S4: stomach physiology & pathology Flashcards
Describe the functions of the stomach
Storage facility
Starts digestion of proteins
A little bit of carb and fat digestion (salivary amylase & lingual lipase)
Disinfect – innate defence (hostile to any microorganisms)
Describe the anatomy of the stomach
3 parts – fundus, body & antrum
2 sphincters – lower oesophageal sphincter & pyloric sphincter
Stomach lining (simple columnar) has rugae so it can expand without increasing pressure too much
Describe the lower oesophageal sphincter
Intrinsic smooth muscle & right crus of diaphragm (loops around the sphincter & acts to close it when intra-abdominal pressure increases)
Can stop reflux – acute angle of entry also helps
Describe receptive relaxation
Peristalsis causes reflex relaxation of proximal stomach = RECEPTIVE RELAXATION
Fundus distends
Stomach can fill without significant rise in pressure
Describe the muscles of the stomach
3 layers – oblique, circular & longitudinal
Cause forceful contractions to mix and grind contents
Thinner walled proximally and more muscular distally – can be dilated proximally & is narrowed distally
Describe the surface of the stomach
Surface mucous cells – produce mucus which forms a protective layer to protect epithelium from the acidic conditions
Gastric pits – invaginations of the epithelium
-in the pits, there are gastric glands which have 3 types of cells: parietal cells, chief cells & G cells
Describe the mechanisms that exist to protect the stomach epithelia against an acidic environment
Stomach is made of protein – needs to protect itself from the proteases
1) High turnover of epithelial cells – if one gets damaged, replaced quickly to keep barrier intact
2) Production of alkaline mucus layer
3) Prostaglandins – increase mucosal blood flow, which supports the mucus layer
Describe the different states of the parietal cell
Resting phase – tubulovesicles (contain proton pumps, lack K+ permeability) and apical membrane (contains K+ channels) are not in contact
Stimulated phase – canaliculi cause the tubulovesicles and apical membrane to be in contact – H+ can be secreted in exchange for K+
What stimulates acid production?
1) Sensory triggers – smell, taste & sight (CEPHALIC PHASE – 30% OF HCL)
2) Gastric triggers – stretch & presence of amino acids + small peptides (GASTRIC PHASE – 60% OF HCL)
3) Intestinal triggers – chyme in duodenum -> presence of partial digested proteins (INTESTINAL PHASE – 10% OF HCL)
List the three ways a parietal cell is stimulated
1) Gastrin receptors
2) Histamine receptors
3) Muscarinic receptors
Describe gastrin stimulation of parietal cells
Peptides in stomach lumen stimulate G cell
G cell produces gastrin
Gastrin binds to CCK receptor on parietal cell
Describe vagal stimulation of parietal cells
Can stimulate G cells to produce gastrin -> binds to CCK receptor
GRP and ACh binds to receptors on G cell
Also directly binds to muscarinic receptors on parietal cells
Describe histamine stimulation of parietal cells
ECL (entero-chromaffin like cell) – produces histamine which goes on to bind to H2 receptor on parietal cell
ECL has muscarinic & CCK receptor which stimulates it to produce histamine
Describe how acid secretion is inhibited
Drop in pH detected by D cell
D cell produces somatostatin
Inhibits secretion of gastrin
How is HCl produced in the parietal cell?
H20 and CO2 combine to produce H2CO3 (catalysed by carbonic anhydrase)
Carbonic acid then spontaneously dissociates into H+ and HCO3-
H+ transported into stomach lumen by the H+/K+/ATPase
HCO3- is transported out of the cell by the anion exchanger (Cl- comes in; this is transported into the stomach lumen via chloride channel)
H+ and Cl- combine in lumen to produce HCl
Alkaline tide – transient rise in blood pH due to bicarbonate
Define dyspepsia
Complex of upper GI tract symptoms which are typically present for four or more weeks
Include upper abdominal discomfort, heartburn, acid reflux, nausea and/or vomiting
Describe gastro-oesophageal reflex disease (GORD)
Reflux of stomach contents into oesophagus
Symptoms: heart burn, acidic taste (potential dental erosion), cough & asymptomatic
Risk factors: obesity, pregnancy, LOS dysfunction, hiatus hernia & delayed gastric emptying
What is a hiatus hernia?
LOS herniates through diaphragm into the thorax – loss of crural muscles
Describe complications of GORD
Oesophagitis Ulceration Haemorrhage Strictures (scar tissue) Metaplastic changes
What is Barrett’s oesophagus?
