Gastric Motility and Secretions and Drugs Flashcards
What are the 5 functions of the stomach?
To store food
To minimise ingestion of bacteria
To dissolve and partially digest the macromolecules in food
To regulate the rate at which the contents of the stomach empty into the small intestine
To secrete intrinsic factor
What is the one indispensable function of the stomach?
To secrete intrinsic factor
Gastric motility allows the stomach to:
Serve as a reservoir for large volumes of food
Fragment food and mix it with gastric secretions
Empty gastric contents into the duodenum at a controlled rate
Name the 3 divisions of the stomach
Fundus
Body
Antrum
What are the four layers of the stomach, from the lumen outwards?
Mucosa
Submucosa
Muscularis
Serosa
In which layer of the stomach do the enteric neurons lie?
Submucosa
Name the three layers of the mucosa, from the lumen outwards
Epithelium
Lamina propria
Muscularis mucosae
When the stomach is empty, which 2 layers are folded and what are they called?
The mucosa and submucosa are folded into rugae
Name the 2 plexus found in the enteric nervous system.
Myenteric plexus
Submucosal plexus
Where does the enteric nervous system get input from?
Autonomic nervous system:
Parasympathetic
- vagus nerves
- pelvic nerves (sacral spinal cord)
Sympathetic postganglionic fibres
In which layer of the stomach/GI tract is the submucosal plexus found in?
Submucosa
In which layer of the stomach/GI tract is the myenteric plexus found?
Muscularis
Outline the 3 stages of receptive relaxation of the stomach
It is mediated by the vagus nerve (CN X)
CN X coordinates with the enteric nerve plexuses
Enteric neurons release (NO) and serotonin, which relax the smooth muscle of the stomach
What 2 chemicals do the enteric neurons release to mediate receptive relaxation?
Nitric oxide (NO)
Serotonin
Describe the peristaltic wave movements in the stomach
Begin in the body and move towards the antrum
What is retropulsion?
When strong peristaltic movements force food towards the antrum of the stomach, closing the pyloric sphincter. This then forces food backwards towards the body of the stomach
Define peristalsis
Waves of alternating contractions and relaxations of smooth muscle layers
Define segmentation
Cycles of contraction that mix contents but do not push them in any one direction.
Aims to mix gastric contents with secretions
What 2 types of electrical activity start contractions in the GI tract?
Slow waves
Action potentials
What is the basic electrical rhythm of the GI tract?
When smooth muscle cells undergo spontaneous cycles of depolarisation and repolarisation (spontaneous movement of Na+)
What is the rate of gastric slow waves?
3 per minute
Where is the rhythm of gastric slow waves generated?
In the pacemaker zone in the body of the stomach
What are slow waves?
Fluctuations in membrane potential spreading to adjacent sections of muscle
Describe the relationship between slow waves and action potentials
They do not elicit contractions, but coordinate them by controlling the appearance of action potentials.
They set the rate of contractions by controlling action potentials
Action potentials elicit ___
Muscle contraction
What determines the strength of a muscle contraction?
The number of action potentials appearing at the peak of a slow wave
Why is it important to regulate gastric emptying?
It allows for optimal digestion and absorption of ingested material
What is the pyloric sphincter?
A ring of smooth muscle and connective tissue between the gastric antrum and the duodenum
What are the 2 functions of the pyloric sphincter?
Allows regulated gastric emptying at a rate consistent with the ability for the duodenum to process it
To prevent regurgitation of duodenal contents into the stomach
What do sympathetic nerves do to the pyloric sphincter?
Increase constriction of it
fight or flight, ANS
What do vagal (parasympathetic) nerves do to the pyloric sphincter?
Can be excitatory or inhibitory
What hormones act on the pyloric sphincter?
Gastrin
Cholecystokinin (CCK)
Gastric inhibitory peptide (GIP)
Secretin
What do hormones do to the pyloric sphincter?
Constrict it
What 3 things decrease the rate of gastric emptying?
High fat
Low pH
Hypertonic solution
What can the duodenum and jejunum detect in chime?
Where are these receptors found?
Why is this useful?
Acidity
Osmotic pressure
Fats
Amino acids
Peptides
Mucosae of the duodenum and jejunum
The receptors cause the release of intestinal hormones, which inhibt antral contractions and/or elicit constricting the pyloric sphincter, decreasing the rate of gastric emptying
What are the four main components of gastric secretion?
