BASIC GASTROENTEROLOGICAL DISEASES

Basic symptoms of gastroenterological diseases and diagnostic methods in gastroenterology

ANATOMIC CONSIDERATIONS

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The gastrointestinal (GI) tract extends from the mouth to the anus and comprises several organs with distinct functions. The organs are separated by specialized independently controlled thickened sphincters... The gut wall is organized into well-defined layers that contribute to the functional activities in each region. The mucosa serves as a barrier to luminal contents or as a site for transfer of fluids or nutrients. Gut smooth muscle mediates propulsion from one region to the next. Many GI organs have a serosal.

Interactions with other organ systems serve the needs both of the gut and the body. Pancreaticobiliary conduits send bile and enzymes into the duodenum. A rich vascular supply is modulated by GI tract activity. Lymphatic channels assist in gut immune activities. Gut wall nerves provide the basic controls for propulsion and fluid regulation.

FUNCTIONS OF THE GASTROINTESTINAL TRACT

The GI tract serves two main functions—assimilation of nutrients and elimination of waste. In the mouth, food is processed, mixed with salivary amylase, and delivered to the luminal GI tract. The esophagus propels the bolus into the stomach, and the lower esophageal sphincter prevents oral reflux of gastric contents. The propulsive activities of the esophagus are coordinated with relaxation of the upper and lower esophageal sphincters upon swallowing.

The stomach acts in food preparation by mixing the bolus with pepsin and acid. Gastric acid also sterilizes the upper gut. Gastric motor activity propels processed meal bolus into the duodenum. Also the stomach secretes internal factor for vitamin B₁₂ absorption.

The small intestine serves the nutrient absorptive function of the gut with specialized enzymes and transporters. Food from the stomach is mixed with pancreatic juice and bile in the proximal duodenum. Pancreatic juice contains the main enzymes for carbohydrate, protein, and fat digestion as well as bicarbonate to optimize the pH for activation of these enzymes. Bile secreted by the liver and stored in the gallbladder is essential for intestinal lipid digestion. The proximal intestine is optimized for rapid absorption of nutrient breakdown products and most minerals, while the ileum is better suited for absorption of vitamin B₁₂ and bile acids. The small intestine also aids in waste elimination. The small intestine terminates in the ileocecal junction, a sphincteric structure that prevents coloileal reflux and maintains small-intestinal sterility.

The colon prepares the waste material for controlled evacuation. The colonic mucosa dehydrates the stool, decreasing daily fecal volumes from the1500 mL delivered from the ileum to the 100 - 200 mL expelled from the rectum. The proximal colon serves to absorb fluid, while the distal colon exhibits peristaltic contractions to expel the stool.

OVERVIEW OF GASTROINTESTINAL DISEASES

GI diseases develop as a consequence of abnormalities within or outside of the gut and range in severity from mild symptoms to an adverse outcome. Diseases may be localized to a single organ or exhibit diffuse involvement at a number of sites.

CLASSIFICATION OF GI DISEASES

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GI diseases are manifestations of alterations in nutrient assimilation or waste evacuation or in the activities supporting these main functions.

1. Impaired Digestion and Absorption

Diseases of the stomach, intestine, biliary tree, and pancreas can disrupt nutrient digestion and absorption. Lactase deficiency, produces flatus and diarrhea, celiac disease, bacterial overgrowth, infectious enteritis, Crohn's ileitis, and radiation damage produce anemia, dehydration, electrolyte disorders, or malnutrition. Biliary obstruction from stricture or neoplasm may impair fat digestion. Impaired release of pancreatic enzymes in chronic pancreatitis or pancreatic cancer decreases intraluminal digestion and can lead to profound malnutrition.

2. Changed Secretion

Selected GI diseases result from dysregulation of gut secretion. Gastric acid hypersecretion occurs in Zollinger-Ellison syndrome, G-cell hyperplasia, duodenal ulcer disease. Conversely, patients with atrophic gastritis or pernicious anemia release little or no gastric acid. Inflammatory and infectious small-intestinal and colonic diseases produce fluid loss through impaired absorption or enhanced secretion and diarrhea.

3. Changed Gut Transit

Changes in gut transit are commonly secondary to mechanical obstruction. Esophageal occlusion often results from acid-induced stricture or neoplasm. Gastric outlet obstruction develops from peptic ulcer disease or gastric cancer. Small-intestinal obstruction may also occur with Crohn's disease, radiation- or drug-induced strictures, and malignancy. The most common cause of colonic obstruction is colon cancer, although inflammatory strictures develop in patients with inflammatory bowel disease, after certain infections, or with some drugs.

