21 : Disease of extrahepatic biliary tract : Jumana Abu Hamour : 6/12/2015 : Dr. Samir Bashir 1 P a g e
*Check last page please before you start. Cholelithiasis: -Small, round stones in the gallbladder. It is a common disease affecting 10-20% of adults. And more than 80% of patients are asymptomatic. -It is due to the precipitation of bilirubin calcium salts (pigmented) or cholesterol in the bile. Pathogenesis: a) Supersaturation: due to a high concentration of cholesterol or bilirubin which leads to the precipitation of either. b) Decreased phospholipids (e.g. lecithin) or bile salts. Their function is to solubilize for example cholesterol. However, if for some reason such as a drug binding to them, they will decrease. This will increase the risk of the nucleation (precipitation) of cholesterol. Nucleation is also promoted by calcium salts. c) Gall bladder stasis with cholesterol crystals remaining long enough to aggregate. These 3 points all relate to each other. When there are low amounts of phospholipids (lecithin) and bile salts, this will lead to the supersaturation of cholesterol. This leads to the nucleation of cholesterol and the gallbladder will become hypo-motile (meaning the occurrence of gallbladder stasis). This results in the formation of 2 P a g e
monohydrate cholesterol crystals. Mucus hypersecretion in the wall of the gallbladder and calcium salts both promote the accretion 1 of the formation of the gall stones (the final step). 1 Accretion: the process of growth or increase, typically by the gradual accumulation of additional layers or matter. 3 P a g e
Types of Gallstones: 1) Cholesterol stones: most common type of stones especially in the West. They are usually radiolucent which means they cannot show up on x-rays. -Location: exclusively in Gallbladder -Appearance: ovoid firm, single or multiple, multi-faceted, most are radiolucent. Pure (just cholesterol): pale yellow Mixed (20%): gray white to black, containing calcium carbonate, phosphates & bilirubin (it becomes radioopaque). Risk Factors: 4 P a g e - Age: elderly > young adults Gender (F:M is 2:1) : females (as estrogen increases the activity of HMG-CoA reductase which in turn increases
cholesterol production. Estrogen also increases lipoprotein receptors and this increases cholesterol uptake. Oral contraceptives (OCPs), pregnancy which also increase HMG-CoA. Demography: Western World; Native Americans Gallbladder stasis Inborn disorders of bile acid metabolism Obesity Hyperlipidemia Rapid weight loss Treatment with the hypocholesterolemic agent Clofibrate (a lipid lowering agent): increases HMG-CoA reductase and it also decreases conversion of cholesterol to bile acids. If there is a low amount of bile acids, the cholesterol will be less soluble. 2) Pigmented stones: usually radio-opaque (show up on x-rays). Location: anywhere in biliary tree Appearance: contain calcium salts of unconjugated bilirubin, calcium salts (e.g. Calcium carbonate), mucin glycoproteins & cholesterol. i. Black: in sterile (not infected) Gallbladder bile, small, numerous, friable (easily crumbled); 50-75% are radio-opaque. ii. Brown in infected intra- or extra-hepatic ducts, single or few, soft & greasy and radiolucent. 5 P a g e
- Risk Factors: Demography: Asians, rural areas Chronic hemolytic syndromes* Biliary infections by viruses, bacteria or parasites. Gastrointestinal disorders: Ileal disease, e.g. Crohn s disease Ileal resection or bypass Cystic fibrosis with pancreatic insufficiency 6 P a g e
*Chronic Hemolytic syndromes: For example in extra vascular hemolysis, a large amount of unconjugated bilirubin is produced by the reticulo-endothelial system (in particular the splenic macrophages). When the splenic macrophages eat the RBCs, they break down the hemoglobin into heme and globin. Then the heme is broken down into iron and protoporphyrin. The iron is recycled but the protoporphyrin is converted into unconjugated bilirubin (biliverdin was reduced producing bilirubin). Once the liver conjugates it, it will throw all that extra bilirubin into the bile increasing the risk for the formation of bilirubin gallstones. doctor didn t talk about this picture. **The Clinical presentations of Cholelithiasis: 7 P a g e