Hydrochloric acid (HCl)
Mucus
Enzymes
Intrinsic factor
Where is gastric juice secreted from?
Gastric glands of the gastric mucosa
What 2 types of enzyme does the stomach secrete?
Pepsinogens
Gastric lipase
Name the 5 major cell types found in the mucosa of the stomach in gastric glands
Surface mucus cell
Mucous neck cell
Parietal cell
Chief cell
G cell
What does the parietal cell secrete
HCl
Intrinsic factor
Which type of cell secretes HCl and intrinsic factor?
Parietal cell
What do chief cells secrete?
Pepsinogen
What type of cell secretes pepsinogen?
Chief cells
What do G cells secrete?
Gastrin
What type of cell secretes gastrin?
G cell
Where are parietal cells (HCl, IF) found?
Proximal 80% of the stomach
What does the body of the stomach secrete?
Mucus
Pepsinogen
HCl
What does the antrum of the stomach secrete?
Mucus
Pepsinogen
Gastrin
Where are G cells found?
In the antrum of the stomach
Where are gastric hormones secreted from?
Gastric glands
What is the purpose of gastric hormones?
To control the secretion of gastric juice
What are the 3 gastric hormones?
Gastrin
Histamine
Somatostatin
Which of the 3 gastric hormones has a paracrine effect?
Histamine
Name the 3 gastric effects of gastrin
Stimulates secretion of acid, pepsinogen, mucus, HCO3-
Stimulation of gastric motility
Inhibition of gastric emptying
Name the 3 GI wide effects of gastrin
Stimulation of pancreatic enzyme and HCO3- secretion
Stimulation of insulin release
Stimulation of intestinal motility
Which cells secrete histamine?
Enterochromaffin-like (ECL) cells
Name the 2 gastric effects of histamine
Stimulation of acid secretion
Increased local blood flow to support the increase in metabolism
Which cells secrete somatostatin?
D cells
Where are D cells found?
Antrum and body of the stomach
What are the 2 gastric effects of somatostatin?
Inhibition of gastrin release
Inhibition of acid secretion
What is the average gastric luminal pH?
pH 1-2
How much HCl does the stomach secrete per day?
2-3 litres
Describe the shape and structure of a parietal cell
Truncated pyramidal shape, apex towards lumen
Invaginations of the luminal membrane (canaliculi), membranes lined with ion pumps
High mitochondrial content
Why is a parietal cell’s structure related to it’s function
High mitochondrial content = lots of ATP for ion pumps to push acid into stomach
Large surface area to secrete HCl
What are the 4 stages of acid secretion by the parietal cell?
- H+ and HCO3- are produced from CO2 and H2O
- H+ is pumped into lumen by H+/K+ ATPase pump
- HCO3- moves out of basolateral membrane in antiport with Cl-
- Cl- passively diffuses into the lumen via Cl- channel
Which enzyme converts CO2 and H2O into H2CO3 (carbonic acid)?
Carbonic anhydrase
What 3 things stimulate acid secretion?
Gastrin
Acetylcholine
Histamine
What 3 things inhibit acid secretion?
Somatostatin
Prostaglandins E2 and I2
Intestinal hormones
DIAGRAM:
Draw out the relationship between an ECL cell, parietal cell, with muscarinic, gastrin, and H2 receptors
Slide 44 of gastric motility lecture
What 5 receptors does a parietal cell have on its surface and what hormones act on those receptors?
Muscarinic receptor - ACh
H2 receptor - Histamine
Gastrin receptor - Gastrine
Somatostatin receptor - somatostain (inhibitory)
PGE2 receptor - prostaglandin E2
What is the name given to the H+/K+ ATPase pump on the parietal cell?
Proton pump
Which 2 cells does ACh act on?
ECL cell (increase histamine –> parietal cell)
Parietal cell (direct acid stimulation)
Give 3 functions of somatostatin
Inhibit gastrin (stops stimulation of ECL and parietal cell)
Inhibit the action of the parietal cell (slow production of HCl)
Inhibit the action of the ECL cell (inhibit histamine production –> less stimulation of parietal cell to produce HVl)
Give 3 symptoms and 3 complications of reflux oesophagitis
Heartburn
Regurgitation
Haematemesis
Oesophageal ulceration
Peptic stricture
Barrett’s oesophagus
What are prostaglandins?
