Digestive tract diseases

Adam Stefański

Esophagitis - causes

• gastroesophageal reflux

• infectious esophagitis (in patients who are immunocompromised)

• radiation

• direct erosive effects of ingested medication or corrosive agents.

Pathophysiology of esophagitis

Reflux esophagitis develops when gastric contents are passively regurgitated into the esophagus. Gastric acid, pepsin, and bile irritate the squamous epithelium, leading to erosion and ulceration of esophageal mucosa. Eventually, a columnar epithelial lining may develop. This lining is a premalignant condition termed Barrett esophagus.

Esophagitis - medical history

• The most common complaint is heartburn (dyspepsia), a burning sensation in the mid chest caused by contact of stomach acid with inflamed esophageal mucosa. Symptoms often are maximal while supine, when bending over, when wearing tight clothing, or after large meals

• Water brash is a bitter taste of refluxed gastric contents often associated with heartburn

• Other common symptoms include upper abdominal discomfort, nausea, bloating, and fullness. Less common symptoms include dysphagia, odynophagia, cough, hoarseness, wheezing, and hematemesis

Esophagitis - medical history

• The patient may experience chest pain indistinguishable from that of coronary artery disease. Pain often is midsternal with radiation to the neck or arm and may be associated with shortness of breath and diaphoresis. Chest pain may be relieved with nitrates if esophageal spasm is involved, further confounding diagnostic evaluation.

• Infants with reflux are at greater risk of aspiration. Symptoms include weight loss, regurgitation, excessive crying, back arching, respiratory distress, and apnea.

Esophagitis – physical examination

• Physical examination usually is not helpful in uncomplicated esophagitis, but evaluate other potential sources of chest pain such as the chest wall and abdomen.

• Perform a rectal examination for occult bleeding.

Conditions that may increase risk of reflux esophagitis

– Pregnancy– Obesity– Scleroderma– Smoking– Alcohol, coffee, chocolate, fatty or spicy foods– Certain medications (eg, beta-blockers, nonsteroidal anti-inflammatory

drugs [NSAIDs], theophylline, nitrates, alendronate, calcium channel blockers)

– Mental retardation requiring institutionalization– Spinal cord injury– Immunocompromised patients– Radiation therapy for chest tumors– Pill esophagitis, thought to be secondary to chemical irritation of

esophageal mucosa from certain medications (eg, iron, potassium, quinidine, aspirin, steroids, tetracyclines, NSAIDs), especially when swallowed with too little fluid

Esophagitis - differentials

• Acute Coronary Syndrome• Cholecystitis and Biliary Colic• Esophageal Perforation, Rupture and

Tears• Foreign Bodies• Gastrointestinal Gastritis and Peptic Ulcer

Disease • Myocardial Infarction

Esophagitis - Lab Studies

• Laboratory tests usually are not helpful unless complications are present (eg, upper GI hemorrhage). Bleeding, a potentially serious complication of esophagitis, may be excluded on physical examination with stool guaiac.

• Troponin T and cardiac enzymes may be needed when myocardial infarction is suspected

Esophagitis – imaging studies

• Routine radiography is not indicated in emergency departments (EDs) unless complications (eg, perforation, obstruction, bleeding) are suspected.

• Perform a double-contrast esophageal barium study as a first-line test if dysphagia is a primary complaint. This is useful in structural complications such as strictures and tumors.

Esophagitis – other tests

• Direct endoscopy allows visualization and biopsy of esophageal mucosa. Endoscopy is useful in evaluating the degree of mucosal damage and is indicated in patients with hematemesis, heme-positive stools, or suspected esophageal obstruction.

• Endoscopy may be indicated on an emergency basis in cases of upper GI hemorrhage, obstruction, or perforation.

• Early endoscopy is indicated in those older than 50 years with new onset of symptoms, those with alarm features (eg, abdominal mass, anemia, vomiting, dysphagia), or those who fail repeated trials of medical therapy.

Esophagitis - treatment

• Esophagitis has no specific prehospital care regimen. Care is directed toward complications (eg, bleeding, perforation) that require hemodynamic stabilization. Chest pain of esophageal origin cannot be differentiated from that of coronary artery disease.

• Oxygen generally is indicated when the cause of the pain is not certain

• Treatment generally is not indicated in an Emergency Department setting unless complications, such as bleeding, obstruction, dehydration, or perforation, occur

• Patients with moderate-to-severe bleeding, perforation, or suspected obstruction should consult a gastroenterologist.

Esophagitis - medication

• Treatment goals are pain relief, decreased acid production, decreased acid reflux, and protection of the esophageal mucosa.

• Multiple pharmacologic agents are available:– histamine-2 receptor antagonists (ranitidine)– proton pump inhibitors (omeprazole)– gastroprokinetic agents (cisapride)– protective agents (sucralfate).

Esophagitis -medication• Histamine-2 receptor antagonist therapy has been recommended as

the initial treatment previously. Newer evidence in cost-effectiveness analysis and symptomatic relief suggests proton pump inhibitors (omeprazole 20 mg daily, pantoprazole 40 mg daily, or lansoprazole 30 mg daily for 4-8 wk) to be superior to ranitidine, cimetidine, and placebo.

• Cisapride, a gastroprokinetic agent, and sucralfate, a coating agent, are less effective but may be useful in selected patients or as second-line agents.

• Although there is no consensus on treatment choice, it is reasonable to prescribe for 2-4 weeks with reassessment. Some patients with relapse may require long-term maintenance therapy.

• Some authorities suggest proton pump inhibitors and histamine-2 receptor antagonists for patients with ulcerlike dominant symptoms (eg, nocturnal symptoms, relief with food) and gastroprokinetic agents for patients with dysmotility dominant symptoms (eg, nausea, bloating)

Esophagitis - complications• Common complications are bleeding and stricture formation.• Barrett esophagus, in which the normal squamous epithelium of the

esophagus is replaced with columnar epithelium, is linked to development of esophageal cancer. A systematic review also indicated a link between Barrett esophagus and colonic cancer (7.6% in Barrett esophagus vs 1.6% in controls).

