Lecture 5: Biliary tree and gallstones Flashcards
Describe the structure of the biliary tree
Hepatocytes produce the bile which gets secreted into the bile canaliculi that originate between the hepatic cells.
The bile flows in the canaliculi toward the interlobular bile ducts and then into progressively larger ducts, septal bile ducts, intrahepatic ducts, left and right hepatic duct, common hepatic duct and finally reaching the common bile duct.
From these ducts the bile either empties directly into the duodenum (ampulla of Vater) or is diverted for minutes up to several hours through the cystic duct into the gallbladder.
Common bile duct passes ____ the duodenum where it meets the pancreatic duct
Behind
Flow of the bile is regulated by the ?
Sphincter of Oddi (smooth muscle)
The initial portion is secreted by the principal functional cells of the liver, the hepatocytes; this initial secretion contains?
- Bile acids
- Cholesterol
- and other organic constituents.
In its course through the bile ducts, a second portion of liver secretion is added to the initial bile. What is this additional secretion that is added?
Sodium and bicarbonate ions secreted by epithelial cells that line the ductules and ducts
Sodium and bicarbonate ions secreted by epithelial cells that line the ductules and ducts are stimulated by which hormone?
Secretin
What is the volume capacity of the gallbladder?
30 to 50 mL
What is the epithelium that lines the gallbladder?
Simple columnar epithelium
Where anatomically does the gallbladder lie
It lies in the gallbladder fossa on inferior surface of the right lobe of the liver
The maximum volume that the gallbladder can hold is only 30 to 60 milliliters. Nevertheless, as much as 12 hours of bile secretion (usually about 450 milliliters) can be stored in the gallbladder because the gallbladder concentrates the bile
Describe how this is done?
- Most of this gallbladder absorption is caused by active transport of sodium through the gallbladder epithelium, and this transport is followed by secondary absorption of chloride ions, water, and most other diffusible constituents.
Murphy’s point is the anatomical surface sign for which structure?
The gallbladder
What are the components of bile
- Conjugated bilirubin
- Bile acids
- Cholesterol
- Water
- Electrolytes
- Phospholipids
Describe how bilirubin is formed
- Old red blood cells break down after 120 days
- Most components are recycled
- Haem from haemoglobin is broken down to biliverdin
- Biliverdin is converted to unconjugated bilirubin
Bilirubin is formed by the _____ in the form of ______
A) Spleen
B) Unconjugated bilirubin
_____ bilirubin is insoluble in water so is transported in the blood bound to ____.
A) Unconjugated
B) Albumin
Describe Gilbert’s syndrome
genetic defect on chromosome 2 for the locus coding for the UGT-1A1 protein.
This enzyme is important in the conjugation of bilirubin (from unconjugated to conjugated bilirubin)
Without it, bilirubin cannot be conjugated and therefore secreted in bile.
The precursor of the bile salts is ?
Cholesterol
Describe the formation of bile salts
Hepatcytes synthesis the primary bile salts
Cholesterol derivatives are conjugated with the amino acids glycine and taurine to form primary bile acids
Bacterial action in the gut convert primary bile acids to secondary bile acids
Which hormone(s) causes the contraction of the gallbladder
Cholecystokinin
Vagal stimulation
What does cholecystokinin do in relation to the biliary tree
Causes:
- Gallbladder contraction
- Relaxation of the sphincter of Oddi
What hormone causes:
- Gallbladder contraction
- Relaxation of the sphincter of Oddi
Cholecystokinin (CCK)
What hormone(s) causes:
- Gallbladder relaxation
- Contraction of the sphincter of Oddi
Sympathetic nerves
Vasoactive intestinal polypeptide (VIP)
Somatostatin
Vagal stimulation causes ____ of the gallbladder.
Sympathetic stimulation causes ____ of the gallbladder.
A) Contraction
B) Relaxation
About 94 percent of the bile salts are reabsorbed into the blood from the small intestine.
What two mechanisms cause the bile salts to be reabsorbed
- About one half of this by diffusion through the mucosa in the early portions of the small intestine
- The remainder by an active transport process through the intestinal mucosa in the distal ileum.
- They then enter the portal blood and pass back to the liver.
•Synthesis of new bile acids in the liver compensates for ___ loss
Faecal
Describe the enterohepatic circulation of bile salts
- This recirculation of the bile salts
- Bile salts are reabsorbed into the blood from the small intestine
- The bile salts enter the portal blood and pass back to the liver.
