Liver & Pancreas Flashcards
What are the main GI tract functions of the liver and pancreas?
Secretion
A number of drugs and waste products are excreted in the bile
What is produced in the liver?
How does it travel to its final destination?
Bile is produced in the liver and enters the bile duct
The bile enters the cystic duct, which passes to the gallbladder
How is the common hepatic duct formed?
The right hepatic duct (which drains bile from the right lobe of the liver) joins with the left hepatic duct
How is the common bile duct formed?
From the common hepatic duct joining with the cystic duct
The pancreas then joins the common bile duct before it enters the duodenum
How do bile and secretions from the pancreas enter the small intestine?
They enter the duodenum via the common bile duct
What is the role of the sphincter of Oddi?
It can close off the common duct to prevent substances entering the duodenum
What causes the sphincter of Oddi to relax?
It relaxes in response to CCK
This allows the secretions to enter the duodenum and mix with the food
CCK is produced when what type of food is eaten?
What effect does this have?
CCK is produced when fatty food is consumed
This will contract the gallbladder and relax the sphincter of Oddi
Why is the sphincter of Oddi closed most of the time?
How does this affect the gallbladder?
The pancreas does not release secretions very often
The liver produces bile all the time and if it cannot pass through the sphincter, it passes down the cystic duct to be stored in the gallbladder
What is the Ampulla of Vater?
a small prominence where the common bile duct enters the duodenum
what is the duct of Santorini?
an accessory pancreatic duct that joins the pancreas to the common bile duct
What initiates the cephalic phase?
Sensory inputs such as sight, smell, taste and mastication lead to the anticipation of food
These sensations lead to the first phase of pancreatic secretion - cephalic phase
What happens during the cephalic phase?
Vagal inputs from the medulla stimulate the release of ACh
ACh stimulates secretion of enzyme components in the pancreas and bile production in the liver
What initiates the gastric phase?
What is important in this phase?
The entry of food into the stomach initiates the gastric phase of pancreatic secretion
The vagus nerve is important in this phase
What will block the gastric phase?
Atropine and vagotomy
What is vagotomy?
a surgical operation in which one or more branches of the vagus nerve are cut, typically to reduce the rate of gastric secretion
What initiates the intestinal phase of pancreatic secretion?
The release of acidic chyme into the duodenum
Where is gastrin produced?
What is its stimulus, type of pathway and primary target?
Produced by G cells in the stomach
Stimulus: neural, amino acids, peptides
Pathway: endocrine
1st target: ECL and parietal cells
Where is cholecystokinin produced?
What is its stimulus, type of pathway and primary target?
Produced by I cells in the duodenum
Stimulus: fatty acids and some amino acids
Pathway: endocrine and paracrine
1st target: vagal afferent terminals, gallbladder
Where is secretin produced?
What is its stimulus, type of pathway and primary target?
Produced by S cells in the duodenum
Stimulus: acid in the small intestine
Pathway: endocrine and paracrine
1st target: vagal afferent terminals, pancreatic duct cells, cholangiocytes
Where is motilin produced?
What is its stimulus, type of pathway and primary target?
Produced in the intestine
Stimulus: neural, fasting
Pathway: paracrine
1st target: upper GI motility
Where is vasoactive intestinal peptide produced?
What type of pathway does it follow and what is its primary target?
Produced by nerve terminals throughout the GI tract
Pathway: neurocrine
1st target: smooth muscle, secretory cells
What is the role of motilin?
It increases the motility of the GI tract
What are APUD cells?
amine precursor uptake and decarboxylation cells
They are a form of neuroendocrine cells
What is the role of vasoactive intestinal peptide?
It modulates the activity of smooth muscle and secretory cells:
- increases the fluid and bicarbonate component
- increases GI motility through relaxation of smooth muscle
What is the role of gastric inhibitory peptide (GIP)?
It acts to decrease gastric motility
Where is gastrin mainly produced?
Most gastrin is produced in the antrum of the stomach
A small amount is produced in the duodenum
where are CCK and secretin produced?
CCK is mainly produced in the duodenum and jejunum, with a small amount being produced in the ileum
Secretin is produced in the duodenum
Where are GIP and motilin produced?
In the duodenum and jejunum
Why does CCK have similar effects on similar receptors to gastrin?
CCK is made from 33 amino acids
The last 5 amino acids of CCK are identical to the last 5 amino acids of gastrin
Where is CCK released from and what stimulates CCK release?
