Session 4: Pathophysiology of Gastric Disease Flashcards
Definition of dyspepsia.
Used to describe a complex of upper GI tract symptoms which are typically present for four or more weeks. Including upper abdo pain or discomfort, heartburn, acid reflux, nausea and/or vomiting.
Give examples of common gastric disorders.
GORD Acute and chronic gastritis Peptic ulcer disease
What is GORD?
Gastro-oesophageal reflux disease.
Symptoms of GORD.
Chest pain Acid taste in mouth Cough
Consequences of GORD.
Nothing Oesophagitis Strictures Barrett’s oesophagus
Triggers of GORD.
Obesity Pregnancy Hiatus hernia LOS dysfunction Delayed gastric emptying
Explain the properties of LOS preventing GORD.
Muscular elements tightening the sphincter The right crus of the diaphragm also tightens it. Angle of entry is oblique Intra-abdominal pressure is lower than thoracic pressure.
Explain hiatal hernias and its role in GORD.
The neck of the stomach herniates into the thoracic cavity. This causes a higher risk of developing GORD. The basal tone of the sphincter gets reduced and the pressure in that region is higher than if it were to be in the abdomen.
Treatment of GORD.
Lifestyle modifications
Antacids
H2 antagonists like cimetidine
PPIs like omeprazole
Surgery (rare)
Briefly explain acute gastritis.
Difficult to define but basically a symptom complex
Inflammation of the stomach mucosa where cell injury and regeneration is present along with neutrophils.
What is the difference between gastritis and gastropathy?
In gastropathy inflammatory cells are rare or absent but have similar presentation to gastritis.
What is the symptom complex of gastritis?
Pain
Nausea
Vomiting
Bleeding
Give causes of acute gastritis.
Heavy use of NSAIDs
Lots of alcohol
Chemotherapy
Bile reflux
Acute mucosal erosion or haemorrhage
Portal hypertension
Reduced mucin and bicarbonate secretion
Hypoxaemia and decreased O2 delivery
Ingestion of harsh chemicals
Helicobacter pylori
Explain how NSAIDs can cause acute gastritis.
Inhibition of cyclooxygenase leads to inhibition of the synthesis of prostaglandin E2. Prostaglandin is a protective factor which maintains the mucosal barrier and stimulates secretion of HCO3-.
Gastric injury is the greatest in non-selective NSAIDs like aspirin, ibuprofen, naproxen.
Causes of chronic gastritis.
Helicobacter pylori (85%)
Autoimmune gastritis (10%)
Chronic NSAIDs
Chronic alcohol abuse
Reflux of bile
Symptoms of H. pylori chronic gastritis.
Asymptomatic or similar to acute gastritis.
Complications of H. pylori chronic gastritis.
Peptic ulcers
Adenocarcinoma
MALT lymphoma
Explain the pathogenesis of H. pylori in chronic gastritis.
A gram-negative bacterium spread oral to oral or faecal to oral.
It can colonise in the gastric mucus because of urease.
Urease converts urea to NH3 and NH3 alkalinise the local environment so the bacteria can survive.
The bacteria then binds to the gastric epithelium via adhesins damaging the epithelium.
NH3 is also in balance with NH4+ and NH4+ is also damaging to the lining of the stomach.
H. pylori also release cytotoxins which cause direct epithelial injury.
Where do the H. pylori usually colonise?
In the antrum
Explain the consequence of H. pylori colonising in the antrum.
Increased gastrin secretion or decreased D cell activity which release somatostatin.
This increases parietal cell acid secretion.
This leads to duodenal epithelial metaplasia and colonisation of duodenum leading to duodenal ulceration.
The H. pylori can also inhibit gastric bicarbonate transported by ammonium.
Why can H. pylori chronic gastritis be asymptomatic?
If it colonise predominantly in the body of the stomach you won’t get symptoms.
Consequences of H. pylori colonisation of the body of the stomach.
Atrophic effect leading to gastric ulcers and intestinal metaplasia.
This can lead to dysplasia and cancer.
Tests to diagnose H. pylori chronic gastritis.