Retardation of propulsion also develops from disordered gut motor function. Achalasia is characterized by impaired esophageal body peristalsis and incomplete lower esophageal sphincter relaxation. Gastroparesis is the symptomatic delay in gastric emptying of solid or liquid meals. Intestinal pseudoobstruction causes marked delays in small-bowel transit due to injury to enteric nerves or intestinal smooth muscle. Slow transit constipation is produced by diffusely impaired colonic propulsion. Constipation is also produced by outlet abnormalities such as rectal prolapse, invagination, or failure of anal relaxation upon defecation.

Disorders of rapid propulsion are less common than those with delayed transit. Rapid gastric emptying occurs in postvagotomy dumping syndrome and with gastric hypersecretion. Accelerated transit with hyperdefecation is noted in hyperthyroidism.

4. Impaired Gut Blood Flow

Different GI regions are at variable risk for ischemic damage from impaired blood flow. Rare cases of gastroparesis result from blockage of the celiac and superior mesenteric arteries. More commonly cases are intestinal and colonic ischemia due to arterial embolus, arterial thrombosis, venous thrombosis, or hypoperfusion from dehydration, sepsis, hemorrhage, or reduced cardiac output. These may produce mucosal injury, hemorrhage, or even perforation. Some cases of radiation enterocolitis exhibit reduced mucosal blood flow.

5. Neoplastic Degeneration

All GI regions are susceptible to malignant degeneration to varying degrees. In the United States, colorectal cancer is most common and typically presents after age 50. Worldwide, gastric cancer is especially prevalent in certain Asian regions. Esophageal cancer develops with chronic acid reflux or in those with an extensive alcohol or tobacco use history. Small-intestinal neoplasms are rare and occur with underlying inflammatory disease. Anal cancers may arise with prior anal infection or inflammation. Pancreatic and biliary cancers shows with severe pain, weight loss, and jaundice and have poor prognoses. Hepatocellular carcinoma usually arises in the setting of chronic viral hepatitis or cirrhosis secondary to other causes.

6. Disorders without Obvious Organic Abnormalities

The most common GI disorders show no abnormalities on biochemical or structural testing and include irritable bowel syndrome (IBS), functional dyspepsia, noncardiac chest pain, and functional heartburn. These functional bowel disorders mostly exhibit changed gut motor function. Symptoms in some patients result from changed processing of visceral pain sensations in the central nervous system. Patients with functional bowel abnormalities with severe symptoms may exhibit significant emotional disturbances.

7. Genetic Influences

Although many GI diseases result from environmental factors, others exhibit hereditary components. Family members of inflammatory bowel disease (IBD) patients show a genetic predisposition to disease. Colonic and esophageal malignancies arise in certain inherited disorders. Hereditary pancreatitis is caused by mutation in the cationic trypsinogen gene. Rare genetic dysmotility syndromes are described. Familial clustering is even observed in the functional bowel disorders, although this may be secondary to learned familial illness behavior rather than a true hereditary factor.

SYMPTOMS OF GASTROINTESTINAL DISEASE

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The most common GI symptoms are abdominal pain, heartburn, nausea and vomiting, changed bowel habits, GI bleeding, and jaundice (Table 1). Others are dysphagia, anorexia, weight loss, fatigue, and extraintestinal symptoms.

TABLE  1 Common Causes of Common GI Symptoms

Abdominal Pain Nausea and Vomiting Diarrhea GI Bleeding Obstructive Jaundice Appendicitis Gallstone disease Pancreatitis Diverticulitis Ulcer disease Esophagitis GI obstruction Inflammatory bowel disease Functional bowel disorder Vascular disease Gynecologic causes Renal stone Medications GI obstruction Motor disorders Functional bowel disorder Enteric infection Pregnancy Endocrine disease Motion sickness Central nervous system disease Infection Poorly absorbed sugars Inflammatory bowel disease Microscopic colitis Functional bowel disorder Celiac disease Pancreatic insufficiency Hyperthyroidism Ischemia Endocrine tumor Ulcer disease Esophagitis Varices Vascular lesions Neoplasm Diverticula Hemorrhoids Fissures Inflammatory bowel disease Infectious colitis Bile duct stones Cholangiocarcinoma Cholangitis Sclerosing cholangitis Ampullary stenosis Ampullary carcinoma Pancreatitis Pancreatic tumor

