Lecture 31 Flashcards
Does ACh have a positive or negative innervation of the ECL, parietal and G cells?
A positive innervation
What receptor does ACh bind to on the parietal cells, ECL calls and G cells and what is the effect of this? When does this occur?
M3 receptor
During feeding, ACh binds to these receptors which causes activation of PLC which generates DAG and IP3 which activates PKC which would phosphorylate lots of stuff and overall lead to an increase in the gastric acid secretion.
What receptor does ACh bind to on the D cells and what is the effect of this? When does this occur?
During fasting conditions, ACh binds to either M2 or M4 to decrease cAMP do have a negative effect on the gastric acid secretion
During which phases is there stimulation of gastric acid secretion? What are the stimuli for each?
- cephalic phase: sight, smell, thought, CNS -> PNS -> ENS
- gastric phase: stretch (CNS, ENS) and products of digestion (antrum)
During which phases is there stimulation of gastric acid inhibition? What are the stimuli for each? What is the effect?
The intestinal phase: H+, amino acids and fat which causes the release of CCK and secretin
CCK and secretin go into the blood to effect the _____ and ______ cells
G
parietal
Where is CCK released from? What is this in response to? What is the effect of this?
It is released from I cells in the duodenum in response to fat and protein digestive products. This inhibits gastrin secretion in the antrum and increases protein secretion from the pancreatic acini
Where is secretin released from? What is this in response to? What is the effect of this?
It is released from S cells in the small intestine due to the acidification of the duodenum. This increases the fluid secretion in the pancreatic duct and stops the release of gastric acid
How do CCK and secretin reduce the gastric acid secretion?
They bind to a receptor on the D cells in the antrum which causes the release of somatostatin which stops the release of gastric acid from the G cell
How do CCK and secretin reduce the gastric acid secretion?
They bind to a receptor on the D cells in the antrum which causes the release of somatostatin which stops the release of gastric acid from the G cell
What are the two parts of the pancreas and what is each of their function?
- there is an exocrine part (which releases high bicarbonate fluid and digestive enzymes)
- there is an endocrine part (which releases insulin and glucagon)
Describe the structure of the exocrine part of the pancreas
There are lobules of acinar cells and ducts which are intercalated and secrete common bile.
Where do the two ducts of the pancreas fuse?
They fuse at the sphinctor of oddi and go into the duodenum.
Describe the acinus: What is the purpose of the acini? What do they secrete? How many are there per lobule?
They are the site of the primary fluid secretion.
There are 15-20 cells per lobule.
Inside there is the synthesis of proteins and they secrete these proteins and an isotonic NaCl solution
What do the duct cells in the pancreas secrete?
They modify the primary secretion by secreting HCO3- rich fluid to neutralise the acid in the intestines
What percentage of fluid is secreted by the acinar cells and what percentage is by the duct cells?
25% by the acinar cells and 75% by the duct cells
What is the osmolarity and tonicity of the pancreatic secretions?
It is isosmotic and/or isotonic but it is not really isotonic because the HCO3- is much greater in the pancreatic secretions than in the plasma
Where does the HCO3- come from?
The parietal cells secrete HCO3- into the blood side when they secrete H+ into the luminal side.
HCO3- enters the liver and this secretes HCO3- too along with the pancreas.
What happens when HCO3- neutralises the H+ in the intestine?
It forms H2O and COs and is absorbed in the intestine
How much of each part of the secretions are secreted by the pancreas?
1-1.5 L of alkaline fluid and 5 -15 g protein secreted per day
Where are proteins secreted from in the pancreas?
From the acinar cells
What proteins are secreted from the acinar cells?
20 different proteins secreted - mainly digestive enzymes like zymogens - inactive precursors of digestive enzymes
such as trypsinogen, chymotrypsinogen, procarboxypeptidase
also amylase, lipase, colipase
(ie. enzymes for all major nutrient groups)
Where is the alkaline fluid secreted from? What is this and what is its purpose?
The intercalated duct cells
This is essentially an isosmotic NaHCO3 solution and it neutralises the acidic chyme from the stomach
In the absence of food, what is the basal secretion like from the pancreas?
It is low
When is there the largest volume of secretions from the pancreas?
During the intestinal phase
What is the stimulus for the secretion of CCK?
fat, products of protein digestion in the duodenal wall (also get minor regulation via vagus: acetylcholine)
What is the stimulus for the secretion of secretin?
Acidic chyme is the duodenal lumen
also get minor regulation via vagus: acetylcholine
How do CCK and secretin affect the concentrations of the ions?
Secretin increases the concentration of HCO3- and decreases the concentration of Cl- and doesn’t change the conc of Na+ or K+ when the secretory rate increases.
CCK doesn’t change the concentration of any of them.
Why does CCK not change the concentration of the ions?
This is because CCK is secreted and affect the acinar cells (along with the vagus nerve). This causes a secretion of small volumes of isotonic NaCl solution and mainly digestive enzymes.
This is only 25% of the total pancreatic solution
Why does secretin change the concentration of the ions?