70-80% are asymptomatic If symptomatic, these signs would appear: Biliary colic (constant) which is waxing and waning right upper quadrant pain due to a gallbladder contracting against stone lodged in the cystic duct. It is associated with the inflammation of the gallbladder. Complications: Cholecystitis: Empyema: formation of pus Perforation due to inflammation and irritation of mucosa. Fistulae with adjacent organs Inflammation of biliary tree Obstructive cholestasis Pancreatitis Intestinal obstruction ( gallstone ileus ) due to cholecystitis with fistula formation between gallbladder and small bowel. Inflammation of the gallbladder Almost always associated with gallstones One of the most common indications for abdominal surgery Epidemiologic distribution similar to cholelithiasis 8 P a g e
Classification: o Acute calculous o Acute acalculous o Chronic Acute Cholecystitis: o Acute & chronic Acute calculous cholecystitis: caused by obstruction of Gallbladder neck or cystic duct by stones. Chemical irritation & inflammation of GB wall: Mucosal phospholipases hydrolyze biliary lecithin to toxic lysolecithin Disruption of protective glycoprotein mucous layer Prostaglandin release within GB wall which leads to local inflammation Blood Flow compromised due to GB distension & pressure Symptoms may be mild or sudden & severe (most commonly it is a severe case and requires immediate surgical attention as in a cholecystectomy). Acute acalculous cholecystitis ( no stones): 5-12% of cases Seen in post-operative states, severe trauma, severe burns, sepsis & postpartum 9 P a g e
Factors: dehydration (loss of body volume), GB stasis & sludging (GB hypomotility), vascular compromise, bacterial contamination. * Gross appearance of acute cholecystitis with subserosal hemorrhage. Morphology of Acute Cholecystitis: Enlarged (2-3x), tense GB with discolorations due to subserosal hemorrhages. Serosal fibrinous or suppurative exudate. Stones obstructing GB neck or cystic duct in 90% of cases. GB lumen filled with turbid bile, +/- fibrin, hemorrhage & pus Empyema of gallbladder: full of pus 10 P a g e
Thickened edematous hyperemic wall Gangrenous cholecystitis: black necrotic GB Histology: edema, WBC infiltration (in acute mainly neutrophils), congestion & necrosis (especially if there is sloughing of the mucosa of the GB). Chronic Cholecystitis: recurrent infection of the GB +/- history of acute cholecystitis Gall stones almost always present, but stones & obstruction do not play major role in initiation of inflammation. Supersaturation of bile predisposes to chronic inflammation & stone formation. Bacteria are isolated in 1/3 of cases. Variable morphologic appearance: minimal changes, contraction, enlargement, mucosal ulceration or wall thickening. Histology: lymphocytic infiltration, fibrosis. This is a gross appearance of Chronic Cholecystitis. There is thickening of GB wall due to fibrosis. 11 P a g e
Clinical Features of Cholecystitis: Acute & chronic calculous cholecystitis have similar & variable symptoms: minimal nonspecific symptoms to biliary colics to severe Right Upper Quadrant (RUQ) pain. Fever, nausea, leukocytosis & prostration (loss of strength). Conjugated hyperbilirubinemia usually due to obstruction of the bile ducts. Acute acalculous cholecystitis: symptoms obscured by general conditions. Acute acalculous cholecystitis is extremely hard to diagnose. X-rays won t help as there are no stones present. It has very similar symptoms as most infections; fever, abdominal pain, chills, anorexia, diarrhea. These are called constitutional symptoms or general symptoms. If it is not diagnosed correctly, you will lose your patient as it requires urgent cholecystectomy. However, it will show on some imaging like on a CT scan or an MRI. Fat intolerance in chronic patients. o Diagnosis: Ultrasonography o Complications: cholangitis (inflammation f the bile ducts), sepsis, GB perforation, abscess, rupture, cholecyst-enteric fistula, intestinal ileus,... Choledocholithiasis: Stones present within the biliary tree due to accumulation of bilirubin. 12 P a g e
Stones may be: 1) Derived from gallbladder 2) Primary ductal & intrahepatic stone formation Stones do not necessarily obstruct major bile ducts Asymptomatic in 10% Symptoms due to: biliary obstruction, pancreatitis, cholangitis, hepatic abscess, chronic liver disease with secondary biliary cirrhosis, or acute acalculous cholecystitis. Extrahepatic Biliary Atresia Major cause (1/3) of neonatal cholestasis Two forms: fetal form and prenatal form ( most common) 1:10,000 live births Complete bile flow obstruction due to destruction or absence of all or part of extrahepatic bile ducts Not a true atresia: an acquired inflammatory disorder of unknown cause Slight female preponderance Normal birth weight infants Lab: conjugated hyperbilirubinemia Biopsy is essential for diagnosis 13 P a g e
