Peptic Ulcer Disease- Fich Flashcards
3 types of chronic gastritis
A – autoimmune
Not peptic disease, Autoantibodies to gastric parietal cells. Ex: Hypochlorhydria/achlorhydria. Loss of gastric intrinsic factor leads to malabsorption of vitamin B12 with macrocytic,megaloblastic anaemia.
B – bacterial (helicobacter)
C – chemical (bile reflux, drugs damaging gastro mucosa)
Protective and Damaging Factors Balancing Mucosal Integrity
Protective: HCO3, mucus, neural alarm system, epithelial restitution/turnover, Prostaglandins, NO, CGRP.
Damaging: H+, pepsin, H. pylori, Activated PMNs, ischemia, bile salts, smoking, NSAIDs
What are the receptors on parietal cells that regulate acid secretion?
Histamine, Gastrin and Acetylcholine.
H2 blockers are specific to histamine receptors on parietal cells.
Proton pump inhibitors block H+/K+ exchanger (on epical side).
Also relieve peptic disease.
NSAIDs causation of gastroduodenal injury
Local effects on protective mucosal environment but also systemic effects on prostaglandin, bicoarbonate and mucus production.
Gastric vs duodenal ulcers
and potential complications
Gastro: pain increased by food. Can be early manifestation of gastric carcinoma, Normal or decreased basal&nocturnal acid, Rarely benign in the fundus, Multiple biopsies
Duodenal: pain alleviated by food, epigastric pain wakes at night. Usually benign in first part, latter is unusual. Usually < 10mm, Increased basal&nocturnal acid, Malignancy-extremely rare, No biopsy
Potential complications: first mainfestation: bleeding, perforation hematemesis or malaena (need up to 150mL of blood before in stool)
Treatment of peptic ulcer disease
Surgery (not anymore except complications), H2 blockers, omeprazole, mainly now: antibiotics for H. pylori.
Properties of H. Pylori
Flagellated Spiral organism
Releases Urease: converts urea to ammonia and CO2. Also mucinase, cytotoxins, phospholipase and platelet-activating factor.
Present only in gastric type mucosa (not isolated in any other part of body unless gastric metaplasia)
Present in most cases of duodenal ulcers, gastric ulcers, gastric cancer (especially lymphoma)
- Adheres to gastric epithelium
- Lives within mucous gel layer overlying gastric epithelium
- Penetrates intercellular junctions
- Invades gastric glands and canaliculi of parietal cells
- Produces cytotoxins that may play role in pathogenicity
- Induces epithelial cytolysis and disrupts intercellular junctions
- Increases permeability of mucous layer to hydrogen ions and pepsin
- Enables gastric acid and pepsin to create ulcer craters
- Evades host immune defenses
- Damages tissue
- Secretes urease to produce ammonia, which protects it from gastric acid
Gastritis progression after H. pylori infection
No prior infection or gastritis
5 days after ingestion: acute inflammation (PMNs) in antrum, rise in pH, hypochlorhydia
11 days after ingestion: chronic inflammation with mononuclei infiltration in antrum, inflammation in fundus
after 30 days, pH normalized
continuous fundal and antral gastritis-forever (until treated).
Confirmation if H. pylori cultured from gastritis can be grown in a healthy organism.
Pathogenesis of H. pylori for duodenal ulcers
Diagnosis of H. pylori
Non-endoscopic: antibody detection (better for epi, present in treated pts), urea breath test, stool antigen.
Endoscopic: Biopsy urease test (color change), histology (H/E, Warthin-Starry Silver Stain), Culture
Indications for checking and treatment:
Established:
Active peptic ulcer disease
Confirmed history of peptic ulcer disease
Gastric MALT lymphoma (low grade)
After endoscopic resection of early gastric cancer
Uninvestigated dyspepsia (depending upon H. pylori prevalence)
Unexplained iron deficiency anemia
Controversial:
Non-ulcer dyspepsia
GERD
The use of aspirin and NSAIDs
High risk populations for gastric cancer
Treatment of H. pylori
Standard (triple therapy): 7-14d: PPI bid + 1g amoxicillin + 500mg clarithromycin. If allergic to penicillins: metronidazole 500mg
Sequential therapy (more effective): 5 days PPI+ 1 g of amoxicillin, twice daily, Followed by 5 days PPI+500 mg of clarithromycin + 500 mg tinidazole, twice daily
2nd line: 14d PPI bid + 1g amox + 500mg metronidazole
Quadruple therapy (third line): PPI bid + 120mg bismuth qid + 500mg metronidazole bid + 500mg tetracycline qid
4th line: 14d bid bismuth + PPI + 1g amoxicillin + 250mg levofloxacin/ 300mg rifabutin qd / 200mg bid furazolidone
PPI raises pH which makes antibiotics more bacteriocidal. Need to treat with a different regiment if the first doesn’t work.