Released from I cells of the small intestine
CCK release is stimulated by lipids and peptides in the small intestine
which receptors are better for CCK, and which are better for gastrin?
CCK-A receptors are better for CCK
CCK-B receptors are better for gastrin
What are the main effects of CCK?
- stimulation of pancreatic enzyme secretion
- stimulation of gallbladder emptying
It also causes relaxation of the sphincter of Oddi
How is CCK release stimulated initially?
What type of secretion is involved?
Epithelial cells detect fatty acids and amino acids and release CCK-releasing peptide into the SI lumen
This is paracrine secretion
How does CCK-releasing protein lead to the release of CCK?
CCK-releasing peptide binds to receptors on the I cells
This causes the release of CCK
What will the CCK do after it has been released?
- CCK goes to the pancreas to generate the production of enzymes
- CCK causes the release of the monitor peptide
What is the role of the monitor peptide?
It binds to the I cells to cause them to release more CCK
This is positive feedback
What happens if there is not much protein present in the lumen of the small intestine?
Trypsin digests the CCK-releasing peptide and the monitor peptide
This prevents more enzymes from being released
What happens to trypsin is there is a lot of protein present in the lumen of the small intestine?
The trypsin focuses on digesting the protein
This allows the monitor peptide to pass through, and cause more enzymes to be released when more protein is present
What is secretin?
Where is it released from and what triggers this?
It is a peptide hormone consisting of 27 amino acids
It is secreted by the S cells of the small intestine in response to acid in the SI
What is the main effect of secretin?
It stimulates bicarbonate secretion by ductal cells in the pancreas and liver
what are the other effects of secretin?
- it has a trophic effect on the pancreas
this means is no secretin is present, the pancreas will atrophy away
- it has modest inhibition of gastric acid production
What are the stages that lead to secretin production and its effects?
- S cells in the small intestine detect acid (and fats)
- S cells produce secretin
- Secretin increases bicarbonate production, which is released into the small bowel
How is secretin involved in a negative feedback effect?
Secretin increases bicarbonate production
The bicarbonate enters the small bowel to neutralise the acid
What are the 4 components of bile?
- bile acids/salts
- phospholipids and cholesterol
- bile pigments from the breakdown of haemoglobin
- inorganic ions
Where are bile acids/salts synthesised?
Why are they amphipathic?
How often are they recycled?
Synthesised by the liver
They are amphipathic as the polar groups are all on one side of the molecule
They are recycled up to 8 times per day
What do bile acids form at high concentrations?
Why is this significant?
With the help of cholesterol, they form micelles at high concentrations
Micelles mean the gallbladder can store large amounts of bile salts
Why are there more cations in bile than anions?
Bile acids carry a negative charge, which attracts the positive cations
How are primary bile acids formed?
The liver adds hydroxyl groups onto cholesterol molecules
It then chops off the end and replaces it with a carboxyl group
what is significant about the actions of the liver during primary bile acid formation?
The side of the primary bile acid on the interior of the micelle has many polar groups
The outer side has lipophilic properties
How are secondary bile acids formed?
If primary bile acids pass into the colon, they are converted to secondary bile acids by bacteria
The bacteria do this through dehydroxylation
How does the liver deal with secondary bile acids?
It cannot make them
It can reuse them when they are reabsorbed and recirculated
How are bile salts formed?
The carboxyl group of the secondary bile acid is linked to an amino acid
This increases the charge to make molecules more polar and more amphipathic
What amino acids are usually involved in conjugation with bile salts?
taurine and glycine
what is an example of bile salt formation using cholic acid?
- cholesterol is converted to the primary bile acid, cholic acid
- cholic acid is converted to deoxycholic acid
- deoxycholic acid is conjugated with glycine
Where is bilirubin produced and how?
The spleen will break down RBCs to release haemoglobin
The Hb is then converted to bilirubin
How is bilirubin conjugated in the liver and why is this necessary?
The liver conjugates bilirubin by adding it to glucuronic acid
This makes it more soluble so it is more easily transported in the intestinal fluid
What is the action of bacteria on bilirubin glucuronide?
They can reduce bilirubin glucuronide and deconjugate it
This produces urobilinogen
This is excreted in faeces or enters the bloodstream, where it is excreted as urine
What is meant by the liver having a dual blood supply?
- it receives oxygenated blood from the hepatic artery
2. it receives deoxygenated blood containing foodstuffs from the hepatic portal vein
Where do the hepatic artery and the hepatic portal vein come together?
