Bile, Gall Bladder and Stones Flashcards
Gross Anatomy of the Biliary System
what is the gall bladder important for?
How is the gall bladder linked to the liver?
What is the ampulla of vater?
The gallbladder is important for storage of bile, which itself is important for modifying of fats so they can be digested.
The biliary tree can be seen within the liver. The components being held in the gall bladder has been synthesised in the liver.
Ampulla of vater (hepatopancreatic duct or hepatopancreatic ampulla) formed out of the union of pancreatic duct and common bile duct; near the duodenal papillla
Physiology and Functions of the Gallbladder
What does gallbladder do? How does it concentrate its components?
How does bile become more acidic? What do we compare to when we mean acidic? what is it’s actual pH in gall bladder?
How does the secretions from the gall bladder and pancreas come? what is their function?
The gallbladder stores and concentrates bile, it is concentrated because of active Na+ transport from the gallbladder and H2O follows.
Gallbladder is important due to how common gallstones are and cholecystectomy.
The bile becomes more acidic as Na+ is exchanged for H+, but [Na+] increases as more Cl- and HCO3- are lost.
Note that by acidic we are talking about it relative to the bile that would have been in the hepatic duct, the gall bladder bile is around pH 7.
Pancreatic juice contains bile salts, bile pigments and dissolved substances in alkaline electrolytes.
The secretions from the gallbladder and pancreas come together and go into the duodenum, it is important as they have to neutralise the acidic chyme from the stomach, especially the HCO3- is important.
Bile Formation
what 5 substances are secreted into the bile? across which membrane? how do these substances get into the bile? how do other substances get into bile? what substances are these?
how do cholesterol gallstones form? what is the correct ratio?
what is bile formed from? where is it fromed? what happens as it moves?
waht are cholangiocytes?
what do the ductules do to reduce the growth of bacteria?
what else do the ductules do?
how are bile salts made?
How does bile flow from liver?
what is bile canaliculi?
Substances that are secreted into the bile (across the bile canalicular membrane) include:
- Bile acids
- Phosphatidylcholine (phospholipid)
- Conjugated bilirubin
- Cholesterol
- Xenobiotics
There are specific transporters to ferry the above substances into the bile. Substances such as water, glucose, Ca2+, GSH (glutathione), amino acids and urea enter the bile by diffusion
Deviation from the correct ratio of substances, bile acids: phosphatidylcholine: cholesterol in the canalicular bile (usually held in a ratio of 10:3:1) can lead to cholesterol gallstones as cholesterol precipitates out.
Bile that is formed in the liver, from bile acids, moves through larger ductules and ducts and as they go through their composition is modified by movement of Na+ and H+.
Water may be added by specific tight junctions within the ductules, which are lined by a cell type called cholangiocytes, which have tight junctions. (Cholangiocytes = epithelial cells of the bile duct)
The ductules scavenge and remove glucose, AA, GSH is hydrolysed, this is because too much glucose etc. could result in bacteria.
The ductules also secrete IgA for mucosal protection and HCO3- in response to secretin in the postprandial period//after a meal.
Bile salts are formed from bile acid + a cation e.g. Na+ (this is one definition)
Bile flows as follows: hepatocytes →bile canaliculi (merge to form ductules) →terminal bile ducts → hepatic ducts (left and right) →common bile duct
Bile canaliculi (singular Bile canaliculus) = bile capillaries; it’s the tube that collects bile secreted by hepatocytes
Primary and Secondary Bile Acids
what are the 4 major bile acids found in humans?
what happens to bile acids in the intestine? what happens to them next?
Why must the process at the intestine take place?
conversion of primary to secondary bile acids? give names of primary and secondary
how are these removed from the intestine? where do they go?
what are bile acids made from? what are they joined to? ( 2things) why do they join to these molecules (2 reasons)
There are four major bile acids found in humans
- Cholic acid (50%)*
- Chenodeoxycholic acid (30%)*
- Deoxycholic acid (15%)
- Lithocholic acid (5%)
Once in the intestine, bacteria deconjugate these bile acids. Deconjugated bile acids are excreted or reabsorbed.