Secretin acts on the duct cells which secrete large volumes of isosmotic NaHCO3 solution which makes up 75% of the total pancreatic secretions
Pancreatic secretion
A. is hypotonic due to high Na+ re-absorption in pancreatic ducts.
B. is stimulated by somatostatin.
C. contains trypsinogen released from zymogen granules.
D. is elevated during the gastric phase.
C. contains trypsinogen released from zymogen granules.
What are acinar cells specialised for?
Protein secretion
CCK and ACh stimulate the secretion of proteins from the acinar cells via an increase in what? What does this cause?
intracellular Ca2+
This activates a Ca2+ dependent apical Cl- channel and stimulates the secretion of enzymes
Acinar cells secrete isotonic NaCl solution by electrogenic Cl- secretion. Explain how this happens
The acinar cells in the pancreas are leaky epithelium. In the basolateral membrane there is Na+/K+ ATPase and K+ channels used to set up the resting membrane potential. There is also an NKCC1 which brings Cl- into the cell. Cl- leaves the cell via the apical membrane through a Cl- channel. Na+ follows paracellularly due to the electrical gradient and then H2O follows due to the osmotic driving force. This produces an isotonic primary secretion
Overall, what is secreted from the acinar cells?
A small volume of isosmotic NaCl solution containing a high concentration of digestive enzymes
What do the duct cells secrete?
Large volumes of HCO3- rich solution
What are the roles of the HCO3- rich solution that the duct cells secrete?
- _________ proteins secreted by the _________ cells
- it _________ the solution bathing ________
- it flushes ___________ out of the _________ into the small intestine
- it ___________ the gastric __________
- hydrates proteins secreted by the acinar cells
- it alkalinises the solution bathing proteins
- it flushes protein out of the ducts into the small intestine
- it neutralises the gastric acid
What is the secretion of HCO3- from the duct cells stimulated by?
secretin (the main stimulus) and ACh
How do the duct cells produce HCO3-? What is importance of CFTR? What is the effect of secretin?
HCO3- comes from the CA reaction or from the blood.
This is pumped out of the cell via the apical membrane in exchange for Cl-. There is a CFTR channel in the apical membrane which lets Cl- out of the cell in order to maintain the driving force of HCO3-. The presence of HCO3- in the lumen drives the movement of Na+ and water through the paracellular pathway to create an isosmotic NaHCO3 solution. When secretin binds to the duct cells, it activated cAMP which activates the CFTR channel to increase the release of Cl-
What sort of epithelium are the duct cells in the pancreas?
leaky
What is the effect of cystic fibrosis?
During cystic fibrosis there is no H2O secretion because the CFTR is not functional so you can’t flush out enzymes into the duodenum. This means that you can’t digest and reabsorb food
Is the Cl-/HCO3- exchanger very active at rest?
no it is inactive
The secretion of a bicarbonate-rich solution by pancreatic duct cells is driven by CCK, BECAUSE
bicarbonate secretion in stimulated pancreatic duct cells is facilitated by CFTR.
D: first statement false and second true
What are the two main functions of the liver?
- the processing of absorbed nutrients and the control of metabolism
- secretion and excretion
Explain the “processing of absorbed nutrients and control of metabolism” function of the liver
gluconeogenesis, glucose buffering, fatty acid oxidation, synthesis of plasma proteins (e.g., albumin)
Explain the “secretion and excretion (exocrine function)” function of the liver
- provision of bile acids and alkaline fluid to:
- aid digestion and absorption of fats
- neutralise gastric acid
- degradation and conjugation of waste products of metabolism
- detoxification of poisonous substances
- excretion of waste metabolites and detoxified substance in bile
How is the function of the liver assisted by blood supply?
We absorb stuff in the small intestine and then it travels in the blood to the liver. The liver can make some medication non-functional to excrete them back into the intestine
Briefly describe the anatomy of the liver and what it secretes
Bile is secreted by hepatocytes lining the canaliculi. The ducts secrete HCO3- rich fluid
What is the storage and secretion rate for the liver like?
The secretions are secreted continuously but are stored and concentrated in the gall bladder between meals
Describe the volume and composition of secretions from the liver
- 5 L/day consisting of:
- excretory products
- bile pigments (waste products)
- cholesterol (excreted by liver) - steroids, heavy metal, drugs - products associated with digestion
- HCO3- rich fluid (secreted by duct cells)
- bile salts
What are bile salts?
These are amphipathic compounds (ie. have both a hydrophilic and hydrophobic surface) which consist of bile acid (cholic acid)
What are the two sources of bile salts?
newly synthesised and enterohepatic circulation
______ of the secreted bile salts are reabsorbed
95%
Describe the mechanism of the enterohepatic circulation
In the small intestine there is limited passive absorption and active absorption in the ileum. In the colon there is limited role
Explain the control of biliary secretion during the different phases
There are three mechanisms: nervous, hormonal and bile salts.
During the cephalic and gastric phases, the secretion is minor and via the PNS.
During the intestinal phase there is hormonal secretion:
secretin stimulates production of HCO3- rich solution by ducts and CCK stimulates contraction of gallbladder.
There is also bile salts: arrival of bile salts in portal venous blood stimulates absorption by liver and subsequent secretion
The liver produces a bicarbonate-rich bile, BECAUSE bile acids are required to reabsorb protein in the intestine.
C: first statement true and second false
