e n i c i d e m y r a n o m u P l 197 Table 6.15 Causes of interstitial lung disease Granulomatous diseases Tuberculosis Sarcoidosis Amiodarone Bleomycin Busulfan Nitrofurantoin Sulfasalazine Ankylos ing spondylitis Rheumatoid arthritis SLE Systemic sclerosis Bird fancier \200\231s lung Drugs Connective tissue diseases Extrinsic allergic alveolitis/Hyper- Sensitivity pneumonia (EAA) (p. 184) Farmer \200\231s lung Malt worker \200\231s lung Mushroom picker \200\231s lung Pigeon fanc ier \200\231s lung Asbestosis Berylliosis Pneumoconiosis Silicosis Industrial dust diseases 198 Radiation Chronic pulmonary edema (mitral stenosis) Bronchiolitis obliterans/ organizing pn eumonia Idiopathic pulmonary fibrosis Individuals without evidence of mesothelioma yet with a history of asbestos exposure, with calcified or noncalcified pleural plaques, should be followed regularly; a routine asbestos evaluation includes a history and physical exam and pulmonary function studies, along with CXR and, if necessary, chest CT for detection of pleural or lung parenchyma neoplastic typ e changes and for detection of functional lung changes. Diagnosis: Histology of tissue, fol lowing a pleural biopsy, video-assisted thoracic surgery, or limited thoracotomy. Often the diagnosis is made postmortem. Management/Treatment: Symptomatic care; no effective radiati on therapy or chemotherapy. Prognosis is very poor (<2 yrs, produces 2,400 deaths/yr in the United States). Cor pulmonale Cor pulmonale is defined as secondary right-sided cardiac modifications and r ight ventricular dilation and/or hypertrophy in response to primary lung disease, either pu lmonary vascular or lung parenchymal disorders. Causes include COPD, interstitial fibrosis, pulmonary vascular disorders, and neuromuscular and skeletal diseases (see Table 6.16). Al though cor pulmonale or right-heart failure results from primary lung conditions, the most common caus e of cor pulmonale is left-heart failure. Clinical features Symptoms include dyspnea, fatig ue, or syncope. Signs : Cyanosis, tachycardia, raised JVP with prominent a and v waves, rig ht ven- tricular heave, loud P 2 , pan-systolic murmur (tricuspid regurgitation), early dia stolic Graham Steell murmur, hepatomegaly and edema. Investigations CBC: Hemoglobin and hem atocrit \206\221 (secondary poly- cythemia). ABG: Hypoxia, with or without hypercapnia and /or presence of respiratory acidosis. CXR: Enlarged right atrium and ventricle, prominent p ulmonary arteries. ECG: Right axis deviation; right ventricular hypertro- phy/strain; enlar gement of P waves, P pulmonale. Pulmonary function studies assist in differentiating betwee n obstructive airways disease and restrictive pulmonary disease and in defining severity. E chocardiography reveals pulmonary hypertension, right ventricular func- tion, right ventric ular size, thickness, and paradoxical intraventricular sep- tum motion and gives an assessm ent of left ventricular function and mitral/ aortic valve functions. Management \212Treat underlying cause (e.g., COPD, pulmonary infections, or treatment of e n i c i d e m y r a n o m u P l left ventricular failure). \212Treat respiratory failure : In the acute situation, give 24% oxygen if P a O 2 <60 mm Hg. Monitor ABG and gradually increase oxygen concentration if P a CO 2 is stable. In COPD patients, LTOT for 18 h/d improves survival. Patients with chronic hypoxia, when clinically stable, should be assessed for LTOT. \212Treat cardiac failure with diuretics such as furosemide (e.g., 40 \200\223160 mg/24 h PO). Monitor electrolytes; treat with potassium supplements if neces- sary. Alternative : S pironolactone. 199 Table 6.16 Causes of cor pulmonale \212Lung disease Asthma (severe, chronic) COPD Bronchiectasis Pulmonary fibrosis Lung resection \212Pulmonary vascular disease PE Pulmonary vasculitis Primary pulmonary hypertension Pulmonary hypertension secondary to left-heart failure Sickle-cell disease Parasite infestation \212Thoracic cage abnormality Kyphosis Scoliosis Thoracoplasty \212Neuromuscular disease Myasthenia gravis Poliomyelitis Motor neuron disease \212Hypoventilation Sleep apnea/hypopnea syndrome Obesity Cerebral vascular disease \212 \212 Prognosis Poor; once symptoms and signs of cor pulmonale develop, 50% of patien ts die within 5 yrs. Consider Consider phlebotomy if the hematocrit is >55%. heart \200\223lung transplantation in young patients. Obstructive sleep apnea/hypopnea syndrome Obstructive sleep apnea/hypopnea syndrome is defi ned as daytime sleepi- ness associated with a minimum of five obstructive-type breathing ev ents per hour of sleep; the events are apnea, defined as pauses of breathing last- ing >10 sec, and hypopnea, defined as reduced ventilation by at least 50% for >10 sec during contin uous breathing. The cause of sleep