Gastric Motility/Secretion + Drugs to treat disorders Flashcards
What are the functions of the stomach?
Sally’s Stomach Makes Cool Sounds Post Risotto
Secretes HCl
Secretes IF
Minimises Ingested bacteria
Chyme (by mixing
Storage of food
Partial Digestion
Regulates stomach emptying
What are the functions of the pyloric sphincter?
Prevents regurgitation
Regulates emptying into duodenum
What is receptive relaxation?
Empty stomach:
Stomach contracts, mucosa & submucosa highly folded into rugae
After swallowing:
Smooth muscle in orad region relaxes allowing expansion of the stomach up to 1.5L
What is the term used to describe the function of the stomach allowing it to expand to accomodate food after swallowing?
Receptive Relaxation
Describe how stomach motility is innervated?
Autonomic NS
Parasymp. branch - increases motility, opens sphincters
Symp. branch - decr motility, constricts sphincters
+ INTRINSIC innervation from ENTERIC NS: MYENTERIC PLEXUS controls motility
What are the two components of the Enteric nervous system, and what do they control?
Myenteric Plexus - Controls Motility
Submucosal Plexus - Controls Secretion
What are the two movements in gastric motility which move food through the gut tube?
Peristalsis and Segmentation
Describe Peristalsis
Waves of alternating contractions of circular and longitudinal muscle that PUSHES the bolus through the GI tract.
What is Retropulsion?
When peristaltic contractions force the antrum contents into the body of the stomach
What is the term used to describe the process whereby food is moved from the antrum to the body of the stomach due to peristalsis?
Retropulsion
What is Segmentation?
Cycles of contractions that MIX contents of the stomach. Churns and fragments the bolus of food, mixes the contents of the stomach with intestinal secretions.
What is the name used to describe the cycles of contractions that MIX contents of the stomach. Churns and fragments the bolus of food and mixes the contents of the stomach with intestinal secretions.
Segmentation
What two main electrophysiological processes cause gastric motility?
Slow Waves and Action Potentials
Describe Slow Waves
Fluctuations in membrane potential spreading to adjacent smooth muscle cells via gap junctions. Approx 3/minute.
Rhythm generated in the pacemaker zone
What is the name used to describe fluctuations in membrane potential spreading to adjacent smooth muscle cells via gap junctions?
Slow waves
How do action potentials cause smooth muscle contraction in the stomach?
NTs/Hormones depolarise the membrane, increase the amplitude of the slow waves. If the peak of the slow wave reaches the threshold, action potential occurs and elicits muscle contraction.
What does the stomach secrete?
Gastrin
Histamine
Somatostatin
Intrinsic Factor
Pepsin
HCl
Mucus
Where is Gastrin secreted and what are its actions?
G-Cells
Stimulates acid secretion, pepsinogen secretion, HCO3- release and mucus secretion.
Stimulates gastric motility and inhibits emptying.
Where is Histamine released and what are its actions?
Enterochromaffin like cells (ECL cells)
Actions- Stimulate acid secretion and increase local blood flow
Where is Somatostatin released and what are its actions?
D-Cells
Actions: Inhibits gastrin release and acid secretion
Where is Pepsin released and what are its actions?
Chief Cells
Actions - Accelerates protein digestion
How is pepsin secreted?
Secreted from Chief cells as pepsinogen, cleaved by HCl to form active pepsin.
- Activated by low pH in lumen of the stomach.
Where is Intrinsic Factor secreted?
What are its actions?
Parietal Cells
Actions: Forms a complex with B12 so it can be absorbed in the ileum. B12 is essential for RBC maturation. def = pernicious anaemia
Why is intrinsic factor important?
It is needed for B12 absorption - forms a complex so B12 can be absorbed in the ileum.
Vital for RBC maturation, deficiency = pernicious anaemia
Where is HCl secreted?
What are its actions?
Parietal Cells
Cause a low pH (2) for optimum conditions for pepsin & natural gut flora, protection against foreign bacteria
Where is mucus secreted?
What are its functions?
Mucous cells
Protection for the stomach wall against acid, it is viscous so will not mix with stomach contents.
How are parietal cells specialised to carry out their function?
Truncated pyramid shape with apex facing the stomach lumen
Invaginations of membrane to form canaliculi lined with ion pumps
High mitochondrial content.
How is HCl formed in the parietal cell?
- Carbonic Anhydrase catalyses the reaction between carbon dioxide and water to form bicarbonate and H+ ions.
- H+ ions exit the cell across the canilicular membrane via H+/K+-ATPase pump which moves H+ions out of the cell and K+ into the cell against its concentration gradient via energy from ATP hydrolysis.
- HCO3- moves across the basolateral membrane of the parietal cell via antiport with CL- which moves through the cell and diffuses passively into the lumen.
- Cl- & H+ join to form HCl in the lumen.
How does Cl- enter the parietal cell?
Enters via the basolateral membrane in an antiport transporter in exchange with HCO3-
How does HCO3- leave the parietal cell?
Via an antiport transporter with Cl- through the basolateral membrane
How do H+ ions enter the lumen of the stomach?
