Cholelithiasis (Gallstones and biliary colic)

Question 1

Define cholelithiasis and choledocholithiasis.

Answer 1

Cholelithiasis is the presence of solid concretions in the gallbladder. Gallstones form in the gallbladder but may exit into the bile ducts (choledocholithiasis).

Question 2

Describe the differences between the presentation of biliary colic, cholecystitis, choledocholithiasis, acute pancreatitis.

Answer 2

Biliary colic - steady, severe pain (>5/10 intensity), RUQ pain lasting >15-30min but resolves within 5 hours.

Cholecysitis - biliary pain >5hrs with inflammation: fever, marked RUQ tenderness and leukocytosis.

Choledocholithiasis - stone obstructs bile ducts, biliary pain is accompanied by cholestasis which manifests as jaundice. More sinister version of this is acute cholangitis characterised by Charcot’s triad and is a medical emergency.

Acute pancreatitis - epigastrc pain which radiates to back and results from bile duct stones obstructing pancreatic ducts. Inflammatory features include peritonitis.

Question 3

Define biliary colic.

Answer 3

When a colic (sudden pain) occurs due to a gallstone temporarily blocking the cystic duct.

Question 4

How common are gallstones?

Answer 4

• 10-15% of people have cholelithiasis in the US/Europe
• Asymptomatic in >80% of people
• 3% will then go on to get complications (acute cholecystitis, cholangitis, acute pancreatitis)
• Only 0.1-0.3% of all will experience major complications

Question 5

What are the types of gallstones?

Answer 5

• Cholesterol stones (80%) - yellow to dark green made of 80% cholesterol by weight
• Pigment stones (20%) - dark/black and small made of bilirubin, calcium phosphate (bile salts), <20% cholesterol.
• Mixed stones - 20-80% cholesterol, calcium carbonate, bile pigments,

Question 6

What is the normal composition of bile?

Answer 6

• 70% bile salts and acids - amphipilic (both hydrophilic and hydrophobc sides to be more soluble), It is the bile acids which cause itching.
• 10% cholesterol
• 5% phospholipids - lecithin
• 5% proteins
• 1% bilirubin
• Other - water, electrolytes, bicarbonate

Question 7

What are the three ways in which cholesterol stones form?

Answer 7

1. Bile salts and acids become supersaturated with cholesterol and cholesterol precipitates out (because they make chol more soluble in bile)
2. Not enough salts/acids or phospholipids - so less cholesterol is in solution
3. Gallbladder stasis- cholesterol separates from solution

Question 8

Which stones are visible on X Ray?

Answer 8

• Only those which have CaCO3 (formed by Ca and bicarbonate) - radioopaque –> visible on X Ray
• Cholesterol stones are NOT visible - i.e. radioluscent

Question 9

In what form is bilirubin present in bile?

Answer 9

• 98-99% conjugated
• 1-2% unconjugated bilirubin → unclear mechanism forming stones e.g. calcium bilirubinate(unconjugated). Radiopaque.

Question 10

What is the molecular difference between conjugated and unconjugated bilirubin?

Answer 10

Conjugated has an R-group - glucuroinc acid which makes it water soluble

Unconjugated has an OH group - at the pH of bile is in anionic form that binds with calcium (but usually bile salts bind with the Ca to stop them precipitating UCB)

Question 11

Describe extra bilirubin production from breakdown of RBC.

Answer 11

Extravascular haemolysis with macrophages phagocytosis → UCB production → conjugated by the liver → sent to gall bladder.

But if there is more conjugated bilirubin there will also be more UCB eventually so calcium will start to bind it and precipitate out to form black pigmented stones.

Question 12

What are the risk factors for cholesterol gallstones?

Answer 12

Female, fat, fertile, forty.

Question 13

What are the risk factors for developing pigment stones?

Answer 13

• Age
• chronic haemolytic anaemia
• Cirrhosis
• Cystic fibrosis
• Ileal disease

Question 14

What do mixed stones consist of and what are the risk factors for them?

