3-5 Gastric Phase Flashcards
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A: Gastric Phase occurs when food is in the stomach. The STOMACH is IMP to motility because it MIXES SECRETIONS (H+ & pepsin with food) and brings food down to (1 mm) before moving on is..
º temporary meal storage spot
ºSecretes H+ for killing stuff and [converting Pepsinogen–>Active Pepsin]
ºExclusively Secretes [Intrinsic Factor] needed for [Vitamin B12 Absorption in [iLeum mucosa]º –>This is actually very sensitive to stomach trauma/surgery
ºSecretes HCO3 as protective gastric mucosa
ºSecretes Water to lubricate bolus & suspend nutrients in solution
B: Stomach also coordinates smooth m. motor activity and emptying of stomach into duodenum
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Stomach Regulations:
**Neural = Intrinsic AND EXtrinsic =
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**Paracrine = Histamine is a POWERFUL Paracrine stimulator for [Parietal cell H+ Secretion]. Secreted from ECL, it binds to H2 receptors and uses 2nd messenger cAMP for activation. cimetidine blocks H2 receptors–>Blocks Histamine
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**Endocrine=
ºgastrin (G CELLS OF [stomach antrum] & duodenum) stimulates acid
vs.
ºSomatostatin (D CELLS of [stomach FUndus] /duodenum/Pancreas) BLOCKS ACID SECRETION. Somatostatin is stimulated by the release of Acid. pH under 2 or 3
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Stomach Functional Anatomy:
1st: [LES and Cardia] = secretes [Mucus & HCO3] and prevents reflux, regulates belching and food entry
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2nd: [Fundus and Body] {{thin muscular wall}} = secretes
- [Mucus & HCO3]
- [Intrinsic factor] exclusively**
- H+
- Pepsinogens
- Lipase
- Somatostatin
and is used as a Reservoir and adds [Tonic force during emptying]
- ———————————————————————————–3rd: [Antrum & Pylorus] {{THICK MUSCULAR WALL}} = secretes
- [Mucus & HCO3]
- Gastrin
NEED FOR MIXING / GRINDING / SIEVING / REGULATES GASTRIC EMPTYING
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A: Fundus and Antrum have 6 types of SECRETORY CELLS
1. [Parietal Oxyntic] = secrete HCL and [Intrinsic Factor]
- [Mucous Neck] = Secretes Mucus!
- [Chief Peptic] = secrete Pepsinogen–>when converted into pepsin catabolizes 20% of our total protein in stomach
- [ECL Enterochromaffin-like] = Secrete [Histamine Paracrine] which A POWERFUL stimulator of HCL
Endocrine:
5. (G CELLS OF [stomach antrum] & duodenum)= Gastrin
vs.
6. (D CELLS of [stomach FUndus] = Somatostatin
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B: There are 3 Stomach Glandular Regions
1st: [Cardiac Glandular Region] below LES
2nd: [Parietal Oxyntic Gland Region] in the Fundus
3rd: [Pyloric Gland Region] in [Gastric Antrum]
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C: In healthy people [Intrinsic Factor] is the ONLY ESSENTIAL UNIQUE component of Gastric Juice. All other components [HCO3/HCL/Pepsin] are redundant in function
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A: [Parietal Oxyntic Cells] Secrete HCL because their cytoplasm has a tubulovesicular system which contain transport proteins on its membrane for HCL. When activated these membranes FUSE with membranes of [Intracellular Secretory canaliculus]—> INC [H/K ATPase ANTIporters] on [Intracellular Secretory canaliculus] membrane.
B: During Gastric Acid Secretion:
1. CO2 and H2O—> H2CO3–> H+ and HCO3
- H+ is secreted OUT into stomach lumen ACTIVELY in exchange for K+ coming into [Parietal Oxyntic cell] using ATP. THE [H/K ATPase pump] ALLOWING THIS CAN BE BLOCKED BY OMEPRAZOLE TO TREAT GERD!
