Upper Gastrointestinal

Diseases
 Upper GI Diseases

 Esophagus
 Stomach
 Duodenum
Esophageal Diseases
 Esophageal Diseases

 Esophageal Symptoms
 Esophageal Motility Disorders
 Gastroesophageal Reflux
 Swallowing

 The act of swallowing

– higher brain center activates swallowing center in brainstem
– nucleus ambiguous, dorsal motor nucleus in medulla
– pharyngeal contraction and UES relaxation coordinated
 Swallowing

 The act of swallowing

 primary peristalsis
– food propelled along esophagus, but insufficient to transport
food bolus all the way to stomach
 secondary paristalsis
– initiated when esophagus is distended by food bolus or
gastric contents this peristaltic wave complete transport of
food bolus into stomach
 Esophageal Swallowing Disorders

Esophageal Symptoms
 Dysphagia = difficulty swallowing
– oropharyngeal dysphagia = difficulty initiating
swallow or transferring food from mouth into
esophagus. Can also experience nasopharyngeal
regurgitation (comes out nose) or pulmonary
aspiration.
– esophageal dysphagia = food gets stuck in
esophagus after swallowing
 Causes of Dysphagia
 Obstruction
– tumor/abscess of oropharynx
– Strictures, rings and webs
 CNS injury
– stroke, MS, ALS
 PNS injury
– bulbar poliomyelitis
 Skeletal muscle disorder
– inflammatory myopathy (polymyositis)
– muscular dystrophies, etc
 NM (neuromuscular) transmission disorder
– Myasthenia Gravis
 Esophageal Motility Disorders

 Achalasia (failure to relax)

 Diffuse Esophageal Spasm (DES)
 Achalasia

 most often results from post-ganglionic

denervation of smooth muscle of esophagus
absence of inhibitory neural input to LES →↑
LES pressure
 functional esophageal obstruction → can lead
to esophageal dilatation
 Similar disorder in Chagas disease
(Trypanosoma cruzi causes injury to
myenteric plexuses of esophagus)
 Diffuse Esophageal Spasm (DES)

 periodic chest pain & dysphagia high

amplitude, simultaneous, repetitive SM
contractions
– can be spontaneous or initiated by swallow
 barium swallow → “corkscrew” appearance to
esophagus
 pathogenesis unknown
 Gastroesophageal Reflux (GER)

 A little bit of GER is normal in all of us

– Normally, thoraxic cavity has negative pressure
during inspiration
– GER would occur continuously without antireflux
mechanisms
– a portion of esophagus is below the diaphragm →
intra-abdominal pressure (+5 mm Hg) can
reinforce LES pressure (antireflux effect)
– Loss of subdiaphragmatic LES → correlation
between esophageal hernia and GERD
 Gastroesophageal Reflux (GER)

 Normal anti-reflux mechanisms

– Competent LES (primary barrier to GER)
– LES pressures are ↓ in GERD patients but LES
pressure alone does NOT account for GER in
most GERD patients
 Gastroesophageal Reflux (GER)
Mechanisms
 Incompetent anti-reflux mechanisms
 Ineffective esophageal clearance
 Decreased gastric emptying
 Gastroesophageal Reflux (GER)
Mechanisms
 Incompetent anti-reflux mechanisms:
– weak basal LES pressure
– inadequate LES response to ↑ abdominal
pressure due to disruption of
diaphragmatic sphincter
– transient LES relaxation
 Gastroesophageal Reflux (GER)
Mechanisms
 Ineffective Esophageal Clearance
– delayed clearance occurs in up to 50% of patients
w/ esophagitis
– Mechanisms:
• impaired esophageal peristalsis
• “re-reflux” = to and from movement of refluxed material
associated with hiatus hernias
– may be especially important in patients with
nocturnal GERD
– while asleep, ↓ salivation and ↓ swallowing (primary
peristalsis)
 Gastroesophageal Reflux (GER)
Mechanisms
 Ineffective Esophageal Clearance
– Neutralization of refluxed acid by salivary
bicarbonate
• decreased during sleep and in cigarette smokers
– Esophageal mucosal resistance
• diffusion of H+ can lead to cellular acidification and
necrosis
 Gastroesophageal Reflux (GER)
Mechanisms
 Decreased gastric emptying
– Primary disorders
– Secondary disorders
• Alcohol
• Fats
 Gastroesophageal Reflux (GER)
Risk factors
 Obesity  Theophylline
 Pregnancy  Caffeine
 Smoking  Coffee
 High-fat foods  Chocolate
 High levels of
estrogen/progesterone
 Gastroesophageal Reflux (GER)

 Pyrosis
 Dyspepsia
 Regurgitation
 Dysphagia
 Gastroesophageal Reflux (GER)

Diagnosis of GER
 Best test: pH probe
– checks for existence of acid reflux and association
between esophageal acid and chest pain
 Other tests
– Barium swallow
– Esophagoscopy
– Esophagial biopsy
 Gastroesophageal Reflux (GER)

 Complications of GERD
– Erosive esophagitis
– Esophageal ulcer
– Bleeding
– Esophageal stricture
– Intestinal metaplasia (Barrett’s)
– Adencarcinoma from Barrett’s
– Lung diseases
Gastritis and Ulcer Disease
Peptic Ulcer Disease – Range of injury

 Ulcer:
A lesion on an epithelial surface (skin or mucous
membrane) caused by superficial loss of tissue.

