Stomach Flashcards
What layers of the stomach wall contain components of the enteric nervous system?
Submucosal plexus (submucosa) + Myenteric plexus (muscularis externa)
What glandular cells are present in the surface epithelium of the stomach mucosa?
Mucous neck cells -> mucus
Parietal cells -> acid
Chief cells -> enzymes
Endocrine cells -> gastrin
What are the functions of gastrin? What stimulates and inhibits gastrin secretion?
Endocrine secretion
Polypeptide hormone which stimulates acid, enzyme, and intrinsic factor secretion
Amplified by histamine
Stimulated by ACh & peptides (presence of digested proteins)
Inhibited by low pH (empty stomach; gastrin inhibited so stomach is not digested)
What are the functions of acetyl choline? What stimulates and inhibits acetyl choline secretion?
Neurotransmitter (post-ganglionic parasympathetic) which acts on mACh receptors on parietal cells
Stimulates acid and enzyme secretion (parietal & chief cells??)
Amplified by histamine
Stimulated by stomach distension (food filling stomach)
What are the functions of histamine? What stimulates and inhibits histamine secretion?
Chemical messenger produced by mast cells (paracrine secretion)
Binds to H2 receptors on the surface of parietal cells (less common histamine receptor)
Stimulates acid and enzyme secretion by c.AMP (chief & parietal cells????)
Outline how parietal cells secrete acid into the stomach lumen.
Water split into H+ & OH- ions by mitochondria (oxidative phosphorylation)
H+ ions pumped into the canaliculi by active transport by proton pump (inhibited by proton pump inhibitors) -> then diffuse into stomach lumen
OH- ions react with CO2 to produce HCO3- which diffuses into the bloodstream (alkaline tide which travels in the bloodstream to neutralise acid after the stomach?????)
What are the different stages of digestion in the stomach?
CEPHALIC PHASE = detection/ingestion of food e.g. smell, taste, sight of food, chewing causes ACh & histamine to stimulate parietal cells
GASTRIC PHASE =
- alkaline saliva buffers stomach acid (increase in pH) -> gastrin disinhibited
- stomach distends -> ACh released
- peptides produced by initial digestion -> gastrin release
- histamine amplifies gastrin & ACh actions
INTESTINAL PHASE =
- stomach begins to empty and chyme enters the duodenum -> stimulates release of secretin, somatostatin, cholecystokinin, etc. which antagonise gastrin
- accumulation of acid in stomach inhibits gastrin
How is the stomach wall protected from digestion?
H+ ions slowly diffuse into the unstirred mucus layer above epithelium and react with HCO3- secreted by surface epithelial cells and basic groups on mucus
Prostaglandins & most factors stimulating acid secretions stimulate mucus production?
note: when mucus layer is disrupted it “self-heals” to form an uninterrupted impermeable seal
What factors disrupt the mucus layer?
- alcohol (causes alcoholic gastritis -> temporary ulcers unless drinking continues)
- Helicobacter pylori (most common cause of peptic ulcers)
- Non-steroidal anti-inflammatory drugs (NSAIDs): inhibit prostaglandins e.g. aspirin converted to non-ionised form by acid -> passes into cells -> re-ionises -> kills cells -> peptic ulcers
note: if NSAIDs must be taken longterm, give PPIs as well to reduce acid secretion
What are the clinical features of peptic ulcers?
Worst at night (some gastric secretions remain in stomach which directly contact ulcers)
Helicobacter pylori implicated (NSAIDs increase risk of ulcers)
Treatment:
- H2 receptor antagonists e.g. cimetidine (prevents amplification of gastrin & ACh)
- PPIs e.g. omeprazole
- antibiotics (to eliminate Helicobacter pylori): clarithromycin/metranidazole + amoxicillin (antibiotics absorbed by mucus layer in stomach)
note: peptic ulcer disease includes gastric ulceration and duodenal ulceration
note: gastritis (mucosal inflammation) causes ulceration (mucosal breakdown), therefore ulcers always present with gastritis UNLESS caused by NSAIDs
How does the stomach move during digestion?