apnea/hypopnea syndrome is related to relaxation of uppe r airway musculature and resultant inward movement of the upper airway soft tissue in inspi ration during sleep. Predisposing factors include excessive weight, BMI of >30; male sex; s hortened jaw and/or mandible; and age 40 \200\22365 yrs. The syndrome may occur in children with enlarged tonsils and adenoids. Clinical points important in completion of the diagnos is include daytime sleepiness, reduced cognitive performance, depression, disturbed sleep, hypertension, morning headaches, decreased libido, increased incidence of auto accidents. C linical factors related to the sleep apnea/hypopnea syndrome are a greater risk of cardiova scular and cerebral vascular events; an association with DM related to increased insulin re sistance; an elevation of liver function stud- ies, unrelated to obesity; and, last, a high er risk of anesthesia and surgical procedures. Diagnosis \212 \212 \212 Investigations S imple studies (pulse oximetry, video recordings) may be all that are required for diagnosis . Polysomnography (which monitors oxy- gen saturation, airflow at the nose and mouth, ecg, and electromyogram [emg] of chest and abdominal wall movement during sleep) is diagnostic. The occurrence of \211 15 episodes of apnea or hypopnea during 1 h of sleep indicates sig nificant sleep apnea. The comparison of home- versus hospital-/ office-based sleep studies reveals the home studies (especially in screening scenarios) are more cost effective, with similar clinical outcomes. Management \212 \212 \212 \212 200 Detailed history from patient and patient \200\231s partner Sleep questionnaire Physical ex amination; BP readings; jaw and oral pharynx exams Weight reduction Avoidance of tobacco and alcohol CPAP Continuous positive airway pressure during sleep is effective. Surgical procedures to relieve pharyngeal obstruction (tonsillec tomy, uvulopalatopharyngoplasty, or tracheostomy) are occasionally necessary. Treatment/Outcomes \212 \212 \212 \212 \212 Without daytime sleepiness and other dayti me performance aberrations, patients with obstructive sleep apnea/hypopnea syndrome have do ubtful clinical outcomes. Reduces sleepiness and improves quality of life Improves cognition Diminishes driving risk Hypertension resolves or is more easily controlled Betterment of work performance Lung transplantation Lung transplantation is performed at a frequency of approximately 2,20 0 cases per year. The underlying pulmonary diseases for which lung trans- plantation is a t reatment option are COPD,30%; interstitial lung disease, 30%; CF, 15%; 1 -antitrypsin de ficiency, 3%; and primary pulmonary artery hypertension, 2%. Recipients of donor lungs basi cally do not have therapeutic options; their predictive transplant survival should be subst antially greater than their native lung disease prognosis. Additionally, the recipient \200 \231s quality of life should be predictably better with lung transplantation than with thei r predicted life quality with their present lung disease. Contraindications for lung transp lantation include HIV infection, chronic hepatitis B and C infection, active smoking, malig nancy (without remission or without cure), and alcohol or drug dependency. The upper age li mit of lung transplant is about 65 \200\22370 yrs. Resistant bacterial infections, noncompl iant persons, and ventilator-dependent individuals are other contraindications for lung tra nsplant. Organ procurement and timing of lung transplantation are based on a pri- ority alg orithm of risk of death on the waiting list versus probability of survival after transplant ation. Candidates are matched for blood type and for lung size. The usual waiting time for transplantation is 6 months; deaths on the waiting list are about 50%. Bilateral lung trans plantation is the surgery of choice, performed in 65% of cases in the United States; bilate ral lung transplants are necessary in CF and in diffuse bronchiectasis, in order to prevent the spread of infection, as may occur in a unilateral transplant scenario. Heart/lung tran splants are utilized in patients with congenital heart-lung disease; single-lung transplant s may be appropriate in other terminal lung diseases. Post-transplant therapy consists of i mmunosuppressive regimens and pro- phylaxis for Pneumocystis -CMV-fungi. Within 3 \200\2236 months after transplanta- tion, stability of lung function occurs; all patients have estab lished follow-up for assessment of quality of life and for screening of complications and s igns of rejection. The most common complication is a primary graft versus host dysfunction, as well as airway complications of bronchiolitis obliterans, acute and chronic rejections, and infections. The cost of single-lung transplantation averages $450,000, whereas the exp ense of