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 Pregnancy Smoking High-fat foods

Theophylline Caffeine Coffee 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.)

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.

Gastric Mucosa & Secretions

Structural Considerations

Mechanisms that maintain mucosal integrity

GastritisGastritis 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 UlcerAn 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.

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

Etiology – Helicobacter pylori

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 – Helicobacter pylori

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

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?

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

PUD – Clinical Presentation

Peptic Ulcer Disease - Diagnosis

Diagnosis of ulcer Diagnosis of H. pylori

Doudenal Ulcer on Endoscopy

Normal doudenal bulb Doudenal Ulcer

Peptic Ulcer Disease - Diagnosis

Gastric Ulcer on Endoscopy

Peptic Ulcer Disease - Diagnosis

Chronic Gastric Ulcers

Duodenal Ulcer on Barium meal

Peptic Ulcer Disease - Diagnosis

Duodenal Ulcer

Gastric Ulcer on Barium meal

Peptic Ulcer Disease - Diagnosis

Gastric Ulcer

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

Diagnosis of H. pylori

Complications of PUD

Bleeding

Perforation

Gastric outlet or duodenal obstruction

Chronic anemia

PUD – Complications

Complications of PUD on Endoscopy

Peptic Ulcer Disease - Complications

Bleeding DU Perforated GU Duodenal stricture