Urea breath test
Stool antigen test
Antibodies
Treatment of H. pylori.
PPIs like omeprazole
Antibiotics; a cocktail of amoxicillin, clarithromycin and metronidazole.
Pathogenesis of autoimmune gastritis.
Usually spares the antrum but induces hypergastrinaemia.
Antibodies to parietal cells and intrinsic factor can be detected in serum.
Loss of parietal cells as well as chief cells.
Leads to reduced serum pepsinogen.
There is also antral endocrine hyperplasia.
Vitamin B12 deficiency
Reduced levels of acid and intrinsic factor secretion.
Usually found in the body of the stomach.
Complications of autoimmune gastritis.
Atrophy
Pernicious anaemia
Adenocarcinoma
Carcinoid tumour
Complications of chronic gastritis.
Peptic ulcer disease
Mucosal atrophy and intestinal metaplasia
Dysplasia
Definition of peptic ulcer disease.
A defect in gastric/duodenal mucosa.
The crucial difference is that it must extend through muscularis mucosa.
What is peptic ulcer disease most commonly associated with?
H. pylori
NSAIDs
Smoking
Physiological stress
Where do peptic ulcers most commonly appear?
At mucosal junctions like
First part of duodenum
Lesser curve/antrum of the stomach (where antrum meets body)
Pathogenesis of peptic ulcer disease.
The breakdown of normal defences are more important than excessive acid. This means that ulcers can develop in people with normal or low levels of acid.
This means that H. pylori and NSAIDs which cause a breakdown of normal defences is commonly associated with peptic ulcer disease.
Morphology of peptic ulcer disease.
Generally less than 2 cm diameter
Base of ulcer is necrotic tissue/granulation tissue.
Muscularis propria may be replaced by scar tissue
Clinical consequences of peptic ulcer disease.
Scar tissue shrinking can narrow stomach lumen or cause pyloric stenosis
Perforation
Erosion
Haemorrhage
Malignancy
Symptoms of peptic ulcer disease.
Epigastric pain and sometimes back pain
Burning and gnawing feeling following meal times.
Pain often at night in case of DU
Red flags of peptic ulcer disease
Haematemesis or malaena-bleeding/anaemia
Early satiety
Weight loss
Management of peptic ulcer disease.
Lifestyle modification
Stopping any medication related to NSAIDs
Testing for H. pylori
PPIs
H2 blockers
Endoscopy
Clinical examinations and tests for gastric pathology.
Endoscopy
Biopsies
Urease breath test
Erect chest X-ray to look for perforations.
FBC to look for anaemia
Explain Zollinger-Ellison syndrome
Tumour of the pancreatic islet cells that aren’t beta cells.
These cells will secrete a large quantity of gastrin.
This leads to increased H+ secretion by parietal cells and hyperplasia of parietal cells.
Overwhelms the buffering and leads to ulcers.
Can also cause steatorrhea because low duodenal pH inactivates pancreatic lipase.
Abdominal pain and diarrhoea.
Treatment of Zollinger-Ellison syndrome.
Cimetidine (H2 blocker)
Omeprazole
Surgical removal
Explain stress-related mucosal disease.
Due to severe trauma, extensive burns, intracranial disease or major surgery etc…
Three general types of stress-related mucosal disease.
Stress ulcers (shock, sepsis or severe trauma)
Curling ulcers (prox duodenum associated with severe burns or trauma)
Cushing ulcers (stomach, duodenum or oesophagus due to intracranial disease)
Pathogenesis of stress-related gastric mucosal injury.
Commonly due to local ischaemia like from:
Systemic hypotension
Reduced blood flow
Stress induced splanchnic vasoconstriction
Upregulation and increased release of vasoconstrictor endothelia.
Cushing ulcers thought to be caused by direct stimulation of vagal nuclei resulting in acid hyper secretion.
Symptoms of stomach cancer
Dysphagia due to mass effect
Loss of appetite
Malaena
Weight loss
Nausea/vomiting
Virchow’s nodes
Common risk factors of stomach cancer
Male
H. pylori
Dietary factors
Smoking
