Acid Peptic Disorders The Spotlight is On!

Charmaine Rochester, PharmD, CDE, CDM, BCPS Asst Professor, University of Maryland School of Pharmacy

Objectives

At the end of this presentation, the student should be able to:  Review the anatomy and physiology of the stomach   Discuss the pathophysiology, risk factors, signs and symptoms, complications and diagnosis of ulcers Given a drug associated with ulcer formation, discuss the proposed mechanism of ulceration  Discuss the pathophysiology, risk factors, signs and symptoms, and complications of gastroesophageal disease (GERD)

Acid Peptic Disorders

 Dyspepsia  Peptic Ulcers  Duodenal Ulcers  Stress Ulcers  Gastroesophageal Reflux Disease (GERD)  Gastric Cancers

Dyspepsia

 A constellation of upper abdominal symptoms  Accounts for up 40 - 70% of GI complaints  Significant societal costs  Causes  PUD, GERD, gastric cancer  Food, medications, but commonly idiopathic

Normal Stomach Anatomy

Gastric Antrum

Physiology: The Secretory Epithelial Cells

1. Mucus cells • Mucus 2. Parietal cells • HCL 3. Chief Cells • Pepsinogen 4. G cells • Gastrin Surface Epithelium Opening of gastric pit Parietal cell Chief Cell Parietal cell

Gastric Acid and its Function



Gastric Acid Contents

 HCl, salts, pepsin, mucus, water, intrinsic factor, bicarbonate 

Gastric Acid Function

 to kill micro-organisms  to activate pepsinogen  breaks down connective tissue in food

Mucosal Defenses/Protection

 Mucus layer on gastric surface  Mucosal barrier to damage  Bicarbonate: Abundant in mucus layer  Prevent acidic damage and auto digestion  Prostaglandins are cytoprotective  Increase blood flow and cell regeneration  Mucosal integrity  Maintained by tight cell junctions

Epidemiology of Peptic Ulcer Disease (PUD)

Development of PUD

 4 -10% of Americans  Gastric Ulcer peaks 55-65 th year  Duodenal Ulcer increases with age until 60 years

Pathophysiology of Peptic Ulcer Disease (PUD)

Luminal Aggressors

• H. pylori • NSAIDs • Acid • Pepsin

Mucosal Defenses

• Bicarbonate • Mucus • Prostaglandin • Growth factor • Mucosal regeneration Goldin GF, et al. Gastr Endosco Clin Nor Am. 1996;6;505-526. Saggioro A, et al. Ital J Gastroenterol. 1994;269(suppl 1):3-9. Modlin IN, et al. Acid Related Diseases. 1998;317-362.

Risk Factors/Aggressors of PUD



Major Factors



Helicobacter Pylori

 NSAIDs  Cigarette smoking  Acid and pepsin 

Other Factors

 Genetics  ?Foods

 ?Stress

Helicobacter Pylori

 Bacteria  Gram –ve spiral bacterium  40% of patients >60 yrs are +ve for H.pylori

 Transmitted: possibly person to person  Most common cause of antral gastritis  Mechanism of gastric injury  Cytotoxin  Breakdown of mucosal defenses  Adherence to epithelial cells  Increase gastrin releasing peptide (GRP)  Decrease bicarbonate secretion

Drug Induced PUD Drug Action Iron, K+, Tetracyclines Reserpine. TCA, Anticholinergics Alcohol Caffeine

Corrosive to mucosa  sympathetic,  tone –  parasympathetic acid output  acid output (secretagogue) Causes gastritis, bleeding is possible, not thought to

cause

ulcer  acid production (even decaffeinated); No  in ulcer formation, lowers (LES) so may cause GERD symptoms

NSAIDS

        Inhibits prostaglandin synthesis (COX inhibition) Disrupts functional mucosal integrity  mucosal blood flow  cell regeneration Direct GI irritation Antiplatelet effect (causing bleeding) Ion trapping  acid (basal and maximal stimulation) secretion

Risk Factors for NSAID-Induced GI Injury

 History of ulcer or GI complications  Increasing age  Concomitant anticoagulation therapy  Concomitant corticosteroid use  High dose NSAID use or concomitant aspirin/NSAID use

Conditions Associated with PUD

Fig. 40-2. Feldman: Sleisenger & Fortran’s Gastrointestinal and Liver Disease, 7 th ed.

Smoking

    Impairs ulcer healing Promotes ulcer recurrence Increases the likelihood of ulcer complications       Mechanisms Stimulate gastric acid secretion Stimulate bile salt reflux Causes alteration in mucosal blood flow Decrease mucus secretion Reduces prostaglandin synthesis Decrease pancreatic bicarbonate secretion

Acid and Pepsin

? Mechanism of damage:   gastrin releasing peptide (GRP)  defect in inhibition of acid production      mucosal bicarbonate secretion basal acid secretory drive  postprandial acid secretory response   sensitivity to secretagogues

Diet and Stress Diet

Effects of Diet and Stress

Action

Dyspepsia, may  pain - not believed to cause ulcer or assist healing

Physiologic stress Psychological stress

↓ mucosal blood flow, tissue hypoxia, mucosal lining degradation; e.g. ICU, sepsis, burn, trauma. Associated with multiple erosions & significant bleeding Similar # stressful events in ulcer vs. non-ulcer patients ↓ tolerance to discomfort Recent epidemiological data suggest possible role

