bile , gallbladder and gallstones Flashcards
label the gross anatomy of the biliary system
label this overview of the biliary system
describe the flow of bile
Hepatocytes
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Bile canaliculi (merge to form ductules)
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Terminal bile ducts
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Hepatic ducts (left and right)
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Common bile duct
how is bile modified as it flows through the bile ducts ?
- Initial Bile Secretion
* Bile is first produced by hepatocytes (liver cells).
* It then moves into bile canaliculi, tiny channels between hepatocytes. - Modification in Ductules
* As bile flows into larger ductules and ducts, its composition changes.
* Water may be added through specialized tight junctions in cholangiocytes (epithelial cells lining bile ducts). - Substance Processing in Ductules
* Glucose & amino acids are scavenged (reabsorbed).
* Glutathione (GSH) is hydrolyzed (broken down into smaller components). - Ductular Secretion
* IgA (immunoglobulin A) is secreted for mucosal protection (helps defend against infections).
* Bicarbonate (HCO₃⁻) & water (H₂O) are secreted in response to secretin, a hormone released after eating (postprandial period).
* Bicarbonate helps neutralize stomach acid in the bile before it reaches the intestine.
what do hepatocytes and epithelial cells of the bile ducts secrete ?
Hepatocytes (Liver Cells) Secrete:
* Cholesterol (used for bile salt formation)
* Lecithin (a phospholipid that helps keep cholesterol dissolved)
* Bile Acids (help digest fats)
* Bile Pigments (e.g., bilirubin, biliverdin, urobilin—waste products from hemoglobin breakdown)
Epithelial Cells of Bile Ducts (Cholangiocytes) Secrete:
* Bicarbonate-rich salt solution (helps neutralize stomach acid in the intestine)
* Water (H₂O) is secreted along with bicarbonate
what do secretin and Ach do ?
- Secretin (released after eating) stimulates bicarbonate and water secretion from bile duct cells
- Acetylcholine (ACh) (a neurotransmitter) also promotes bicarbonate and water secretion
when does the sphincter of oddi contract and relax ?
- During fasting → Sphincter of Oddi contracts, preventing bile from entering the intestine (bile is instead stored in the gallbladder).
- During & after meals → Sphincter of Oddi relaxes, allowing bile to flow into the small intestine (stimulated by cholecystokinin, CCK).
what substances are transported across the bile canalicular membrane ?
- Bile acids
- Phosphatidylcholine
- Conjugated bilirubin
- Cholesterol
- Xenobiotics (foreign chemicals/substances, e.g. drugs)
- Specific transporters ferry the above into bile
- Substances such as water, glucose, Ca2+, GSH, amino acids and urea enter the bile by diffusion
what are the compositions of hepatic and gallbladder bile ?
- Hepatic bile = 97% water; cholesterol, lecithin, bile acids, bile pigments, etc.
- Gallbladder bile: 89% water; HCO3-, Cl-, Ca2+, Mg2+, Na+, cholesterol, bilirubin, bile salts, etc.
what are bile acids ?
- Bile acids are important for digestion in the gastrointestinal (GI) system. They are made from cholesterol, which helps lower cholesterol levels in the body.
How Bile Acids Work:
* They are secreted into bile and attached (conjugated) to glycine or taurine.
* This makes them bile salts, which are the main acids in human bile.
Types of Conjugated Bile Acids:
* Cholic Acid
* Glycocholic Acid (Cholic acid + Glycine)
* Taurocholic Acid (Cholic acid + Taurine)
* Chenodeoxycholic Acid
* Glycochenodeoxycholic Acid (Chenodeoxycholic acid + Glycine)
* Taurochenodeoxycholic Acid (Chenodeoxycholic acid + Taurine)
Why Conjugation is Important:
* It makes bile acids more water-soluble (more amphipathic).
* It helps in their secretion into the bile.
* It reduces their toxicity to cells.
what are the 4 major bile acids found in humans ?
- Cholic acid: 50% = quantitatively more important
- Chenodeoxycholic acid: 30%
- Deoxycholic acid: 15%
- Lithocholic acid: 5%
how are primary and secondary bile acids formed ?
describe the function of bile acids as metabolic regulators
Cholesterol Removal:
* Bile acids are made from cholesterol, helping to eliminate excess cholesterol.
* About 5% of bile acids are excreted in feces, which helps remove cholesterol from the body.
Preventing Gallstones
* Bile acids keep cholesterol dissolved in bile, preventing it from forming stones in the gallbladder.
Helping with Vitamin Absorption
* They aid in the absorption of fat-soluble vitamins A, D, E, and K in the intestines.
