Gall bladder: gallstones

Question 1

What are the commenest types of gallstones?

Answer 1

Cholesterol stones (>50% sterol) most common

Pigment stones composed of calcium bilirubinate

Question 2

Describe the three factors associated with formation of cholesterol stones.

Answer 2

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

Question 3

Risk factors for supersaturation of cholesterol

Answer 3

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.

Question 4

What is the role of bile salt composition?

Answer 4

• 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)

Question 5

How does gall bladder motility impact on gall stone formation?

Answer 5

Animal models - gall bladder stasis = mucin hypersecretion = cholesteral crystallization.

These factors thought to account for increased risks in pregnancy, multiparity and diabetes.

Question 6

What are the risk factors for cholesterol gall stones?

Answer 6

• 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

Question 7

What are the differences between black and brown pigment stones?

Answer 7

• 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.

Question 8

What are the risk factors for black and brown pigmented stones?

Answer 8

• 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.

Question 9

How are gallstones frequently detected?

Answer 9

Ultrasound scan

Question 10

What common abdominal symptoms are not routinely associated with gallstones?

Answer 10

dyspepsia, fat intolerance, flatulence

Question 11

What clinical syndromes are commonly associated with gallstones?

Answer 11

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

Question 12

Common symptoms associated with gallstone related disease.

Answer 12

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

Question 13

What symptoms are associated with acute cholecystitis

Answer 13

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.

Question 14

What investigations can be performed to diagnose cholecystitis?

Answer 14

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)

Question 15

How to treat cholecystitis?

Answer 15

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.

Question 16

Acute cholecystitis management

Answer 16

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).

Question 17

Risks of cholecystectomy?

Answer 17

biliary leak

injury to bile duct (symptomatic soon after surgery) - stricture and secondary biliary liver.

0.2% mortality

Question 18

What is sphincter of Oddi dysfunction?

Answer 18

Biliary or pancreatic pain caused either by -

Sphincter of Oddi stenosis (prior instrumation for stones)

Sphincter of Oddi hypertension (serum liver biochemistry, amylase)

Question 19

What are the types of sphincter of oddi dysfunction?

Answer 19

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

Question 20

What are the clinical features of acute cholangitis? (ascending cholangitis)

Answer 20

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

Question 21

Diagnostic Tests in Acute Cholangitis?

Answer 21

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

Question 22

What are the differential diagnoses for Acute Cholingitis?

Answer 22

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.

Question 23

Treatment for cholangitis

Answer 23

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

Question 24

Complications of gallstones?

Answer 24

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

Question 25

Acalculous Cholecystitis

Answer 25

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

Question 26

Primary sclerosing cholangitis

Answer 26

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)

Question 27

How is Primary sclerosing cholangitis detected?

Answer 27

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.

Question 28

What is haemobilia?

Answer 28

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.

Question 29

Gall bladder polyps risk?

Answer 29

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.

Question 30

Adenocarcinoma of gallbladder

Answer 30

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%

Question 31

Cholangiocarcinoma

Answer 31

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.

Question 32

what other cancers can involve the biliary tree?

Answer 32

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)