Alterations in Gastrointestinal Function

Dr. Gerrard Uy

Dysphagia

• a sensation of "sticking" or obstruction of the passage of food through the mouth, pharynx, or esophagus

• often used as an umbrella term to include other symptoms related to swallowing difficulty

Definition of terms

• Aphagia – signifies complete esophageal obstruction

• Odynophagia– painful swallowing

• Globus pharyngeus – is the sensation of a lump lodged in the throat

• Phagophobia– meaning fear of swallowing

Physiology of Swallowing

Pathophysiology of Dysphagia

• oral, pharyngeal, and esophageal • mechanical dysphagia - caused by a large

bolus or a narrow lumen• motor dysphagia - due to weakness of

peristaltic contractions or to impaired deglutitive inhibition causing nonperistaltic contractions and impaired sphincter relaxation

Oral phase dysphagia

• associated with poor bolus formation and control

• food may either drool out of the mouth or overstay in the mouth

• patient may experience difficulty in initiating the swallowing reflex

• premature spillage of food into the pharynx and aspiration into the unguarded larynx and/or nasal cavity

Pharyngeal phase Dysphagia

• associated with stasis of food in the pharynx due to poor pharyngeal propulsion and obstruction at the UES

• leads to nasal regurgitation and laryngeal aspiration during or after a swallow

• Nasal regurgitation and laryngeal aspiration during the process of swallowing are hallmarks

Esophageal Dysphagia

• the esophageal lumen can distend up to 4 cm – When the esophagus cannot dilate beyond 2.5 cm

in diameter, dysphagia to normal solid food can occur

– when the esophagus can’t distend beyond 1.3 cm, dysphagia ALWAYS occurs

History

• can provide a presumptive diagnosis in >80% of patients

• Nasal regurgitation and tracheobronchial aspiration with swallowing are hallmarks of pharyngeal paralysis or a tracheoesophageal fistula

• Hoarseness– precedes dysphagia, the primary lesion is usually in

the larynx– following dysphagia may suggest involvement of the

recurrent laryngeal nerve

History

• Type of food– Difficulty only with solids implies mechanical

dysphagia with a lumen that is not severely narrowed

– dysphagia occurs with liquids as well as solids in advanced obstruction

• Duration– Transient dysphagia may be due to an

inflammatory process– Progressive, lasting days to weeks - carcinoma

Physical Examination

• Careful inspection of the mouth and pharynx• Neck should be examined for thyromegaly or

spinal abnormality• Physical examination is often unrevealing in

esophageal dysphagia

Diagnostic Procedures

• Video endoscopy is the diagnostic procedure of choice

Heartburn

• Pyrosis• Characterized by burning retrosternal discomfort

that may move up and down the chest• Characteristic symptom of reflux esophagitis• Aggravated by bending forward, straining, or

lying recumbent• Worse after meals• Relieved by upright posture, swallowing saliva or

water, and antacids

Odynophagia

• Painful swallowing• characteristic of non reflux esophagitis,

herpes, and pill induced esophagitis• May occur with peptic ulcer of the esophagus,

carcinoma, and caustic damage

Regurgitation

• Effortless appearance of gastric or esophageal contents in the mouth

• Associated with incompetence of both UES and LES

• May result in chronic coughm, laryngitis, and laryngeal aspiration

• Water Brash – reflex salivary hypersecretion that occurs in response to peptic esophagitis

Peptic Ulcer Disease

Dr. Gerrard Uy

Peptic Ulcer Disease

• Characterized by burning epigastric pain exacerbated by fasting and improved with meals

• Ulcer – disruption of the mucosal integrity of the stomach and/or duodenum leading to a local defect or excavation due to active inflammation

Gastroduodenal Mucosal Defense

• Preepithelial– Mucus– Bicarbonate– Surface actvie phospholipids

• Epithelial– Cellular resistance– Restitution– Growth factors– Cell proliferation

Gastroduodenal Mucosal Defense

• Subepithelial– Blood flow– Leukocyte

Mucus Bicarbonate Layer

• First line of defense• Serves as a physicochemical barrier to

multiple molecules• Mucous gel functions as a nonstirred water

layer impeding diffusion of ions and molecules such as pepsin

• Bicarbonate forms a ph gradient from 1 to 2 at the gastric luminal surface

Cellular Resistance

• Next line of defense• Consist of ionic transporters maintaining

intracellular ph• Intracellular tight junctions

Restitution

• If the preepithelial barrier were breached, gastric epithelial cells bordering the site of injury can migrate to restore a damaged region

• Occurs independent of cell division

Cellular Proliferation

• When larger defects are present that are not effectively repaired by restitution

• Regulated by prostaglandins and growth factors

Prostaglandins

• Play a central role in gastric epithelial defense• Functions:– Regulate the release of mucosal bicarbonate and

mucus– Inhibit parietal cell secretion– Maintains mucosal blood flow and epithelial

restitution

Prostaglandins

• Derived from arachidonic acid, which is formed from phospholipids

• rate limiting enzyme is cyclooxygenase (COX)• 2 isoforms – cox1 and cox2• COX1 – constitutively expressed– Stomach– Platelets– Kidneys– Endothelial cells

Prostaglandins

• COX2 – inducible by inflammatory stimuli– Macrophages– Leukocytes– Fibroblasts– Synovial cells

Subepithelial Defense

• Key component is the elaborate microvascular system providing HCO3

• Neutralizes acid generated by the parietal cells

• Provides adequate supply of micronutrients and oxygen while removing toxic metabolites