bilateral lung transplants is $657,000. Positive outcomes include restoration of lu ng function and an improvement in quality of life; the sur- vival half-life for lung transp lantation is 4 \200\2236 yrs. e n i c i d e m y r a n o m u P l 201 Gastroenterology Ellen M. Stein , M.D. y g o o r e t n e o r t s a l Contents Oral manifestations of GI diseases 202 Healthy, enjoyable eating 203 Dysphagia or odynophag ia 206 Nausea and vomiting 207 Dyspepsia and peptic ulceration 208 Gastroesophageal reflux disease 209 Diarrhea 210 Constipation 213 Jaundice 215 Upper GI bleeding 1 217 Upper GI ble eding 2 and bleeding varices 219 Endoscopy and biopsy 221 Radiological and other GI procedu res 222 G 7 Liver failure 224 Cirrhosis 227 Alcoholism 229 Hereditary hemochromatosis 231 Autoimmune he patitis 232 Wilson \200\231s disease/hepatolenticular degeneration 233 1 -Antitrypsin de ficiency 233 Primary biliary cirrhosis 234 Primary sclerosing cholangitis 235 Liver tumors 236 Ulcerative colitis 238 Crohn \200\231s disease 241 202 Irritable bowel syndrome 242 Carcinoma of the pancreas 244 Nutritional disorders 245 Carcin oid tumors 245 Gastrointestinal malabsorption 248 Oral manifestations of GI diseases The oropharynx can provide diagnostic clues to a variety of GI diseases. Some examples are noted below. Leukoplakia A potentially premalignant whit e thickening of the tongue or oral mucosa. When in doubt, refer all intraoral white lesions . Causes: Poor dental hygiene, smoking, sepsis, aphthous stomatitis, squamous papilloma, ve rruca vulgaris, secondary syphilis. Oral hairy leukoplakia is a painless, shaggy, whitish, streaky patch on the side of the tongue due to Epstein-Barr virus (EBV) that is often seen in patients with AIDS. Necrotizing stomatitis Severe periodontal disease characterized by i nflammation and necrosis of gingiva to adjacent soft tissue and nonalveolar bone. Often see n in patients with AIDS. Aphthous ulcers Minute, painful, shallow white ulcers distributed along mucous membranes. Affects 20% of the population. Causes: Associated conditions includ e oral dental appliances (due to recurrent trauma), inflam- matory bowel disease, Beh et disease, trauma, celiac sprue, erythema mul- tiforme (see PLATE 17), lichen planus, pemphi gus, pemphigoid, infections (herpes simplex, syphilis). Can be seen in otherwise healthy individuals. Treatment can be difficult: Steroid creams, treatment of underlying condition. Candidiasis (thrush) White pa tches or erythema of the buccal mucosa. Patches may be hard to remove and bleed if scraped. Risk fac- tors : Extremes of age, diabetes mellitus (DM), antibiotics, immunosuppres- sion (long-term corticosteroids, including inhalers; cytotoxics; malignancy; HIV). Oropharyngea l candidiasis in an apparently healthy patient suggests underlying HIV infection Treatment: Nystatin swish-and-swallow suspen- sion, fluconazole. Angular cheilitis Fissuring at the a ngles of the mouth. Commonly associated with vitamin B deficiencies (riboflavin, niacin, an d pyridoxine). Infectious causes include Staphylococcus and Candida . Gingivitis Gum inflam mation hypertrophy occurs with poor oral hygiene, drugs (phenytoin, cyclosporin, and nif edipine), pregnancy, vitamin C deficiency (scurvy), acute myeloid leukemia (p. 627), or Vin cent \200\231s angina. Microstomia The mouth is too small due to thickening and tightening of the perioral skin after burns or in epidermolysis bullosa (destructive skin and mucous m embrane blisters ankyloglossia) or systemic sclerosis (p. 412); look for facial telangie ctasia, sclerodactyly, Raynaud \200\231s, calcinosis. Oral pigmentation Perioral melanin sp ots characterize Peutz \200\223Jeghers \200\231 syndrome. Multiple telangiectasias of the b uccal cavity suggest Osler \200\223 Weber \200\223Rendu syndrome. Blue rubber bleb nevi syn drome can present with a mound-like venous anomaly on mucous membranes. Can be a cause of c linically overt or occult GI bleeding Teeth A blue line at the gum \200\223tooth margin sug gests lead poisoning. Prenatal or childhood tetracycline exposure causes yellowish-brown di scoloration. Tongue Ulcerated tongue: May be seen in patients with graft-versus-host diseas e. Associated with tetrad of painful oral mucositis, enteritis, dermati- tis, and hepatic d ysfunction. Glossitis A smooth, red, sore tongue is often caused by iron, folate, or B 12 d eficiency. If local loss of papillae leads to ulcer-like lesions that change in color and s ize, use the term geographic tongue (harmless migratory glossitis). Macroglossia Diffusely enlarged tongue. Look for evidence of repeated tongue biting. Causes: myxedema, acromegaly, amyloid. y g o o r e t n e o r t s a G l 203 Healthy, enjoyable eating There are no good or bad foods, and no universally good or bad di ets. We must not consider