Digestive Secretions Flashcards
How is bile drained from the liver?
- Right hepatic duct and left hepatic duct which form common hepatic duct within liver
- Common hepatic duct leaves liver at liver hilum
- Joins cystic duct from gall bladder forming common bile duct
- Common bile duct join pancreas duct (within pancreas)
- Ampulla of vater –> end of common bile duct that enters into duodenum
Is the pancreas retro or intraperitoneal?
Retroperitoneal (apart from tail which is intra)
Where is bile produced?
Liver
Where is bile stored?
Gallbladder
How does bile and secretions from pancreas enter duodenum? Where does this duct enter the duodenum?
Via common duct
Enteres via Ampulla of Vater
What is the sphincter of Oddi?
Closes off common duct that allows bile and secretions from pancreas to enter duodenum
Allows secretions to enter and mix with food
What does the sphincter of Oddi relax in response to?
Relaxes in response to CCK-PZ
What are APUD cells?
Amine Precursor Uptake and Decarboxylation – neuroendocrine cells
What is gastrin produced by and where?
G cells
Stomach
What is effect of noradrenaline on ACh?
Inhibits release of ACh
What is cholecystokinin (CCK) secreted by?
I cells (duodenum)
What is secretin secreted by?
S cells (duodenum)
What is the main job of the pancreas?
Produce digestive enzymes
What are the 3 phases of pancreatic secretion?
- Cephalic
- Gastric
- Intestinal
What are pancreatic secretions of the cephalic phase under control of?
Autonomic control by vagus nerve though release of ACh
What can the pancreas be divided into?
- Exocrine gland (containing the acinar and duct tissue)
- Endocrine gland (containing the islets of Langerhans)
What is the majority of the pancreas made up of?
The exocrine portion (85% by mass)
What does the exocrine portion secrete?
Secretes digestive enzymes, water and bicarbonate to assist in digestion.
What is function of bicarbonate?
- Helps in neutralising the stomach acid. This is a vital part of digestion as the small intestine is not specialised to withstand the strong acids from the stomach
- The digestive enzymes secreted by the pancreas reach their optimum function at a basic pH
What are acinar cells?
Specialised in enzyme synthesis, storage and secretion
What is the duct system of the pancreas?
Modifies the aqueous secretions
What is the exocrine portion of the pancreas stimulated/inhibited by?
Stimulated by the parasympathetic system and inhibited by the sympathetic system
How are digestive enzymes produced in the pancreas?
The acinar cells produce digestive enzymes on the RER. They are then moved to the Golgi complex where they form condensing vacuoles. These condensing vacuoles are then concentrated into inactive zymogen granules in pancreatic acinar cells and stored for secretion
Where are digestive enzymes produced in the pancreas secreted into?
Into the main pancreatic duct, which merges with the bile duct at the head of the pancreas and forms the Ampulla of Vater
What enzymes are secreted by the pancreas?
- Proteases
- Pancreatic lipase
- Amylase
Other enzymes include ribonuclease, gelatinase, elastase etc.
What are the proteases secreted by the pancreas? What is their function?
Chymotrypsinogen and Trypsinogen
Digest proteins and peptides to single amino acids
What is the function of pancreatic lipase?
Digests triglycerides, monoglyceride and free fatty acids
What is the function of amylase?
Starch and maltose (disaccharides)
How is bicarbonate formed?
Water and carbon dioxide combine in a reaction catalysed by the enzyme carbonic anhydrase. The product formed is carbonic acid (H2CO3).
Carbonic acid then dissociates into hydrogen ions (H+) and bicarbonate ions (HCO3–)
H2CO3 -> H+ + HCO3–
How are H+ ions transported out of the pancreatic ductal cells into the blood?
In exchange for Na+ ions by an H+/Na+ antiporter. The Na+ ions that enter the cell are then removed by the Na+/H+/ATPase.
How is bicarbonate transported into the intercalated ducts of the pancreas?
In exchange for Cl-
How is an intracellular build up of Cl- avoided?
By a chloride channel which allows chloride ions to return to the lumen of the intercalated ducts.
What then moves through the intercalated ducts of the pancreas?
The bicarbonate ions, Na+ ions and water then move through the intercalated ducts and end up at the main pancreatic duct ready for secretion into the duodenum upon an appropriate stimulus.
How does vagal innervation affect the pancreas?
Stimulates the secretion of enzymes (stimulates acinar cells)
What is a cholinergic receptor?
Uses ACh as its neurotransmitter
Where is ACh synthesised?