• Although rare, perforation with mediastinitis is a serious complication.

• Volume depletion and weight loss may occur secondary to inability to swallow.

• Laryngitis, aspiration pneumonitis, and bronchospasm may occur if gastric contents are refluxed to the level of the larynx.

• Esophagitis also has been linked to failure to thrive and apnea in infants.

• Helicobacter pylori (HP) eradication therapy has been inversely related to reflux esophagitis. It is postulated that the ammonia (alkaline) produced by HP reduces the acidity of the stomach and, hence, protects the esophagus from acid spillage.

Esophagitis – miscellaneous (1)

• Do not misdiagnose cardiac chest pain as esophageal pain. Pain can be similar, particularly in elderly patients and women.

• Always consider cardiac causes of chest discomfort and treat appropriately. If the diagnosis is unclear, admission for further evaluation is suggested

Esophagitis – miscellaneous (2)• Infectious esophagitis primarily is seen in patients who are

immunocompromised. The most common causes are fungal (Candida species), herpetic (herpes simplex virus), and viral (cytomegalovirus). Odynophagia is a common presenting complaint. Endoscopy with biopsy and cultures is required for diagnosis. Treatment is directed toward the causative organism(s).

• Radiation esophagitis may occur with radiation treatment for cancers located in the chest (ie, lung, esophagus, mediastinum). Healing may not occur for several months after cessation of radiation therapy. Treatment is with viscous lidocaine and sucralfate. Stricture formation is a common complication and may require endoscopy for dilation.

• Pill-induced esophagitis is caused by ingesting medication with insufficient liquid and may be prevented by drinking larger quantities of fluid with medication. Certain medications (eg, iron, potassium, quinidine, tetracyclines, NSAIDs, aspirin, steroids) are more likely to cause esophagitis.

Esophageal carcinoma – pathophysiology

• Esophageal carcinoma arises in the mucosa. Subsequently, it tends to invade the submucosa and the muscular layer and, eventually, contiguous structures such as the tracheobronchial tree, the aorta, or the recurrent laryngeal nerve.

• The tumor also tends to metastasize to the periesophageal lymph nodes and, eventually, to the liver, lungs, or both.

• Unfortunately, by the time the first symptoms manifest, the cancer has already spread to lymph nodes (mediastinal, cervical, celiac) in most patients

Esophageal cancer - epidemiology

• Esophageal cancer is the seventh leading cause of cancer death worldwide. Incidence of esophageal carcinoma can be as high as 30-800 cases per 100,000 persons in particular areas of northern Iran, some areas of southern Russia, and northern China. Unlike in the United States, squamous cell carcinoma is responsible for 95% of all esophageal cancer worldwide.

• In the USA over the last 2 decades, the incidence of adenocarcinoma of the distal esophagus and gastroesophageal junction has progressively increased

• more common in men than in women, with a male-to-female ratio of 7:1

• occurs most commonly during the sixth and seventh decades of life

Esophageal cancer – medical history

• Dysphagia is the most common presenting symptom.– Dysphagia is initially experienced for solids, but eventually it

progresses to include liquids.– A complaint of dysphagia in an adult should always prompt an

endoscopy to help rule out the presence of esophageal cancer. A barium swallow study is also indicated.

• Weight loss is the second most common symptom.• Pain can be felt in the epigastric or retrosternal area. It

can also be felt over bony structures, representing a sign of metastatic disease.

• Hoarseness caused by invasion of the recurrent laryngeal nerve is a sign of unresectability.

• Respiratory symptoms can be caused by aspiration of undigested food or by direct invasion of the tracheobronchial tree by the tumor. The latter also is a sign of unresectability.

Esophageal cancer – physical

• The goals of the workup are to establish the diagnosis and to stage the cancer.

• The examination findings often are normal.

• Lymphadenopathy in the laterocervical or supraclavicular areas represents metastasis and, if confirmed by needle aspiration or biopsy findings, is a contraindication to surgery

Esophageal cancer – causes

• The etiology of esophageal carcinoma is thought to be related to exposure of the esophageal mucosa to noxious or toxic stimuli, resulting in a sequence of dysplasia to carcinoma in situ to carcinoma.

Esophageal cancer – causes

• Potential contributing factors for squamous cell carcinoma include the following:– Chronic ingestion of hot liquids or foods is a contributing factor.– Vitamin or nutritional deficiencies have been recognized as contributing

factors.– Poor oral hygiene may lead to esophageal cancer.– Exposure to nitrosamines in the environment or food has been linked to

esophageal cancer.– In Western cultures, cigarette smoking and chronic alcohol exposure are

the most common etiological factors for squamous cell carcinoma.– Certain medical conditions (eg, Plummer-Vinson syndrome) and caustic

injury to the esophagus are associated with an increased incidence of esophageal cancer.

– Human papilloma virus infection has been recognized as a contributing factor.

– Tylosis palmaris at plantaris is also implicated.

Esophageal cancer – causes

• GERD is the most common predisposing factor for adenocarcinoma of the esophagus.

– As a consequence of the irritation caused by the reflux of acid and bile, 10-15% of patients who undergo endoscopy for evaluation of GERD symptoms are found to have Barrett epithelium.

– Adenocarcinoma may develop in these patients, representing the last event of a sequence that starts with the development of GERD and progresses to (Barrett) metaplasia, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma

– In 1952, Morson and Belcher first described a patient with adenocarcinoma of the esophagus arising in a columnar epithelium with goblet cells. In 1975, Naef et al emphasized the malignant potential of Barrett esophagus. With the premalignant nature of Barrett esophagus well established, many investigators have searched for markers of esophageal carcinoma that could facilitate earlier diagnosis and follow-up of tumor recurrence.