Via a H+/K+-ATPase transporter in the luminal membrane which transports H+ out of the cell and K+ into the cell against the concentration gradient via energy from the hydrolysis of ATP.
Which enzyme catalyses the reaction between carbon dioxide and water in the parietal cell?
Carbonic Anhydrase
What is acid secretion stimulated by?
Acetylcholine acting on muscarinic receptors
Histamine
Gastrin
What is acid secretion inhibited by?
Somatostatin
Prostaglandins,
Intestinal Hormones
What are the two regions of the stomach?
ORAD and CAUDAD
What attaches to the greater curve of the stomach?
The greater omentum
What attaches to the lesser curve of the stomach?
Lesser omentum
What does mucus consist of?
Glycoproteins & glycopolysaccharides
What are the functions of the gastric mucosal barrier?
- Protects stomach against acid, proteolytic enzymes and mechanical damage
What are the consequences of the gastric mucosal barrier not being renewed sufficiently?
Short- term = Gastritis
Longer-term = Ulcers
What will happen if there is local irritation to the mucus?
Causes release of prostaglandins which will increase the production of mucus and HCO3-. Inhibit acid secretion and promote the healing of local damage
Why do NSAIDs have a detrimental effect on the stomach lining?
NSAIDs inhibit the COX enzyme involved in producing prostaglandins from arachadonic acid.
What is an Antacid?
A substance, generally a base which counteracts stomach acidity.
Acts by buffering stomach acid, raising gastric pH
E.g. Calcium carbonate + magnesium carbonate (Rennie’s)
Aluminium hydroxide & Magnesium hydroxide
SE: Diarrhoea, Al salts can cause constipation
What is an Alginate?
Anionic polysaccharides, form a viscous gel upon binding water
Often combined with antacids for use in reflux oesophagitis
Viscous gel raft floats on the surface of the stomach contents, reducing symptoms of reflux
E.g. Sodium alginate, sodium bicarbonate calcium carbonate (Gaviscon)
How do Histamine (H2) receptor antagonists work to treat disorders of acid secretion?
Competitively inhibit Histamine at H2 receptors on parietal cell, blocking the receptor but not activating.
E.g. Cimetidine, Ranitidine
SE:Weak inhibitor of cytochrome P450 enzymes
How do Proton pump inhibitors work to treat disorders of acid secretion?
- More effective than H2 antagonists which only block acid secretion from H2 receptors
- Target the molecule secreting the acid stimulated from any source
- Irreversibly inhibit the H+/K+-ATPase pump (terminal step in acid secretory pathway)
- Accumulate in secretory canaliculi of parietal cells, activated in acidic environment (very specific site of action)
How are proton pump inhibitors administered and how do they reach their site of action?
- Degrade rapidly at low pH so administered as a pro-drug (lipophilic) covered in enteric granules
- Absorbed across wall of the small intestine and enter circulation, enter the parietal cell via the basolateral membrane
- Moves across the cell to the canalicular membrane into the lumen, activated by low pH, binds to the proton pump and irreversibly inactivates.
- More pumps must be made via protein synthesis to restore acid secretion
E.g. Omeprazole
Name acid secretion disorders which would require drug treatment
- Reflux oesophagitis
- GORD
- Peptic ulcers
Name 2 causes for peptic ulcers
- Long-term use of NSAIDs
- Helicobacter Pylori
What is reflux oesophagitis?
How would this be treated?
- Inflammation of the lower oesophagus produced by persistent episodes of reflux.
- Arises from GORD - liquid contents of stomach regurgitating into oesophagus
- Symptoms: Heartburn, Haematemesis, regurgitation
Treatment: OTC Antacids/Alginates, H2 receptor antagonists, PPIs are prescribed drug of choice for all but mild cases.
How can long-term use of NSAIDs cause peptic ulcers?
- NSAIDs impair renewal of the gastric mucosal barrier
- NSAIDs inhibit COX enzyme which forms Prostaglandins from arachadonic acid
- Prostaglandins usually stimulate gastric mucus and bicarbonate production and inhibit gastric acid secretion.
- Impaired protection can result in erosion and the causing/worsening of ulcers
How does H.Pylori bacteria cause peptic ulcers?
- Spiral shaped gram neg. bacterium
- Damages stomach and duodenal tissue
- Produces and secretes urease which breaks down urea into CO2 and NH3 (ammonia)
- NH3 neutralises gastric acid, enables bacteria to burrow through mucosal barrier
- H.Pylori burrows through barrier and facilitates acid production
- NH3, bacteria & excess acid damage the epithelial cells
How would you treat peptic ulcers caused by H.Pylori?
- Combination of antibiotics & PPI
- Eradication of H.Pylori = long term remission of ulcers
What causes under-secretion of gastric acid & what are the consequences?
- Achlorhydria/Hypochlorydria
- Abscense of HCl in gastric juice
- Can be iatrogenic - caused by prescribed drugs or atrophy of gastric mucosa (older adults)
- Consequences - impaired ability to digest and absorb iron and B vitamins Also increased vulnerability to GI bacterial infections