- HCO3 is ReAbsorbed into Blood in exchange for Cl- coming into [Parietal Oxyntic Cell]. (THIS WILL CAUSE [ALKALINE TIDE /high pH] IN GASTRIC VENOUS BLOOD AFTER MEAL). HCO3 is eventually secreted BACK into GI lumen via pancreas.
- Cl- passively diffuses down gradient (following H+) into stomach lumen via channel
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C: The [Parietal Oxyntic Cell] also has [Na/K ATPase pump] basolaterally that pumps K+ into The cell and Na+ ReAbsorbed
D: Sympathetics INC [intracell Ca+ and cAMP]—> INC [lumen conductance of K+ and Cl-] —> INC Acid Secretion
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A: The Stomach Lumen [Mucosal Barrier] is a COMBINATION of HCO3 STUCK in [Viscous Mucus Gel(made by [Mucus Neck cells])].
A2: [Stomach Surface Epithelium] create watery fluid tht contains [Na & Cl concentrations similar to plasma] BUT IT ALSO HAS [LOTS OF K and HCO3 CONCENTRATION]. HCO3 becomes STUCK in the viscous mucus and forms the [Mucosal Barrier].
B: Mucus Gel is made of many [mucin tetramers] which are vulnerable for [PEPSIN CLEAVAGE] at the [Nonglycosylated peptide core] where disulfide bridges join 4 Mucus subunits.
B2:Since proteolytic fragments CAN NOT form Mucus Gel, once [PEPSIN CLEAVAGE] occurs to [mucin tetramers]—> Disruption of the Protective mucus layer
C: in the Stomach Lumen, [Mucus Gel] SEPARATES…
[HCO3 Rich Secretions (from Stomach Surface Epithelium cells)]
and
[Acidic content]
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A: PARAsympathetics via vagus n. is the strongest H+ secretion stimulant. Extrinsic Efferent fibers terminate on intrinsic neurons and innervate [Parietal / ECL / G Cells]
B: Vagal n. ALSO stimulates pepsinogen / mucus / HCO3 and [intrinsic factor]
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C:3 substances cause [Parietal Cell H+ Secretion]
-AcH (neurocrine) is released from Vagus and binds to [M3 Muscarinic receptors] at activate [Parietal Cell H+ Secretion]
. It uses 2nd messengers IP3/Ca+ for activation
- **Histamine (Paracrine) **
- Gastrin (Endocrine)= secreted by [Stomach G Cells] this binds to [Cholecystokinin B] receptors on parietal cells for activation and uses (IP3/Ca+)) as its 2nd messengers
D: These 3 working together (or independently) to regulate [Rate of H+ Secretion] = POTENTIATION! This is can occur because they work on diff receptors AND Histamine uses diff 2nd messenger (cAMP)
D2: so… ex:[Histamine POTENTIATES the actions of AcH and Gastrin!] Cimetidine DIRECTLY blocks Histamine and indirectly blocks [histamine-potentiated effects]
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A: Cephalic & Oral phase cause 30% of Total HCL secretion when a person smells/taste/chews/anticipates food.
B: This occurs because:
- VAGUS DIRECTLY stimulates parietal cells via muscarinic receptors
- Vagus INdirectly stimulates G cells using [Gastrin-Releasing Peptide]
- Vagus INdirectly stimulates (ECL cells–>Histamine) using ACh
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A: Gastric Phase causes 60% of Total HCL secretion and is stimulated by stomach distension / Amino Acids / small peptides.