– The risk of adenocarcinoma among patients with Barrett metaplasia has been estimated to be 30-60 times that of the general population.

– The oncosuppressor gene TP53 and various oncogenes, particularly erb-b2, have been studied as potential markers. Casson and colleagues identified mutations in the TP53 gene in patients with Barrett epithelium associated with adenocarcinoma.

– A nationwide population-based case-control study performed in Sweden found an odds ratio of 7.7 (95% confidence interval, 5.3-11.4) for adenocarcinoma among persons with recurrent symptoms of reflux, as compared with persons without such symptoms, and an odds ratio of 43.5 (95% confidence interval, 18.3-103.5) among patients with long-standing and severe symptoms of reflux.

Esophageal cancer – differentials

• Esophageal Stricture

Esophageal cancer – lab studies

• Complete blood cell count may demonstrate anemia secondary to iron deficiency or chronic disease.

• Findings from a chemistry 18 panel may demonstrate liver function abnormalities due to ingestion of alcohol or may reflect hepatic metastases. Patients with squamous cell carcinomas may demonstrate hypercalcemia.

• Prothrombin time and activated partial thromboplastin time coagulation study findings may demonstrate hepatic insufficiency or nutritional deficiencies and are part of preoperative screening.

Esophageal cancer – imaging studies

• Barium swallow is very sensitive for helping detect strictures and intraluminal masses

• Performing esophagogastroduodenoscopy allows direct visualization and biopsies of the tumor

• Endoscopic ultrasound is the most sensitive test to help determine the depth of penetration of the tumor (T staging) and the presence of enlarged periesophageal lymph nodes (N staging).

• Abdominal and chest CT scans are useful to help exclude the presence of metastases (M staging) to the lungs and liver and may be useful to help determine if adjacent structures have been invaded

• Bronchoscopy is indicated for cancers of the middle and upper third of the thoracic esophagus to help exclude invasion of the trachea or bronchi.

• Bone scan is indicated in patients with complaints suggestive of bone metastases.

• Laparoscopy and thoracoscopy have a greater than 92% accuracy in staging regional nodes.

• A new modality for staging is positron emission tomography scanning, which can help elucidate hypermetabolic foci of disease activity.

Esophageal cancer – treatment

• Surgery• Nonoperative therapy is usually reserved for

patients who have esophageal carcinoma and are not candidates for surgery. The goal of therapy for these patients is palliation of dysphagia, allowing them to eat. A single best method of palliation cannot be applied to every situation. Most patients require more than one palliative method to sustain lumen patency during the course of their disease.

Esophageal cancer – treatment

– Chemotherapy as a single modality has limited use. Only a few patients achieve a modest and short-lived response.

– Radiation therapy is successful in relieving dysphagia in approximately 50% of patients. In patients with advanced esophageal cancer, the preoperative combination of chemotherapy and radiotherapy has shown good results. In a large multicenter study, Herskovich and colleagues reported a 2-year survival rate of 38%, with a median survival of 12.5 months.

– Laser therapy (Nd:YAG laser) can help achieve temporary relief of dysphagia in as many as 70% of patients. Multiple sessions are usually required to keep the esophageal lumen patent.

– Patients may be intubated with expandable metallic stents, which can be deployed by endoscopy under fluoroscopic guidance and can keep the esophageal lumen patent. They are particularly useful when a tracheoesophageal fistula is present.

Esophageal cancer – prognosis

• Survival depends on the stage of the disease. Lymph node metastases or solid organ metastases are associated with low survival rates.

• A recent report of 1085 patients who underwent THE (transhiatal esophagectomy) for cancer showed that the operation was associated with a 4% operative mortality rate and a 23% 5-year survival rate. A subgroup of patients with a better 5-year survival rate (48%) was identified. These patients received preoperative radiation and chemotherapy (ie, neoadjuvant therapy), with complete response (ie, disappearance of the tumor).

• The overall 5-year survival rate for esophageal cancer remains approximately 20-25% for all stages.– Patients without lymph node involvement have a significantly better

prognosis and 5-year survival rate compared to patients with involved lymph nodes.

– Stage IV lesions are associated with a 5-year survival rate of less than 5%

Hiatal hernia

• occurs when a portion of the stomach prolapses through the diaphragmatic esophageal hiatus

• association with gastroesophageal reflux disease (GERD) and its complications

• the majority of hiatal hernias are asymptomatic and are discovered incidentally

• on rare occasion, a life-threatening complication, such as gastric volvulus or strangulation, may present acutely.

Hiatal hernia

• hiatal hernias are more common in Western countries. The frequency of hiatus hernia increases with age, from 10% in patients younger than 40 years to 70% in patients older than 70 years.

• fiber-depleted diet leads to a state of chronic constipation and straining during bowel movement, which could explain the higher incidence of this condition in Western countries

Hiatal hernia - epidemiology

• Paraesophageal hernias generally tend to enlarge with time, and sometimes the entire stomach is found within the chest. The risk of these hernias becoming incarcerated, leading to strangulation or perforation, is approximately 5%.

• More common in women than in men (pregnancy?)

• Muscle weakening and loss of elasticity as people age is thought to predispose to hiatus hernia, based on the increasing prevalence in older people

Hiatal hernia – medical history

• Most people with hiatal hernias are asymptomatic

• Hiatal hernias may predispose to reflux or worsen existing reflux in a minority of individuals

• Patients can have reflux without a demonstrable hiatal hernia.

• No clear correlation exists between the size of a hiatal hernia and the severity of the symptoms

Hiatal hernia – medical history

• Esophageal complications

– By far, the majority of hiatal hernias are asymptomatic.

– Often, patients are left with the impression that they have a disease when a hiatal hernia is diagnosed.