It is important that the bile acids were conjugated in the first place because the bile acids on their own can be very cytotoxic, it also enhances their solubility.
Anaerobic bacteria in the colon can modify the primary bile acids (cholic acid and chenodeoxycholic acid) to secondary bile acids.
o Cholic acid -> Deoxycholic acid
o Chenodeoxycholic acid -> Lithocholic acid and Ursodeoxycholic acid
May get asked in exam which is primary or secondary bile acids.
Both primary and secondary bile acids are removed by the intestine into the liver via the portal circulation.
Bile acids are important in the GIT, they are made from cholesterol and secreted into bile conjugated to glycine or taurine.
o Conjugation helps to increase the ability of bile acids to be secreted and also decreases their cytotoxicity.
Main Functions of Bile Acids: Metabolic Regulators
2 functions with cholesterol?
lipids?
own transport? what is the name?
how do they regulate energy expenditure?
- Bile acids can be used to eliminate cholesterol (5% are excreted in faeces)
- It also reduces precipitation of cholesterol in the gallbladder, bile acids and phospholipids help solubilise cholesterol in the bile
- Facilitate digestion of triglycerides, they work with phospholipids (licthin) and monoglycerides to ensure emulsification of fats
o They facilitate the absorption of fat-soluble vitamins (ADEK) - They also regulate their own transport and metabolism via enterohepatic circulation
- They regulate lipid and glucose metabolism (regulate energy expenditure)
Composition of Hepatic and Gallbladder bile:
where does the bile get stored? when does this particulary take place? what needs to remain closed?
How is bile concentrated?
Compare hepatic bile to gallbladder bile - components and relative water and the cell that secretes it
what hormones influences secretion of bicarbonate and water? when is this highest and why?
what regulates bile secretion into bile canaliculi?
how do we prevent bile release during fasting? what happens when we eat?
is bile essential for life as gall bladder can be removed?
Bile gets stored in the gallbladder particularly between meals when the sphincter of Oddi is closed.
Bile is concentrated in the gallbladder (NaCl and some H2O loss, this increases the solid content)
- Hepatic bile is roughly 97% water, it also contains cholesterol, lecithin, bile acids, bile pigments etc.
- Gallbladder bile is about 87% water, contains HCO3-, Cl-, Ca2+, Mg2+, Na+, cholesterol, bilirubin etc.
The components of bile are secreted by two different cell types:
Hepatocytes = Cholesterol, lectithin, bile acids, bile pigments (bilirubin, biliverdin, urobillin)
Epithelial cells of bile duct = Bicarbonate rich salt solution
Secretin is an important hormone that influences secretion of bicarbonate-rich solution and H2O.
Secretion of bile is greatest during and after a meal, this is for a good reason as we want to digest the food, particularly if we have taken a fatty meal.
Increased bile salt concentration in the blood -> increased bile salt secretion into the bile canaliculi. So, it seems something regulating bile secretion into the canaliculi is the bile conc. in the blood.
The sphincter of Oddi contracts during periods of fasting, so any bile goes back up to the gall bladder
The sphincter of Oddi relaxes during and after meals
Is bile essential for life? Because we know people have their gall bladders removed. In general, cholecystomised patients can have a good quality of life, so long as they don’t take too much fatty foods etc. They also have to lose weight.
Contraction of Gallbladder: Control
what happens to gall bladder when we eat?
how is bile release similar to stomach acid release? what will taste, smell and presence of food in the mouth initate/innervate?
what happens in the gastric phase?
what happens in the intestinal phase? which two hormones are useful for this phase and gall bladder secretions?
what two things allow pancreatic/gall bladder secretions to enter the duodenum? how do these secretions help?
what will distension of the duodnenum lead to? what is the response and via what?
what happens if you eat a really fatty meal? what is released and what does it do?