Regulating Their Own Levels
* Bile acids are reabsorbed and reused through enterohepatic circulation, controlling their production and transport.
Digesting Fats
* Bile acids help break down fats by working with phospholipids (like lecithin) and monoglycerides.
How? They act as emulsifiers, breaking large fat droplets into smaller ones, making them easier for pancreatic lipases to digest.
what are the mechanisms that control bile secretion into the duodenum ?
Hormonal Control:
* Cholecystokinin (CCK): Released from the small intestine (duodenum) in response to fats in food.
Stimulates the gallbladder to contract, releasing bile.
Relaxes the sphincter of Oddi, allowing bile to flow into the duodenum.
* Secretin: Released in response to acidic chyme from the stomach.
* Stimulates the liver to produce more bile (rich in bicarbonate) to help neutralize acid.
Neural Control:
* Vagus nerve (parasympathetic stimulation) enhances bile production and gallbladder contraction during digestion.
Bile Salt Recycling (Enterohepatic Circulation):
* Bile salts are reabsorbed in the ileum and returned to the liver via the portal vein, stimulating further bile secretion.
Continuous Basal Secretion:
* The liver continuously produces bile, which is stored in the gallbladder and released when needed.
how does the Prescence of a fatty meal stimulate the release of CCK ?
give a summary of the release of bile into the duodenum
what is enterohepatic circulation ?
The cycling of bile from intestine to liver and back to intestine
what happens if enterohepatic circulation is interrupted ?
- When enterohepatic circulation is interrupted (e.g., due to disease, surgery, or other factors that prevent proper recycling of bile salts), the body cannot reabsorb bile salts from the intestine effectively. This leads to the following chain of events:
Why the Liver Increases Bile Salt Synthesis:
* Normally, bile salts are recycled from the intestine to the liver. If this process is disrupted, the liver detects a reduction in bile salt levels in the bloodstream.
* In response, the liver increases the synthesis of bile salts to compensate for the loss, trying to maintain adequate levels for digestion and fat absorption.
Why the Kidneys Excrete Bile Salts:
* Since the usual recycling route through the intestines is unavailable, the liver releases excess bile salts into the bloodstream.
* The kidneys filter out these excess bile salts (and some cholesterol) from the blood, and excrete them in urine, as they can no longer be efficiently returned to the liver for recycling.
what are gallstones and how are they formed ?
- Several factors can lead to increased cholesterol levels in bile, which contribute to the formation of gallstones:
Excess Cholesterol Secretion by the Liver:
* The liver may produce more cholesterol than needed, leading to higher cholesterol content in bile.
Reabsorption of Salt and Water:
* If there’s excessive reabsorption of salt and water from bile in the gallbladder, the bile becomes more concentrated. This can increase the cholesterol concentration, which may lead to cholesterol crystals forming.
Formation of Gallstones:
* When there is too much cholesterol in the bile, it can begin to precipitate (crystallize), forming cholesterol crystals. These crystals may eventually grow into gallstones.
* Additionally, bile pigments (like bilirubin) can also precipitate, forming pigment stones.
what are the types of gallstones ?
- Cholesterol stones (85%): obesity; ↓ bile acids; ↓ phospholipids
- Calcium bilirubinate stones – due to ↑ conjugated bilirubin (haemolytic anaemia)
what are the factors involved in gallstone formation ?
Bile Stasis:
* Gallstones form when bile is not flowing properly. If bile remains stagnant in the gallbladder (instead of flowing into the duodenum), it can lead to stone formation.
Decreased Bile Acids:
* Malabsorption conditions like cystic fibrosis or Crohn’s disease can reduce the amount of bile acids available for digestion. When bile acids are low, the balance of bile is disturbed, and gallstones are more likely to form.
* In cystic fibrosis, thick mucus can block the gallbladder and cystic ducts, interfering with bile flow.
Chronic Infection:
* Bacterial infections in the gallbladder can promote the formation of pigment stones (which are made from bile pigments like bilirubin) by changing the chemical composition of bile.
Super-saturation of Bile with Cholesterol:
* If the bile becomes too rich in cholesterol (due to liver overproduction or concentration), the cholesterol can crystallize, forming cholesterol gallstones.
Presence of Nucleation Factors (e.g., Glycoproteins):
* Nucleation factors like glycoproteins can act as a “seed” or nucleus around which cholesterol or other substances can begin to crystallize, making it easier for gallstones to form.
describe gallstone effects and complications
Small Gallstones:
* Small gallstones can easily pass through the bile duct into the duodenum and may not cause any symptoms.
Larger Gallstones:
* Larger gallstones can get stuck at the opening of the gallbladder or in the bile duct, causing pain in the right upper quadrant (RUQ) of the abdomen and possibly leading to jaundice (yellowing of the skin and eyes due to high bilirubin levels).
