GI Exam Lecture 3 Flashcards
The Gastric phase is when food is ______
What are the major functions of the stomach?
(hint there are 7)
Gastric Phase is when food is in the stomach
Major functions of the stomach are:
- Storage: temp storage of a meal
- Secretion of H+ (kills microorganisms and activates pepsin)
- Secretion of Intrinsic Factor: essential for absorbption of vitamin B12
- Secrete mucus and HCO3- : protects gastric mucosa
- Secretes water
- Motor activity: mixing secretions with bolus
- Coordination of motor activity of smooth muscle and emptying of stomach contents into duodenum
Regulation of Stomach Function:
- Regulation of moth motor and secretory responses via:
- Neural: _____ and _____
- Paracrine: histamine is a powerful stimulator of ____ stimulation
- Endocrine:
- gastrin (____ and _____): stimulates _____ secretion
- somatostatin: (___, ___, ___): _____ gastrin secretion
- gastrin (____ and _____): stimulates _____ secretion
Regulation of Stomach Function:
Regulation of both motor and secretory responses via:
- Neural: intrinsic and extrinsic
- Paracrine: histamine is a powerful stimulator of H+ secretion
- Endocrine
- Gastrin (stomach and duodenum) - stimulates gastric acid secretion
- Somatostatin (stomach, duodenum, pancreas) - inhibits gastric secretion
Functional Anatomy of the Stomach:
Explain the three regions, what they secrete, and what kind of motolity they do
- LES and cardia: secrete mucus and HCO3- (important for prevention of reglux, entry of food, belching)
- Fundus and body: secrete H+, IF, Pepsinogens, Lipase, mucus HCO3- (important for food reservoir, tonic force during emptying)
- Antrum and pylorus: secrete mucus and HCO3- (important for mixing, grinding, sieving, regulation of emptying)
Functional Anatomy of the Stomach:
- The lining of the stomach contains _____ epithelium folded into “______”
- Each _____ is the opening where gastric glands empty
Functional Anatomy of the Stomach:
- The lining of the stomach contains columnar epithelium - folded into gastric pits
- Each gastric pit is the opening where gastric glands empty
The fundus and antrum contains 6 types of secretory cells…. name them
The fundus and antrum contains 6 types of secretory cells:
- Parietal Cells
- Mucous Neck cells
- Chief/peptic cells
- ECL cells
- D cells
- G cells
Explain what the following cells secrete in the fundus and antrum:
- Parietal cells
- Mucous Neck Cells
Within the Fundus/Antrum:
- Parietal Cells secrete:
- HCl : kills bacteria. allows activation of pepsin from pepsinogen, low pH for effective pepsin action
- Intrinsic Factor : essential factor, it is a glycoprotein that binds vitaming B12 making it absorbable
Reminder: Intrinsic Factor is the ESSENTIAL FACTOR
-
Mucous Neck Cells secrete
* Mucus : protects gastric mucosa
Explain what the following cells within the fundus/antrum secrete:
Chief/Peptic Cells
ECL cells
D cells
G cells
Chief Cells: secrete pepsinogens (which are cleaved into pepsin in acidic enviornment)
ECL Cells: secrete histamine (paracine): most powerful stimulator of HCl secretion
D cells: secrete somatostatin (endocrine) - powerful inhibitor of HCl secretion
G cells (pyloric region): secrete Gastrin (endocrine)
Summary Slide:
Draw a gastric pit
Show the 6 types of cells within the gastric pits of the stomach and show what they secrete
The cells of the gastric mucosa secrete a fluid called ____________
The major gastric secretions are:
1.
2.
3.
4.
In a healthy human, ______ is the only essential component of gastric juice
The cells of gastric mucosa secrete a fluid called Gastric Juice
The major gastric secretions are:
- HCl (H+ activates pepsinogen to pepsin, pepsin initiates protein digestion in stomach 20% but is not essential)
- Pepsinogen : inactive proenzyme of pepsin
- Bicarb + Mucus : protects gastric mucosa
- Intrinsic Factor: glycoprotein, required for normal absorption of vitamin B12 in the ileum
In a healthy human, intrinsic factor is the only essential component of gastric juice, the functions of other components are redundant
Parietal Cells secrete ___ and have distint ultrastructure
Explain a resting parietal cell vs an activated parietal cell
Parietal Cells secrete HCl and have distinct ultrastructure
Resting parietal cell cytoplasm contains a tubulovesicular system (whose membranes contain transport proteins needed to secrete H+ and Cl-). In the resting state, that system is all over cytoplasm
Once activated, the tubulovesicular membranes fuse with the plasma membrane of secretory caniculi (increases the amount of things that can be transported) and opens to the lumen of the gland
Draw a gastric parietal cell
Show which transporters are on the lumanal and blood side
What enzyme is within the cell itself?