Receptive relaxation (swallowing stimulates vagus nerve): prevents pressure from rising (limits reflux) and allows us to consume large meals
Waves of peristalsis spread towards antrum (accelerates as lumen narrows)
Peristalsis overtakes larger lumps of food, which are driven back into the fundus (can continue to be digested)
Small squirt ejected, peristalsis reaches pylorus and shuts it
How is gastric emptying controlled?
Volume of each squirt affected by the rate of acceleration of peristaltic waves & intestinal hormones
Gastric emptying slowed by: fat, low pH & hypertonicity in the duodenum (reduced rate of digestion/absorption in the small intestine)
How do the different areas of the stomach vary by secretion?
Upper 2/3 of stomach: secretion of HCl & pepsinogen (parietal & chief cells respectively)
Lower 1/3 of stomach: secretion of mucus & gastrin (mucous neck cells & endocrine cells respectively)
What sphincters are present in the stomach?
Gastro-oesophageal junction
Pyloric sphincter
Define dyspepsia.
“Indigestion” = disordered digestion, usually applied to pain or discomfort in the lower chest or upper abdomen after eating, and sometimes accompanied by nausea, vomiting, or a feeling of unease or fullness after eating
May lead to early satiety (cannot finish a meal)
Akin to IBS of the upper gut
How does Helicobacter pylori cause peptic ulcers?
Protection from stomach acid:
- burrows into mucus bicarbonate layer where it is protected from stomach acid
- produces urease -> breaks down urea to produce an ammonia cloud -> neutralises stomach acid
Pathogenicity:
- produces cytotoxins which cause inflammation (gastritis) and eventually destroy parietal cells, causing achlorhydria (low acid in stomach)
- produces an antigen which can cause lymphoma
Colonisation:
- antrum (duodenal ulcers) - resultant increased gastrin secretion stimulates increased acid production by parietal cells -> damage to the duodenal cap & metaplasia of gastric mucosa to duodenal tissue (this is why H. pylori can cause duodenal ulcers despite only colonising gastric mucosa)
- antrum & body (largely asymptomatic)
- body (gastric ulcers + gastric cancer)
Aetiology:
Common in current elderly population but reducing in abundance in the UK (commonly found in Pacific Rim countries, causing increased incidence of gastric cancer in Japan, Colombia, Iran)
Outline the steps in gastric cancer development.
Helicobacter pylori causes chronic, active non-atrophic gastritis
Causes multi-focal atrophy -> intestinal metaplasia -> dysplasia -> carcinoma
H. pylori virulence factors (depends on strain) and host gene polymorphisms influence how likely gastric cancer formation is
+ dietary factors
+ environmental factors
How is the stomach involved in the protection against infection? Give some examples of bacteria and viruses which are resistant to this mechanism.
Gastric acid kills majority of bacteria and viruses
Bacteria:
- Mycobacterium tuberculosis
- Helicobacter pylori
Viruses:
- Epstein-Barr
- Poliovirus
- Coxsackie virus
- Echo virus
- Ebola virus
- Rhinovirus
What can cause reduced stomach acid, and what is this called? What complications can this cause?
Achlorhydria = absence of HCl in stomach
Pernicious anaemia (vit. B12 deficiency)
H2 antagonists e.g. cimetidine
PPIs e.g. omeprazole
More vulnerable to shigellosis, cholera, Salmonella, Clostridium difficile
Give some examples of organisms resistant to gastric acid.
Mycobacterium tuberculosis (acid & alcohol fast bacterium)
Helicobacter pylori
Enteroviruses:
- Hep. A
- Polio
- Coxsackie
What area of the stomach is prone to ulceration?
Lesser curve
What are the functions of the stomach?
Sterilisation/disinfection
Digestion/physical disruption
How does gastrin production vary during digestion?
Increased during gastric phase - food entering stomach can start to be digested
Decreased during intestinal phase - inhibited by secretin, somatostatin, cholecystokinin (CCK)
