STOMACH Flashcards
Major functions of the stomach
- Temporal storage for food
- Absorption of water-soluble and lipid-soluble substances
- E.g. alcohol, some drugs
- Preparation of the “chyme” (semi-fluid material produced by gastric digestion of food) for digestion in the small intestine
Digestion in the stomach
- Physical - muscles contract and relax
- Chemical - pepsin breaks down proteins
- Requires acidic medium
Name the major cells of the gastric (oxyntic) gland and what they secrete
- Surface mucous cells - mucus (more alkaline & viscous), HCO3-, water
- Mucus neck cells - soluble mucus, HCO3-, water
- Parietal (oxyntic) cells: HCl & intrinsic factor
- Chief (zymogen) cells - pepsinogen
- D cell - somatostatin
- Enterochromaffin-like (ECL) cells: histamine
- G cell - gastrin
What cells are found in teh basal region of gastric glands?
Chief (zymogen) cells
What cells are found in the antrum?
D cells
What cells are found in the pyloric region?
G cells
Functions of HCl & intrinsic factor from parietal cells
-
HCl -
- Denatures proteins
- Breaks up cell membranes
- Activates pepsinogen
- Antibacterial
- Solubilizes calcium salts
- IF - absorption of vitamin B12 in ileum for production of mature RBCs
Pepsin
Endopeptidase auto-catalytically activated from chief cells’ inactive pepsinogen
refers to all enzymes activated at a pH below 3 by HCl
Somatostatin from D cells
inhibits acid secretion & gastrin release
Histamine from ECL ells
Stimulates acid secretion
Increases local blood flow
Gastrin from G cells
Secreted into the blood (not stomach lumen) to stimulate gastric juice secretion & gastrin/intestinal motility
Function of gastric acid
- Digestion of proteins via acid & proteolytic enzyme production
- Absorption, esp vitamin B12
- Protects mucosa from bacteria & autodigestion from its own acid & proteolytic enzymes
Gastric lipase
Homologous to lingual lipase
Loss of intrinsic factor causes
achlorhydria & pernicious anemia
Gastric juice:
- mucous
- pepsin
- gastric lipase
- intrinsic factorHCl
- Other electrolytes: ___, __, and ___
HCO3- from mucous cells
K+ for H,K-ATPase
Na+ from mucous cells
How do [HCl], [K+], and [Na+] change as the rate gastric juice secretion increases?
HCl increases sharply (food acts a buffer)
K increases a bit
Na+ falls
As the stomach empties, what happens to the rate of H+ secretion?
It increases
What makes the parietal cell distinct?
Intracellular canliculi
Abundance of mitochodnria
Extensive smooth ER (tubulovesicular membranes)
Resting state of parietal cell vs Stimulated for acid secretion
Resting state: tubulovesicles w H/K-ATPase are underneath the plasma membrane on the apical side.
Stimulation: tubulovesicle membranes fuse into the canalicular membrane to increase the apical membrane’s surface area
- –> increases the # of H/KATPase, K+ and Cl- channels into the plasma membrane
- –> increases O2 consumption to support acid secretion
Name the transporters in the parietal cell on the apical vs the basoalteral membrane
- Apical:
- H,K-ATPase
- K+ channel
- Cl- channel
- Basolateral:
- Na,K-ATPase
- K+ channel
- Cl-/HCO3- exchanger
Secreted H+ from the parietal cell are derived mostly from ___
During active HCl secretion, the blood coming from the stomach contains a lot of ___.
H+ secretion is derived mostly from the dissociation of water & the carbonic anhydrase rxn
The blood coming from the stomach contains a lot of HCO3- (alkaline tide)b
Name the parietal cell receptors for gastrin, Ach, and histamine (secretagogues) and hwo they mediate their effects
Gastrin: gastrin-cholecystokinin (CCK-B)
Ach: muscarinic receptor, M3
HIstamine: H2 receptor
CCK-B & M3 increase intracellular Ca2+ –> HCl secretion
H2 increases intracellular cAMP –> HCl secretion
Potentiation effect
The effect of any 2 stimulants is greater than the effect of either stimulant alone.
The effect of gastrin, Ach, and histamine will result in an increase in cAMP & Ca2+ –> greatly enhances H/K-ATPase –> more acid secretion
Describe parietal cell activation
- Stomach distension stimulates mechanoreceptors
- Activates parietal directly thru
- Short local reflexes
- Long vago-vagal reflexes (traveling on vagus n)
Direct vs Indirect action of secretagogues
- Direct: Ach, gastrin, and histamine bind directly to their respective receptors on the parietal cell –>stimulate & potentiate gastric acid secretion
- Ach from vagus n (CN10)
- Gastrin from D cells
- Histamine from ECL cells
- Indirect: ACH & gastrin stimulate histamine release from ECL cells & mast cells (histaminocytes) in the lamina propria
Cimetidine & Ranitidine
H2 recepto rblockers
The block H2 receptors on parietal cells, thus also blocking Ach & gastrin indirect stimulation
Phases of gastric acid secreiton
- Basal (inter-digestive period)
- Cephalic
- Gastric
- Intestinal
Cephalic phase (shortest)
Initiated by thought, sight, smell, and taste of food; also influenced by emotion
-
Neuro influence: parasympathetic vagus n releases Ach to stimulate acid secretion by
- stimulating parietal cells, G cells, and ECL cells
- stimulating chief cells for pepsinogen
- Endocrine mechanism: Vagal stimulation also causes gastrin release, which acts like Ach
Gastric phase (longest)
Triggered by presence of food in stomach due to distension & chemical nature
- Neuro: stomach distension stimualtes mechanoreceptors –> parasympathetic secretion of Ach
-
Endocrine: Amino acids & peptides activate G cells –> Gastrin –> acid secretion & histamine reslease
- Gastrin falls when
- stomach pH falls between 2-3
- somatostatin is released from D cells
- Gastrin falls when
Intestinal phase
Triggered by chyme in the duodenum –> eneterogastric relfelx
- Acid in duodenum –> secretin: inhibits G cells & the parietal response to gastrin
- Fatty acids in duodenum –> gastric inhibitory peptide (GIP) and cholecystokinin (CCK) inhibits acid secretion and suppress gastrin release
Gastritis & peptic ulcers are ____ caused by ___
Both are inflammation of gastric mucosa cauased by bacterial infection of the mucosa (e.g. h pylori) that stimulates gastric secretion
H Pylori
- Survives acid bc it produces urease (hydrolyzes urea to produce ammonia, which neutralizes gastric acid)
- Adheres to epithelial cells and stimulates adhesins, ammonia, proteases, and immune response
- Induces G-cells to secrete gastrin –> HCl from parietal cells
- However, its augmentation occurs at a moderate rate
What factors predispose to ulcers?
- Smoking - increased nervous stimulation of stomach secretory glands
- Alcohol - breaks down mucosal barrier
- Aspirin & NSAIDs - breaks down mucosal barrier
How to differentiate between H pylori infection and Zollinger-Ellison Syndrome (ZES)
In ZES, there’s an abnormally high gastric acid secretion rate associated w duodenal ulcers and tumors - whereas, gastric ulcers do not produce excessive gastric secretion.
Zollinger-Ellison syndrome
Gastrinomas secrete very high amts of gastrin unregulated –> extremely high rates of gastric acid secretion
- Usually comes w gastric and duodenal ulcers
- Gastrinomas are typically located in the pancreas
-
Tx:
- Proton pump inhibitor
- H2R blocker
- Surgical removal of gastrinoma
