02-14 PUD Flashcards
1. Understand the clinical presentation of peptic ulcer disease 2. Understand the multifactorial causes of peptic ulcer disease, in particular Helicobacter pylori and non-steroidal anti-inflammatory drugs. 3. Understand the aggressive forces and mucosal defense factors important in the balance between gastroduodenal mucosal health and disease. 4. Be familiar with the complications of peptic ulcer disease. 5. Know the various methods of treating peptic ulcer disease and preventing its recurr
OBJECTIVE: What is the clinical presentation of PUD?
• May be asymptomatic
• May present with epigastric “gnawing” pain
• Pain often relieved by eating, drinking or antacids (i.e. hyperphagic»_space; anorexic)
• Pain worse on empty stomach, usu. 2-3 hrs post-prandial
• Pain may awaken from sleep
BLEEDING: Appx 20% of pts present w/ melena and 30% present w/ hematemesis, whereas 50% have both melena and hematemesis initially. Up to 5% ha`ve bleeding brisk enough to cause hematochezia.
OBJECTIVE: What are the multifactorial causes of ulcers?
- H. Pylori: attaches gastric epithelium w/o invading
– May alter cell & activate bacterial functions making them more toxic
– Underlying mucosa made more vulnerable to peptic acid damage by disrupting overlying mucous, adhering epithelium, & inciting inflammatory host response - Mucosal injury (e.g. NSAID, gastritis, H. pylori)
- Mucosal metaplasia (‘intestinalized’ ?by H, pylori)
- Cigs, EtOH (causes gastritis but probs not chronic ulcers), Coffee (not causal; but dyspepsia +worse sx in), ?Type A personality
OBJECTIVE: Explain the aggressive forces and mucosal defense factors important in the balance between gastroduodenal mucosal health and disease.
These forces are in balance in health. When aggressive forces ↑ or defensive forces ↓ → ulceration.
1. Aggressive factors (H+,pepsin, H.pylori, NSAIDs) 2. Mucosal defense factors (membrane integrity, mucus/bicarbonate barrier, regeneration, prostaglandin-mediated "cytoprotection")
OBJECTIVE: List the complications of PUD.
- hemorrhage
- perforation or penetration to adjacent organ (e.g. causing pancreatitis)
- gastric outlet obstruction: Consequence of chronic persistent ulceration, with associated scarring leading to stenosis of the gastric outlet (pylorus or pyloric channel) or duodenum, just proximal to pylorus. Can be partial or complete. Vomiting is a prominent feature, often containing old residual food.
OBJECTIVE: What are the various methods of treating PUD and preventing its recurrence?
1) neutralize or stop acid secretion (nowadays PPI, formerly antacids, then H2 antagonists)
2) eradicate H. pylori, also prevents recurrence
TRIPLE THERAPY:
—OAC: omeprazole, amoxicillin, and clarithromycin
3) enhance mucosal protection, also prevents recurrence:
—Avoid ulcerogenic drugs (NSAIDs, EtOH)
—Stop smoking (important! speeds healing)
—Rx Sulfated disaccharides (e.g. Rx sucralfate) that bind and protect damaged mucosa
—Rx PGE2 class (e.g. Rx Misoprostol) - work by enhancing mucosal protection & ↓ gastric acid secretion
OBJECTIVE: Differentiate Zollinger-Ellison syndrome from chronic PUD.
ZE caused by gastrinomas (usu. w/in stomach wall, sometimes in pancreas, often metastatic and diffuse)
Dx: severe unrelenting ulcer diathesis (can go all the way down to prox jejunum, high serum gastrin levels, and positive secretin stimulation test if needed.
—normally secreting suppresses gastrin, but in ZE it ↑s
—may have diarrhea (osmotic) and steatorrhea (lipase inactiv. by acid)
Screen pt and family for MEN1 Syndrome
OBJECTIVE: Differentiate acute stress ulceration from chronic PUD.
