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

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Dr.p.Falla abed
Thorasic surgeon
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)
Causes gastritis, bleeding is
possible, not thought to cause
ulcer
Caffeine
 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, 7th 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
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





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
Less common
(associated with
hematemesis, coffee
grind emesis), melena
Perforation:
Common
When in anterior
wall of duodenum
More common in
anterior wall of stomach
Obstruction: ? Common
Rare
Malignancy:
Rare
7%
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










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