Physiology of Gastric Secretion

• Hydrochloric acid and pepsinogen – principal gastric secretory products capable of

inducing mucosal injury

• Acid secretion occurs under basal and stimulated conditions

• Basal secretion is controlled by cholinergic input via vagus nerve and histaminergic input from local gastric sources

Physiology of Gastric Secretion

• 3 phases of stimulated gastric acid secretion– Cephalic– Gastric– intestinal

Physiology of Gastric Secretion

• Cephalic– Sight, smell, and taste of food– Stimulates gastric secretion via vagus nerve

• Gastric– Activated once food enters the stomach– Driven by amino acids and amines that directly

stimulate the G cells to release gastrin

Physiology of Gastric Secretion

• Intestinal– Mediated by luminal distention and nutrient

assimilation

Pathophysiologic Basis of Peptic Ulcer Disease

• Encompasses both gastric and duodenal ulcers• Ulcers are defined as breaks in the mucosal

surface > 5mm in size with depth to the submucosa

Peptic Ulcer Disease

Gastric Ulcers• occur later in life• More common in males• Can represent a malignancy• Benign GUs most often

found distal to the junction of the antrum and mucosa

• H. pylori and NSAID induced injury

Duodenal Ulcers• Occur most often in the first

portion of the duodenum (90% - within 3cm of the pylorus)

• Usually < 1cm in diameter• Malignany is rare• H. pylori and NSAID induced

injury

H. Pylori and Acid Peptic Disease

• Initially named Campylobacter pyloridis• Gram negative microaerophilic rod• Most commonly found in the deeper portions

of the mucous gel coating the gastric mucosa• Under normal conditions, does not invade

cells• S – shaped and contains multiple sheathed

flagella

H. Pylori and Acid Peptic Disease

• First step in infection is dependent on the bacteria’s motility and its ability to produce urease

Epidemiology

• In developing countries, 80% maybe infected by the age of 20

• 20 – 50% in industrialized countries

Epidemiology

• Factors that favor colonization rate– Poor socioeconomic status– Less education– Birth or residence in a developing country– Domestic crowding– Unsanitary living conditions– Unclean food and water– Exposure to gastric contents of infected

individuals

Pathophysiology

• Virtually always associated with chronic active gastritis

• Only 10-15% develop frank peptic ulceration• Bacterial factors:– Urease– Chemotactic surface factors– protease

• Host factors:– Inflammatory response

Pathogenetic Factors in Acid Peptic Disease

• Cigarette smoking– Decrease healing rates– Impair response to therapy– Increases ulcer related complications

• Genetic predisposition– Blood group O

• Psychological stress

Pathogenetic Factors in Acid Peptic Disease

• Diet– Highly acidic diet– Beverages containing alcohol and caffeine

• Chronic Disorders– Systemic mastocytosis– Chronic pulmonary disease– Chronic renal failure– Cirrhosis

Pathogenetic Factors in Acid Peptic Disease

• Chronic Disorders– Nephrolithiasis– Polycythemia vera– Coronary artery disease– Chronic pancreatitis

Clinical Features

• Epigastric pain – burning/gnawing discomfort• Usually ill defined, aching sensation or as

hunger pain• DU– Pain occurs 90 mins to 3 hrs after a meal– Frequently relieved by antacids or food– Awakens the patient from sleep (between

midnight and 3am)

Clinical Features

• GU– Discomfort is usually precipitated by food– Nausea and weight loss is more common

Modified Johnsons Classification

• Type I: Ulcer along the body of the stomach, most often along the lesser curve at incisura angularis along the locus minoris resistantiae

• Type II: Ulcer in the body in combination with duodenal ulcers. Associated with acid oversecretion.

• Type III: In the pyloric channel within 3 cm of pylorus. Associated with acid oversecretion.

Modified Johnsons Classification

• Type IV: Proximal gastroesophageal ulcer• Type V: Can occur throughout the stomach.

Associated with chronic NSAID use (such as aspirin)

Physical Examination

• Epigastric tenderness – most frequent finding• Tachycardia suggests dehydration• Severe boardlike abdomen suggests

perforation• Succussion splash indicates retained fluid in

the stomach suggesting gastric outlet obstruction

PUD related Complications

• Gastrointestinal bleeding– Most common complication

• Perforation– 2nd most common– DUs tend to penetrate posteriorly into the panceas– Gus tend to penetrate into the left hepatic lobe

• Gastric Outlet Obstruction– Least common occurring in 1 – 2% of patients

Differential Diagnosis

• Nonulcer dyspepsia (NUD)– Functional dyspepsia or essential dyspepsia– Heterogeneous disorders typified by upper

abdominal pain without ulceration

• Proximal gastrointestinal tumors• GERD• Pancretobiliary disease• Gastroduodenal crohn’s disease

Diagnostic Evaluation

• Endoscopy– most sensitive and specific approach– Permits direct visualization of the mucosa– Tissue biopsy can be done to rule out malignancy

• Serology• Urea breath test• Stool antigen

Treatment

• Acid neutralizing/Inhibitory drugs– Antacids• Aluminum hydroxide• Magnesium hydroxide• Ca carbonate• Na bicarbonate

– H2 receptor antagonist• Famotidine• Cimetidine• ranitidine

Treatment

• Acid neutralizing/Inhibitory drugs– Proton pump inhibitors• Omeprazole• Esomeprazole• Lansoprazole• pantoprazole

Treatment

• Cytoprotective Agents– Sucralfate– Bismuth containing preparations– Prostaglandin analogues