– In rare cases, however, a hiatal hernia may be responsible for intermittent bleeding from associated esophagitis, erosions (Cameron ulcers), or a discrete esophageal ulcer, leading to iron-deficiency anemia. This particular complication is more likely in patients who are bed-bound or those who take nonsteroidal anti-inflammatory drugs. Massive bleeding is rare.

• Nonesophageal complications– Incarceration of a

hiatal hernia is rare and is observed only with paraesophageal hernia.

– When this occurs, it can present abruptly, with a sudden onset of vomiting and pain, sometimes requiring immediate operative intervention.

Hiatal hernia - physical

• The physical examination usually is unhelpful. Certain conditions predispose to the development of hiatus hernia. These include obesity, pregnancy, and ascites

Hiatal hernia – lab studies

• The typical reasons for evaluation are symptoms of GERD or a chest x-ray suggesting a paraesophageal hernia

• Barium upper gastrointestinal series– Although a chest x-ray may reveal a large hiatal hernia, and

many incidentally diagnosed hiatal hernias are discovered in this manner, a barium study of the esophagus helps establish the diagnosis with greater accuracy.

– Typical findings include an outpouching of barium at the lower end of the esophagus, a wide hiatus through which gastric folds are seen in continuum with those in the stomach, and, occasionally, free reflux of barium.

– A barium study helps distinguish a sliding from a paraesophageal hernia. In rare cases, the entire stomach may herniate into the chest. The stomach may then undergo volvulus and subsequent incarceration and strangulation.

Hiatal hernia – lab studies (2)

• Endoscopy– Hiatal hernia is diagnosed easily using upper gastrointestinal

endoscopy.– The diagnosis of a hiatal hernia actually is incidental, and

endoscopy is used to diagnose complications such as erosive esophagitis, ulcers in the hiatal hernia, Barrett esophagus, or tumor.

– A hiatal hernia is confirmed when the endoscope is about to enter the stomach or on retrograde view once inside the stomach. If any doubt remains, the patient may be asked to sniff through the nose, which causes the diaphragmatic crura to approximate, seen as a pinch, closing the lumen.

– Endoscopy also permits biopsy of any abnormal or suspicious area.

Hiatal hernia – treatment

• When hiatal hernias are symptomatic, acid reflux usually produces the symptoms. If the hernia itself is causing chest discomfort or other symptoms, surgery may be necessary.

• When symptoms are due to GERD, the goals of treatment include prevention of reflux of gastric contents, improved esophageal clearance, and reduction in acid production. This is achieved in the majority of patients by a combination of the following:– Modifying lifestyle factors– Neutralizing acid or inhibiting acid production– Enhancing esophageal and gastric motility

Hiatal hernia – treatment (2)• Most patients with a paraesophageal hernia remain asymptomatic.

In this type of hernia, symptoms from acid reflux usually do not occur. Instead, the most common symptom is epigastric or substernal pain. Some patients complain of substernal fullness, nausea, and dysphagia.– A significant proportion of patients with this type of hernia develop

incarceration of the hernia and possible gastric volvulus, which can lead to perforation.

– If perforation occurs, the mortality rate is high. Because of this, many surgeons advise elective repair when the diagnosis is made.

– The goal of surgery is to remove the hernia sac and close the abnormally wide esophageal hiatus.

– Some surgeons then tack the stomach down in the abdomen to prevent it from migrating upwards again, or, they perform a temporary gastrostomy to help decompress the stomach and anchor it in place in the abdominal cavity.

Hiatal hernia – medication

• An appropriate diet maintains an ideal body mass index. Obesity predisposes to reflux disease.

• fiber-depleted diet leads to a state of chronic constipation and straining during bowel movement

• Symptomatic acid reflux can be treated medically either by neutralizing acid with antacids or blocking acid secretion with H2-receptor blocking drugs or the more potent PPIs.

• Hiatal hernias per se only require attention if they are causing symptoms because of their size or are at risk of strangulation where surgery may be indicated.

Hiatal hernia – pitfalls

• Physicians may miss cardiac disease, chronic lung disease, Barrett esophagus, strictures, and asthma.

• Distinguishing the more common and benign sliding hernia from the paraesophageal type is important

Gastritis

• includes a myriad of disorders that involve inflammatory changes in the gastric mucosa, including erosive gastritis caused by a noxious irritant, reflux gastritis from exposure to bile and pancreatic fluids, hemorrhagic gastritis, infectious gastritis, and gastric mucosal atrophy

Peptic ulcer disease

• refers to a discrete mucosal defect in the portions of the gastrointestinal tract (gastric or duodenal) exposed to acid and pepsin secretion.

• presentations of gastritis and PUD usually are indistinguishable in the Emergency Department and the management is generally the same.

Gastritis and PUD - pathophysiology

• The mechanisms of mucosal injury in gastritis and PUD are thought to be an imbalance of aggressive factors, such as acid production or pepsin, and defensive factors, such as mucus production, bicarbonate, and blood flow.

• Erosive gastritis usually is associated with serious illness or with various drugs. Stress, ethanol, bile, and nonsteroidal anti-inflammatory drugs (NSAIDs) disrupt the gastric mucosal barrier, making it vulnerable to normal gastric secretions

Gastritis and PUD - pathophysiology

• Infection with Helicobacter pylori, a short, spiral-shaped, microaerophilic gram-negative bacillus, is the leading cause of PUD and is associated with virtually all ulcers not induced by NSAIDs. H pylori colonize the deep layers of the mucosal gel that coats the gastric mucosa and presumably disrupts its protective properties. H pylori is thought to infect virtually all patients with chronic active gastritis.

• NSAIDs and aspirin also interfere with the protective mucus layer by inhibiting mucosal cyclooxygenase activity, reducing levels of mucosal prostaglandins. Many people with known H pylori colonization or who are taking NSAIDs do not suffer from gastritis or PUD, which indicates other important causative factors must be involved.