diet out of context with a desired lifestyle, nor should we assum e that everyone wants to be thin, healthy, and live forever. Excess body weight has been sh own to increase the risk of progression of diseases like DM, osteoarthritis, and coronary d isease. Providing sound nutritional advice to patients from many backgrounds requires sensi tivity to cultural differences in diet (see Figure 7.1). Current recommendations are based on three facts \212 Obesity is an escalating epidemic, with as much as one-third of the U.S. population now est imated to be obese and estimated costs exceeding $147 billion annually in the United States alone. DM is burgeoning: The Centers for Disease Control (CDC) estimated the U.S. incidenc e of obesity at 9.1% in 2009 [http://www.cdc.gov/diabetes/ statistics/incidence/fig2.html]. Past advice has not changed eating habits in large sections of the population. \212 \212 2010 U.S. Preventive Services Task Force (USPSTF) guidelines recom- mend screening children >6 for obesity and offer intervention and referral. Screening of adults continues to be re commended as well. Advice is likely to focus on: 1 Understand and use body mass index (BMI) : Weight in kilogram/(height in meters) ; aim for 18.5 \200\22325; i.e., eat less, move mor e . Controlling quantity may be more important than quality. In hypertension, eating the \200\234right \200\235 things lowered blood pressure (BP) by 0.6 mm Hg, but controlling wei ght caused a 3.7 mm Hg reduction in 6 months in one randomized trial. BMI 25 to 30, overwei ght; BMI >30, obese. Consider referral to bariatric surgery if diet and exercise fail to im prove BMI, and if BMI is >35 with a comorbidity or BMI >40 alone. (See Surgery.) 2 Consider fish oil: Eat fish rich in omega-3 fatty acid (e.g., mackerel, herring, salmon). This helps those with hyperlipidemia. If canned fish, avoid those in unspecified oils. Nut s are also valuable: Walnuts lower total choles- terol and have one of the highest ratios o f polyunsaturates to saturates (7:1). Soya protein lowers cholesterol, low-density lipoprot eins (LDL), and triglycerides. 3 Use less refined sugar: See Figure 7.1 for its deleterious effects. Use fruit to add swee tness. Have low-sugar drinks. Don \200\231t add sugar to drinks or cereals. 4 Eat enough fruit and fiber: See Figure 7.1. 5 Reduce salt. Avoid this diet if: \212 \212 <5 yrs old Need for low residue (Crohn \200\231s, ulcerative colitis [UC, p. 238]) or speci al diet (celiac [p. 248]) If weight \212 Emphasis may be different in dyslipidemia (p. 108), DM, obesity, constipa- tion, live r failure, chronic pancreatitis, renal failure (less protein), BP \206\221 . loss is expected (e.g., HIV +ve). 204 y g o o r e t n e o r t s a G Figure 7.1 Traditional low-fat nutritional advice: The bal- ance of good health l Fruits and vegetables Bread, other cereals, and potatoes Foods containing fat Foods containing sugar This shows rough proportions of food types that make up the putatively ideal meal. It is a model against which other diets are compared St archy foods: Bread, rice, pasta, potatoes, etc. form the main energy source (especially who lemeal). Increase fluid intake with a diet high in nonstarch poly- saccharide (NSP)(e.g., 8 cups [1 \200\2232 pints] daily). Warn about bulky stools. NSP \206\223 calcium and iron absorption, so restrict main intake to one meal a day. Fruit, vegetables: E.g., >6 differe nt pieces of fruit (ideally with skins) or portions of pulses, beans, or lightly cooked gre ens per day. This may reduce cardiovascular and cancer mortality. Meat and alternatives: Me at should be cooked without additional fat. Lower fat alternatives, such as white meat (pou ltry, without skin), white fish, and vegetable protein sources (e.g., pulses, soya) are enc ouraged. Dairy foods: Low-fat skim milk/yogurt; cottage cheese. Fat and sugary foods: Avoid ing extra fat in cooking is advised ( \200\234grill, boil, roast, steam, or bake, but don \200\231t fry \200\235). Fatty spreads (e.g., butter) are kept to a mini- mum and snack foo ds (potato chips, candies, cookies, or cake) are avoided. Avoiding obesity: Excess sugar ca uses caries, DM, and obesity (this con- tributes to osteoarthritis, cancer, and hypertensio n, and raises oxidative stress, thus raising cardiovascular mortality). Diets for obesity? Recent studies have shown a greater benefit for Mediterranean diets than for low-fat diets at inducing clinically relevant long-term changes in cardiovascular risk and inflammatory m arkers. The Mediterranean diet has been associated with lower all-cause mortality. The Medi terranean diet refers to a primarily plant-based diet originat- ing from the habits of the peoples of Greece and southern Italy. The diet features high intake of fruits, vegetables, legumes, nuts, cereals, and whole-grains; use