Transcript Bio and Patho of Acid Peptic Disorders: What caused the Ulcer?

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

Bicarbonate: Abundant in mucus layer
 Prevent

barrier to damage
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
55-65th 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 Corrosive to mucosa
Reserpine. TCA,
Anticholinergics
 sympathetic,  parasympathetic
tone –  acid output
Alcohol
 acid output (secretagogue)
Caffeine
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

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
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
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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, 7th ed.
Smoking




Impairs ulcer healing
Promotes ulcer recurrence
Increases the likelihood of ulcer
complications
Mechanisms



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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
Effects of Diet and Stress
Diet and Stress
Action
Diet
Dyspepsia, may  pain - not believed to
cause ulcer or assist healing
Physiologic
stress
↓ mucosal blood flow, tissue hypoxia,
mucosal lining degradation; e.g. ICU,
sepsis, burn, trauma. Associated with
multiple erosions & significant bleeding
Psychological
stress
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

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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
Common in
posterior wall of
duodenal bulb,
associated with
melena
When in anterior
wall of duodenum
Less common
(associated with
hematemesis, coffee
grind emesis), melena
Perforation:
Common
Obstruction: ? Common
More common in
anterior wall of stomach
Malignancy:
Rare
7%
Rare
Rare
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

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





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
Composition
acid/pepsin
-Volume of
refluxate
Loss of LES
pressure
-Inappropriate
relaxation
-Increase in intraabdominal
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
Proteins,
carbohydrates
Caffeine, Carminatives,
Chocolates, Citrus, Garlic, Fat,
Tomatoes
Drugs
Alpha-agonists
Beta-blockers
Cholinergics
Cisapride
Metoclopramide
Alcohol, άantagonists,
Anticholinergics
Barbiturates
Beta-agonists
Calcium
channel
blockers
Diazepam
Dopamine
Adapted from Gonzales et al. DICP 1990;24:1065
Meperidine
Methylxanthines
Narcotics
Nicotine
Nitrates
Progesterone
Prostaglandins
Tricyclic
antidepressants
Estrogen
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
Reflux Effects
 Acid aspiration  Chronic airflow
trapping,
irritates airways diaphragmatic
flattening may reduce
 VagallyLES competency
mediated
 Lung Dx: -ve
bronchospasm intrathoracic
pressure/+ abdominal
via transient
pressure
acid reflux
 Bronchodilators 
LES pressure