Bile, Gallbladder and Gallstones Flashcards
What is the function of the gallbladder?
Storage and concentration of bile
Why is bile so concentrated and acidic in the gallbladder?
Concentrated because of active Na+ transport (and H2O) from gallbladder
The pH of bile drops (becomes “acidic”) as Na+ is exchanged for H+
What is the composition of pancreatic juice?
bile salts, bile pigments and dissolved substances in alkaline electrolytes
When does bile move to the gallbladder?
between meals
When is bile modified?
Bile → larger ductules and ducts (composition is modified) Water is (may be) added via specific tight junctions within ductules (cholangiocytes)
What is the purpose of bile travelling through so many ducts and ductules?
The ductules scavenge glucose, amino acids; GSH is hydrolysed
Ductules secrete IgA (mucosal protection), HCO3- and H2O in response to secretin in the postprandial period
Outline the flow of bile
Hepatocytes
↓
Bile canaliculi (merge to form ductules)
↓
Terminal bile ducts
↓
Hepatic ducts (left and right)
↓
Common bile ductWhat are the 2 types of cells secreting bile components?
Hepatocytes
Epithelial cells of bile ducts
Which components of bile do hepatocytes secrete?
cholesterol, lecithin, bile acids, bile pigments (bilirubin, biliverdin, urobilin, etc.)
What components of bile is secreted via epithelial cells of the bile ducts?
bicarbonate-rich salt solution
Secretin influences the secretion of bicarbonate-rich salt solutions and H2O
When is bile secretion the greatest?
Secretion of bile is greatest during and after a meal
Increased [bile salt]blood causes ↑ bile salt secretion into bile canaliculi
Increased secretion leads to ↑flow of bile
Explain the motility of the sphincter of Oddi during and after meals
Sphincter of Oddi contracts during periods of fasting
Sphincter of Oddi relaxes during and after meals due to vagal innervation & CCK
Which substances cross the bile canalicular membrane?
Bile acids Phosphatidylcholine Conjugated bilirubin Cholesterol Xenobiotics (foreign chemicals/substances, e.g. drugs)
How are substances transported across the canlicular membrane?
Specific transporters ferry substnces into bile
Substances such as water, glucose, Ca2+, GSH, amino acids and urea enter the bile by diffusion
What is the composition of hepatic bile?
97% water; cholesterol, lecithin, bile acids, bile pigments, etc.
Describe the composition of gallbladder bile
89% water; HCO3-, Cl-, Ca2+, Mg2+, Na+, cholesterol, bilirubin, bile salts, etc.
Where is bile synthesised and transported to?
Bile synthesised in liver → cross canalicular membrane → bile canaliculi → gallbladder
Explain the movement of bile to the gallbladder
Bile concentrated in gallbladder (NaCl and H2O loss → increased solid content)
Bile goes to the gallbladder between meals when sphincter of Oddi is closed
What are bile acids made from?
cholesterol
Explain the significance of bile acids in bile
Secreted into bile and conjugated to glycine or taurine
What is the purpose of conjugating bile acids?
Conjugation helps to increase the ability of bile acids to be secreted (more soluble) and also decreases their cytotoxicity
How many bile acids are there?
There are 4 major bile acids found in humans:
- Cholic acid: 50% = quantitatively more important
- Chenodeoxycholic acid: 30%
- Deoxycholic acid: 15%
- Lithocholic acid: 5%
- primary bile acids formed in liver
- secondary bile acids formed in colon
How do bile acids affect cholesterol in the body?
Elimination of cholesterol to bile acids (5% excreted in faeces)
Synthesis + excretion of bile acids in faeces is a significant mechanism for excess cholesterol elimination
Reduces cholesterol precipitation in gallbladder; bile acids + phospholipids help solubilise cholesterol in bile
How do bile acids affect vitamins in the body?
Facilitate the absorption of fat-soluble vitamins (ADEK)
What affect do bile acids have on dietary fats?
Facilitate the digestion of triglycerides - work in concert with phospholipids (licithin) and monoglycerides to ensure the emulsification of fats
Facilitate the digestion of dietary fats by acting as emulsifying agents that render fats accessible to pancreatic lipases
What is the significance of bile acids?
Regulate their own transport and metabolism via enterohepatic circulation
Explain the stages of gallbladder contraction
Cephalic, Gastric and intestinal
Explain what occurs in the gallbladder during the cephalic phase
taste, smell and presence of food in the mouth → impulses via vagus nerve
What happens during the gastric phase?
distension of stomach generates impulses in vagus nerve
What effect does the intestinal phase have on the gallbladder?
Period of most gallbladder emptying; key mediators for increased release are
CCK in response to lipids → secrete bile to emulsify fat for digestion by pancreatic lipases
=> causes gallbladder contraction
=> sphincter of Oddi relaxtation
Secretin in response to high acidity - stimulates duct cells
What is the role of the vagus nerve in the GI tract?