Gastritis and PUD - epidemiology

• Frequency of PUD is decreasing in the developed world but increasing in developing countries

• Complications of gastritis include PUD and, rarely, extensive bleeding.

• The mortality rate is low.• Male-to-female ratio of gastritis is approximately 1:1• Male-to-female ratio of PUD is approximately 2:1• An estimated 60% of Americans older than 60 years

harbor H pylori.• Duodenal ulcers usually occur in those aged 25-75

years.• Gastric ulcer incidence peaks in those aged 55-65 years

Gastritis and PUD – medical history

• Patients typically present with abdominal pain that has the following characteristics:– Epigastric to left upper quadrant– Frequently described as burning– May radiate to the back– Usually occurs 1-5 hours after meals– May be relieved by food, antacids (duodenal), or vomiting

(gastric)– Typically follows a daily pattern specific to patient

• NSAID-induced gastritis or ulcers are usually silent.• Sudden onset of symptoms may indicate perforation.• Gastritis may present as bleeding, which is more likely in

elderly patients.• Symptoms consistent with anemia (eg, fatigue, dyspnea)

may manifest.

Gastritis and PUD – physical

• Epigastric tenderness is present and usually mild.

• Bowel sounds are normal.

• Signs of peritonitis or GI bleeding may manifest. Perform a rectal examination and Hemoccult testing.

Gastritis and PUD – causes

• H pylori (most common cause of ulceration)• NSAIDs, aspirin• Gastrinoma (Zollinger-Ellison syndrome)• Severe stress (eg, trauma, burns), Curling ulcers• Alcohol• Bile reflux• Pancreatic enzyme reflux• Radiation• Staphylococcus aureus exotoxin• Bacterial or viral infection

Gastritis and PUD – differentials

• Acute Coronary Syndrome [Aneurysms, Abdominal]• Cholangitis Cholecystitis and Biliary Colic Cholelithiasis • Diverticular Disease • Esophagitis • Gastroenteritis • Hepatitis • Inflammatory Bowel Disease• Mesenteric Ischemia • Myocardial Infarction • Pancreatitis • Pulmonary Embolism• Renal Calculi

Gastritis and PUD – differentials

• Gastric cancer• Esophageal varices• Mallory-Weiss tears• Atrophic gastritis• Nonulcer dyspepsia• Functional gastrointestinal disorder• Atypical appendicitis in the pregnant

patient

Gastritis and PUD – lab studies

• Complete blood count test is used to evaluate acute or chronic blood loss.

• Electrolytes, BUN, and creatinine are useful tests for critical-appearing patients who require fluid resuscitation.

• Type, crossmatch, and screen are indicated if transfusion in unstable or potentially critical patients is needed.

• While a blood test for H pylori exists, it is of limited value in the acute setting.

Gastritis and PUD – other studies

• A chest x-ray may be useful to detect free abdominal air when perforation is a possibility

• Relief of symptoms with a GI cocktail is not a diagnostic indicator

• Placement of a nasogastric (NG) tube is helpful to evaluate for upper GI bleeding.

Gastritis and PUD – treatment

• Most patients do not require acute interventions.• Antacids or a GI cocktail (ie, typically an antacid with an anesthetic such as viscous

lidocaine and/or an antispasmodic) may be used therapeutically.• Administer supportive therapy as needed.• Massive gastric bleeds are the most difficult complication to treat. Mainstays of

resuscitation include the following:– Begin volume replacement, initially with crystalloid. In the face of continued hypotension

after 2 L, consider blood transfusion.– NG suction helps to keep the stomach empty and contracted.– IV H2 antagonists are recommended but unproven in acute upper GI bleeds.

• Emergent surgical or endoscopic intervention may be required.• The ED is not the place to distinguish between gastritis and PUD, which usually

requires endoscopy or contrast radiography. Gastric mucosal biopsy culture, 13C-urea breath test, or enzyme-linked immunosorbent assay (ELISA) for H pylori immunoglobulins aid the physician in diagnosing H pylori infection. These tests are not performed in the ED.

• H2-receptor blockers and proton pump inhibitors probably have no major effect on the acute management of gastritis and peptic ulcer disease. Effect of treatment takes several weeks.

Gastritis and PUD – treatment (2)

• Treatment goals are the relief of discomfort and protection of the gastric mucosal barrier to promote healing.

• Eradication of H pylori infection is a prolonged and complicated process requiring confirmation of the presence of the organism

• Cessation of the causative agent and antacids may be sufficient outpatient therapy in mild cases.

• Most patients require an H2-receptor antagonist or a proton pump inhibitor, which has been proven to provide faster and more reliable healing than antacids.

• Either an H2-receptor blocker or a proton pump inhibitor can be used as a first-line agent. With continued symptoms, they may be used together. In refractory cases, sucralfate also may be indicated

Gastritis and PUD – medication (1)

• Antacids -- Aluminum-containing and magnesium-containing antacids can be helpful in relieving symptoms of gastritis by neutralizing gastric acids. These agents are inexpensive and safe

• H2-receptor antagonists -- Inhibit the action of histamine on the parietal cell, which inhibits acid secretion. The 4 drugs in this class are all equally effective and are available over the counter in half prescription strength for heartburn treatment. Although the IV administration of H2 blockers may be used to treat acute complications (eg, GI bleeding), the benefits are yet to be proven.