Pancreatic Duct and Bile Duct Junction:
* The pancreatic duct (which carries digestive enzymes) and the bile duct (which carries bile) join before entering the duodenum.
* If a gallstone gets stuck at this junction, it blocks the flow of both bile and pancreatic enzymes, which can cause pressure to build up in the ducts. This leads to RUQ pain and jaundice.
Nutritional Deficiency:
* When the bile and pancreatic enzymes are blocked, the digestion of fats becomes inefficient because bile is needed to break down fat, and pancreatic enzymes are needed for digestion.
* This can lead to nutritional deficiencies due to poor fat digestion.
Increased Pressure and Pain:
* Continued blockage can lead to even more pressure in the bile duct, causing more pain in the right upper quadrant and worsening jaundice due to bile backing up and increased bilirubin in the blood.
how are gallstones diagnosed ?
- Ultrasonography and computer tomography: explore the right upper quadrant of gallbladder to detect gallstones
- Cholescintigraphy: administer tecnetium-99m-labelled derivative of iminodiacetic acid (radioactive tracer)
→ acquire images of gall bladder and ducts - Endoscope retrograde cholangiopancreotography (ERCP): inject contrast media from an endoscope channel and visualise the biliary tree
- Insert device(s) and remove gallstone fragments that may be obstructing the bile flow, pancreatic juice or both
what are the clinical features of gallstones ?
- 85% of cases are asymptomatic (gallstones remain in gallbladder)
If the neck of the cystic duct is impaired → biliary pain of right upper quadrant ensues (acute cholecystitis) - Gallstones that impact common bile duct → obstruction of bile flow and cholestatic jaundice which can cause bacterial infections (cholangitis) and right upper quadrant pain
- Gallbladder will secrete mucus if inflamed and rupture (mucocele or hydrops)
What type of diet must Mrs Mendy be advised to adopt after gallbladder removal?
A low-fat diet
List 2 functions of bile acids
- Decrease the precipitation of cholesterol in the gallbladder by solubilising cholesterol
- Facilitate the digestion of triacylglycerols by making them accessible to pancreatic lipases
- Eliminate cholesterol and excrete it in faeces
- Control metabolic processes like energy expenditure, glucose, and lipid metabolism
Which of the following is the most abundant bile acid?
a) Bilirubin acid
b) Chenodeoxycholic acid
c) Cholic acid
d) Deoxycholic acid
e) Lithocholic acid
c) Cholic acid
Which of the following is a primary bile acid?
a) Cholesterol
b) Cholic acid
c) Deoxycholic acid
d) Lithocholic acid
e) Ursodeoxycholic acid
b) Cholic acid
Name the two different cell types that secrete the components of bile and their main secretions.
- Hepatocytes: cholesterol, phospholipids (lecithin), bile pigments
- Epithelial cells of bile ducts: bicarbonate-rich salt solutions
Which of the following best describes the effects of secretin on the gallbladder?
a) Concentrates the bile in the gallbladder
b) Enhances stimulatory effects of proteins on CCK release
c) Inhibits vagal stimulation of the gallbladder
d) Modulates shunting of bile into the gallbladder during fast
e) Stimulates gallbladder to secrete bile and bicarbonate-rich solutions
e) Stimulates the gallbladder to secrete bile and bicarbonate-rich solutions into the duodenum
Which of the following best describes a bile salt?
a) Bile acid conjugated to taurine
b) Bile acid deconjugated by intestinal bacteria
c) Bile acid conjugated to stercobilin
d) Bile acid conjugated to cholic acid
e) Bile acid conjugated to lecithin
a) Bile acid conjugated to taurine
Which of the following best describes the function of bile salts?
a) Aids action of pancreatic lipase by emulsifying fats in the duodenum
b) Facilitates digestion by emulsifying fats in the large intestine
c) Facilitates absorption of fat-soluble vitamins
d) Have a hydrophobic, but no hydrophilic side
e) Produced in the gallbladder to aid solubilisation of fats
a) Aids the action of pancreatic lipase by emulsifying fats in the duodenum
What is the medical term for the presence of excess fat in the faeces due to gallstones?
Steatorrhoea
What is the function of CCK on the gallbladder?
CCK contracts the gallbladder and causes the release of bile stored in it
What is the function of CCK on the sphincter of Oddi?
CCK relaxes the sphincter of Oddi and allows the secretion of bile and pancreatic juice into the duodenum
Name the cell type that secretes bicarbonate salt solution into bile.
Epithelial cells of bile ducts
Name one symptom associated with gallstones.
Right upper quadrant pain – acute cholecystitis
