the gallbladder wall may result from inflammation and adhesion formation. ­ Fistulas into the duodenum are most common, followed by, the hepatic flexure of the colon, stomach or jejunum, abdominal wall, and renal pelvis.

4.

Gallstone ileus ­ Mechanical intestinal obstruction resulting from the age of a large gallstone into the bowel lumen. ­ The site of obstruction by the impacted gallstone is usually at the ileocecal valve, provided that the more proximal small bowel is of normal caliber.

5.

Porcelain gallbladder ­ Calcium salt deposition within the wall of a chronically inflamed gallbladder may be detected on the plain abdominal film. ­ Cholecystectomy is advised in all patients with porcelain gallbladder because in a high percentage of cases this finding appears to be associated with the development of carcinoma of the gallbladder.

ACUTE GANGRENOUS CHOLECYSTITIS

REFERENCES 1.

https://clinicalgate.com/infectious-and-inflammatory-disorders-ofthe-gallbladder-and-extrahepatic-biliary-tract/

2.

Harrison’s Principles of Internal Medicine, 19th Edition

3.

Davidson’s Principles and Practice of Medicine, 22nd Edition

4.

Robbin’s Basic Pathology, 9th Edition

5.

Bailey and Love’s Short Practice of Surgery, 26th Edition

CHOLANGITIS

Prepared by Darien Liew Daojuin 12 May 2017

CHOLANGITIS Cholangitis – acute inflammation of the wall of bile ducts, almost always caused by bacterial infection of the normally sterile lumen. It can result from any lesion obstructing bile flow, most commonly choledocholithiasis, and also from surgery involving the biliary tree. Other causes include tumors, indwelling stents or catheters, acute pancreatitis, and benign strictures. Bacteria most likely enter the biliary tract through the sphincter of Oddi, rather than by the hematogenous route.

CHOLANGITIS Ascending cholangitis refers to the propensity of bacteria, once within the biliary tree, to infect intrahepatic biliary ducts. The usual pathogens are E. coli, Klebsiella, Enterococci, Clostridium, and Bacteroides. Two or more organisms are found in half of the cases. Bacterial cholangitis usually produces fever, chills, abdominal pain, and jaundice.

In some world populations, parasitic cholangitis is a significant problem. Causative organisms include ­ Fasciola hepatica or schistosomiasis in Latin America and the Near East, ­ Clonorchis sinensis or Opisthorchis viverrini in the Far East ­ cryptosporidiosis in persons with acquired immunodeficiency syndrome.

CHOLANGITIS Suppurative cholangitis – purulent bile fills and distends bile ducts, with an attendant risk of liver abscess formation. Because sepsis rather than cholestasis is the predominant risk in cholangitic patients, prompt diagnosis and intervention are imperative.

RISK FACTOR

CLINICAL PRESENTATION Charcot’s Triad ­ Fever ­ Jaundice ­ RUQ Pain

Reynold’s Pentad ­ Charcot’s Triad ­ Mental status change ­ Sepsis

Fever is present in approximately 90% of cases, with chills and rigors. Abdominal pain and jaundice is thought to occur in 70% and 60% of patients, respectively. Patients present with altered mental status 10-20% of the time and hypotension approximately 30% of the time.

DIAGNOSIS The diagnosis of the cause of cholangitis can be made on magnetic resonance cholangiography (MRC) as it is non-invasive and involves no exposure to radiation, but diagnostic and therapeutic (drainage of the biliary system) modalities include endoscopic retrograde cholangiopancreatography (ER) and percutaneous transhepatic cholangiography (PTC). MRC is preferred before ERC or PTC, as it indicates the level of the block (eg, high or low) and the patency of the biliary ductal confluence; this helps in the selection of the therapeutic procedure for drainage of the biliary system (ie, ERC for low blocks and PTC for high blocks with confluence but not patency).

REFERENCES 1.

http://emedicine.medscape.com/article/774245-overview

2.

Davidson’s Principles and Practice of Medicine, 22nd Edition

3.

Robbin’s Basic Pathology, 9th Edition

EXTRAHEPATIC BILIARY PATHOLOGY

Last Reviewed 19 May 2017