• Proton pump inhibitors -- Bind to the proton pump of parietal cell, inhibiting secretion of hydrogen ions into gastric lumen. Proton pump inhibitors relieve pain and heal peptic ulcers more rapidly than H2 antagonists. Drugs in this class are equally effective. They all decrease serum concentrations of drugs that require gastric acidity for absorption, such as ketoconazole or itraconazole. There are now five drugs FDA approved in this category. Omeprazole will soon go off patent and be available as a generic

Gastritis and PUD – medication (2)

• Gastrointestinal agents (Sucralfate) -- Are effective in the treatment of peptic ulcers and in preventing relapse. Their mechanism of action is not clear. Multiple doses are required, and they are not as effective as the other options

• Prostaglandins (Misoprostol - Cytotec) -- Can prevent peptic ulcers in patients taking NSAIDs and may be used with NSAIDs in patients at a high risk of complications.

Gastritis and PUD - Inpatient care

• Patients with significant or potentially significant hemorrhage require admission, usually to the intensive care unit. While in the ED, their care should focus on restoration of intravascular volume by infusion of saline or blood through large bore IV lines as clinically indicated. A central venous catheter to monitor such resuscitation may be considered.

• High-risk patients include those with the following characteristics:– Bleeding with hemodynamic instability– Repeated hematemesis or any hematochezia– Failure to clear with gastric lavage– Coagulopathy– Comorbid disease (especially cardiac, pulmonary, or renal)– Advanced age

• Patients with evidence of gastric perforation require operative repair.• Hospitalization usually is necessary for gastric outlet obstruction to provide

gastric rest and IV fluids. Surgical treatment usually is indicated for persistent or recurrent obstruction. Anticholinergic agents are contraindicated.

Gastritis and PUD - outpatient care

• A follow-up visit should be made in 2-6 weeks to evaluate efficacy of treatment.

• Severe or recurrent symptoms indicate prompt referral for endoscopy and testing for H pylori.

• Symptomatic relief with therapy does not preclude malignancy

Gastritis and PUD - complications

• Malignancy

• Hemorrhage

• Perforation

• Obstruction

Gastritis and PUD - pitfalls

• Failure to consider other more catastrophic etiologies for epigastric pain, including myocardial infarction and abdominal aortic aneurysm

• Failure to consider gastric hemorrhage in absence of abdominal pain, especially in elderly patients

• Failure to refer patients for follow-up care may result in failure to diagnose H pylori infection or gastric cancer

Crohn disease

• An idiopathic, chronic, transmural inflammatory process of the bowel that can affect any part of the GI tract from the mouth to the anus.

• The condition is believed to be the result of an imbalance between proinflammatory and anti-inflammatory mediators.

• Most cases involve the small bowel, particularly the terminal ileum.

• The characteristic presentation of Crohn disease is with abdominal pain and diarrhea, which may be complicated by intestinal fistulization, obstruction, or both.

• Unpredictable flares and remissions characterize the long-term course of this illness.

Crohn disease - epidemiology

• Crohn disease usually has a chronic, indolent course regardless of the site of involvement.

• The chance of death increases with the duration of the illness. • As the disease progresses, medical therapy becomes less effective,

and most patients develop complications requiring surgery. • The disease frequently recurs after surgery. • more common in whites than in blacks or Asians • 2- to 4-fold increase in the prevalence of Crohn disease has been

found among the Jewish population in the United States, Europe, and South Africa compared to other ethnic groups.

• The male-to-female ratio is 1.1-1.8:1. • The onset of Crohn disease has a bimodal distribution. The first

peak occurs between the ages of 15-30 years; the second, between 60-80 years. However, most cases begin before age 30 years

Crohn disease – medical history (1)

• Patients with Crohn disease most commonly present with symptoms related to a chronic inflammatory process involving the ileocolic region.– Low-grade fevers, weight loss, and generalized

fatigability are usually reported.– The patients may develop crampy or steady right

lower quadrant or periumbilical pain. The pain precedes and is often relieved by defecation. Diarrhea is nonbloody and often intermittent.

– If the colon is involved, patients may report diffuse abdominal pain accompanied by mucus, blood, and pus in the stool.

Crohn disease – medical history (2)

• Patients may also present with complaints suggestive of intestinal obstruction.– Initially, the obstruction is secondary to inflammatory edema and spasm

of the bowel and manifests as postprandial bloating, cramping pains, and loud borborygmi. Once the bowel lumen becomes chronically narrowed, patients complain of constipation and obstipation. Complete obstruction may sometimes be caused by impaction of undigested foods.

– Perianal fissures or fistulae are common.– Cologastric, enterovesical, enterovaginal, and enterocutaneous fistulae

may manifest as feculent vomiting, recurrent urinary tract infections and pneumaturia, feculent vaginal discharge, and feculent soiling of the skin.

– Development of fistulae into the mesentery may result in intra-abdominal or retroperitoneal abscess formation.

– Patients may also have perianal disease, including perianal fissures, abscesses, and fistulae

Crohn disease – medical history (3)

• Patients may have problems related to extraintestinal manifestations of the disease, which may involve the skin, joints, mouth, eyes, liver, and bile ducts.

• Young people with Crohn disease commonly experience unexplained growth failure and delayed puberty

Crohn disease – physical

• Physical examination should focus on the patient's temperature, weight, nutritional status, presence of abdominal tenderness or a mass, perianal and rectal examination findings, and extraintestinal manifestations.

• Physical findings may typically reveal right lower quadrant tenderness. A mass can sometimes be felt secondary to thickened or matted loops of inflamed bowel.

• Perianal involvement manifests as skin tags, fistulae, abscesses, and scarring.

Crohn disease – causes

• Genetic?

• Environmental?

• Microbial?

• Immunologic?

• Dietary?

• Vascular?

• psychosocial factors?

Crohn disease – differentials

• Amebiasis• Carcinoid Tumor• Intestinal

Diverticulitis

Other Problems to be Considered: • Acute appendicitis• Ileocecal tuberculosis• Systemic vasculitis• Tubo-ovarian pathologies• Endometriosis • Yersinia enterocolitica

Crohn disease – lab studies (1)• Laboratory study findings may indicate the presence of

inflammatory activity or nutritional deficiencies.– Anemia may be due to multiple causes, including chronic

inflammation, iron malabsorption, or, more likely, chronic blood loss and malabsorption of vitamin B-12 or folate.

