Gall bladder: gallstones Flashcards
What are the commenest types of gallstones?
Cholesterol stones (>50% sterol) most common
Pigment stones composed of calcium bilirubinate
Describe the three factors associated with formation of cholesterol stones.
Consequence of cholesterol crystallization from gall bladder bile:
1) Cholesteral supersaturation of bile (hepatic uptake from the diet & 20% hepatic biosynthesis)
2) Crystallization -promoting factors within the bile
3) Motility of the gall bladder
Cholesterol will only crystallize when it is supersaturated relative to the bile salt and phospholipid content
Risk factors for supersaturation of cholesterol
HMG-CoA reductase catalyses the rate limiting step in the synthesis of cholesterol. Excess activity of this enzyme has been associated with supersaturation.
Insulin resistance and metabolic syndrome associated with increased secretion
High cholesterol diet increase cholesterol secretion and decreases bile salt synthesis.
However supersaturation does not inevitably lead to gallstone formation.
? Role of statins as they act by inhibiting HMG CoA reductase.
Leptin has been shown to increase cholesterol secretion into bile therefore increased levels during rapid weight loss account for increased formation of gallstones.
Bile salt loss in e.g. terminal ileal resection/involvement in Crohn’s disease = supersaturation.
What is the role of bile salt composition?
- Increase in secondary hydrophobic bile acid (deoxycholic acid) in the bile acid pool
- Linked with slow colonic transit - enabling primary bile acid and cholic acid to undergo microbial enzyme metabolism
- Additionally research into role of genetic changes which impact on transporters on the hepatocyte canalicular membrane which enables biliary secretion of cholesterol, bile salts and phospholipids (deficiencies in the later two)
How does gall bladder motility impact on gall stone formation?
Animal models - gall bladder stasis = mucin hypersecretion = cholesteral crystallization.
These factors thought to account for increased risks in pregnancy, multiparity and diabetes.
What are the risk factors for cholesterol gall stones?
- Increasing age
- F>M
- Family hx and genetics
- Multiparity
- Obestiy+/- metabolic syndrome
- Rapid weight loss
- Diet high in animal fat low in fibre?
- Drugs (e.g. contraceptive pill)
- Crohns - ileal disease or resection
- Cirrhosis
- Spinal cord injury
- Diabetes mellitus
- Acromegaly treated with octreotide
- Total parental nutrition
What are the differences between black and brown pigment stones?
- Black pigment stones: mucin glycoproteins with salts like calcium carbonate and/or calcium phosphate
- Brown pigment stones: alternating brown/tan layers. Contain calcium salts of fatty acids as well as calcum bilirubinate. They can be found in any part of the biliary tree secondary to chrnoic stasis and in the presence of anaerobic bacterial infection.
What are the risk factors for black and brown pigmented stones?
- Risk for Black pigment stones = hyperbillirubinbilia so haemolytic anemias (e.g. spheroctosis, sickle cell disease and thalassaemia) or subclinical haemolysis form prosthetic valve replacement, malaria, hypersplenism form hepatic cirrhosis and foot trauma from long distance runners. Also Gilbert syndrome. ? in ileal disease/resection increase solubility and reabsorption of bilirubin and therefore increase circulation in biliary hepatic system. Subclinical bacterial colonisation of the biliary tree produce glucuronidase and phospholipase - facilitate stone formation.
- Risk for brown pigment stones: bile stasis and/or biliary infection nearly always present.
- Oriental hepatolithiasis syndrome (recurrent pyogenic cholangitis) most serious manifestation. Biliary strictures form. (? fluke infection ascaris lubricoides, clonorchis sinensis and Opisthorchis viverrini)
- Following cholecystectomy brown stones associated with recurrent bile duct stones and in intrahepatic bilde ducts in stenosing bilieary disease such as Caroli syndrome and primary sclerosing cholangitis.
How are gallstones frequently detected?
Ultrasound scan
What common abdominal symptoms are not routinely associated with gallstones?
dyspepsia, fat intolerance, flatulence
What clinical syndromes are commonly associated with gallstones?
Often asymptomatic, but…
Biliary Colic
Impacted cystic duct: Acute cholecystitis
Biliary Obstruction, Common Bile Duct: Acute Cholangitis
Pancreatic duct/Ampulla of Vater: Gallstone related Pancreatitis
Ascending cholangitis
Common symptoms associated with gallstone related disease.
