Gastric Acid Secretion Flashcards
Components of gastric juice
Water
Organic compounds (intrinsic factor, pepsinogen, lipase, mucus)
Ions (Na, K, H, Cl, HCO3)
6 types of cells you can find in the gastric mucosa
Superficial epithelial cells Mucus neck cells Stem/regenerative cells Parietal (oxyntic) cell Chief cell Paracrine or endocrine cell
Gastric glands in fundus and body: What does 1. Parietal cell 2. Chief cell 3. Mucus neck cell 4. Paracrine cell release?
- HCl, intrinsic factor
- Pepsinogen, lipase
- Mucus
- Histamine, somatostatin
Pyloric glands in antrum What does 1. Mucus neck cells 2. Endocrine cells 3. Paracrine cells Release?
- Mucus, bicarb
- Gastrin
- Somatostatin
Intrinsic factor
Released from parietal cells into canaliculi
Facilitates vitamin B12 absorption in the small intestine
Activating of the parietal cell causes…
Tubulovesicles (with the proton pumps and intrinsic factor) fuse with invaginated areas of the apical membrane
Leads to the formation of many microvilli
Generates canaliculi (tunnels continuous with lumen)
H/K proton pump facilitates HCl production
Bicarb is pumped into the interstitial space, enters bloodstream and buffers
Proton pump
Transports H out of the cell, and K into the cell
3 major ion transport pathways in an active parietal cell
- Proton pump (H out, K in)
- NaCl uptake drive by Na/H (basally - Na in, H out) and HCO3/Cl (HCO3 out, Cl in) - gradients driven by Na/K pump
- K and Cl move out of the cell apically down a [ ] gradient
4 functions of gastric acid
Bacteriostatic
Activates pepsinogen and lipase
Initiates protein denaturation
Facilitates absorption of iron, Ca, and vitamin B12
Chief cells
Secretes pepsinogens and gastric lipases via exocytosis
Pepsinogens are inactive (zymogens), need to be activated by acid hydrolysis and autocatalysis
Gastric lipase activity is increased at low pH
Apical mucus layer functions
Protects the lumenal epithelium from acid and pepsin-based hydrolysis as well as microorganisms
Barrier contains protective glycoproteins/mucins and pH neutralizing bicarb ions
How is secreted mucus held in place?
By apically-targeted ‘surface active phospholipids’
Located in the lumenal membrane of mucus epithelial cells
How is bicarb taken up into the basal surface of the mucus cells?
Via a Na/HCO3- co-transporter
Released into the lumen, and neutralizes acid in the mucus
3 major secretagogues that stimulate both pepsinogen and acid production
Can act on chief and parietal cells
Gastrin
Histamine
Acetylcholine
G cells
Secrete gastrin
Found at the base of pyloric glands
Secretory vesicles are found basally
Gastrin
Polypeptide hormone released from G cells
Can act locally or travel through the blood
Binds to gastrin receptors (CCK 2/B)
Activates parietal and chief cells
Production of gastrin is stimulated by GRP from enteric neurons, and by digested protein in the gastric lumen
Enterochromaffin-like cells
Found at the base of gastric glands Produce histamine (paracrine factor) Histamine production is stimulated by ACh from intrinsic enteric neurons, or gastrin from G-cells
Receptors on parietal cells for
- ACh
- Histamine
- Gastrin
- M3 receptors
- H2 receptors
- CCK2/B receptors
Cephalic stimulatory phase of acid secretion
Taste, smell, sight, or thought of food activates your hypothalamus
Sends signals to dorsal vagal motor nucleus
Vagus nerve travels to stomach and can act on G cells or parietal cells to increase acid secretion in prep for a meal
Acid secretion from the stomach can be ___ or ___
Neuronal
Non-Neuronal
Gastric stimulatory phase of acid secretion: neuronal
Hypothalamus activates dorsal vagal motor nucleus, vagus travels to stomach, activates G cells and parietal cells
Activation of stretch receptors can stimulate G cells, and can travel via the vagus to the nodose ganglion, which connects into the above path at the dorsal vagal motor nucleus
Nodose ganglion
Inferior ganglion of vagus nerve
Receives visceral sensory/afferent nerves
Gastric stimulatory phase of acid secretion: non-neuronal
Food enters the stomach
As its broken down you get buffering of the intragastric pH and the production of peptones and amino acids
Peptones and amino acids stimulate G cells
Food and buffering stimulate parietal cells
Intestinal phase of acid production
When peptones in the chyme reach the duodenum, G cells there are stimulated to produce more gastrin that acts on the parietal and chief cells in the gastric glands
(via gastrin’s hormonal action)
Cephalic inhibitory phase of acid secretion
Hypothalamic satiety and feeding nuclei are activated, activate the dorsal vagal motor nucleus
Through vagus sends inhibitory signals to parietal cells
Gastric inhibitory phase of secretion
Acid in the pyloric antrum stimulates somatostatin release to inhibit meal-stimulated gastrin secretion
Somatostatin works in paracrine way
Intestinal inhibitory phase of secretion
Chyme into the duodenum stimulates a neuronal enterogastric reflex arc through the sympathetic celiac ganglion
Also stimulates the production of enterogastrones
These inhibit he G cell, parietal cell, and chief cell activity, as well as smooth muscle contraction in the stomach
Enterogastrones
Hormones that feedback to inhibit the G cell, parietal cell, and chief cell activity, as well as smooth muscle contraction in the stomach
Include: secretin, CCK, GIP, and GLP-1
5 functions of prostaglandins
Inhibit acid secretion
Prevent surface epithelial cell exfoliation
Increase mucosal blood flow
Stimulate mucus and bicarb secretion
Enhance synthesis of surface-active phospholipids
Prostaglandins are anti-secretory and protective
Do you want to inhibit COX1 or COX2
COX2! Its the pain pathway
Chronic use of COX1/2 inhibitors is problematic in the gastric mucosa
H. pylori
Gram negative flagellated bacterium
Produces urease (converts urea to ammonia and CO2 to protect from acid)
Requires special media for growth
H. pylori negative ulcers are usually due to…
NSAIDs
6 survival factors for H. pylori
High mutation rate Motility (chemotactic - away from acid) Ability to attach to epithelial cells of the gastric mucosa (adhesions bind surface receptors on epithelial cells) Virulence factors (cagA, VacA) Urease activity Evasion of the adaptive immune response
Action of H pylori’s virulence factors
Injected into epithelial cells
Cause the cells to release nutrients and urea that are used by the bacteria
Also damage epithelial cells and disrupt tight junctional barrier between cells. facilitated local inflammation
Inflammation results in local production of cytokines that stimulate G cells and inhibit D cells = increased acid production and further local tissue injury inflammation
Urease
Converts urea into NH3 and CO2
Neutralizes acid which allows for further protection of bacteria attached to epithelial cells
Facilitates further gastrin secretion
Treatment for H pylori
Most often its a combined proton pump inhibitors and antibiotics