– Leukocytosis may be due to chronic inflammation, abscess, or steroid treatment.

– Hypoalbuminemia, hypocholesterolemia, hypocalcemia, hypomagnesemia, and hypoprothrombinemia may reflect malabsorption.

– Acute inflammatory markers, such as C-reactive protein and orosomucoid, correlate closely with disease activity. The erythrocyte sedimentation rate is thought to be more helpful in assessing the disease activity of Crohn colitis than ileitis.

– Stool samples should be tested for routine pathogens, ova, parasites, and Clostridium difficile toxin.

Crohn disease – lab studies (2)

• Two serologic tests are available to attempt to differentiate ulcerative colitis (UC) from Crohn disease.– Perinuclear antineutrophil cytoplasmic antibody (p-

ANCA), a myeloperoxidase antigen, is more commonly found in UC, whereas antibodies to the yeast Saccharomyces cerevisiae (ie, anti-S cerevisiae antibodies [ASCA]) are more commonly found in Crohn disease.

– Therefore, a test result positive for p-ANCA antigen and negative for ASCA suggests the diagnosis of UC; conversely, a test result positive for ASCA and negative for p-ANCA antigen suggests the presence of Crohn disease

Crohn disease – imaging studies(1)

• Barium contrast studies– These studies are very useful in defining the nature, distribution, and severity of the disease.

An experienced radiologist should perform these studies to obtain the most information.– An upper GI series, together with a small-bowel follow-through and spot films of the terminal

ileum is the initial diagnostic procedure of choice in most patients presenting with typical symptoms of Crohn disease.

– Barium enema may help evaluate colonic lesions once the patient can tolerate the procedure. Barium contrast studies are useful in evaluating features such as rigidity, pseudodiverticula, fistulization, and submucosal edema. These studies are noninvasive and usually well tolerated. In patients with ileitis, the terminal ileum may not be visualized, possibly because of spasm of the ileocecal valve.

– Radiographic findings in both the small and large bowel parallel the clinical pattern.– Edema and ulceration of the mucosa in the small bowel may appear as thickening and

distortion of valvulae conniventes. Edema of the deep layers of the bowel wall results in separation of the barium-filled bowel loops.

– Tracking of deep ulcerations, both transversely and longitudinally, results in a cobblestone appearance.

– Ileitis can also manifest as a sting sign on barium study secondary to spasm or, rarely, because of fibrotic stricturing.

– Enteroenteric fistula and fistula to nearby organs can also be detected by barium studies.

Crohn disease – imaging studies(2)

• CT scan is helpful in assessing extramural complications such as fistulae, abscesses, and hepatobiliary and renal complications.

• MRI can be superior to CT scanning in demonstrating pelvic lesions.

• Ultrasound is helpful in differentiating tubo-ovarian pathology.

• Radionucleotide scans may be helpful in assessing the severity and extent of the disease in patients who are too ill to undergo colonoscopy or barium studies

Crohn disease – procedures (1)

• Colonoscopy– Consider colonoscopy if a single-contrast barium

enema has proved to be less informative in evaluating a colonic lesion.

– Colonoscopy is useful in obtaining biopsy tissue, which helps in differentiation of other diseases, in evaluation of mass lesions, and in performance of cancer surveillance.

– Colonoscopy also enables dilatation of fibrotic strictures in patients with long-standing disease.

Crohn disease – procedures (2)

• Upper endoscopy– Upper endoscopy with biopsy is helpful in

differentiating Crohn disease from peptic ulcer disease in patients with upper GI tract symptoms.

– Endoscopic retrograde cholangiopancreatography is helpful as both a diagnostic and a therapeutic tool in patients with sclerosing cholangitis and stricture formation.

Crohn disease – treatment (1)• Diarrhea

– Chronic diarrhea responds well to antidiarrheal agents such as loperamide (2-4 mg), diphenoxylate with atropine (1 tab), and tincture of opium (8-15 gtt). Such agents may be administered up to 4 times daily but should not be given to patients with active colitis because of the risk of developing toxic megacolon.

– Patients with terminal ileal disease cannot absorb bile acids, which can lead to secretory diarrhea in the colon. These patients benefit from bile acid sequestrants (eg, cholestyramine [2-4 g], colestipol [5 g] bid/tid ac). Those who have extensive ileal disease or resection of more than 100 cm of ileum have defective bile salt absorption and develop steatorrhea. These patients benefit from a low-fat diet. Bile sequestrants exacerbate this type of diarrhea.

– Diarrhea may also develop because of bacterial overgrowth, short-bowel syndrome, and lactase deficiency.

– Abdominal cramps may be reduced with propantheline (0.125 mg), dicyclomine (10-20 mg), or hyoscyamine (0.125 mg). These drugs should not be used if a bowel obstruction is considered possible.

Crohn disease – treatment (2)• For colon and small-bowel inflammation, anti-inflammatory drugs or antibiotics are

helpful.– Sulfasalazine is mainly useful in colonic disease because the active compound, 5-

aminosalicylic acid (5-ASA), is released in the large bowel by bacterial degradation of the parent compound. Sulfasalazine does not alleviate small-bowel disease. Products such as mesalamine (Asacol) that release 5-ASA in the distal small bowel secondary to pH changes are more useful in patients with small intestinal Crohn disease. Long-term maintenance with mesalamine (800 mg tid) may delay clinical relapse. Sulfasalazine does not have an additive effect or a steroid-sparing effect when used in conjunction with corticosteroids. In contrast to its action in UC, it does not seem to maintain remission in Crohn disease.