Biliary colic - pain characterised by sudden onset, severe, constant, crescendo character, sometimes linked to overindulgence and/or high fat meal
Timing often mid evening till early hours of the am.
Pain located epigastric to right upper quadrant and possible radiation to right shoulder and right subscapular region.
Ass. symptoms - Nausea and vomiting in more severe cases
What symptoms are associated with acute cholecystitis
Cystic duct block preventing gall bladder emptying.
Increased gall bladder glandular secretions, progressive distention with potential vascular supply compromise. Inflammatory response to retained bile.
Progression of biliary colic to include severe right upper quadrant pain, parietal peritoneal involvement - tenderness, muscle guarding or rigidity. Positive murphy’s sign (pain on inspiration with gall bladder palpated).
Gall bladder destention with pus and empyema or rarely acute gangrenous cholecystitis.
What investigations can be performed to diagnose cholecystitis?
Abdominal ultrasound (stones visualised particulalry in neck of gall bladder or cystic duct, focal tenderness, thickening of gall bladder wall) check for pericholystic abscess.
CT with IV contrast can also be used to check the biliary tree
DD - thickening of the gall bladder wall also seen in hypoalbuminaemia, portal hypertension and acute viral hepatitis.
blood test
FBC - moderate leucocytosis (WBC)
raised inflammatory markers e.g. CRP
LFTs - may have small marginal rise in serum bilirubin, alkaline phophatase and aminotransferase levels.
DD biliary colic: IBS, carcinoma of right side of colon, atypical peptic ulcer disease, renal colic and pancreatitis
DD Acute cholecystitis: acute pancreatitis, perforated peptic ulcer or intrahepatic abscess (above diaphragm - basal pneumonia and MI)
How to treat cholecystitis?
Cholecystectomy treatement of choice in nearly all symptomatic gall stones. Complications warrent procedure within period of admission. NICE recommendation for acute cholecystitis is laparoscopic cholecystectomy within one week. Elective in pain alone, but within 4 months
Laparotomy only in patients with C/I extensive upper abdominal surgery, ongoing bile duct obstruction or portal hypertension (adhesions may also require).
Also management with IV fuids, monitoring, Abx and analgesia.
Acute cholecystitis management
conservative initially - nil by mouth, IV fluids, opiate analgesia, IV antibiotics
Delayed cholecystectomy to allow symptom improvement.
No improvement ?empyema or gangrene in the gall bladder? - transabdominal US or CT scan
Radiologically placed drain if unfit for surgery (i.e. ongoing sepsis).
Risks of cholecystectomy?
biliary leak
injury to bile duct (symptomatic soon after surgery) - stricture and secondary biliary liver.
0.2% mortality
What is sphincter of Oddi dysfunction?
Biliary or pancreatic pain caused either by -
Sphincter of Oddi stenosis (prior instrumation for stones)
Sphincter of Oddi hypertension (serum liver biochemistry, amylase)
What are the types of sphincter of oddi dysfunction?
Biliary
- Type I - biliary type pain with raised serum bilirubin, Alkaline phophatase (ALP) or aminotransferases (AST or ALT) and distended common bile duct on imaging
- Type II - biliary type pain, abnormal liver biochem or distended bile duct
- Type III - recurrent biliary-type pain (no abnormal liver or CBD)
- Type I-II endoscopic sphincterotmy
- Pancreatic SOD
- Type I - recurrent pancreatic pain, raised serum amylase and dilated pancreatic duct
- Type II - as above, but either or
- Type III - pain only
What are the clinical features of acute cholangitis? (ascending cholangitis)
Biliary colic, fever (commonly with rigors) and jaundice. Abdo pain, typically RUQ is the most significant feature.
Charcots triad
Jaundice level tends to fluctuate more than with malignant disease.
Reynolds pentad adds shock (hypotension, and tachycardia) and confusion
Diagnostic Tests in Acute Cholangitis?
FBC - raised WCC if complicated
Elevated neutrophil count and raised CRP
Raised serum bilirubin (mild and transient) >200micromol/L indicates complete CBD obstruction
Serum ALP & GGT similarly elevated similarly to hyperbilirubinaemia.
Aminotranserase levels, mildly elevated ALT>AST
Serum amylase levels slight elevated unless pancreatic involvement (then much higher)
Prothrombin time prolonged if bile duct obstruction sustained over several days (decreased vitamin K).