Answer 14

• Consist of UCB and calcium salts of long-chain fatty acids, cholesterol and mucin.
• Stasis and infection = bile strictures (from partial biliary obstruction) or parasitic infestation* represent the major risk factors

*e.g. Clonorchis sinensis, Opisthorchis species and Fasciola hepatica

Question 15

What is the pathophysiology of biliary colic?

Answer 15

Gallstones which pass into the bile ducts cause obstruction and biliary pain (cholangitis).

Question 16

What is Bouveret syndrome?

Answer 16

Cholecystoenteric fistula forms when a gallstone erodes through the gallbladder wall and leads to duodenal obstruction = Bouveret syndrome

Obstruction in the narrowest segemnt of an otherwise healthy bowel causes gallstone ileus.

Question 17

What are the symptoms of gallstones?

Answer 17

• RUQ pain or epigastric area pain after food consumption
• Pain increases in intensity and lasts for several hours (pain of <30min is not biliary colic, while that >5hrs is cholecytitis or another major complication)
• Nausea

Question 18

What are the signs of gallstones on examination?

Answer 18

RUQ/epigastric pain

Jaundice (uncommon)

Question 19

What are the risk factors for gallstones in general?

Answer 19

• Age
• Famela
• Hispanic/native-American
• FH
• Pregnancy, exogenous oestrogen
• Obesity, diabetes, metabolic syndrome
• TPN
• octreotide, incretin-based drugs, ceftriaxone
• terminal ileum disease or resection
• haemoglobinopathy

Question 20

What investigations would you do for cholelithiasis?

Answer 20

Bloods:

• FBC - normal in simple biliary colic (WBCs in inflammation from acute cholecystitis, cholangitis, pancreatitis)
• LFTs - normal in gallstones; elevated ALP and bilirubin in choledocholithiasis
• Lipase/amylase - elevated (x3 upper limit of normal) in acute pancreatitis

Scans:

• Abdominal US - stones
• MRCP - if stones not confirmed by US
• ERCP - offers diagnosis and therapy for patients with high risk of bile duct stones.
• CT abdo - if you suspect ascending cholangitis or gallstone pancreatitis

Question 21

What is the management of biliary colic (i.e. symptomatic gallstones)?

Answer 21

1. Analgesia - e.g. diclofenac or indometacin PO or IM; opioid if ineffective
2. +/- Anti-spasmodic - hyoscine 20mg IV/IM
3. Exclude cholecystitis and (refer to secondary care) offer laparoscopic cholecystectomy - usually elective, but if pain uncontrollable and hospital admission then offer immediate
4. +/- Bile duct clearance - ERCP, surgical or laparoscopic bile duct exploration

Question 22

What are the complications of gallstones?

Answer 22

• ERCP-associated pancreatitis - managed with bowel rest, analgesia, IV fluids
• Iatrogenic bile duct injuries
• Post-sphincterotomy bleeding (ERCP complication) - commonly recognised at time of procedure and treated with endoscopic haemostatic techniques
• Bouveret syndrome (duodenal obstruction)
• Gallsone ileus (obstructs narrowest part of healthy bowel, terminal ileum usually)
• Cholecystitis
• Ascending cholangitis
• Acute biliary pnacreatitis
• Mirizzi syndrome

Question 23

What is the prognosis for cholelithiasis?

Answer 23

• Management by cholecystectomy is best for prognosis
• RF for recurrent choledochal problems are common with: bile duct dilation to >13mm, periampullary diverticulum, brown pigment stones, or with gallbladder being left intact.

Question 24

What is the management of asymptomatic gallstones?

Answer 24

Observation - prophylactic cholecystectomy only in certain cases:

1. Risk of gallbladder carcinoma e.g. gallstones >3cm or partially calcified gallbladder
2. Risk of complications e.g. patient with SCD