– A short course of steroid therapy is indicated in patients with severe systemic symptoms (eg, fever, nausea, weight loss) and in those who do not respond to anti-inflammatory agents. Prednisone (40-60 mg/d) is generally helpful in acute inflammation. Once remission is achieved, slowly taper steroids (5-10 mg q1-2wk).

– In patients who relapse after withdrawal of steroids, other treatment options are required. Steroids are not indicated for maintenance therapy because of serious complications such as aseptic necrosis of the hip, osteoporosis, cataract, diabetes, and hypertension.

– In patients with a tender palpable mass, exclude an underlying abscess before starting steroids. Adding antibiotics is always beneficial if coexisting infection is considered likely.

– Consider immunosuppressants such as azathioprine (2 mg/kg/d) or its active metabolite, 6-mercaptopurine (6-MP), if steroid withdrawal proves difficult. Response is usually observed within 3-6 months. Careful supervision is needed because of the risk of bone marrow suppression.

– If medical therapy fails, surgical resection of the inflamed bowel, with restoration of continuity, is indicated. Urgent surgery may be required in rare cases of sustained or recurrent hemorrhage and toxic megacolon.

Crohn disease – treatment (3)• Fistulae between bowel loops (eg, ileoileal, ileocecal, ileosigmoid)

are usually benign and may not produce any major problems. • Enterovesicular, enterocutaneous, cologastric, and coloduodenal

fistulae are more serious. Surgical intervention is rarely required unless fistulae are complicated by progressive obstruction or abscess formation or a large segment of bowel is bypassed, leading to severe diarrhea and malabsorption. Otherwise, medical management is used to treat underlying infections and symptoms with oral metronidazole (1 g/d) for at least 1-2 months. Ciprofloxacin confers additional benefit if no improvement occurs.

• Antimetabolites are beneficial in reducing drainage and closing fistulae in 30-40% of patients. Total parenteral nutrition (TPN) and bowel rest may promote fistula healing during medical therapy.

Crohn disease – treatment (4)• New medical therapies:

– Anti–tumor necrosis factor (TNF) antibody: TNF, a key inflammatory cytokine and mediator of intestinal inflammation, is expressed prominently in IBD. Infliximab is a chimeric mouse-human monoclonal antibody against TNF and shows promise in Crohn disease. It blocks TNF in the serum and at the cell surface, leading to the lysis of TNF-producing macrophages and T cells. In one study, nearly 65% of refractory cases of Crohn disease responded well to treatment with infliximab (5 mg/kg), and a third went into complete remission. Patients who relapsed after initial response responded again to further infusions. Infliximab is also effective in patients who have refractory perianal and enterocutaneous fistulae. On average, the effect lasts for 12 weeks. Important adverse effects include the development of a lupuslike syndrome and an increased incidence of tuberculosis. Anti–double-stranded DNA is not always associated with clinical lupus.

– Immunosuppressive agents: Tacrolimus may be effective in treating extensive Crohn disease.

– Mycophenolate mofetil acts by inhibiting a de novo pathway of purine synthesis in lymphocytes, leading to intracellular depletion of guanosine monophosphate. This results in the suppression of cytotoxic T cells and formation of antibodies by activated B cells. A dose of 500 mg twice a day in 2 divided doses is well tolerated by patients and can be used to reduce the steroid dose.

– Anti-inflammatory cytokines: Interleukin 10 (IL-10) and interleukin 11 (IL-11) are anti-inflammatory cytokines and have been found by some researchers to elicit a moderate response in Crohn disease; however, more trials are needed.

Crohn disease – medication

• Anti-inflammatory agents (Mesalamine) -- Reduce inflammation by acting on host responses

• Immunosuppressants (Infliximab) -- Interfere with development of immunological responses

• Antibiotics (Metronidazole) -- Treatment of bacterial infections that may be associated with the underlying disease processes.

• Corticosteroids (Prednisolone) -- Exert both anti-inflammatory and immunosuppressant effects.

Crohn disease – complications• Obstruction: in the initial stages; caused by bowel edema and spasm, which is intermittent and

reversible. • Fistulae occur because of the penetration of a sinus tract through the bowel wall to adjacent

viscera.– Most fistulae are enteroenteric and enteromesenteric. They usually cause no symptoms and

require no treatment.– Coloenteric and cologastric fistulae may result in bacterial overgrowth, diarrhea, and weight

loss.– Enterovesical and enterovaginal fistulae are often complicated by infection.– Enterocutaneous fistulae usually occur at the site of previous surgery, tracking the path of

least resistance.– Many of these fistulae close with the use of TPN but recur when oral feeding resumes.

• Abscess: Tender abdominal mass, fever, and leukocytosis indicate a possible underlying abscess. A CT scan helps confirm the diagnosis. Abscesses are treated with surgical drainage and broad-spectrum antibiotics.

• Hemorrhage: Severe hemorrhage is unusual in Crohn disease.• Malabsorption may occur owing to multiple reasons such as bacterial overgrowth in an

enterocolic fistula, strictures and stasis, extensive disease of the small bowel, and resection of large portions of the small intestine.

• Carcinoma: Patients with colonic disease have an increased risk of colon cancer. The role of screening colonoscopy in such cases is unclear.

Crohn disease – prognosis

• Although Crohn disease is chronic with recurrent relapses, appropriate medical and surgical therapy help patients to have a reasonable quality of life.

• Medical therapy becomes less effective with time, and surgery for underlying complications is required in nearly two thirds of patients at some point in their disease.

• The mortality rate increases with the duration of the disease, and GI tract cancer is the leading cause of disease-related death.

• Acute regional enteritis, often discovered during laparotomy for suspected appendicitis, has an excellent prognosis. The acute episode is treated conservatively, and two thirds of patients may not have subsequent evidence of regional enteritis.

Crohn disease – medication(2)

• Corticosteroids -- Exert both anti-inflammatory and immunosuppressant effects.