In the sinusoids
These are chambers lined with hepatocytes, which allow substances to pass into the hepatocytes
What are bile canaliculi?
Small bile ducts between the sinusoids
They will come together to form the bile duct
Where does the blood drain from the liver?
All of the blood vessels join and drain into a central vein towards the centre of the lobule
What is significant about the endothelium of the sinusoid?
What lies either side of the endothelium?
The endothelium of the sinusoid is quite leaky
The space of Disse lies between the endothelium and the hepatocyte
what is the role of the space of Disse?
It allows material to pass from the sinusoid lumen, through the endothelium, and be picked up by a hepatocyte
Where do the apical and basolateral membranes of the hepatocyte face?
The apical membrane faces into the bile canaliculus allowing substances to be secreted into the bile duct
The basolateral membrane faces the space of Disse
Where are stellate cells found and what can they cause?
Found in the space of Disse
They cause the scarring in fibrosis
What substances are actively secreted by the hepatocyte into the bile canaliculus?
- bile acids
- phosphatidylcholine
- conjugated bilirubin
- xenobiotics
What substances pass through the bile canaliculus by passive permeation?
- water
- glucose
- calcium
- glutathione
- amino acids
- urea
What happens to bile as it flows along the bile ducts formed from the bile canaliculi?
Bicarbonate, salt and water are added to it
How does bicarbonate enter the bile?
It is exchanged for chloride ions through bicarbonate/chloride anion exchangers and the CFTR channel
What is the effect of the Cl- efflux on the volume of the bile?
It means that Na+ and water can move paracellularly to increase the volume of the bile
What stimulates the process of exchanging chloride for bicarbonate?
Secretin
There are minor effects from glucagon and VIP
How is the composition and function of the bile altered in cystic fibrosis?
The volume of the fluid made with the bile is decreased due to the absence of CFTR proteins
The function is not majorly impaired as other Cl- channels are present
How does salt and water reabsorption affect the gallbladder?
It allows the gallbladder to store up to 450 ml of secretions in 50 ml
How does bile components forming micelles affect the fluid?
It means that it remains isotonic
the osmotic pressure remains the same
What is significant about proton exchange in the bile?
Net proton excretion acidifies the bile and leads to protonation of bile salts
Protons are exchanged for Na+
Protonation of bile salts makes them less lipophilic and favours formation of micelles
What is significant about acidifying the bile?
It reduces the risk of precipitation of Ca2+ salts
This reduces the risk of gallstones
If bile salts are conjugated, what happens to them in the distal ileum?
They are picked up by sodium-linked cotransporters to be recycled
If bile salts are deconjugated, what happens to them?
They enter the colon, where bacteria will make them less charged
They are then reabsorbed passively and appear as secondary bile acids in the liver
They will then be reconjugated
Why are proteases secreted from the pancreas as zymogens?
Zymogens are inactive precursors
This prevents them from digesting parts of the pancreas before they are secreted
What are the main zymogen proteases secreted by the pancreas?
- trypsinogen
- chymotrypsinogen
- proelastase
- procarboxypeptidases A and B
- trypsin inhibitors
What is the role of trypsin inhibitors?
why are they important?
They inactivate any trypsin that is activated whilst in the pancreas
If trypsin is activated, it will rapidly activate more trypsin
What is the main enzyme secreted by the pancreas that will break down carbohydrates?
Pancreatic a-amylase
What are the main pancreatic lipases that are produced?
- pancreatic lipase
- nonspecific esterase
- prophospholipase A2
- procolipase
Procolipase is NOT an enzyme, it facilitates the action of the lipases
What are the nucleases produced by the pancreas?
- deoxyribonuclease breaks up DNA
2. ribonuclease breaks up RNA
What else is produced by the pancreas?
Monitor peptide
This is controlled by trypsin activity and is involved in positive feedback
What are the steps involved in pancreatic acinar cell secretion?
- chloride enters the cell
- Cl- channels are opened and there is Cl- efflux
- this leads to the movement of Na+ and water paracelluarly, into the acinus
- the action of CCK is indirect as it increases ACh release from neurones
What stimulates pancreatic duct secretion of bicarbonate?
secretin
this is potentiated by CCK, via the vagus nerve
what is the primary chloride ion channel in pancreatic ducts?
CFTR
what is the result on pancreatic secretions in cystic fibrosis patients?
what does this lead to?
pancreatic secretions are thick and sticky due to mutations in the CFTR protein
this leads to pancreatic failure and the need for dietary supplementation with pancreatic enzymes