of olive oil rather than other fat sources; m oderate consumption of fish and poultry and overall low consumption of red meat; moderate u se of wine with meals is permitted. Meat, fish, and alternatives Milk and dairy foods 205 (Continued) Figure 7.1 (Continued) Drugs for obesity? Indicated for a BMI of \211 30 or BMI \211 27 with obesity-related c ondition: high blood pressure (BP), type 2 DM, or dyslipidemia. Orlistat lowers fat absorpt ion (hence SE of oily fecal incontinence). Previous drugs were withdrawn from the market: S ibutramine (volun- tarily withdrawn in 2010) and fenfluramine/dexfenfluramine (withdrawn 19 97). Dysphagia or odynophagia Dysphagia is difficulty in swallowing, and odynophagia is pain wit h swallow- ing. Progressive or new-onset dysphagia lasting >3 wks deserves detailed investi gation. Causes May be classified as oropharyngeal or esophageal: Mechanical block Malignant stricture Esophageal cancer Metastatic cancer Benign strictures Esophageal web or ring Peptic stricture Extrinsic pressure Lung cancer Mediastinal lymph no des Retrosternal goiter Aortic aneurysm Left atrial enlargement Motility disorders Achalasia Diffuse esophageal spasm Systemic sclerosis Myasthenia gravis Bulbar palsy Pseudobulbar palsy Syringobulbia Bulbar poliomyelitis Chagas disease 206 Others Esophagitis Eosinophilic esophagitis Infection ( Candida , herpes simplex virus [HSV ]) Pharyngeal pouch Reflux esophagitis Globus hystericus Clinical features A careful history can establish whether dysphagia or odynophagia is oroph aryngeal or esophageal in location and whether it is neuromuscular or structural in origin. Some discerning questions to ask include: \212 Does dysphagia occur within 1 sec of swallowing? This implicates the oropharyngeal location . Is the dysphagia localized to the retrosternal or subxiphoid region? Often implicates an esophageal source. Was there difficulty in swallowing liquids and solids from the onset? If yes, then likely a motility disorder (achalasia, neurological dysfunction) is pres- ent; i f no, likely a structural abnormality exists (stricture, ring, or web). Is it painful to sw allow? Implicates mucosal disease (e.g., esophageal ulcer- ations due to malignancy, infect ions, or esophagitis). \212 \212 \212 \212 Is the dysphagia intermittent or progressive? Intermittent implies esopha- geal spasm. Does the neck bulge or gurgle on drinking? Suspect a pharyngeal pouch (e.g., Zenker diverticulu m). y g o o r e t n e o r t s a G \212 l Investigations The first question is whether to obtain a barium swal- low study prior to up per endoscopy. Patients with suspected oropha- ryngeal dysphagia or cervical esophageal dys phagia may benefit from a cine-esophagram first. When an endoscopy is performed, the endosc ope is often passed quickly through the upper cervical esophagus. Guiding images can be saf er for patients with strong suspicion of high strictures. In practice, a structural abnorma lity is often adequately treated with upper endoscopy. Findings suggestive of esophageal dy smotility or spasm should be further evaluated with esophageal manometry pH-impedance pr obe. Treatment is based on diagnosis. Specific conditions Diffuse esophageal spasm (DES) is a disease charac- terized by rapid, nonperistaltic wave progression through the esophagus. Symptoms include intermittent dysphagia (30 \200\22360%) chest pain (80 \200\22390%). B arium swallow : Abnormal, nonperistaltic contractions; corkscrew esopha- gus. Manometry : > 20% premature (e.g., contractions or nonperistaltic rapid contractions occurring during wet swallows). Medical therapy includes ade- quate acid control, smooth muscle relaxants, or t ricyclic antidepressants. Achalasia is the most recognized motor disorder of the esophagus, and is characterized by incomplete relaxation of the lower esophageal sphincter (LES) (due to degeneration of the myenteric plexus). Secondary achalasia can result from Chagas \200 \231 disease and pseudoachalasia. Symptoms include dysphagia, regurgitation, substernal cra mps, and weight loss. Barium swal- low : Dilated tapering esophagus (bird \200\231s beak), delay of clearance of barium, and usually without peristalsis. Diagnosis made with manometr y reveals nonpropagating, low-amplitude aperistaltic contractions of the esophagus and inco mplete LES relaxation. Treatment : Chosen depending on age and comorbidities. Surgery : Lap aroscopic Heller myotomy often done with partial fundoplication. Endoscopy: Pneumatic ballo on dilatation, injection of Botox, peroral endoscopic myotomy (POEM; available at specializ ed academic centers). Medication : Smooth muscle relaxants, acid suppression. Benign esopha geal stricture: Caused by gastroesophageal reflux disease (GERD) (p. 209), corrosives, surg ery, or radiotherapy. Treatment is with endoscopic dilatation. Esophageal cancer: Associati ons : GERD, tobacco, alcohol, Barrett esophagus, achalasia. Paterson \200\223Brown \200\223 Kelly (Plummer \200\223Vinson) syndrome: Postcricoid web + iron-deficiency anemia. 