 Erosion:
A lesion on an epithelial surface (skin or mucous
membrane) caused by superficial loss of tissue
which is limited to the mucosa.
 Peptic Ulcer Disease – Location

 Stomach:
– typically in antrum (distal stomach
– normally lined by columnar
epithelium that does not secrete
acid - more susceptible to peptic
ulceration)
– parietal cells located in
body/fundus (proximal stomach -
ulcers not found as often here)
 Peptic Ulcer Disease – Location

 Duodenum:
– within duodenal bulb
– can cause outlet obstruction
– usually single
– multiple/large/more distal ulcers (Zollinger-Ellison sdr.)
 Gastric Mucosa & Secretions
 The inside of the stomach is bathed in about two 
liters of gastric juice every day. 

 Gastric juice is composed of digestive enzymes 
and concentrated hydrochloric acid, which can 
readily tear apart the toughest food or 
microorganism. 

 The gastroduodenal mucosal integrity is 
determined by protective (defensive) and 
damaging (aggressive) factors.
 Gastric Mucosa & Secretions
 The defensive forces
– Bicarbonate
– Mucus layer
–    Mucosal blood flow
– Prostaglandins
– Growth factors

 The aggressive forces
– Helicobacter pylori
– HCl acid
– Pepsins
– NSAIDs
– Bile acids
– Ischemia and hypoxia. 
– Smoking and alcohol

 When the aggressive factors increase or the defensive 
factors decrease, mucosal damage will result, leading to 
erosions and ulcerations. 
 Structural Considerations

Mechanisms that maintain mucosal integrity

 Gastritis
Gastritis
 Inflammation of the gastric mucosa caused by any
of several conditions, including infection
(Helicobacter pylori), drugs (NSAIDs, alcohol), and
autoimmune phenomena (atrophic gastritis).
 Many cases are asymptomatic, but dyspepsia and
GI bleeding sometimes occur.
 Diagnosis is by endoscopy.
 Treatment is directed at the underlying cause but
often includes acid suppression and, for H. pylori
infection, antibiotics.
Gastritis
 Causes of Acute Gastritis

 Alcohol
 NSAIDs
 Helicobacter
 Stress/ICU associated
 Mechanisms of Acute Gastritis

 Drugs (non-steroidal anti-inflammatory

drugs NSAID), alcohol cause acute
erosion (loss of mucosa superficial to
muscularis mucosae).Can result in
severe haemorrhage
 Acute Helicobacter infection has a
prominent neutrophil infiltrate
 Chronic Gastritis

 A – autoimmune
 B – bacterial
(helicobacter)
 C - chemical
 Chronic Gastritis

 Type A - Autoimmune (associated with

vitamin B12 malabsorption (pernicious
anaemia)
 Type B - Helicobacter pylori infection
 Type C - Chemical damage (bile reflux,
drugs)
 Autoimmune Gastritis

 Autoantibodies to gastric parietal cells

 Hypochlorhydria/achlorhydria
 Loss of gastric intrinsic factor leads to
malabsorption of vitamin B12 with
macrocytic,megaloblastic anaemia
 Helicobacter Pylori

 Adapted to live in
association with surface
epithelium beneath mucus
barrier
 Causes cell damage and
inflammatory cell infiltration
 In most countries the
majority of adults are
infected
 Helicobacter Gastritis

 Acute inflammation mediated by

complement and cytokines
 Polymorphisms infiltrate epithelium and
may be partly responsible for its
destruction
 An immune response is also initiated
(antibodies may be detected in serum)
 Helicobacter Gastritis

2 patterns of infection
– Diffuse involvement of body and antrum
(“pan gastritis” associated with diminishing
acid output)
– Infection confined to antrum (antral
gastritis, associate with increased acid
output)
 Chemical Gastritis

 Commonly seen with bile

reflux (toxic to cells)
 Prominent hyperplastic
response (inflammatory
cells scanty)
 With time – intestinal
metaplasia
 Consequences of Gastritis

 Peptic
ulcer disease (Helicobacter)
 Adenocarcinoma (all types)
 Definitions
 Peptic Ulcer
An ulcer of the alimentary tract
mucosa, usually in the stomach
or duodenum, and rarely in the
lower esophagus, where the
mucosa is exposed to the acid
gastric secretion.