Pathology: 1) inflammation & fibrosing stricture of hepatic or common bile ducts, with progressive destruction of intrahepatic biliary tree 2) Periductal inflammation of intrahepatic ducts 3) Liver: marked bile duct proliferation, portal tract edema & fibrosis, parenchymal cholestasis 4) Periportal fibrosis & cirrhosis within 3-6 months Px: death within 2 years of birth Rx: liver transplantation Intrahepatic Biliary Tract diseases: Biliary tract diseases are divided into: 14 P a g e
1) Intrahepatic diseases 2) Extrahepatic diseases Intrahepatic biliary tract disease: I. Due to general liver disease a) Drug toxicity b) Viral hepatitis c) Liver transplantation II. Due to biliary tract disease a) Biliary cirrhosis Primary Secondary b) Primary sclerosing cholangitis Primary Biliary Cirrhosis: Chronic autoimmune progressive & often fatal cholestatic liver disease, characterized by destruction of intra-hepatic bile ducts, portal inflammation & scarring. Primary feature: nonsuppurative granulomas Florid duct lesions: where medium-sized bile ducts show intense chronic inflammation and damage to their walls (lymphatic infiltration). 15 P a g e
It is not necessary for the patient to have cirrhosis immediately, as it may happen decades later. Primary Biliary Cirrhosis Disease of middle-aged women, onset 20-80 yrs Insidious onset: pruritis; later jaundice appears Cirrhosis & hepatic failure develops over 2 or more decades, with s & s of portal hypertension & hepatic encephalopathy Lab: alk. phosph. & cholesterol; bilirubin is a late development, indicating hepatic decompensation Autoantibodies: anti-mitochondrial Ab in >90% of patients (mitochondrial pyruvate dehydrogenase) Associated extra-hepatic conditions: Sjogren s, scleroderma, thyroiditis, RA, celiac disease Rx: Liver transplantation 16 P a g e
Autoimmune disease involving lymphocyte-mediated destruction of bile duct epithelium Primary Sclerosing Cholangitis Inflammation, obliterative fibrosis & segmental dilation of the obstructed intrahepatic & extrahepatic bile ducts Chronic cholestatic disorders Onion skinning shape around bile ducts. 17 P a g e
Irregular strictures & dilations of affected bile ducts produces characteristic beading picture in barium contrast radiography 70% of patients have associated ulcerative colitis About 4% of UC patients have PSC 3rd-5th decades; M:F=2:1 Clinical picture: progressive fatigue, pruritis & jaundice; signs & symptoms of chronic liver disease Lab: alkaline phosphatase Autoantibodies: <10% of patients Px: protracted (extends) course over many years; increased risk of cholangiocarcinoma Rx: Liver transplantation 18 P a g e
Primary biliary cirrhosis Pre-cirrhosis: Florid duct lesion with granulomas, lymphocytes, macrophages, plasma cells & eosinophils; bile duct proliferation, inflammation & necrosis of periportal hepatic parenchyma Secondary biliary cirrhosis Pre-cirrhosis: Prominent bile stasis in bile ducts, bile duct proliferation with surrounding neutrophils, portal tract edema. Coarse fibrous septa with distended ducts embedded in septa. Pylephlebitis & cholangitic abscess Primary sclerosing cholangitis Pre-cirrhosis: Fibrosing cholangitis of bile ducts; concentric "onion skin" fibrosis, progressive duct atrophy & luminal obliteration Secondary Biliary Cirrhosis: Prolonged obstruction to extrahepatic biliary tree results in profound damage to the liver Causes: 1) Extrahepatic cholelithiasis 2) Biliary atresia 3) Tumors of biliary tree & pancreas head 4) Strictures secondary to previous surgery 19 P a g e
Pathology: Initially, reversible features of cholestasis Periportal fibrosis, scarring, & nodule formation Subtotal obstruction causes secondary ascending cholangitis, mostly due to coliforms & enterococci. Ascending Cholangitis: Acute inflammation of the wall of bile ducts Caused by any lesion obstructing bile flow: 1) Choledocholithiasis 2) Tumors 3) Indwelling catheters or stents 4) Acute pancreatitis 5) Benign strictures 6) Microorganisms: fungi, viruses, protozoa & bacteria Fever, chills, abdominal pain, jaundice Suppurative cholangitis: risk of liver abscess Complications: Sepsis 20 P a g e
* I would really recommend you watch pathoma as it is only about 10 minutes. Here is the link: https://onedrive.live.com/?authkey=%21agdxiriedpsbrei&cid=3096eb B0D8D0A903&id=3096EBB0D8D0A903%211855&group=0&parId=3 096EBB0D8D0A903%211824&o=OneUp I have included all the slides as the doctor depended very much on them. If there are any mistakes or questions, please inform me. This is the last pathology lecture. 21 P a g e