207 Nausea and vomiting Nausea is the subjective sensation of an impending urge to vomit, and v omit- ing is the forceful evacuation of gastric contents via the mouth. Causes of nausea an d vomiting are protean and may originate from different body systems. Gross classifications include medications, central nervous system (CNS) disorders, GI and peritoneal disorders, endocrine and metabolic abnormalities, and infectious and miscellaneous causes (such as pre gnancy). Tests Blood tests including comprehensive metabolic panel. A metabolic alkalosis ( pH >7.45, HCO 3 \200\223 \206\221 ) suggests severe vomiting. A plain upright AXR may sug gest a suspected bowel obstruction. Consider upper GI endoscopy if vomiting persists. Ident ify and treat the underlying cause . Treatment Fluids: Give IV fluids for rehydration. Drug s: Various antiemetics may be chosen and administered IV or per rectum, if not tolerated or ally. Avoid those antiemetics with prokinetic properties until bowel obstruction is ruled o ut. Metoclopramide 10 mg IV for GI causes (except intestinal obstruction). Avoid drugs in p regnancy. Dyspepsia and peptic ulceration Dyspepsia (indigestion) is a nonspecific group of symptoms (abdominal pain, bloating, and nausea) related to the upper GI tract. Causes of dys- peptic symptoms may include peptic ulcer disease (duodenal and gastric ulcers), gastritis, esopha gitis, GERD, malignancy, or nonulcer dyspepsia (diagnosis of exclusion). Symptoms and signs Physical examination, often normal, may reveal epi- gastric tenderness, tympanic percussio n due to bloating, etc. These physical examination signs are non-specific. Management of dy spepsia The initial management of patients with unin- vestigated dyspepsia remains controve rsial. Clinical suspicion and econom- ics often dictate when to test and perform invasive p rocedures on patients. For patients \211 50 yrs with long-standing symptoms or with alarm signs, upper endoscopy is indicated as part of the initial diagnostic workup. A rea- sonab le approach for all patients without alarm symptoms or age <50 is to prescribe an empiric t rial of a proton-pump inhibitor for 4 \200\2238 wks. American College of Gastroenterology ( ACG) Guidelines advise treatment based on Helicobacter pylori prevalence within a community . If H. pylori prevalence is >10%, then dyspepsia patients should be tested and treated for H. pylori first; then, if symptoms persist, try proton pump inhibitor (PPI). 1 Peptic ulce r disease Abdominal pain occurs in 94% of patients with peptic ulcer disease (PUD). Typical ly described as burning, nonradiating epigastric pain that is often relieved with food or a ntacids. The pain may awaken patients in the middle of the night. Two-thirds of duodenal ul cer patients and one-third of gastric ulcer patients present with symptoms. Symptomatic pai n is nonspecific, however, since one-third of patients with nonulcer dyspepsia also have si milar pain. Warning signs of complicated PUD include signs of perfora- tion, penetration, o r hemorrhage. Ask for acute exacerbations in frequency, location, or severity of symptoms. Question patients for melena (90% of melena is due to upper GI hemorrhage), hematemesis, an d radiating pain. Duodenal ulcers (DU) are 4 \227 more common than GU. Risk factors : H. p ylori ( 90%), drugs (aspirin, NSAIDs, steroids). Diseases associated with DU include Zollin ger \200\223Ellison syndrome, systemic mastocytosis, multiple endocrine neoplasia type I, c hronic pulmonary disease, chronic renal failure, cirrhosis, nephrolithiasis, and 1 -anti trypsin deficiency. Diagnosis: Upper GI endoscopy. Test for H. pylori (see p. 73 ). Gastrin con- centrations should be measured if Zollinger \200\223Ellison syndrome is suspected. Ga stric ulcers (GU) occur primarily in the elderly, on the lesser curve of the stomach. Ulcer s elsewhere are more likely to be malignant. Risk factors : H. pylori ( 70%), smoking, NSAI Ds, stress-related ulcers (Cushing or Curling ulcers). Diagnosis: Upper GI endoscopy must b e performed to exclude malignancy; take multiple biopsies from the rim and base of the ulce r (histology, H. pylori ) and brushings (cytology). Treatment of peptic ulcers Lifestyle: A void food that worsens symp- toms. Stop smoking (slows healing in GU; hastens relapse rates in DU). Medical therapy includes antacids, H 2 receptor antagonists, proton-pump inhibitor s, and cytoprotective agents (sucralfate, misoprostol). Misoprostol is contraindicated in w omen of childbearing age, and dose-related diarrhea is often the limiting factor in patient compliance. H. pylori eradication: Triple 2 or quadruple therapy. NSAID-associated ulcers: Stop NSAID if possible 208 1 Talley N, Vakil N. Guidelines for the management of dyspepsia. Am J Gastroenterol . 