It has to be deep enough to

penetrate the muscularis
mucosa.
 Etiology
 The two most common causes of PUD are:
– Helicobacter pylori infection
– Non-steroidal anti-inflammatory drugs (NSAIDS)

 Other uncommon causes include:

– Gastrinoma (Gastrin secreting tumor)
– Stress ulceration (trauma, burns, critical illness)
– Viral infections
– Vascular insufficiency
Etiology – Helicobacter pylori

Helicobacter pylori
 Etiology – Helicobacter pylori
Helicobacter pylori as a cause of PUD

 The majority of PUD patients are H. pylori

infected.

 Studies show that about 95% of patients with

DU and 85% with GU are infected with H. pylori

 Cure of H. pylori infection reduces ulcer

recurrence.
 Etiology – Helicobacter pylori
Helicobacter pylori as a cause of PUD

 Over a 10 year period 1 out of 133 (0.75%)

individuals without H. pylori developed a peptic
ulcer, compared with 35 out of 321 (11%) with
H. pylori infection.

 The incidence of peptic ulcers in H.pylori

infected people is about 1% per year.
 Etiology – NSAIDs

Non-steroidal anti-inflammatory drugs (NSAIDs)

 Symptomatic GI ulceration occurs in 2% to 4% of

patients treated with NSAIDs for 1 year.

 In view of the million of people who take NSAIDs

annually, these small percentages translate into
a large number of symptomatic ulcers.

 The effects of aspirin and NSAIDs on the gastric

mucosa ranges from mucosal hemorrhages to
erosions and acute ulcers.
 Etiology – NSAIDS
Effect of NSAIDS

 All NSAIDs reduce the mucosal production of

prostaglandins from precursor membrane fatty
acids.

 The drugs also generate oxygen-free radicals and

products of the lipoxygenase pathway that may
contribute to ulceration.
 Etiology – NSAIDS
 Users of NSAIDs are at approximately 3 times greater
relative risk of serious adverse gastrointestinal events
than nonusers.

 Additional risk factors include:

– Age greater than 60 years
– Smoking
– Previous history of GI events
– Concomitant corticosteroid use. In terms of serious
complications, the combination of steroids and
NSAIDs leads to a 10-fold increase in GI bleeding
and a 20-fold increase in GI-related death.
Etiology: NSAIDS + H. pylori = ??

 Are patients on NSAIDs who are also infected

with H. pylori more likely than those who are
not infected to have dyspepsia, mucosal
damage, or ulcers?
 PUD – Clinical Presentation
Symptoms of PUD
 Pain
– Epigastric pain
– Hunger pain
– Nocturnal pain
 Other symptoms
– Waterbrash
– Heartburn
– Vomiting
 Asymptomatic
– 1% - 3% adults endoscopy volunteers
– 20% of complicated ulcers present without previous
symptoms
Peptic Ulcer Disease - Diagnosis
 Diagnosis of ulcer
 Diagnosis of H. pylori
 Peptic Ulcer Disease - Diagnosis
 Doudenal Ulcer on Endoscopy

Normal doudenal bulb Doudenal Ulcer

 Peptic Ulcer Disease - Diagnosis
 Gastric Ulcer on Endoscopy

Chronic Gastric Ulcers

 Peptic Ulcer Disease - Diagnosis
 Duodenal Ulcer on Barium meal

Duodenal Ulcer
 Peptic Ulcer Disease - Diagnosis
 Gastric Ulcer on Barium meal

Gastric Ulcer
 Diagnosis of H. pylori
Tests for Helicobacter pylori

Non-invasive
 C13 or C14 Urea Breath Test
 Stool antigen test
 H. pylori IgG titer (serology)

Invasive
 Gastric mucosal biopsy
 Rapid Urease test
 Diagnosis of H. pylori
Tests for Helicobacter pylori
C13 or C14 Urea Breath Test
 Diagnosis of H. pylori
Tests for Helicobacter pylori
Stool Antigen test
 Diagnosis of H. pylori
Tests for Helicobacter pylori
Mucosal Biopsy
 Diagnosis of H. pylori
Tests for Helicobacter pylori

Rapid Urease Test

 This test is based on the
urease enzyme present in
the H. pylori
 Urea is split into NH3 and
CO2

 The change in pH causes a

color change in the medium
 PUD – Complications
Complications of PUD

 Bleeding

 Perforation

 Gastric outlet or duodenal obstruction

 Chronic anemia
 Peptic Ulcer Disease - Complications
 Complications of PUD on Endoscopy

Bleeding DU Perforated GU Duodenal stricture