DISORDERS OF THE BILIARY TREE Flashcards
Which lobes of the liver does the gallbladder lie between?
The inferior aspects of the right lobe and quadrate lobe
Whats the anatomical structure of the gallbladder?
Fundus at the top where it protects into the inferior surface of the liver
Body is the largest part
Neck is where the gallbladder tapers to become continuous with the cystic duct, leading into the biliary tree
Whats the Hartmanns pouch?
A mucosal fold in the neck of the gallbladder
A common location for gallstones to become lodged, causing cholestasis
Whats the storage capacity of the gallbladder?
30-50ml
Outline the structure of the biliary tree?
Bile is initially secreted from hepatocytes and drains from both lobes of the liver via canaliculi, intralobular ducts and collecting ducts into the left and right hepatic ducts. These ducts amalgamate to form the common hepatic duct, which runs alongside the hepatic vein.
As the common hepatic duct descends, it is joined by the cystic duct – which allows bile to flow in and out of the gallbladder for storage and release. At this point, the common hepatic duct and cystic duct combine to form the common bile duct.
The common bile duct descends and passes posteriorly to the first part of the duodenum and head of the pancreas. Here, it is joined by the main pancreatic duct, forming the hepatopancreatic ampulla (commonly known as the ampulla of Vater) – which then empties into the duodenum via the major duodenal papilla. This papilla is regulated by a muscular valve, the sphincter of Oddi.
Whats the arterial supply to the gallbladder?
The cystic artery (a branch of the right hepatic artery)
Whats the venous drainage of the gallbladder?
Cystic veins which drain directly to the portal vein
What innervates the gallbladder?
Coeliac plexus for sympathetic and sensory fibres
Vagus nerve delivers parasympathetic innervation
What mediates secretion of bile into the cystic duct?
Cholecystokinin
Also parasympathetic stimulation produces contraction of the gallbladder
What makes up bile?
70% Bile salts and acids
10% Cholesterol
5% Phsopholipids
5% proteins
1% bilirubin
Electrolytes
Water
Bicarbonate
What are the 2 main groups of constituents of bile?
Bile acid-dependant - produced by hepatocytes e.g. bile acids, bile pigments and cholesterol
Bile acid-independant - produced by ductal cells that line bile ducts - secrete an alkaline solution stimulated by secretin
What are the 2 primary bile acids?
Cholic acid
Chenodeoxycholic acid
What are bile salts?
When bile acids are conjugated with the amino acids glycine and taurine they form bile salts
These are more soluble than bile acids and act as detergents to emulsify lipids (they are a amphipathic)
What are the bile pigments?
Biliverdin (green pigment)
Bilirubin - breakdown product of Hb and is conjugated in the liver and secreted into bile
What is the enterohepatic Circulation of Bile Acids?
the movement of bile acid molecules from the liver to the small intestine and back to the liver
The enterohepatic circulation allows the liver to recycle and preserve a pool of bile acids.
Whats intestinal bacteria’s role in producing bile salts?
In the intestine, the primary bile acids are often converted by colonic bacteria to the secondary bile acids, predominantly deoxycholic acid and lithocholic acid.
Whats the average total bile flow?
600ml a day
Outline the production of bilirubin?
RBC broken down by Kupffer cells in the liver and reticuloendothelial system
Iron and globin are removed from haem and reused
Haem forms biliverdin which is changes to unconjugated bilirubin via biliverdin reductase
Bilirubin is taken to the liver via albumin where it dissociates and is taken up by hepatic cell membranes and transported to the endoplasmic reticulum by cytoplasmic proteins. Here its conjugated with glucuronic acid and excreted into bile
Conjugated bilirubin is actively secreted into biliary canaliculi and excreted into the intestine within bile
In the terminal ileum, bacterial enzymes hydrolyse the molecule to release free bilirubin
It is then reduced to urobilinogen; some of this is excreted in stool as stercobilinogen and the remainder is absorbed bu the terminal ileum and passes to the liver via the enterohepatic circulation and is re-excreted into bile
Urobilinogen bound to albumin enters circulation and is excreted in urine via the kidneys
What is biliary colic?
Pain in the RUQ/epigastrium which is associated with the temporary obstruction of the cystic or common bile duct, usually by a stone migrating from the gallbladder
Usually a sudden onset of severe constant pain lasting from 30 minutes to 6 hours. Typically has a crescendo characteristic
Not associated with fever or abdominal tenderness!
Pain of <30 mins is less likely to be biliary colic
What is cholelithiasis?
refers to the development of a solid deposit or ‘stone’ within the gallbladder.
What is choledocholithiasis?
Gallstones within the biliary tree
What is acute cholecystitis?
Acute inflammation of the gallbladder, most commonly caused by gallstones
What is acute cholangitis?