2005; 100:2324 \200\2232337. 2 Triple therapy for 7 \200\22314d: (1) PPI (e.g., lansoprazole 30 mg bid),(2) amoxicillin 1 g bid, (3) clarithro- mycin 500 mg bid. (if not, use H 2 -receptor antagonist, PPI, or misoprostol for prevention). If symptoms per sist, re-endoscope, recheck for H. pylori , and reconsider the differential diagnosis. Surg ery (p. 495): May be indicated for complications of PUD. y g o o r e t n e o r t s a G l Gastroesophageal reflux disease The development of signs, symptoms, or complications relate d to the ret- rograde passage of gastric contents into the esophagus is termed GERD. GERD i s extremely common, with equal prevalence among genders; how- ever, there is a male predomi nance for complications. Factors associated with GERD include the acidity of the refluxate, antireflux barriers, luminal acid clearance mechanisms, esophageal tissue resistance, and gastric emp- tying. Dysfunction of the lower esophageal sphincter predisposes to the gastro esophageal reflux. If reflux is prolonged or excessive, it may cause inflammation of the es ophagus (esophagitis), benign esophageal stricture, Barrett \200\231s esophagus, and esopha geal adenocarcinoma. Associations Smoking, alcohol, hiatal hernia, pregnancy, obesity, larg e meals, myotomy of the lower esophageal sphincter for achalasia, drugs (tricyclics, antich olinergics, nitrates), systemic sclerosis. GERD may have a correlation with pulmonary or ot her extraintestinal manifestations. Symptoms Heartburn (burning, retrosternal discomfort re lated to meals, lying down, and straining, relieved by antacids), belching, acid brash (aci d or bile regurgitation), water brash (excessive salivation), odynophagia (painful swallowi ng (e.g., from esophagitis or stricture), nocturnal asthma (cough/ wheeze with apparently m inimal inhalation of gastric contents). Complications : Esophagitis, ulcers, iron deficienc y anemia, benign stric- tures, Barrett esophagus, eosinophilic esophagitis, and esophageal adenocarcinoma. Tests Isolated symptoms do not require investigation. Indications for upper GI endoscopy: Age >50 yrs, longer symptom duration (>4 wks), dysphagia, persistent symptom s despite treatment, relapsing symptoms, weight loss or other alarm signs/symptoms. Barium swallow may show hiatus hernia. 24 h esophageal pH monitoring esophageal manometry may b e needed to distinguish refractory or hard to treat GERD from other causes, such as achalas ia. The Los Angeles (LA) classification: Minor diffuse changes (erythema, edema, friability ) are not included and the term mucosal break is used to encompass the old terms \200\234e rosion \200\235 and \200\234ulceration. \200\235 There are four grades. A One or more muco sal breaks <5 mm long, not extending beyond two mucosal fold tops. A mucosal break is a wel l-demarcated area of slough/ erythema. 209 B Mucosal break >5 mm long limited to the space between two mucosal fold tops. C Mucosal break continuous between the tops of two or more mucosal folds but which involves <75% of the esophageal circumference. D Mucosal break involving \211 75% of the esophageal circumference. Treatment \212Lifestyle: Encourage weight loss; raise bed head; small, regular meals. Avoid hot drinks, alcohol, and eating <3 h before be d. Avoid drugs affecting esophageal motility (nitrates, anticholinergics, tricyclic antidep ressants) or that damage the mucosa (NSAIDs, K + salts, alendronate). \212Drugs: Antacids to relieve symptoms. If symptoms persist for >4 wks (or weight \206 \223 ; dysphagia; excessive vomiting; GI bleeding), refer for GI endoscopy . If esophagitis confirmed, try a PPI (the most effective option). Prokinetic drugs: These help gastric emp tying (e.g., metoclopramide; dystonias and tardive dyskinesia can be a serious side effect [see FDA Black Box warning]). \212Surgery: Endoscopic options such as Stretta or EndoCinch (endoscopic plication methods ) have fallen out of use. Laparoscopic fundoplication performed by an experienced surgeon i s a reliable therapeutic option for patients with proven reflux disease to achieve prolonge d symptom relief. Diarrhea The normal daily stool weight is 100 \200\223200 g, and, in the United States, a d aily stool weight >200 g is abnormal. Diarrhea means increased stool water (hence increased stool volume, e.g., >200 mL daily), and thus increased stool frequency and the passage of liquid stool. If it is the stool \200\231s fat content that is increased, the diarrhea is t ermed steatorrhea . Distinguish both from fecal urgency (may be caused by cancers or UC). C onditions that cause diarrhea are broadly classified into osmotic diar- rhea (stool