In cholinergic neurones
What can ACh bind?
Either muscarinic or nicotinic receptors
What is CCK?
A peptide hormone
What is CCK produced by?
I cells from the SI
What is the pro enzyme of CCK?
Pro CCK
Describe chain of CCK
Consists of 33 amino acids (last 5 are identical to those of gastrin) (in all the CCK types)
What is the release of CCK mainly stimulated by?
Lipids and peptides in the small intestine
What are CCK-A receptors better for?
CCK
What are CCK-B receptors better for?
Gastrin
What are the 2 main effects of CCK?
- Stimulation of pancreatic secretion
2. Stimulation of gallbladder emptying
What is the predominant CCK receptor for GI functions?
CCK-A or CCK1 receptor
What is the predominant CCK receptor found in the brain?
CCK-B / CCK2 receptor
Found expressed in pancreatic islet cells. Identical to gastrin receptor.
How does positive feedback of CCK occur?
Acinar cells in the pancreas release ‘monitor peptide’ which binds to receptors on I cells to stimulate secretion of CCK
CCK-releasing factor (CCK-RF) is released from intestinal epithelial cells. In the absence of proteases such as Trypsin, they bind to CCK-A receptors on I-cells to stimulate CCK secretion.
How does negative feedback of CCK occur?
When trypsin released from pancreas it inactivates CCK-RF decreasing CCK secretion. However, when a protein load enters duodenum from stomach this competes for trypsin (to digest food) and CCK-RP can bind to receptors on I-cells.
Thus the protease concentration in the duodenum is intimately linked to pancreatic secretion through this negative feedback loop.
What is secretin?
Peptide hormone, consists of 27 amino acids
What is secretin secreted by?
S cells of the SI
What is the release of secretin mainly stimulated by?
Acid in the SI
What is the main effect of secretin?
Stimulate bicarbonate secretion by ductal cells in the pancreas and liver (to neutralise acid)
What is the effect of secretin on the pancreas?
Trophic effect (growth)
What is the inactive form of secretin?
Preposecretin
Where are S cells found?
In Crypts of Leiberkhun in small intestinal crypts as well as surface epithelial cells. mainly duodenum but to lesser amount jejunum
What is the secretin receptor?
a classical G-protein couple receptor which results in production of cAMP within the target cells.
What is the effect of secretin on gastric acid?
Modest inhibition
What is the function of secretin?
- Stimulate bicarbonate and some enzyme secretion from pancreatic ducts and acinar cells
- Increase bile secretion and gastric pepsin secretion
- It acts on the stomach to reduce gastric acid secretion, food related gastrin secretion
- Decreases small intestinal motility
- Increases oesophageal sphincter tone.
- It acts on islet cells to increase insulin secretion after glucose meal.
- It acts on brown adipose tissue to increase energy production and decrease appetite.
What are proteases secreted as?
Zymogens - inactive precursors (Trypsinogen, Chymotrypsinogen, Proelastase, Procarboxypeptidases A and B, (Trypsin inhibitors)
Why are proteases formed as inactive precursors?
Proteases are dangerous to cells
What is a trypsin inhibitor?
A protein and a type of serine protease inhibitor (serpin) that reduces the biological activity of trypsin by controlling the activation and catalytic reactions of proteins.
Where are trypsin inhibitors contained?
Secretory vesicles that are diluted out after vesicle exocytosis
How is trypsinogen converted to trypsin? Where is this found?
By enterokinase found in the intestinal mucosa
How is chymotrypsin activated??
By trypsin
What do proteases in epithelial cells of SI do?
Convert peptides into single amino acids
What is another name for proteases?
Peptidases
What do pancreatic lipases require to work?
Sufficient concentration of bile salts in duodenum
What pancreatic lipases are secreted by the pancreas?
Pancreatic lipase
Nonspecific esterase
Prophospholipase A2
(Procolipase)
What nucleases are secreted by the pancreas?
Deoxribonuclease
Ribonuclease
What is monitor peptide secreted by?
Pancreas
What are CCK and ACh potent stimulators of?
Cl- secretion
What does the presence of Na/K pump on the basolateral membrane generate?
Creates inwardly directed Na+ gradient which drives Na/K/Cl cotransporter to increase intracellular Cl- ions (driven by Na+ gradient)
What does intracellular accumulation of Cl- cause>
Electrochemical gradient that drives Cl- secretion into the acinar lumen through apical membrane Cl- channels
What does the movement of Cl- into the lumen cause?