Linear shallow defects in gastric (occasionally duodenal) mucosa, usually superficial to muscularis w/ acute inflammatory necrotic and hemorrhagic ∆s
Usu. w/ other serious d/o: shock, sepsis, severe trauma, stressful extensive surgery
Present w/ severe bleeding which w/ severity of concomitant d/o carries high mortality.
A. PATHOGENESIS
- Patients are not hypersecretors, in fact frequently are hyposecretors. However, gastric acid must be present to cause such ulcerations. The exception to the rule is that patients with intracranial trauma, surgery or tumors have excessively HIGH acid secretion (so-called Cushing’s ulcer).
- Result from a breakdown of gastric mucosal defense mechanisms (↓ mucous, mucosal ischemia)
- Risk factors: shock, sepsis, hepatic and renal failure, multiple trauma, burns, head or spinal trauma.
B. STRESS ULCER PROPHYLAXIS: antacids, H2 blockers, sucralfate, proton pump inhibitors have all been shown to help prevent this severe complication and are widely used in severely ill patients (usually in the intensive care unit setting).
Malignant vs. peptic ulcer appearance on endoscopy
Peptic: discrete, excavated lesions with a whitish base (edges of benign ulcers usu smooth and regular, and symmetrically thickened (inflamm) folds typically radiate to the ulcer base.
—malignant:irregular edges, and the surrounding, asymmetrical folds do not radiate to the base of the ulcer.
Stages of presentation of perf’d ulcer
INITIAL PHASE: caused by gastric juice in peritoneal cavity → intense abdominal pain often w/ hypotension lasting minutes to hours
LATENT: patient looks and feel better (?b/c juice is buffered fluid that pours out of injured tissue) BUT exam usu c/w peritonitis
FRANK PERITONITIS: pain and signs of systemic inflammatory response intensify. Death ensues w/o appropriate tx, which should be initiated well before this point.
Besides peptic ulcers, what other sequelae of H. pylori infection exist?
80% - mixed gastritis w/ normal acid level
15% - antral predom gastritis w/↑acid (assoc w/ duod ulcer)
5% - corpus predom w/ ↓ acid & atrophy (assoc: gastricCA)
OBJECTIVE: H2 antagonist indications, MoA and ADRs
- H2 - receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine): reduce acid secretory responses to histamine, cholinergic stimulation, gastrin and ??food. All four agents have been shown equally effective in healing DUs and GUs (about 80%-90% healing after 6-8 weeks of therapy).
a. Cimetidine
Side effects:
(1) confusion (geri w/ renal or hepatic dysfxn)
(2) Gynecomastia (usu w/ long-term use)
(3) Interferes w/ P450 (warfarin, others)
b. Ranitidine, famotidine, nizatidine
Side effects:
(1) Advantage over cimetidine in that they:
- don’t interfere w/ P450
- Have less-potent anti-androgen
OBJECTIVE: PPI indications, MoA and ADRs
pKa of 4.0 causes them to accumulate in the secretory canaliculus (highly acidic space) of parietal cell. Highest amount of PPI present in parietal cell is after a prolonged fast; therefore take before first meal.
—Heals ulcers more quickly than H2 antagonists (90% healing in 4 weeks).
—Part of most H. pylori regimens & effective in healing NSAID-induced peptic ulcers, even when NSAIDs cannot be d/c.
ADRs: Very few side effects, most common are diarrhea and headache.
OBJECTIVE: sulcralfate MoA
exerts local (not systemic) protective action on ulcer. Rarely used anymore since introduction of the proton pump inhibitors.
OBJECTIVE: Calcium carbonate MoA and ADRs
—Neutralizes acid
—ADRs: Hypercalcemia (Ca++ stimulates acid, enhances cholinergic activity and releases gastrin)
—Tums, Rolaids ( = tums + MgOH)
OBJECTIVE: aluminum hydroxide MoA and ADRs
—Neutralizes acid
—ADRs: Constipating; binds phosphate (leads to anorexia, weakness and bone pain); binds drugs (tetracycline)
—Maalox & Mylanta = magnesium and aluminum hydroxide