Transabdominal ultrasound - initial imaging of choice. Dilatation of intrahepatic biliary radicles, although stones in distal CBD are poorly visualized.
MRCP
CT scanning for exclusion of other causes
Endoscopic untrasound - imaging small stones, but invasive
ERCP
What are the differential diagnoses for Acute Cholingitis?
Can be independent of gall stones in any impaired biliary drainage - sclerosing cholangitis and Caroli syndrome
Cholecystitis with stone in hartmann’s pouch which is compressing CBD from outside - results in jaundice.
Treatment for cholangitis
IV antibiotics and urgent bile duct drainage - ERCP with sphincterotomy and balloon/basket catheters to remove stone or stent to maintain bile duct drainage.
ERCP requires visualisation and access to 2nd part of duodenum if not possible percutaneous biliary drainage. Surgical drainage not advised during acute cholangitic episode.
Eventually laparoscopic cholecystectomy when CBD stones and gall bladder stones with eploration of the CBD
Complications of gallstones?
Acute cholecystitis and acute cholangitis
Gallstone pancreatitis
Gallstone erode through the wall of the gall bladder and into the intestine - biliary enteric fistula resulting in ileus or true obstruction
Acalculous Cholecystitis
Chronic inflammation without gallstones. Inflammation can, in rare cases, result in gall bladder perforation.
Usually in elderly or critically ill
Can occur as a result of reflux of pancreatic enzymes back into the biliary tree
cholecystectomy in absence of evidence of gall bladder stones would be dependent on clinical presentation and evidence of diseased gall bladder on USS
Primary sclerosing cholangitis
This is a chronic cholestatic liver disease (would therefore expect raised ALP) characterised by fibrosing inflammatory destruction of both the intra and extrahepatic bile ducts. Often associated with IBD particularly Ulcerative Colitis. Autoantibody pANCA is found in the serum of 60% patients.
Often discovered due to monitoring in asymptomatic patients with raised ALP. Symptomatic = fluctuating pruritis, jaundice and cholangitis (i.e. inflammation of the CBD)
How is Primary sclerosing cholangitis detected?
MRC scanning will pick up biliary changes, ERCP may be required for more detailed imaging. changes and irregularity of the calibre in intra and extrahepatic ducts may be seen on imaging.
confirmation comes from histology- inflammation of the intrahepatic biliary radicles with associated scar tissue ‘onion skin’. Prognosis extent of fibrosis/cirrhosis. PSC is slowly progressive lesion leading to cirrhosis and decompensation - cholangiocarcinoma in 15%. Liver transplant is the only proven treatment. High dose ursodeosycholic acid has been evaluated in some patients and extrahepatic biliary tree may be amenable to endoscopic intervention with balloon dilatation and stenting.
What is haemobilia?
Bleeding into the biliary tree (can be truama, liver surgery, biopsy). Fistula between a branch of the hepatic artery and intrahepatic bile duct. Should be suspected when malaena presents with RUQ pain and jaundice.
Radiological thrombosis of the artery feeding the one fisulated may manage.
Gall bladder polyps risk?
Comon finding, most non-neoplastic and are inflammatory in origin composed of cholesterol deposits. Adenomas are benign with few having cancerous potential management based on size - only those over 1cm require cholecystectomy.
Adenocarcinoma of gallbladder
More likely women 50-70
gallstones or diffuse calcification (porcelain gall bladder) as a result of chronic colecystitis associated and therefore indication for early cholecystecotomy of gall bladder.
Spread to lymphatics in the liver and biliary tract prevents early curative resection of lesion - no known chemotherapy agent to which it is responsive and only sensitive to radiotherapy in a minority of cases - therefore 5 yr survival is <5%
Cholangiocarcinoma
bile duct malignancy usually presents with jaundice and is associated with choledochal cysts (congenital), chornic infection of the biliary tree and primary sclerosing cholangitis.
Initial USS may raise suspision, but CT and MRCP to id and visualise spread. Spread by lymphatics or local extension. CBD involvement only may enable resection and localised disease warrents aggressive surgical approach. Chemoradiation in small hilar lesions which may enable transplant, but disease likely to return.
what other cancers can involve the biliary tree?
Carcinoma of the head of the bile duct - results in obstruction and jaundice
Melanoma most common neoplasm to result in metastases in the bile ducts. (also lung, breast, colon and pancreas)