The gallbladder contracts when we are feeding which allows bile to be released.
It seems what causes bile acid release is similar to that what causes acid release in the stomach.
In the cephalic phase we have taste, smell and presence of food in the mouth which can lead to initiation of impulses via the vagus nerve.
In the gastric phase, distension of the stomach also initiates impulses via the vagus nerve.
Finally, in the intestinal phase we have the period of most gallbladder emptying, there are certain signals that are also important here in emptying the gallbladder (motility) like CCK // secretin.
[The vagus nerve conveys information about the state of body organs to the CNS]
When we consume food, it has to end up somewhere, the first place after the stomach is the duodenum.
The duodenum is an important area where a lot of components of bile and pancreatic juices are being released and working.
We have the sphincter of Oddi which relaxes, the gallbladder contracts and the pancreatic/gall bladder secretions will occur into the duodenum.
There will be neutralisation of acids and digestion will occur.
Distension of the duodenum will send signals via vagal afferents to the dorsal vagal complex. Signals return via efferents, the relaxation of sphincter of Oddi occurs via NO//VIP.
The gallbladder contracts under stimulation of Ach, CCK is also important in mediating contraction.
All of this is mediated by distension, the neuronal signals and hormonal.
Also important is if we have nutrients that contain fatty components (fatty meal), this stimulates CCK release. CCK can stimulate afferent signals and also act directly on the gallbladder.
Motillin may influence gallbladder motility and volume.
Bile Secretion and Enterohepatic Circulation
what two things are synthesised in the liver?
what is syntheisised by epthelila cells of the duct?
what reabsorbs bile salts? where do they return? what is this recycling pathway called?
what does the liver secrete intio bile and what is the fate of this?
what will be the consequences of interruption of enterohepatoc circulation for example after ileal resection?
Bile salts, lecithin (phospholipids) are synthesised in the liver, bicarbonate and other ions are synthesised within the epithelial cells of the duct (it neutralises acids in duodenum).
Bile salts are the most important as far as GI function is concerned and most bile salts are reabsorbed by Na+-bile salt coupled transporters.
The bile salts are returned to the liver and again secreted into bile.
This recycling pathway from intestine -> liver -> back to intestine = enterohepatic circulation.
If happened with a drug, body would see drug multiple times.
The liver also secretes cholesterol in bile and this is excreted in faeces.
Interruption of the enterohepatic circulation (e.g. after ileal resection) will cause the following:
- Excess synthesis of bile salts by liver (as you would be losing bile salts)
- Kidneys will excrete the synthesised bile salts (and some cholesterol)
Gallstones (cholelithiasis)
ratio compared to women and men? how does incidence increase?
How does the body try to balance higher cholesterol?
why do we have increasec cholesterol? (2 reasons)
types of gallstones (2 reasons)
what are the various factors involved in gallstone formation? (3 things)
what does bile from gallstone sufferers show?
Why are small gallstones not an issue? when do they become an issue? what might be the consequences of this? (3 things)
The ratio of incidence of gallstones is 2:1 in women and men respectively, incidence also increases with age (obesity also seems to be associated with gallstones)
Bile salts (bile compounded with a cation e.g. Na+), cholesterol and phospholipids need to be balanced in the body. The higher the cholesterol content of bile, the greater the concentrations of phospholipids and bile salts (to balance ratio).
Changes in the compositions of bile, it may cause cholesterol to precipitate out and form gallstones. There may also be precipitation of bile pigments.
Why do we have the increased cholesterol?