Reversible change of stratified squamous epithelia to columnar epithelia due to repeated exposure to gastric contents
Columnar -> increases risk of dysplasia -> adenocarcinoma
Describe management of GORD
Lifestyle – weight loss, avoiding trigger foods, eat smaller meals, don’t eat then sleep, decrease alcohol and caffeine & stop smoking
Drugs – proton pump inhibitors (symptom relief & healing inflammation), H2 receptor antagonists
Surgery – fundoplication (fundus is wrapped around the lower oesophagus)
What is gastritis?
Inflammation of the stomach mucosa
Symptoms: pain, nausea, vomiting, haemorrhage
Acute causes: NSAIDS, alcohol, chemotherapy, bile reflux
Chronic causes: infection with H-pylori, autoimmune
Describe the pathological changes in acute and chronic gastritis
Acute 1) Epithelial damage 2) Some epithelial hyperplasia 3) Vasodilation 4) Neutrophil response – infiltrate the lamina propria Chronic 1) Lymphocyte response 2) Glandular atrophy 3) Fibrotic changes 4) Metaplastic changes
Describe how an autoimmune response causes chronic gastritis
Antibodies to parietal cells
Lose parietal cells -> decreased acid production & decreased intrinsic factor
Symptoms – megaloblastic anaemia, neurological symptoms, anorexia & glossitis
Decreased vitamin B12 absorption (can’t be produced in the body)
Describe H-pylori
Helix shape, gram negative, faeco-oral or oral-oral transmission
Microaerophilic – needs some O2 – stomach has the correct O2
Features: flagellae, chemotaxis & adhesins
Contain urease – converts urea + H20 -> CO2 + ammonia (base); produces a local environment where it is less acidic
Describe how H-pylori causes chronic gastritis
Cytotoxin associated gene A – causes inflammation (increases risk of stomach cancer)
Vacuolating toxin A – toxic to stomach epithelium
Ammonia causes damage to stomach epithelium (urease reaction)
Produces mucinase (damage mucus layer), protease & lipase
Describe H-pylori interactions in different parts of the stomach
Antrum – causes over-activity of G cells -> stimulates parietal cells
-too much acid produced & makes chyme leaving the stomach more acidic
Body/fundus – atrophy of the parietal cells
-precursor to dysplastic changes
How is H-pylori diagnosed?
1) Urea breath test – get patients to ingest enriched C13 urea – if present, should breathe out C13 CO2
2) Stool antigen test
3) Endoscopy with biopsy
How is H-pylori eradicated?
Proton pump inhibitor & 2x antibiotics
Side effects: diarrhoea & nausea
Do for 7 days – check success with urea breath test (can be increased to 14 days)
Describe peptic ulcer disease
Defect in the gastric/duodenal mucosa that extends through the muscularis mucosa
Most common place: first part of duodenum & lesser curve of stomach
Gastric ulcers – 70% have H-pylori
Duodenal ulcers – 95-100% have H-pylori
List risk factors for peptic ulcer disease
H-pylori
NSAIDS – decreased prostaglandin synthesis
Smoking
Massive physiological stress
Describe the difference between acute and chronic ulcers
Acute – develop as part of gastritis
Chronic – occur at mucosal junctions
Describe the morphology of PUD
Base of ulcer is made of necrotic & granulation tissue, when heals it is replaced by scar tissue (muscularis externa)
Can narrow the stomach lumen – pyloric stenosis (causes extensive vomiting) if near sphincter
Peritonitis (inflammation of the peritoneal cavity) can occur if ulcer extends all the way through the gut wall -> gut contents can leak out
Describe what happens if an ulcer erodes into a blood vessel
Malaena – black stools
Upper GI bleed -> Haem component is oxidised by passing through the GI tract
If gastro-duodenal artery (most likely)/splenic artery (very rare) is affected – massive haemorrhage of blood & haematemesis (vomiting of blood)
List symptoms of PUD
Epigastric pain – back pain following meals
Pain at night – duodenal ulcers
Resulting from bleeding – haematemesis & malaena
Early satiety
Weight loss
Describe the management of PUD
No active bleeding:
1) H-pylori positive: eradicate H-pylori – promotes ulcer healing
2) H-pylori negative: stop exacerbating medications
Active bleeding:
Adrenaline is injected + cautery +/- clip application
If ulcer is perforated will need to have open surgery
After intervention, test for H-pylori (if present, eradicate)