output diminishes with reduced oral intake), secretory diarrhea (stool output persists despite red uction in oral intake), and mucosal injury categories. In reality, high-output diarrhea is usually a combination of these mechanisms. Normal-output diarrhea (stool volume <200 g/d) i s typically related to anorectal dysfunction. Foul-smelling, greasy stools are character- i stic of steatorrhea. See Table 7.1. Clinical features It is important to take a detailed an d accurate history: Is it acute (<3 wks duration) or chronic (>3 wks duration)? Acute : Usu ally infectious or drug-induced. Ask about recent travel, sexual practices, inges- tion of well water or inadequately cooked food and shellfish. Question for exposure to ill contacts Chronic : Usually requires extensive history and further testing. Ask about prior bowel su rgery and a family history. Additional testing should include stool studies for lactoferrin (fecal leukocytes), ova and parasites, cultures, and Clostridium difficile toxin. Check fo r signs of labs of malabsorption, including vitamins, and evaluate stool for steatorrhea (s udan stain). Often, radiographic and endoscopic evaluation with biopsies is required if abo ve testing is normal. \212Is the large or small bowel the source? Large bowel symptoms : W atery stool blood or mucus, pelvic pain relieved by defecation, tenesmus, 210 Table 7.1 Common causes of diarrhea Common causes Gastroenteritis Uncommon Microscopic colitis Rare Autonomic neuropathy Addison \200\231s disease Ischemic colitis Amyloidosis Tropical e nteropathy Viral Bacterial Parasites/protozoa Irritable bowel Celiac disease Chronic pancreatitis Thyrotoxicosis Laxative abuse; food allergy Drugs (below) Colorectal cancer Ulcerative colitis (UC) Crohn disease Lactose intolerance Ileal/gastric resection Bacterial overgrowth Pseudo membranous colitis Gastrinoma, VIPoma Carcinoid syndrome Medullary thyroid ca Pellagra urgency. Small bowel symptoms: Periumbilical (or right iliac fossa [RIF]) right lower quadr ant (RLQ) pain, not relieved by defecation; watery stool or steatorrhea. y g o o r e t n e o r t s a G l \212Is there blood, mucus, or pus? Bloody diarrhea: Campylobacter , Shigella , Salmonella , E. coli , amebiasis, inflammatory bowel disease, malignancy, pseudomembranous colitis, is chemic colitis. Mucus occurs in irritable bowel syndrome (IBS), colonic adenocarcinoma, pol yps. Pus suggests inflammatory bowel disease or diverticulitis. \212Could there be a non-gi cause? Think of drugs (antibiotics, PPIs, cimeti- dine, propra nolol, cytotoxics, NSAIDs, digoxin, alcohol, laxative abuse) and medical conditions (thyrot oxicosis, autonomic neuropathy, Addison \200\231s disease). Examination Look for weight loss, anemia, dehydration, oral ulcers, club- bing, rashes, and abdominal scars. Feel for: Enlarged thyroid or an abdomi- nal mass. Do a rectal examinatio n: Any rectal mass (rectal carcinoma) or impacted feces (overflow diarrhea)? Test stools fo r fecal occult blood. Tests Blood : In addition to above tests, look for evidence of iron d eficiency or celiac sprue. Stool : For pathogens and C. difficile toxin (pseudomembranous c olitis). Fecal fat excretion or 13 C-hiolein breath test if symptoms of chronic pancreatiti s, malabsorption, or steatorrhea are present. Colonoscopy/barium enema: In colitis, and to exclude malignancy. If normal, consider small bowel radiology or capsule endoscopy (Crohn \200\231s) endo- scopic ultrasound or endoscopic retrograde cholangiopancreatography (ER CP) (p. 222, e.g., chronic pancreatitis). Management Treat causes. Oral rehydration is pref erable to IV rehydra- tion. If severely dehydrated, give 0.9% saline + 20 mmol K + /L IVI. Codeine phosphate 30 mg/6 h PO reduces stool frequency. Avoid antibiotics unless the patien t has infective diarrhea and is systemically unwell. See Figure 7.2. 211 Figure 7.2 Management of infective diarrhea Diarrhea Special circumstances: Food poisoning outbreak Travel (p556 & 558) Recent antibiotic use Re ctal intercourse Immunocompromised host Raw sea food ingested Systemic illness Fever> 39 C Bloody diarrhea lasting>2 weeks Dehydration No systemic signs Symptomic treatment Consider noninfectious causes (see text) Admit to hospital Give oral fluids Consider presumptive antimicrobial therapy* Stool culture not needed Routine stool culture and microscopy Prompt, direct fecal smear (then culture) Confer with microbiologist Polymorphs seen No Polymorphs Parasites seen Specific therapy (p616 \216 p620) Likely culture: Shigella** Campylobacter E coli (Yersinia \216 rare) (Samonella \216 rare) (C difficile*) Likely culture: Salmonella** E coli (C difficile*) 212 NB: Alternatively, classify into secretory (e.g., infections, UC/Crohn \200\231s, etc.) or osmotic causes (if water drawn into the gut, as in laxative use).