SBI241 - Week 8.docx

**SBI241 -- Week 8** **PEPTIC ULCER DISEASE**\ *[Gastric Ulcer]* - The ability of the gastric mucosa to protect and repair itself seems to be defective; in duodenal ulcers, hypersecretion of acid and pepsin is responsible for the erosion of the duodenal mucosa. *[Duodenal ulcer]* Gastric juice -...

**SBI241 -- Week 8** **PEPTIC ULCER DISEASE**\ *[Gastric Ulcer]* - The ability of the gastric mucosa to protect and repair itself seems to be defective; in duodenal ulcers, hypersecretion of acid and pepsin is responsible for the erosion of the duodenal mucosa. *[Duodenal ulcer]* Gastric juice - comprised of pepsin, hydrochloric acid, mucus and intrinsic factor. major stimulant to gastric acid secretion is [protein]. - prostaglandins E2 and I2 inhibit acid secretion - [hormone gastrin + the neurotransmitter acetylcholine + the local hormone histamine] = directly stimulate acid secretion by parietal cells. Gastritis -- Inflammatory disorder of the gastric mucosa 1. acute gastritis -- Caused by chemical injury e.g. NSAIDs, corticosteroids, iron tablets, alcohol, corrosive substances. Ischaemia physical stress like burns, shock, trauma. Initial response to H. pylori infection, HSV or CMV. Pathological features: - Surface epithelial degeneration - Regenerative hyperplasia of pit-lining epithelium - Vasodilatation/congestion - Neutrophil response 2. chronic gastritis - Chronic fundal gastritis - Chronic antral gastritis Helicobacter-associated gastritis - gram negative rod & bind to epithelium Survives the acidic environment as it is associated with intestinal metaplasia, causes risk of developing gastric adenocarcinoma Gram negative organism Buffering mechanism: urease and ammonia H. pylori virulence factors: - Motility - Ammonia production and adhesion ◦ Toxins (local tissue damage) Acute inflammatory response: polymorphs, chemokines, ROS Glandular loss Diagnosis: - Urea breath test - Gastric biopsy: Histology, PCR ◦ Serology - Culture -- uncommon Complications: - Peptic ulcer - Dysplasia - Intestinal metaplasia \*\*It is a spiral (helical)-shaped organism that has evolved to inhabit the highly acidic environment of the stomach, particularly the pylorus.\*\* - The bacterium adheres to the gastric epithelial cells, it breaks down endogenous urea, creating a protective cloud of ammonia and bicarbonate that enables it to protect itself against the effects of gastric acid. - The ability of the bacterium to degrade urea and release carbon dioxide forms the basis of the H. pylori breath test, which is used to detect infestation and also to monitor the effectiveness of drug-mediated eradication. Peptic ulcer A break or ulceration in the protective mucosal lining of the lower oesophagus, stomach or duodenum. ACUTE & CHRONIC ulcers Superficial - Erosions Deep - True ulcers Loss of balance between: +-----------------------------------+-----------------------------------+ | Aggressive factors | Defensive mechanism | +===================================+===================================+ | - NSAIDs | - Tight intercellular junctions | | | | | - H. Pylori infection | - Mucus | | | | | - Alcohol | - Mucosal blood flow | | | | | - Bile salts | - Epithelial renewal | | | | | - Acid | - Bicarbonate secretion | | | | | - Pepsin | | +-----------------------------------+-----------------------------------+ Morphology: - Clear-cut edges that overhang the base - Base: necrotic tissue and PMNs, granulation tissue, fibrous tissue ◦ Arteries within fibrous base can be obliterated - If muscularis propria replaced by fibrous tissue→ shrinkage of tissue (cicatrisation)→ deformities. Duodenal ulcer Most common of the peptic ulcers Developmental factors: - Helicobacter pylori infection toxins and enzymes that promote inflammation and ulceration - Hypersecretion of stomach acid and pepsin - Use of NSAIDs - High gastrin levels - Acid production by cigarette smoking Gastric ulcer tend to develop in the antral region of the stomach, adjacent to the acid-secreting mucosa of the body Pathophysiology: The primary defect is an increased mucosal permeability to hydrogen ions Gastric secretion tends to be normal or less than normal. Drugs that neutralise or inhibit acid secretion 1. Antacids 2. Cytoprotective agents 3. Proton pump inhibitors 4. H2-receptor antagonist Helicobacter pylori treatment regimens Helicobacter pylori causes chronic active gastritis, is associated with the development of gastric and duodenal ulcers, and is a recognised risk factor in the development of gastric carcinoma. Eradication of H. pylori is considered first-line treatment because it vastly improves the odds of non-recurrence of the ulcer. INFLAMMATORY BOWEL DISEASE 1. Crohn's disease 2. Ulcerative colitis Pathogenesis: inappropriate mucosal immune activation Contributing factors: genetics, epithelial defects and microbiota Clinical features: - Diarrhoea - Fever - Abdominal pain - Bloody stool - Weight loss Diagnosis - Colonoscopy - Biopsy Ulcerative colitis -- Chronic relapsing inflammatory disease. Unkown aetiology Chronic inflammatory disease that causes ulceration of the colonic mucosa. - Sigmoid colon and rectum. Morphology - Diffuse superficial inflammation (mucosa & submucosa) - Shallow ulcers - Crypt abscesses - Crypt atrophy - Psuedopolyps Symptoms - Diarrhoea 10-20 days, blood stools and cramping Treatment - Broad-spectrum antibiotics and steroids - Immunosuppressive agents - Surgery Complications: - Haemorrhage - Electrolyte disturbances - Toxic megacolon - Extra-GI involvement: - Skin pigmentation, pyoderma - Liver-fatty change, cirrhosis - Eye-iritis, uveitis - Joint-arthritis, ankylosing spondylitis, arthralgia \*\*INCREASED COLON CANCER RISK Crohn's Disease -- causes 'skip lesions' Unknown aetiology Mouth to rectum distribution, common in small intestine - Granulomatous colitis, ileocolitis or regional enteritis - Idiopathic inflammatory disorder; affects any part of the digestive tract, from mouth to anus - Difficult to differentiate from ulcerative colitis - Ulcerations can produce longitudinal and transverse inflammatory fissures that extend into the lymphatics - Anaemia may result from malabsorption of vitamin B12 and folic acid - Can cause transmural inflammation = fistula formation -- can form between loops of bowel, bladder and skin. Treatment is similar to ulcerative colitis Morphology - Skip lesions - Cobblestones appearance of mucosa-oedema and deep fissures - Thickened bowel wall obstruction (transmural inflammation) Complications: - Malabsorption - Fistula formation - Perforation - Toxic megacolon - Adenocarcinoma (very rare)  Drug therapy for IBD Current therapy for these conditions: - Corticosteroid prednisolone and budesonide - 5-aminosalicylates (5-ASA) balsalazide, mesalazine, olsalazine and sulfasalazine - Immuno-suppressants azathioprine, mercaptopurine and methotrexate Crohn\'s disease is an indication for the use of the TNF-α antagonists adalimumab and infliximab.