GI Flashcards
What are the main functions of the GI system?
-stomach secretes 2.5l of gastric juice (water + acid) per day. -
mainly pro-enzymes (e.g. pepsinogen), HCL, intrinsic factor
-gastric cells also produce;
-mucus (cytoprotective)
-consists of mucus gel in to which HCO3- is secreted (within gel
matrix, HCO3- neutralises acid diffusing from lumen = creates pH
gradient + gastric mucosa is maintained at neutral pH
-prostaglandins E2 + I2 are synthesised by gastric mucosa (exert
cytoprotective action, by stimulating secretion of mucus +
bicarbonate + by increasing mucosal blood flow)
-bicarbonate (trapped in mucus, protective barrier)
-bicarbonate is a buffer (maintains pH) = prevents cells of stomach
being destroyed by HCL
Disturbance of secretory/protective mechanisms can lead to GORD + peptic ulcers
How is bicarbonate formed?
H2O + CO2 = carbonic acid (H2CO3-)
Carbonic acid dissolves to form protons + bicarbonate (HCO3-)
What are the layers of the stomach lining?
Preepithelial
- mucus
- bicarbonate
- surface active phospholipids
Epithelial
- cellular resistance
- restitution
- growth factors, prostaglandins
- cell proliferation
Supepithelial
- blood flow
- leukocyte
What is needed to bind to receptors of the parietal cells to initiate HCL production process?
Histamine from ECL cell =stimulates production of protons
ACH from vagus nerve = stimulates production of HCL
Gastrin
What is GERD?
Gastro-oesophageal reflux disease
-normally sphincters keep oesophagus protected from chloric acid. If
these sphincters relax, causes chloric acid to reach oesophagus +
erodes epithelium (this doesn’t have protective mucus from chloric
acid)
-if acid enters oesophagus, burning sensations felt ‘heartburn’
-if there is continuous presence of acid in lower oesophagus,
oesophagitis may occur
What is PUD?
Peptic ulcer disease
-in duedenum, excessive chloric acid or weakening of mucosa can lead
to erosion of epithelium, with formation of an ulcer
-associated with abdo pain + acid reflux
-over 95% peptic ulcers caused by NSAIDs
What is the drug treatment for GORD + PUD?
- antacids
- alginates
- anti-cholinergics
- drugs to reduce acid secretion
- H2-receptor antagonists
- proton pump inhibitors
- drugs that protect the mucosa
- bismuth chelate
- sucralfate
- prostaglandin analogues
What are antacids?
Chemicals that counteract acid in stomach
-weak bases that readily combine with HCL + neutralise it
-by neutralising gastric acid -also blocks conversion of pepsinogen into
pepsin = don’t digest proteins
-act on lumen
Examples;
-sodium bicarbonate (can result in secondary rise in acid secretion, risk
of alkalosis long term)
-aluminium hydroxide (slower action, can cause constipation)
-magnesium carbonate (rapid action, can cause diarrhoea)
-magaldrate (combines aluminium + magnesium-counterbalances side
effects)
-sodium alginate (e.g. gaviscon)
Side effects;
-belching -due to formation of CO2 when carbonate preparations react
with stomach acid
-magnesium =laxatives, aluminium =constipation
-high sodium should be avoided in renal + cardiac impairment
What are alginates?
Substances that float on surface of stomach contents + provide mechanical barrier against reflux events
What drugs can be used to reduce acid secretion?
H2-receptor antagonists
-e.g. cimetidine, ranitidine
-block the histamine receptor on the gastric parietal cells + reduce
gastric acid + pepsin secretion by 60%
Side effects;
-cimetidine inhibits P450 drug-metabolising enzymes - inhibits
metabolism of warfarin = stays in body long = increased risk of
haemorrhagic stroke
-diarrhoea
-headaches, dizziness + tiredness
-confusion in elderly
Proton pump inhibitors
- e.g. Omeprazole, lansoprazole (inactive at neutral pH)
- inhibit proton pump, preventing pumping or release of gastric acid
- decreases acid secretion by up to 95% for up to 48h.
Side effects; -may increase risk of infection in GI tract as they reduce the acid secretion -can mask symptoms of gastric cancer -dry mouth -GI disturbances -Omeprazole induces P450 enzymes + can interact with warfarin + phenytoin
What drugs protect the mucosa?
They are cytoprotective + form barrier over surface of ulcer. Allows secretion of HCO3- to re-establish pH gradient
Bismuth chelate
-protects ulcer crater + allows healing
Sucralfate
-in an acid environment (pH <4) it polymerises + forms a sticky gel with mucus that adheres to ulcer site, forming barrier
Side effects;
-may bind with other drugs + interfere with absorption e.g. digoxin,
antibiotics
Prostaglandin analogues
-e.g. misoprostol
-inhibits acid secretion in stomach + aids secretion of mucus
-NSAIDs inhibit formation of prostaglandin E2 (needed for production of
mucosal lining) misoprostol used to prevent ulcers in those who old but
need NSAIDs
Side effects;
- diarrhoea
- uterine contractions (avoid in pregnancy)
- post menopausal bleeding
- cramps + pain
How do anti-cholinergics work?
- e.g. pirenzepine
- blocks gastric acid secretions
- musclarinic M1 ACh receptor antagonists
What is a peptic ulcer and where can you get them?
A peptic ulcer is a sore that develops in lower lining of oesophagus or various parts of small intestine or stomach. It is any ulcer in an area which the mucosa is bathed in the hydrochloric acid + pepsin of gastric juice.
- peptic ulcer in oesophagus = oesophageal ulcer
- peptic ulcer in stomach = gastric ulcer
- ulcer in first part of small intestine (deudenum) = deudenum ulcer
What bacteria causes most stomach acids?
Helicobacter pylori (H pylori)
It can enter through contaminated food/water. Once inside they lodge in mucus layer of stomach or deudenum. As they grow they damage the mucus layer, enabling stomach acid to reach stomach or deudenum lining = forms an ulcer.
Infection may result in chronic hypergastrinaemia, which stimulates acid production + causes ulcers.
How do you detect presence of H pylori?
Urea breath test. Urea is ingested, H pylori possesses urease (enzyme which breaks down urea + produces CO2) this can be detected on breath. Test also used to see if all bacteria’s gone.
