138b/139b - Pathology of Gastric Disorders, PUD, H. Pylori Flashcards
Do benign gastric ulcers occur in pernicious anemia?
No!
- Pernicious anemia is often caused by autoimmune destruction of parietal cells
- => decreased gastric acid
- Any ulcer that forms in the setting of pernicious anemia should be considered for malignancy
Which stimulants of parietal cell gastric acid secretion act through the IP3/Ca2+ pathway?
- ACh
- Released when we think about food (cephalic phase) or secondary to antral distention (gastric phase)
- Gastrin
Which part of the stomach is affected by H. pylori gastritis?
Antrum
Describe the pathophysiology of diarrhea in patinets with Zollinger-Ellison syndrome
ZE = gastrin-secreting tumor
- Increased HCl secretion
- HCL spills into duodenum
- Denatures pancreatic enzymes
- Maldigestion of fat and protein
- Diarrhea
- Directly damages the small intestinal epithelium
- Secretory diarrhea
- Denatures pancreatic enzymes
What is the treatment for Zollinger-Ellison Syndrome?
High dose PPI
- Resect tumor if you can, but they can be hard to find!
Describe the pathophysiology of chronic autoimmune gastritis
- Antibodies against parietal cells and intrinsic factor
- -> Destruction of parietal cells
- -> Hypochlorhydria, high serum gastrin
How does H. pylori cause an increase in gastric acid release?
H. Pylori preferentially destroys D cells
- D cells normally secrete somatostatin
- Normally inhibits gastrin secretion from G cells
- Results in decreased gastric acid release
-
No D cells = no brakes on gastrin secretion
- Lots of gatrin -> lots of gastric acid
Describe the pathophysiology of H. pylori infection in the gastric epithelium
(Starting with ingestion of H. pylori)
- Ingestion of H. pylori
- H. pylori lodges into the mucus using adhesins
- Protected from acid by urease (Urea -> CO2 + NH3)
- NH3 is converted to NH4+ in the acidic stomach; NH4+ cloud protcts H. pylori
- H. pylori multiplies
- Immune response
- Cytokine release
- Damage to mucosa
- H. pylori internalizes in the epithelium
Describe the pathophysiology of a Curling ulcer
Severe burns/trauma -> hypovolemia -> ischemia
What is the eradication rate for H. pylori after antibiotic treatment?
~75% and decreasing due to abx resistance
What is the most common cause of benign peptic ulcer disease?
H. pylori
What are the two subtypes of gastric adenocarcinoma?
How do you tell them apart?
- Intestinal
- Ulcer with raised borders
- Composed of glands
- Diffuse
- Diffusely thickened gastric wall
- Signet ring cells are present
List two hypertrophic gastropaties
How do you tell them apart histologically?
- Menetrier disease (excess TGF-alpha)
- Foveolar hyperplasia
- Zollinger-Ellison syndrome (gastrin-secreting tumor)
- Parietal cell hyperplasia
Endoscopically, both will have enlarged folds
H. pylori typically colonizes in gastric epithelium
How, then, does it caue duodenal ulcers?
- H. pylori colonization in the stomach results in increased post-prandial gastrin release, resulting in increased gastric acid
- Due to destruction of D cells (no brakes on gastrin release)
- Gastric acid spills into the duodenum
- -> Gastric metaplasia
- -> H. pylori colonizes in the gastric metaplasia in the duodenum
What is the effect of somatostatin on gastric acid secretion?
Somatostatin inhibits gastric acid secretion
- Inhibits gastrin secretion from G cells, histamine secretion from HCL cells
Describe the pathophysiology of a Cushing ulcer
- Increased intracranial pressure
- -> Vagal stimulation
- -> Acid production
- -> Ulcer formation
Which of the following mechanisms plays an important role in the development of a gastric ulcer in a 32 year old patient with rheumatoid arthritis taking ibuprofen 800 mg three times daily for one month?
- Reduction in blood flow to the gastric mucosa
- Ion trapping and low pKa of ibuprofen
- Excessive production of acid induced by ibuprofen
- Concomitant infection with H.pylori
- Autoimmune damage to the gastric epithelium
a. Reduction in blood flow to the gastric mucosa
- Ibuprofen is a nonselective COX inhibitor
- -> Decreased prostaglandins production
- -> Decreased blood flow
Ishcemic damage = nidus for ulcer