Infection of the biliary tree, commonly due to an obstructing stone in the CBD
Outline the epidemiology of gallstones?
Prevalence is 10-15% of adults in Europe and the US
Prevalence increases with advancing age before levelling off at 60-70
2-3x more common in women
Tend to affect Caucasians, native Americans and Hispanic ethnicity more (may reflect genetic and dietary factors?)
Rarely seen brefore age 30
What are the risk factors associated with the development of cholelithiasis?
Older age >40
Female
Genetic predisposition
Rapdi weight loss/prolonged fasting
Obesity
NAFLD
Diabetes mellitus
Medications - octreotide, ceftriaxone, glucagon-like peptide-1 analogues, HRT
Crohn’s disease
Diet high in triglycerides and refined carbohydrates and low fibre
(Fat, Fair, Female, Fourty)
What is cholestasis?
Blockage to the flow of bile
What is gallbladder empyema?
Pus in the gallbladder
How does cholelithiasis tend to present?
80% may be asymptomatic
Biliary colic - severe colicky epigastric/RUQ pain often triggered by high fat meals and lasts 30 mins-8 hours. May be associated with nausea and vomiting
Alternatively, pt may present with the complications of gallstones e.g. cholecystitis, cholangitis, obstructive jaundice or pancreatitis
What are the types of gallstones?
Cholesterol stones - 90% of western world gallstones
Pigmented stones (aka bilirubin stones)
Mixed stones
What causes cholesterol gallstone formation?
Cholesterol supersaturation (bile has so much cholesterol that the bile salts/acids/phospholipids can’t hold any more in solution so cholesterol precipitates)
??Accelerate cholesterol crystal nucleation
Not enough bile salts, acids or phospholipids to keep the cholesterol in solution
Impaired gallbladder motility (stasis causes cholesterol to precipitate out)
Where does cholesterol come from?
Hepatic uptake from dietary sources
20% - hepatic biosynthesis
Outline the cholesterol synthesis pathway?
Acetyl CoA -> HMG-CoA -> mevalonate -> IPP -> FPP
-> squalene -> epoxysqualene -> lanosterol -> cholesterol
Whats the rate limiting step in cholesterol synthesis?
HMG coA reductase (catalyses the first step of acetate to mevalonate)
What are black pigment stones?
These are dark stones composed primarily of calcium bilirubinate, accounting for around 10-20% of stones. They occur in people with increased amounts of bilirubin in their bile - hyperbilirubinbilia. This occurs in patients with increased haemolysis
What are brown pigment gallstones?
These stones are a mix of calcium bilirubinate and a calcium salts of fatty acids, accounting for around 5% of stones. They mostly occur in association with infection (bacterial or parasitic) and may develop de novo in the bile duct after cholecystectomy.
What are the features of biliary colic?
Intermittent, self-limiting RUQ pain
Normal observations
Normal or mild tenderness
Normal blood tests
USS shows gallstones
What are the features of acute cholecystitis?
RUQ pain, fever, malaise
Temperature and haemodynamic instability may occur
Tenderness and localised guarding may be present
Raised WCC, CRP with normal or a mild LFT increase
USS shows gall stones, inflamed thickened gallbladder and pericholecystic fluid
What are the features of acute cholangitis?
Charcots triad - fever, jaundice, RUQ pain (+ mental status changes and hypotension to make Reynolds Pentad)
Temperature and haemodynamic instability likely to occur
Tenderness and clinical jaundice may be apparent
Raised WCC, CRP, bilirubin, ALP and ALT
USS shows CBD stone and ducts dilatation
What are complications of gallstones?
Biliary colic
Acute cholecystitis
Acute pancreatitis
Obstructive jaundice
Rarer - acute cholangitis, fistula formation, biliary peritonitis, gallbladder mucocele, gallbladder cancer
What is Bouveret’s syndrome?
a rare variant of gallstone ileus characterized by a gastric outlet obstruction due to the impaction of a gallstone lodged in the duodenum, resulting from a cholecystoduodenal fistula
What is gallstone ileus?
mechanical intestinal obstruction due to impaction of one or more gallstones within the gastrointestinal tract
What is Mirizzi syndrome?
A stone located in Hartmanns pouch or in the cystic duct itself can cause compression on the adjacent common hepatic duct.
This results in an obstructive jaundice, even without stones being present within the lumen of the common hepatic or common bile ducts.
Why can cholelithiasis lead to acute pancreatitis?
this occurs when a stone that has migrated along the common bile duct becomes stuck in the biliopancreatic duct causing pancreatic outflow obstruction
What is Murphy’s sign?
Inspiratory arrest during deep inspiration when examiner palpates the gallbladder fossa just beneath the liver edge
How should you investigate gallstone disease?