Makes transepithelial voltage more lumen netagive, driving Na+ into lumen via tight junctions
Pancreatic ducts secrete bicarbonate. What is this strongly stimulated by?
Secretin (this is increased by CCK via vagus)
Describe pancreatic secretions in CF
In CF, pancreatic secretions are thick and sticky, leading to pancreatic failure and the need for dietary supplementation with pancreatic enzymes
What is the most common mutation in CFTR gene?
Delta F508 mutation which results in loss of a single amino acid but resulting protein is degraded before it reaches cell membrane and therefore there is a lack of fluid in secretions of pancreas making them much more sticky.
Where is bile synthesised?
Liver
Is bile recycled?
Yes
Bile acids/salts are amphipathic. What does this mean?
Polar groups are all on one side
After synthesis, where does bile go?
Bile then enters the gallbladder where it is concentrated or is delivered directly to the intestinal lumen
What are the main functions of bile?
- Major excretory route for potentially harmful exogenous lipophilic substances, endogenous substrates such as bilirubin and bile salts which are not readily filtered or excreted by the kidney
- Emulsify dietary fats and facilitate their absorption
- Major route of elimination of cholesterol
- Protects the organism from enteric infections by excreting IgA ,inflammatory cytokines, and stimulating the innate immune system in the intestine
- Many hormones and pherohormones excreted in bile
What can mutations in UGT1A1 gene result in?
decreased biliary excretion of drugs leading to increased risks of toxicity
What is bilirubin?
the breakdown product of the heme moiety of haemoproteins, including haemoglobin, myoglobin, and several hepatic haemoproteins
What do hepatocytes actively secrete?
Bile components secreted by intercellular canaliculi of the liver (and by intrahepatic bile ducts)
What are the 2 components of the secretion of bile?
Bile salt dependent and bile salt independent
What is active secretion from hepatocyte into canaliculi dependent on?
Energy dependent
What does increased solute concentration within canaliculi result in?
Passive diffusion of other bile components across cell membranes and tight junctions. (water, glucose, calcium, amino acids, urea)
What are bile acids secreted as?
mixed micelles composed of bile acid, lecithin and cholesterol in a ratio of 10:3:1. Such micelles are nearly saturated with cholesterol so that a decrease in concentration of bile salts or lecithin can cause it to precipitate.
As bile flows along the bile duct, what is added? What is this process stimulated by?
Bicarbonate, salt and water
Stimulated by secretin, with minor effects from glucagon and VIP
The liver produces bile continuously. What causes bile to drain into the gall bladder?
Sphincter of Oddi normally closed so bile backs up
During a fasting state, what happens to the gall bladder?
GB undergoes moderate tonic contraction. Keeps bile salts dissolved.
During the digestive period, what occurs in the gall bladder?
Strong GB contractions + relaxation of Sphincter
of Oddi. Bile into duodenum
What causes bile to be released into the duodenum?
Relaxation of sphincter of Oddi
What are micelles?
Lipid molecules that arrange themselves in spherical form in aqueous solutions. The formation of a micelle is a response to the amphipathic nature of fatty acids, meaning that they contain both hydrophilic regions (polar head groups) as well as hydrophobic regions (the long hydrophobic chain).
How does gall bladder fluid remain isotonic?
Bile components form micelles
How is the risk of gallstones reduced?
Net proton secretion acidifies the bile, reducing the risk of precipitation of Ca (and other) salts.
What does bile contain?
bile acids, phospholipids & cholesterol, and bile pigments, in an alkaline fluid.
What does the pancreas secrete digestive hormones in?
An alkaline fluid
The production of these secretions has a basal level but what is it substantially increased by?
neural and hormonal regulators
Where do neurogenic signals that initiate the cephalic phase of gastric secretion originate from? Where are they then transmitted?
From the cerebral cortex, and in the appetite centres of the amygdala and hypothalamus
They are transmitted through the dorsal motor nuclei of the vagi, and then through the vagus nerve to the stomach.
What does the cephalic phase cause ECL cells to secrete?
Histamine
What does the cephalic phase cause G cells to secrete?
Gastrin
Describe the chain of events for the nervous system and hormone system during the cephalic phase?
- Thinking of food (i.e., smell, sight) stimulates the cerebral cortex.
- The cerebral cortex sends messages to the hypothalamus, the medulla, and the parasympathetic nervous system via the vagus nerve, and to the stomach via the gastric glands in the walls of the fundus and the body of stomach.
- The gastric glands secrete gastric juice.
- When food enters the stomach, the stomach stretches and activates stretch receptors.