Whtat reaction is it stimulating?
In the intracellular fluid: Carbonic Anhydrase produces H2CO3 from CO2 and H20
H2CO3 then dissociates into H+ and HCO3-
Draw a gastric parietal cell
Show what transporters are on the lumal surface, vs blood surface
In the lumen (or apical membrane): __ is secreted via the ______. This is inhibited by the drug ____
___ follows ____ by diffusing through channels
Icreased intracellular __ and ___ increase luminal conduction
Gastric Parietal Cell:
In the lumen (or apical membrane): H+ is secreted via the H-K ATPase - active process that transports both H+ and K+ uphill. This transporter is inhibited by the drug omeprazole that is used to treat ulcers and reduce H+ secretion
Cl- follows H+ by diffusing through Cl- channels
Increased intracellular Ca2+ and cAMP increases luminal conduction of Cl- and K+
Gastric Parietal Cells:
Draw a gastric parietal cell, show which transporters are on the blood membrane vs lumen side
In the basolateral membrane: ___ is absorbed into the blood via the ___- exchanger. This absorbed ___ is the reason for the “______” in the gastric venous blood after a meal.
Combination of all of the events leads to net secretion of ____ and net absorption of _____
Gastric Parietal Cell:
In the basolateral membrane: HCO3- is absorbed into the blood via the Cl- HCO3- exchanger. This absorbed HCO3- is the reason for the “alkaline tide” (high pH) in the gastric venous blood after a meal.
This HCO3- is eventually secreted back in the GI tract by the pancreas
Combination of all these events leads to a net secretion of HCl and net absorption of HCO3-
Secretion of HCO3-:
The _________ of the stomach also secrete a watery fluid that contains Na, Cl, K, HCO3
Although Na and Cl concentrations are ___ to plasma, K and HCO3- concentrations are ____
This HCO3- is entrapped by the viscus mucus that coats the stomach lumen - forms a ____
Secretion of HCO3-
The surface epithelial cells of the stomach secrete a water fluid that contains Na, Cl, K, and HC03
Although Na and Cl concentrations are similar to plasma, the K and HCO3 concentrations are higher
This HCO3- is entrapped by the viscous mucus that coats the stomach lumen - together forms a mucosal barrier
Secretion of Mucus:
- Mucus: secretions containing ____ are viscous and sticky - collectively called mucus
- Secreted by ______ cells
- They are 80% ______
- Intact mucins are ____ of 4 similar monomers
- The _____ of the mucin tetramer is susceptible to digestion by ____
Secretion of Mucus:
- Mucus: secretions containing mucins are vicous and sticky - collectively called mucus
- Secreted by mucus neck cells
- They are 80% carbohydrate
- Intact mucins are tetramers of 4 similar monomers
- The central portion of the mucin tetramer, is suceptible to proteolytic digestion by pepsins
Gastric Mucosal Protection and Defense:
- ______ and ____ protects the surface of the stomach from H+ and pepsins
- The protective mucus layer on the luminal side and the alkaline secretions trapped within this form the _________ (protects gastric mucosa)
- Mucus: protects cells from ____ and inactivates ____ that cannot hydrolyze membrane proteins
Mucus and HCO3- protects the surface of the stomach from H+ and pepsins
- The protective mucus layer on the luminal side and the alkaline secretions trapped within this - form the gastric mucosal barrier protects the gastric mucosa
- Mucus: protects cells from H+ and inactivates pepsins that cannot hydrolyze extracellular portions of membrane protens
So the mix of bicarb and mucus make up the gastric mucosal barrier
Regulation of Gastric Secretion:
Parasympathetic stimulation via the ___ nerve is the strongest stimulant for gastric H+ secretion
