Lecture 18 Upper Digestive Diseases

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

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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 

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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 

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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

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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

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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.

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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. 

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

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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

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The aggressive forces – – – – – – –

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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.

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Diagnosis is by endoscopy.

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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 

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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  

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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)

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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.

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Studies show that about 95% of patients with DU and 85% with GU are infected with H. pylori

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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.

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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.

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In view of the million of people who take NSAIDs annually, these small percentages translate into a large number of symptomatic ulcers.

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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.

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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.

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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

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Other symptoms – Waterbrash – Heartburn – Vomiting

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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

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Urea is split into NH3 and CO2

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The change in pH causes a color change in the medium

PUD – Complications Complications of PUD 

Bleeding

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Perforation

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Gastric outlet or duodenal obstruction

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Chronic anemia

Peptic Ulcer Disease - Complications  Complications

Bleeding DU

of PUD on Endoscopy

Perforated GU

Duodenal stricture