B: Everything going on in Cephalic/Oral ALSO occurs in Gastric (they just continue on thru out) + 2 Extra things
C: 2 Extra things=
º[stomach distension]–> vasovagal reflexes–>gastrin release
º[Presence of AA & (small peptides)]–>DIRECT gastrin release
D: Alcohol and Caffeine ALSO STIMULATE HCL SECRETION
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A: Intestinal Phase only contributes 10% of Total HCL Secretion and is regulated by [protein digestion products]
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D:: Feedback Inhibition
Acidic chyme in [gastric antrum] initiates [Negative feedback loop]—>Inhibits any further Acid Secretion. This occurs by…
- stomach lumen pH is lower than 3–>[D-cell Somatostatin release] from endocrine cells. This DIRECTLY inhibits Histamine stimulation by downregulating [2nd messenger cAMP]. It INdirectly inhibits [ECL Histamine release] and [G-cell Gastrin release]
- Prostaglandins ALSO down regulate [2nd messenger cAMP]–>inhibits Histamine stimulation
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A: Some Digestion in stomach but not Required. Pepsin digest 20% of protein so is not essential.
B: Some Amylase digestion in stomach but Amylase is inactive at low pH. If its active sites are occupied with carbs (substrate protection) then it can work
C: Lipid Digestion STARTS in stomach when [gastric lipase] attach to lipid droplet surface—>[free fatty acids & monoglycerides] but this is NOT essential unless pt has pancreatic dz
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A: When mixing strong contractions start in mid stomach and get stronger moving toward Pylorus. This mixes gastric contents and periodically propels a portion into duodenum thru pylorus (which then closes after)
B: Note: A LOT OF THE CHYME NOT EMPTIED INTO DUODENUM IS PROPELLED BACK TO STOMACH FOR MORE MIXING = RETROPULSION!
C: Gastric Motility
[Stretch/AA & small peptide receptors]–(DIRECTLY CONNECT)—> [Intramural plexuses]–> vagal fibers leaving stomach. Vasovagal reflexes are initiated to control acid, gastric wall distension and motility
D: The PARAsympatheitc vagus n. stimulation is EXCITATORY and uses (ACH and [substance P]) in lower stomach to INC [smooth m. Motility].
E: [Gastric Antrum] Contraction RATE is set by [gastric pacemaker] BUT
MAGNITUDE is set by [neural input]
F: Note that in Gastric Phase Pylorus is usually CLOSED so that [antral contractions] can mix gastric contents and Reduce Size = Grinding
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A: Post-Meal the stomach has 1.5L of stuff in it and emptying into duodenum is slow (3 hours)! [Liquids and Isotonic stuff empty Out Faster] and Solids empty after a [log phase].
B: B4 Solids empty into Duodenum, they HAVE to be reduced to less than 1 mm3 via RETROPULSION
C: GLUCOSE EMPTIES INTO DUODENUM FASTER than Protein
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A: Pylorus is made of 2 ring-like thickenings made of CIRCULAR Smooth m. It’s job is it
-FILTERS Large Food Particles
-Empty gastric content at a rate consistent with Duodenum ability to digest chyme
-PREVENT REFLUX back into Stomach
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B: Controlled by hormonal/ paracrine / nervous
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C: Pathologies associated WHEN PYLORUS JACKS UP..=
1) [GASTRIC ulcerations]=gastric mucosa is sensitive to bile from intestine because it has basic pH
2) [Duodenum ulcerations]= intestinal mucosa is sensitive to gastric secretion since it has acidic pH
SO THESE TWO MUST NOT MIX THEIR CONTENTS TOGETHER!
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A: [Peptic Ulcer Dz]= Ulcerative lesion of Gastric OR Duodenal mucosa caused by erosive actions of [H+ and Pepsin] on mucosa
B: This can happen when
1) Losing [protective mucus barrier or protective factors]
2) Too much [H+ and pepsin] or [damaging factors]
3) Combination of Both
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C: [GASTRIC ULCERS] form mostly because of defects in [protective mucosal barrier]–>allows [H+ and pepsin] to digest mucosa. MAJOR CAUSE = [gram-negative H. Pylori] which releases [cagA cytotoxin].
C2: NOTE: In pt with [gram-negative H.Pylori] their H+ secretion rates are naturally LOWER—>Gastrin Secretion is INCREASED as a result and therefore they LACK A NEGATIVE FEEDBACK LOOP