A group of lipids derived from arachidonic acid
Mucus is a mixture of..
Glycoproteins and glycopolysaccharides
What is the gastric mucosal barrier?
Mucus and alkaline secretions entrapped within it
What converts pepsinogen to pepsin?
A low pH environment
Pepsin is used to accelerate…
Protein digestion
What is the oxyntic gland area?
The proximal 80% of the stomach that secretes HCl (parietal cells found here)
What is the pyloric gland area?
The antrum of the stomach that produces gastrin (G cells) near the pyloric sphincter
Which cell does PGE2 have its affect on?
Parietal cell - inhibits acid secretion
Local irritation of the mucosa stimulates….
What effect does this have?
The production of prostaglandins (PGs)
Increase production of mucus and HCO3-
Inhibit acid secretion
The stimulation of acid secretion also promotes mucus and HCO3- secretion
Intrinsic factor is a..
Glycoprotein
Which cells in the stomach secrete HCO3-?
Gastric surface epithelial cells
What 3 types of drugs are used to treat disorders of acid secretion?
Antacids and alginates
Histamine H2 receptor antagonists
Proton pump inhibitors
Describe how NSAIDs impair the renewal of the gastric mucosal barrier
NSAIDs inhibit the enzyme COX - COX converts arachidonic acid into prostaglandins
Prostaglandins inhibit acid production from parietal cells and stimulate gastric mucus production
If prostaglandins are inhibited, they impair the renewal of the gastric mucosal barrier –> less mucus production, more acid production
Give the names of 2 antacids
What is their MoA?
Aluminium hydroxide and magnesium hydroxide
Calcium carbonate and magnesium carbonate
They are a bases which buffer gastric acid, raising the gastric pH
Give the name of an alginate.
What is its MoA?
Sodium alginate, sodium bicarbonate, calcium carbonate
Anionic polysaccharides that form a viscous gel upon binding with water
Increases viscosity of the stomach contents and protects the oesophageal mucosa from acid reflux.
The gel floats on the surface of the stomach contents
Give the name of 2 histamine H2-receptor antagonists
What is their MoA?
Ranitidine
Cimetidine
Competitively inhibit histamine actions at H2-receptors
What does cimetidine inhibit?
P450 enzymes
Give the name of 2 proton pump inhibitors
What is their MoA?
Omeprazole
Lansoprazole
Irreversibly inhibit the H+/K+ ATPase pump.
Inactive at neutral pH
Accumulate in secretory canaliculi of parietal cells
Why does increasing the dose of a PPI disproportionally increase the plasma concentrations of the drug?
Given orally as enteric-coated capsules
Increasing the dose leads to a less acidic environment, which means more of the enteric coating survives through the stomach
More is then available
What is reflux oesophagitis?
Inflammation of the lower oesophagus produces by persistent episodes of reflux
What is the prescribed drug of choice for reflux oesophagitis?
PPIs
Where are the majority of peptic ulcers found?
Duodenum
Which artery is at risk of damage in a duodenal peptic ulcer?
Gastroduodenal artery
How can GI-adverse affects be reduced in NSAID prescriptions?
Alternative drug
Lowest dose, shortest duration
Avoid concomitant NSAIDs
Frequent review
Co-prescription of PPIs in increased risk patients
Helicobacter pylori is gram…..
Negative
Which bacteria is responsible for 80% of peptic ulcers?
H. pylori
Gram-negative bacterial infection
How does H. pylori produce peptic ulcers?
Produces and secretes urease, which breaks urea into CO2 and NH3 (imonia)
NH3 neutralises gastric acid
H pylori then penetrates mucus barrier, facilitating acid penetration to the epithelial cells causing damage = ulcer
What is achlorhydria/hypochlorhydria?
What is it caused by?
What are the consequences?
Absence/deficiency of hydrochloric acid in gastric juice
Iatrogenic (drugs)
Atrophy of gastric mucosa (age)
Impaired ability to digest and absorb iron + B vitamins
Increased vulnerability of GI tract to infection