- The stretch receptors send a message to the medulla and then back to the stomach via the vagus nerve.
- The gastric glands secrete more gastric juice.
- Chemical stimuli (i.e., partially digested proteins, caffeine) directly activate G cells (enteroendocrine cells) that are located in the pyloric region of the stomach to secrete gastrin; this in turn stimulates the gastric glands to secrete gastric juice.
What % of gastric secretions does the cephalic phase account for?
20%
What % of gastric secretions does the gastric phase account for?
2/3
How does ingested food stimulate gastric activity?
By stretching the stomach and raising the pH of its contents
What 3 chemicals is gastric secretions stimulated by?
- ACh
- Histamine
- Gastrin
What is the gastric phase?
The gastric phase is a period in which swallowed food and semi-digested protein (peptides and amino acids ) activate gastric activity
What is ACh secreted by?
This is secreted by the parasympathetic nerve fibres of both the short and long reflex pathways
What reflexes does stomach stretching activate?
A short reflex is mediated through the myenteric nerve plexus; and a long reflex is mediated through the vagus nerves and brainstem.
What is histamine secreted by?
ECL cells (a type of neuroendocrine cell found in the gastric glands of the gastric mucosa beneath the epithelium)
As dietary protein is digested, it is broken down into smaller peptides and amino acids. What do these directly stimulate?
The G cells to secrete even more gastrin –> positive feedback loop that accelerates protein digestion
What is effect of small peptides on stomach acid?
Small peptides also buffer the stomach acid so the pH does not fall excessively low.
As small peptides empty from the stomach what happens to the pH? What is effect of this?
Stomach pH drops lower and lower
What happens as stomach pH drops below 2?
Below pH of 2, stomach acid inhibits the parietal cells and G cells: this is a negative feedback loop that winds down the gastric phase as the need for pepsin and HCl declines.
When does the intestinal phase occur?
The intestinal phase occurs in the duodenum as a response to the arriving chyme, and it moderates gastric activity via hormones and nervous reflexes.
How does duodenum affect gastric secretion?
The duodenum initially enhances gastric secretion, but soon inhibits it
How does the duodenum initially enhance gastric secretion?
The stretching of the duodenum accentuates vagal reflexes that stimulate the stomach, and peptides and amino acids in the chyme stimulate the G cells of the duodenum to secrete more gastrin, which further stimulates the stomach.
How does the duodenum then inhibit gastric secretions?
Duodenum sends inhibitory signals to the stomach by way of the enteric nervous system, while also sending signals to the medulla that inhibit the vagal nuclei. This reduces vagal stimulation of the stomach and stimulates sympathetic neurons that send inhibitory signals to the stomach.
What does chyme stimulate duodenal enteroendocrine cells to release?
Secretin and CCK
What are effects of secretin and CCK?
These hormones primarily stimulate the pancreas and gallbladder, but they also suppress gastric secretion and motility (pyloric sphincter contracts)
What is purpose of duodenum inhibiting stomach?
This gives the duodenum time to work on the chyme it has received before being loaded with more.
What is function of secretion of GIP (gastric inhibitory peptide)?
Decreases the stomach churning in order to slow the emptying of the stomach.
What are the 5 major hormones involved in digestion?
- Gastrin (stomach)
- Secretin (small intestine)
- CCK (small intestine)
- GIP (small intestine)
- Motilin (small intestine)
What is gastrin secretion stimulated by?
Arrival of food in stomach
What does gastrin stimulate?
Gastric glands to secrete pepsinogen and HCl
What is gastric secretion inhibited by?
Low pH
What is secretin secretion stimulated by?
Acid in the duodenum (from chyme)
What does secretin stimulate?
Release of sodium bicarbonate in pancreas and bile in liver (to neutralise acidity)
What is CCK secretion stimulated by?
Introduction of hydrochloric acid, amino acids, or fatty acids into the stomach or duodenum
What does CCK stimulate the release of?
- Digestive enzymes in the pancreas
- Stimulates gallbladder to release stored bile
What is function of GIP?
- Decreases stomach churning in order to slow the emptying of the stomach
- Induce insulin secretion.
What is GIP secreted from?
K cells in upper intestine
What is function of motilin?
- Increases the migrating myoelectric complex component of gastrointestinal motility –> it improves peristalsis in the SI and clears out the gut to prepare for the next meal. A high level of motilin secreted between meals into the blood stimulates the contraction of the fundus and antrum and accelerates gastric emptyin
- Stimulates the production of pepsin