Extrinsic efferent fibers terminate on intrinsic neurons that innervate : ____ cells, ____ cells, _____ cells
Vagal stimulation also secretes ____, ____, ____, and ____
Regulation of Gastric Secretion:
Parasympathetic Stimulation via the vagal nerve is the strongest stimulant for gastric H+ secretion
Extrinsic efferent fibers terminate on intrinsic neurons that innervate: Parietal cells, ECL cells, and G cells
Vagal stimulation also secretes pepsinogen, mucus, HCO3, and intrinsic factor
Three substances stimulate H+ secretion by parietal cells: ACh, Histamine, and Gastrin
Acetylcholine:
- released from _____ nerve innervating gastric mucosa
- binds to _____ receptor on parietal cells
- 2nd messengers are ______
- ______ (inhibits muscarinic receptors) to block ACh effects on parietal cells
Acetylcholine:
- released from vagus nerve innervating the gastric mucosa
- binds to muscarinic (M3) receptors on the parietal cells
- 2nd messengers are IP3/Ca stimulates H+ secretion
- Atropine (inhibits muscarinic receptors) blocks ACh effects on parietal cells
Stimulation: Three substances stimulate H+ secretion by parietal cells: ACh, Histamine, Gastrin
Histamine:
- released from gastric ____ cells : ___ effect
- binds to ___ receptors
- 2nd messenger is _____ : stimulates H+ release by parietal cells
- _______ blocks H2 receptors - blocks histamine’s effect
Histamine:
- released from gastric ECL cells - paracrine effect on parietal cells
- binds to H2 receptors
- 2nd messenger cAMP - stimulates H+ secretion by parietal cells
- Cimitidine blocks H2 receptors - blocks histamine effect
Gastrin:
- secreted into circulation by G cells - endocrine effect
- binds to _____ receptors on parietal cells
- second messengers are ____
Histamine potentiates the actions of ___ and ___… therefore cimitidine will
ACh potentiates the actions of histamine and gastrin…atropine will
Gastrin:
- secreted into circulation by G cells - endocrine effect
- binds to CCKB receptors on parietal cells
- second messengers are IP3/Ca
Histamine potentiates the actions of ACh and gastrin: cimitidine will block direct histamine effects, block histamine potentiated effects of ACh and gastrin
Ach potentiates actions of histamine and gastrin - atropine will block direct effects of ACh, block potentiated effects of histamine and gastrin
Draw a picture showing Vagus Nerve, G cells, ECL cells
what they secrete
what their secretions bind to
the second messenger cascades they have
and their final effects
ALSO, show the effects of atropine, cimitidine, and omeprazole
Stimulation of Gastric Secretion by Parietal Cells:
Cephalic and Oral Phase:
- 30% of total HCl secretion
- Stimuli are smelling, tasting, chewing, swallowing
- Several mechanisms that promote HCL secretion during this phase:
- Direct stimulation of parietal cells by vagus nerve secreting _____ (neural effect)
- INdirect stimulation of G cells to produce gastrin
- Indirect stimulation of ECL cells by ACh and gastrin to produce ____
Several Mechanisms that promote HCl secretion during this phase:
- Direct stimulation of parietal cells by vagus via ACh
- Indirect stimulation of G cells by vagus to produce gastrin
- Indirect stimulation of ECL cells by vagus and gastrin to produce histamine
Draw a picture showing the stimulation of gastric acid secretion by parietal cells
Show how neurons directly stimulate parietal cells
and indirectly stimulate parietal cells through ECL and G cells
Gastric Phase:
- 60% of total HCl secretion
- Stimuli are distention of the stomach, presence of AA and peptides in stomach
- All the mechanisms that are present in cephalic, oral phase also operate here.