Vagus nerve (VIP/NO) - conveys information of contents of the duodenum to the CNS
Outline the mechanism of bile secretion into the duodenum
- Nutrients in duodenum sends vagal afferent signals to
DVN - Vagal efferent from DVN releases ACh at gallbladder
- Nutrients in duodenum stimulate release of CCK via
bloodstream - ACh + CCK cause smooth muscle contraction
What effect does motilin have on gallbladder?
Motilin induces gallbladder emptying and antral contractions in the fasting state
How is gallbladder contraction regulated?
Via CCK - fatty meals stimulates CCK release
=> sphincter of Oddi relaxes
=> gallbladder contracts
=> increased bile flow to duodenum via common bile duct
What components of enterohepatic circulation are synthesised in the liver?
Bile salts, lecithin (phospholipids)
What is the role of HCO₃⁻ and other ions?
neutralise acids in duodenum
What is enetrohepatic circulation?
Most bile salts are reabsorbed by Na+-bile salt coupled transporters
The bile salts are returned to the liver and secreted again into bile
The recycling pathway from intestine to liver and back to intestine = enterohepatic circulation
How much bile is recycled via enterohepatic circulation?
Body’s content of bile acid pool (~3.5g) may be recycled ~twice per meal
What happens to cholesterol in enterohepatic circulation?
Liver also secretes cholesterol in the bile and some of this is excreted in faeces
What is the consequence of enterohepatic circulation interruption?
Interruption of enterohepatic circulation (e.g. after ileal resection) will cause the following:
- Excess synthesis of bile salts by the liver
- Kidneys will excrete synthesised bile salts (+ some
Cholesterol)
What are gallstones (cholelithiasis)?
small stones, usually made of cholesterol, that form in the gallbladder
What is the prevalence of gallstones in women and men?
Ratio of incidence of gallstones = 2:1 in women and men, respectively and incidence increases with age
How does cholesterol affect bile salts?
The higher the cholesterol content of bile, the greater the concentrations of phospholipid and bile salts
Bile salts (bile compounded with a cation, e.g. Na+), cholesterol and phospholipids
What can cause excess cholesterol?
Liver secretes excess
Reabsorption of salt and water
What is teh consequence of excess bile pigments and cholesterol?
The cholesterol crystallises and forms gallstones; Supersaturation of bile with cholesterol
Precipitation of bile pigments
What are the 2 types of gallstones?
Cholesterol stones (85%): - obesity; ↓ bile acids vs ↓ phospholipids
Calcium bilirubinate stones:
- due to ↑conjugated bilirubin (associated with haemolytic
anaemia)
How does bile stasis contribute to gallstones?
Bile stasis: stones form in bile that is sequestered in the gallbladder rather than bile that is flowing in the bile ducts into the duodenum
Explain how problems with bile production can lead to gallstone formation
Decreased amount of bile acids due to malabsorption (in cystic fibrosis – dehydrated and acidic; 10% higher incidence); problems with bile production
How does infection contribute to gallstones?
Chronic infection – bacteria help in the formation of pigment stones
How does size of gallstone affect their location?
Small gallstones have easy passage via bile duct
Larger gallstones lodge in the opening of the gallbladder
How can gallstones cause nutritional deficiency?
Duct from pancreas joins bile duct before it joins the duodenum
Lodging of gallstones at this point causes stoppage of bile + pancreatic secretions (pressure builds up)
Consequence →nutritional deficiency
How do gallstones lodged in bile duct cause decreased bile secretion?
Further pressure build up causes decreased secretion of bile
What causes jaundice?
Increased accumulation of bilirubin in blood
How would we know a patient had gallstones?
People complain of upper right quadrant pain
What pigments are present in bile, urine and faeces?
Bile is yellow because of bilirubin
Urine colour due to uribin
Stercobilin colours faeces
How would we diagnose gallstones?
Ultrasonography and computer tomography:
Cholescintigraphy:
Endoscopic retrograde cholangiopancreatography (ERCP):
Explain how ultrasonography can help detect gallstones?
explore the right upper quadrant of gallbladder to detect gallstones
How does cholescintigraphy diagnose gallstones?
administer technetium-99m-labelled derivative of iminodiacetic acid (radioactive tracer)
→ images of gallbladder and ducts
Explain how you would carry out an ERCP
Allows us to visualise biliary tree by injecting contrast media from an endoscope channel
Insert device(s) and remove gallstone fragments that may be obstructing the bile flow, pancreatic juice or both
What are the symptoms of gallstones in the cystic bile duct?
painful gallbladder contractions
What symptoms would prevail in patients with gallstones blocking the common bile duct?
pain and nausea
lack of bile release
failure to excrete bilirubin = jaundice
What is the effect of a gallstone blocking duodenal papilla?
inappropriate activation of pancreatic zymogens acute pancreatitis (hard to differentiate from appendicitis)
How will the gallbladder respond to inflammation?
Gallbladder will secrete mucus if inflamed and rupture (mucocele or hydrops) - very painful can cause sites of infections
Where are the majority of gallstones found?
85% of cases are asymptomatic (gallstones remain in gallbladder)