Abdominal USS (the absence of stones on scan doesnt exclude their existence)
FBC and CRP - for raised WCC and signs of inflammation
LFTs
Amylase to check for evidence of pancreatitis
Urinalysis + pregnancy test - exclude renal or tubo-ovarian pathology
Consider referral for further investigation if results are normal but clinical suspicion remains high:
MRCP if either LFTs are abnormal or bile duct is dilated even if no stones seen on USS
ERCP can also be done
CT scan may be done to look for any complications
What typically causes raised ALP?
Liver (cholestatic picture) or bone problems
Often raised in pregnancy due to production by the placenta
What is an obstructive/cholestatic picture on LFTs?
ALT and AST slightly raised
Higher raise in ALP
What is an MRCP?
Magnetic resonance cholangio-pancreatography
MRI scan with a specific protocol that produces a detailed image of the biliary system.
It is very sensitive and specific for biliary tree disease, such as stones in the bile duct and malignancy.
What is ERCP?
An endoscopic retrograde cholangio-pancreatography (ERCP) involves inserting an endoscope down the oesophagus, past the stomach, to the duodenum and the sphincter of Oddi. This gives the operator access to the biliary system. It combines x-ray and the use of an endoscope
What can be done during ERCP?
Cholangio-pancreatography: retrograde injection of contrast into the duct through the sphincter of Oddi and x-ray images to visualise biliary system
Sphincterotomy: making a cut in the sphincter to dilate it and allow stone removal
Stone removal: a basket can be inserted and pulled through the common bile duct to remove stones
Balloon dilatation: a balloon can be inserted and inflated to treat strictures
Biliary stenting: a stent can be inserted to maintain a patent bile duct (for strictures or tumours)
Biopsy: a small biopsy can be taken to diagnose obstructing lesions
What are the complications of ERCP?
Excessive bleeding 0.9%
Cholangitis 1.1%
Pancreatitis 1.5%
Duodenal perforation 0.4%
How do you manage someone with asymptomatic gallstones found in a normal gallbladder/biliary tree?
Reassure them that they do not need treatment unless they develop symptoms.
Explain that asymptomatic gallstones are very common.
DONT GIVE PROPHYLACTIC TREATMENT - risk of complications from surgical treatment outweighs the potential risk of developing complications from stones
How do you manage someone with asymptomatic gallstones found in the CBD?
Offer referral for bile duct clearance and laparoscopic cholecystectomy — although they are asymptomatic, there is a significant risk of developing serious complications such as cholangitis or pancreatitis.
How should you manage a person with symptomatic gallstones?
Arrange emergency admission for people who are systemically unwell with a suspected complication of gallstone disease
Refer urgently to gastro or surgery
For severe pain - diclofenac 75mg IM. Second dose after 30 mins if needed
For mild/mod pain - paracetemol or NSAID
Advice people to avoid food and drink that triggers symptoms until they have gallbladder/gallstones removed
Secondary care management is nearly always laparoscopic cholecystectomy - done if symptomatic or there are complications
How do you manage gallbladder empyema?
Cholecystectomy
Or
Cholecystostomy (drainage) later followed by cholecystectomy
What is a Kocher incision?
A subcostal incision used to gain access for the gallbladder and biliary tree
What is post-cholecystectomy syndrome?
A set of symptoms which are similar to the fractures experienced before the cholecystectomy. Its thought to be caused by bile leaking into surrounding area or gallstones being left in bile ducts
In most cases symptoms are mild and short-lived but they can persist for many months
May include - Diarrhoea, indigestion, epigastric or RUQ pain, nausea, intolerance of fatty foods, flatulance
Why are females more at risk for gallstones?
As oestrogen increases the activity of HMG-CoA reductase -> elevates serum cholesterol levels
In what proportion of cases does acute cholecystitis occur secondary to gallstones?
90% of pt
What is acute calculous cholecystitis?
Acute cholecystitis secondary to gallstones
What is alcuculous cholecystitis?
an inflammatory disease of the gallbladder without evidence of gallstones or cystic duct obstruction
typically seen in hospitalised and severely ill patients
associated with high morbidity and mortality rates
What causes acalculous cholecystitis?
multifactorial pathophysiology: gallbladder stasis, hypoperfusion, infection
in immunosuppressed patients it may develop secondary to Cryptosporidium or cytomegalovirus
One example - patients on long periods of fasting where the gallbladder is not being stimulated by food to regularly empty, resulting in a build-up of pressure.
What are the features of acute cholecystitis?
RUQ pain that may radiate to the right shoulder (irritates phrenic nerve)
Associated tenderness and guarding
Nausea and vomiting
Fever and signs of systemic upset (tachypnoeic, tachycardia)
Murphys sign positive
LFTs normal (unless Mirizzi syndrome then may be deranged