Two additional mechanisms exist:
- distension of the stomach activates ______
- A direct effect of amino acids and small peptides on ____ cells
_____ and _____ also stimulate HCl secretion
Gastric Phase:
- 60% of total HCl secretion
- Stimuli are distension of the stomach, presence of AA and peptides
- All the mechanisms that are present in cephalic and oral phase also operate here
Two additional mechanisms exist:
- distention of the stomach activates vasovagal reflexes to stimulate gastrin release
- a direct effect of amino acids and small peptides on G cells stimulate gastrin release
Alcohol and caffeine also stimulate HCl secretion
Inhibition of Gastric Acid Secretion by Parietal Cells:
Acidic chyme in the distal stomach (antrum) initiates a _______ feedback loop to inhibit acid secretion
When the pH of the lumen is below 3 (high proton enviornment), _______ is released by D cells - inhibits proton secretion via direct and indirect pathways
Direct pathway:
Indirect pathway:
Acidic chyme in the distal stomach (antrum) initiates a negative feedback loop to inhibit acid secretion
When the pH of the lumen is below 3, somatostatin is released - inhibits via direct and indirect pathways
Direct pathway: SS binds to receptors in parietal cells to inhibit H secretion
Indirect pathway: SS inhibits histamine relese (ECL cells) and gastrin release (G cells)
Review:
Parietal cells and chief cells are in the ____ part of the stomach
D cells and G cells are in the ______
If the pH is too high, ____ will secrete ____ (explain the effects of this)
If pH gets too low, ____ cells release ___ (explain the effects of this as well)
Parietal cells and chief cells are in the body of the stomach
D cells and G cells are in the antrum of the stomach
If the pH is too high, G cells will secrete Gastrin (the gastrin will bind to CCK receptors on parietal cells, increase intracellular calcium and increase H secretion) (gastrin will also activate chief cells and ECL cells to secrete pepsinogen and histamine)
If pH is too low: D cells will release somatostatin (which directly inhibits parietal cells, and it also binds to and inhibits G cells and ECL cells)
It is also important to remember that ACh can itself inhibit D cells (inhibiting somatostatin release)
Mucosal barrier review:
Explain what it is, what cells are involved and what it does
In the gastric pits of the stomach, there are mucous cells (which secrete the glycoprotein mucin) and neck cells (which secrete bicarb)
Together, the mucous and the bicarb (and water) make the mucosal barrier
This barrier is important in protecting gastric cells from the very acidic enviornment (HCl and pepsin are corrosive)
Gastric Motility:
Based on the differences in motility, the stomach can be divided into two regions
1.
2.
explain what they contain and how thick their walls are
Contractions in the caudad region (generated by strong muscles) mix the food and propel it into the small intestine
Gastric Motility:
Based on differences in motility, the stomach can be divided into two regions:
- orad region (proximal): contains fundus, proximal body and is thin walled
- caudad region (distal) - contains distal body and antrum (thick walled)
Contractions in the caudad region (generated by strong muscles) mix the food and propel it into the small intestine
Gastric Motility:
Explain the concept of receptive relaxation
what is it?
How is it done?
What NT had to be released for it to work?
Receptive Relaxation:
Distension of the lower esophagus by food causes relaxation of the LES- also relaxation of the orad stomach: called receptive relaxation
This is via the vasovagal reflex - mechanoreceptors detect stomach distension, relay this info to the CNS via sensory neurons, and then CNS sends efferent info for smooth muscle of orad stomach to relax
NT released from postganglionic peptinergic fibers is VIP
Gastric Motility:
Mixing and Digestion:
Caudad region - waves of strong contraction start in mid part of stomach- move distally towards pylorus increasing in strength towards pylorus
They mix gastric contents and periodically propel a portion of these into duodemun for sensing
Much of the chyme is propelled back into stomach for further mixing and breakdown - this is known as ______
Mixing and Digestion:
Caudad region: waves of strong contraction start in the mid portion of the stomach, move distally towards pylorus, increasing in strength towards the pylorus
They mix gastric contents and periodically propel a portion of these in the duodenum through pylorus followed by closure of pylorus
Much of the chyme (not emptied into duodenum) is propelled back into the stomach for further mixing and break-down - this is known as retropulsion
Control of Gastric Motility:
Parasympathetic innervation via the vagus nerves is _____ ( ) in the lower stomach causing ___ motility
In the gastric phase, the pylorus is usually _____, the antral contractions mix the gastric contents and reduce size (grinding function)
Control of Gastric Motility:
Parasympathetic innervation via vagus nerves is excitatory (ACh and Substance P) in the lower stomach causing increased motility, magnitude of contractions is regulated by neural input
In the gastric phase, the pylorus is usually closed, the antral contractions mix the gastric contents and reduce size (grinding functions)
Control of Pyloric Muscle Tone
SNS ______ sphincter
PSNS ____ sphincter
PSNS can also _____ sphincter via _____
Control of Pyloric Muscle Tone:
SNS activates pyloric cphincter via NE (pyloric constriction, slowing gastric emptying)
PSNS can activate pyloric sphincter via ACh (pyloric constriction, slowing gastric emptying)
PSNS can also use vagal inhibitory fibers and realx pyloric sphincter via VIP and NO (pyloric relaxation, speeds gastric emptying)