Gastric Ulcer

Duodenal Peptic Ulcers

Stages of Ulcer Formation

Erosion Ulcer Chronic Ulcer Sclerosis

Signs and Symptoms of GU or DU

 Epigastric pain  Not well localized  Annoying, burning, gnawing, aching  Duodenal ulcers  On an empty stomach  During the night  Between meals  Relieved by food and antacids  Episodic followed with symptomatic periods then no occurrence

Complications of PUD

 Hematemesis  Perforation  Diarrhea  Obstruction  Nausea  Vomiting  Weight Loss  Weakness

Complications: PUD

Stress Ulcer Duodenal Ulcer Gastric Ulcer Hemorrhage:

Frequent, associated mortality

Perforation:

Common

Obstruction: ?

Common in posterior wall of duodenal bulb, associated with melena When in anterior wall of duodenum Common Less common (associated with hematemesis, coffee grind emesis), melena More common in anterior wall of stomach Rare

Malignancy:

Rare Rare 7%

Objective Measures

 Melena   Hct, Hgb  Microcytic, hypochromic indices    Pale conjunctiva BUN/Cr Ratio  Heme +ve stool

Diagnosis

 Gastric Ulcer/Duodenal Ulcer  Upper endoscopy (gold standard)  H. pylori  Noninvasive: Urea breath test, serology  Invasive: biopsy (histology, culture, rapid urease)  NSAID- induced  History  Still need to rule out H pylori infection

Gastroesophageal Reflux Disease (GERD)

 Reflux of gastric or intestinal contents  Results in heartburn, “burping” bitter taste

Signs and Symptoms

 Heartburn - hallmark symptom  Typical: Belching, regurgitation  Alarm symptoms: Atypical  Weight loss  Bleeding  Choking  Hoarseness, cough, wheeze  Dysphagia (difficulty swallowing)  Odynophagia (painful swallowing)  Atypical chest pain  Infants: spitting up, vomiting (uncommon: failure to gain weight, Fe def anemia, recurrent pneumonia, near SIDS)

Spectrum of Gastroesophageal Reflux Disease (GERD)  Acid reflux  Esophagitis  Esophageal ulceration  Barrett’s esophagus

Possible Extraesophageal Manifestations of GERD

         

ENT

Pharyngitis Otitis media Sinusitis Vocal cord granulomas Laryngitis Hoarseness Voice changes Chronic cough Dental enamel loss

Pulmonary

  Chronic cough Asthma   Idiopathic pulmonary fibrosis Chronic bronchitis  Pneumonia

Other

   Chest pain Sleep apnea Dental erosions

GERD Pathophysiology

Aggressive Factors

Loss of LES pressure

Composition acid/pepsin -Volume of refluxate

-

Inappropriate relaxation -Increase in intra abdominal pressure

Defects in defense mechanisms -Anatomical -Mucosal resistance -Esophageal clearance -Gastric emptying

Lower Esophageal Sphincter

LES Closed LES Open

Risk Factors

 Factors that decrease LES pressure  Diet  Alcohol  Smoking  Drugs  Factors that increase intra-abdominal pressure  Obesity  Pregnancy  Bending over

Foods and Drugs Affecting LES RAISE LES Pressure LOWER LES Pressure Foods Drugs

Proteins, carbohydrates Alpha-agonists Beta-blockers Cholinergics Cisapride Metoclopramide Caffeine, Carminatives, Chocolates, Citrus, Garlic, Fat, Tomatoes Alcohol, ά antagonists, Anticholinergics Meperidine Methylxanthines Narcotics Barbiturates Nicotine Beta-agonists Nitrates Calcium channel blockers Progesterone Prostaglandins Diazepam Tricyclic antidepressants Dopamine Estrogen Adapted from Gonzales et al. DICP 1990;24:1065

Non Pharmacologic Interventions

Helps 20% of patients  Weight loss  Small size food portions  Loose fitting clothes  Cigarette smoking cessation  Avoid chocolate, alcohol, peppermint, fatty meals, spicy meals, citric juices, cola, beer   Avoid meals 2 hours before lying down Elevate the head of the bed with a 6 8” block

Elevation of Head of Bed

Complications of GERD

 Infants: Failure to Thrive  Esophagitis (histopathological changes)  Gradations  Grade I- erythema, edema  Grade II- isolated erosions  Grade III- confluent erosions, superficial ulceration  Grade IV- erosions, deep ulcers, stricture  Peptic stricture  Worsening obstructive lung disease  Barrett’s esophagus  Malignancy

GERD and Cancer Risk

 Esophageal adenocarcinoma 8 times higher in patients with heartburn, regurgitation, or both at least once a week  Esophageal carcinoma 11 times higher in patients with nighttime symptoms of GERD Lagergren J, et al. New Engl J Med. 1999;240:825-831

GERD in Obstructive Lung Disease

Lung Effects



Acid aspiration irritates airways



Vagally mediated bronchospasm via transient acid reflux

Reflux Effects

 Chronic airflow trapping, diaphragmatic flattening may reduce LES competency   Lung Dx: -ve intrathoracic pressure/+ abdominal pressure Bronchodilators  LES pressure