- Maybe the liver is secreting more into bile
- Maybe there is too much reabsorption of salt and water, producing an environment for them to form
Types of Gallstones
There are two types of gallstones:
- Calcium bilirubinate stones (this will happen if environment changes)
- Cholesterol stones (85%) (due to LOW levels of bile acids in the gallbladder, remember that bile acids are important in reducing precipitation of cholesterol)
There are various factors involved in gallstone formation, these include
Bile stasis:
Stones form in bile that is sequestered in the gallbladder rather than bile that is flowing through the bile ducts.
Decreased amount of bile acids due to malabsorption:
This tend to happen in cystic fibrosis and when there is a lot of dehydration, there could also be problems with bile production.
Chronic infection:
As bacteria can help in the formation of pigment stones. There may also be supersaturation of bile with cholesterol.
Super-saturation of bile with cholesterol
Presence of nucleation factors or glycoprotein
Ex vivo studies (take bile from gallstones sufferers)
o Show that bile from gallstone sufferers stones form quickly (few days)
o In bile from normal individuals, it takes a long time for stones to form (2 week). Possibly due to antinucleating factors.
Small gallstones have an easy passage via the bile duct, so there are no problems. Larger gallstones may lodge in the opening of the gallbladder, blocking the cystic duct or even the common hepatic duct.
Lodging of gallstones where the pancreas joins the bile duct before it joins the duodenum will cause stoppage of bile and pancreatic secretions.
This can result in nutritional deficiency since food is not digested properly, may also get ulcers, further pressure build-up also decreases secretion of bile.
There can also be a jaundice, due to increased accumulation of bilirubin in blood
Bile is yellow because of bilirubin, it colours urine. Stercobilirubin colours faeces.
Diagnosis of Gallstones: Visualising the Gallbladder
3 different techniques
contrast?
ultrasound?
insert something? what is it?
Ultrasonography and computer tomography can be used to explore the upper right quadrant of the gallbladder to detect gallstones.
Cholescintigraphy, is where we administer technetium 99m – labeled derivative of iminodiacetic acid (this ends up within gallbladder, we can inject CCK to see the behaviour of gallbladder)
Endoscope retrograde cholangiopancreatography (ERCP), this is to visualise the biliary tree by injecting contrast media from an endoscope channel.
We can also insert devices to remove gallstone fragments that may be obstructing bile flow, pancreatic juice or both.
Clinical Features of Gallstones
why are most cases not an issue?
when do we get biliary pain?
what if common bile duct gets obstructed> what happens and consequences?
consequences of mucus secretion?
cholangitis?
85% tend to be asymptomatic, as if they are small and sitting within the gallbladder they won’t be causing much of an issue.
However, if the neck of cystic duct gets affected by it (lodging) then biliary pain ensues -> end up with acute cholecystitis.
Gallstones that impact on the common bile duct will obstruct the flow of bile -> cholestatic jaundice which can in turn cause bacterial infections/cholangitis, due to any glucose that may still be in there.
If we impact that area around the common bile duct, some material may stay within the gallbladder causing chemical or acute cholecystitis.
Gallbladder will secrete mucus if inflamed (get mucocele or hydrops forming) and this may rupture.
Model explaining the release of bile into the duodenum (SUMMARY)
what does the chyme stimulate when it enters the duodenum? what do these stimulate?
- Bile is essential for the chemical digestion of fat; it is formed bile salts, pigments and cholesterol. It is secreted from the pancreas when chyme enters the small intestine from the stomach.
- The chyme stimulates enteroendocrine cells of the duodenum to secrete CCK and secretin
- CCK and secretin are absorbed intestinal mucosa into the bloodstream
• CCK and secretin stimulate the
following events:
o Stimulate the liver to synthesise and release bile into the common bile duct.
o CCK Stimulates the gallbladder to contract, ejecting concentrated bile into the cystic duct and common bile duct.
o Hepatopancreatic sphincter (Sphincter of Oddi) relaxes, allowing bile to flow from the common bile duct into the duodenum
• Bile in the duodenum emulsifies, or coats, fat droplets so that the fat can be further broken down by other digestive enzymes (lipases).