- Upon reaching the liver and during first passage through the venous sinusoids, these salts are absorbed almost entirely back into the hepatic cells
- The small quantities of bile salts lost into the feces are replaced by new amounts formed continually by the liver cells.
If the terminal ileum does not absorb bile acids then what happens?
The bile salts reach the colon and cause diarrhoea “bile salt diarrhoea”
When does “bile salt diarrhoea” occur
- After surgery if the terminal ileum or ileocaecal valve is removed
- Disease of the terminal ileum eg Crohn’s disease
What are the 5 Fs associated with gallstones?
Female
Fair - more common in Caucasians
Fertile
Forty - Increasing incidence with age
Fat - Diet (low fibre)
Approx. 15% of the population has gallstones. What is the treatment for these?
- Approx 80% asymptomatic - these do not require any treatment
- Laparoscopic cholecystectomy
What are the 3 main types of gallstones
- Cholesterol stone
- Bile pigment stone
- Mixed stone - most common (80%)
Define Cholecystitis
Inflammation of gallbladder
Define Cholelithiasis?
Gallstones (within gallbladder)
Define Cholecystectomy
Removal of gallbladder
Define Choledocholithiasis
Gallstone within bile duct
Define Cholangitis
Infection of bile duct
Describe the pathogensis of cholesterol gallstones
The liver produces bile that contains an excess of cholesterol because there is either a relative deficiency of bile salts or a relative excess of cholesterol. Cholesterol is solubilised by bile but high levels of cholesterol lead to supersaturation, typical when levels of oestrogen are high.
Additionally, it could be due to biliary stasis or increase in bilirubin production.
Describe the pathogenesis of bile pigment gallstones
They are common in the Far East, where infection allows bacterial β-glucuronidase to hydrolyse conjugated bilirubin to its free form, which then precipitates as calcium bilirubinate. The mechanism of black pigment gallstone formation in developed countries is not satisfactorily explained.
Name some of the complications that can occur from gallstones in the gallbladder
- Biliary colic
- Acute Cholecystitis
- Empyema
- Mucocoele
- Cancer
Name some of the complications that can occur from gallstones in the common bile duct
- Obstructive jaundice
- Cholangitis
- Pancreatitis
Name some of the complications that can occur from gallstones in the small intestine
Gallstone ileus
Describe biliary colic
- This is when there is a gallstone in the gallbladder that is obstructing bile flow.
- Typically right upper quadrant pain following a fatty meal as gallstones obstruct the cystic duct during contraction of the gallbladder.
- Does not cause jaundice as the bile can still be secreted from the liver.
- Liver function test is commonly normal
Describe Acute Cholecystitis
- Impacted gallstone in gallbladder leading to the gallbladder wall oedema/inflammation and development of bacterial infection within the wall.
- Clinical symptoms: Pain, nausea, vomiting, fever, abdominal tenderness
- Investigation: Raised inflammatory markers, sometimes abnormal LFT +/- jaundice
- Treat: antibiotics, analgesia, elective cholecystectomy when symptoms settle
Connect the correct statements
AST/ALT – hepatocyte enzymes (AST also found in cardiac muscle cells)
ALP/GGT – enzymes associated with bile duct cells but different isoenzyme of ALP also produced in bone
Bilirubin – conjugated and secreted by liver
Aspartate aminotransferase (AST) is found in which cells?
present in cytosol and mitochondria of hepatocytes, also in cardiac muscle, skeletal muscle, kidneys, CNS
Alkaline phosphatase (ALP) is found where?
A canalicular enzyme found in microvilli of cells lining bile tubes and sinusoidal surface hepatocytes. Also found in bone
ALP and GGT will be severely raised in which pathology?
A) Obstructive (posthepatic)
B) Hepatic
A) Obstructive (posthepatic)
Define Curvoisier’s Law
“in the presence of a palpable enlarged gallbladder which is non-tender and accompanied with mild painless jaundice, the cause is unlikely to be gallstones”
Name some of the extrinsic compression causes that can result in obstructive biliary tree
Tumours
–Most commonly pancreatic
–Lymph nodes
Inflammation
–Esp pancreatitis
Mirizzi Syndrome
Pancreatic cancer symptoms can include painless or painful jaundice? and why?
Painless jaundice
Because it can obstruct the common bile duct
Name some of the intramural causes that can obstruct the biliary tree
Tumours
–Cholangiocarcinoma
Inflammation
–Primary Sclerosing Cholangitis (PSC)
–IgG4 disease
Scarring / fibrosis
–Post inflammatory
–Post surgical
Name some of the intraluminal causes that can obstruct the flow of bile
- Stones
- Sludge
- Polyps