Abdominal Pain

Abdominal pain results from GI disease and extraintestinal conditions involving the genitourinary tract, abdominal wall, thorax, or spine. Visceral pain is generally midline in location and different in character, while parietal pain is localized and clearly described. Common inflammatory diseases with pain include peptic ulcer, appendicitis, diverticulitis, IBD, and infectious enterocolitis. Other intraabdominal causes of pain include gallstone disease and pancreatitis. Noninflammatory visceral sources include mesenteric ischemia and neoplasia. The most common causes of abdominal pain are irritable bowel syndrome (IBS) and functional dyspepsia.

Heartburn

Heartburn, a burning substernal sensation, is reported intermittently by at least 40% of the population. Classically, heartburn is felt to result from excess gastroesophageal reflux of acid. However, some cases exhibit normal esophageal acid exposure and may result from increased sensitivity of esophageal mucosal nerves.

Nausea and Vomiting

Nausea and vomiting are caused by GI diseases, medications, toxins, acute and chronic infection, endocrine disorders, labyrinthine conditions, and central nervous system diseases. The best-characterized GI etiologies relate to mechanical obstruction of the upper gut; however, disorders of propulsion including gastroparesis and intestinal pseudoobstruction also show prominent symptoms. As with abdominal pain, IBS and functional dyspepsia commonly present with nausea and vomiting.

Changed Bowel Habits

Changed bowel habits are common complaints of patients with GI disease. Constipation is reported as infrequent defecation, straining with defecation, passage of hard stools, or a sense of incomplete fecal evacuation. Causes of constipation include obstruction, motor disorders of the colon, medications, and endocrine diseases such as hypothyroidism and hyperparathyroidism. Diarrhea is reported as frequent defecation, passage of loose or watery stools, fecal urgency, or a similar sense of incomplete evacuation. The differential diagnosis of diarrhea is broad and includes infections, inflammatory causes, malabsorption, and medications. IBS produces constipation, diarrhea, or an alternating bowel pattern. Fecal mucus is common in IBS, while pus characterizes inflammatory disease. Steatorrhea develops with malabsorption.

GI Bleeding

Hemorrhage may develop from any gut organ. Most commonly, upper GI bleeding presents with melena or hematemesis, and lower GI bleeding produces passage of bright red or maroon stools. However, intensive bleeding upper sites can show prominent red rectal bleeding, while slowly bleeding ascending colon sites may produce melena. Chronic slow GI bleeding may present with iron-deficiency anemia. The most common upper GI causes of bleeding are ulcer disease, gastroduodenitis, and esophagitis. Other etiologies include portal hypertensive causes, malignancy, and vascular lesions. The most prevalent lower GI sources of hemorrhage include hemorrhoids, anal fissures, diverticula, and arteriovenous malformations. Other causes include neoplasm, IBD, ischemia, infectious colitis, and other vascular lesions.

Jaundice

Jaundice results from prehepatic, intrahepatic, or posthepatic disease. Prehepatic causes of jaundice include hematological diseases such as hemolytic anemia. Intrahepatic causes of jaundice include hepatitis, cirrhosis, and cancer. Posthepatic causes of jaundice include biliary diseases such as choledocholithiasis, cholangitis, stricture, and neoplasm and pancreatic disorders such as acute and chronic pancreatitis, stricture, and malignancy.

Other Symptoms

Dysphagia, odynophagia, and unexplained chest pain suggest esophageal disease. A globus sensation is reported with esophagopharyngeal conditions but also occurs with functional GI disorders. Weight loss, anorexia, and fatigue are nonspecific symptoms of neoplastic, inflammatory, gut motor, pancreatic, small bowel mucosal, and psychiatric conditions. Fever is reported with inflammatory illness, but malignancies also evoke febrile responses. GI disorders also produce extraintestinal symptoms. IBD is associated with hepatobiliary dysfunction, skin and eye lesions, and arthritis. Celiac disease may present with dermatitis herpetiformis. Conversely, systemic diseases can have GI consequences. Systemic lupus may cause gut ischemia, presenting with pain or bleeding. Overwhelming stress or severe burns may lead to gastric ulcer formation.

EVALUATION OF THE PATIENT WITH GASTROINTESTINAL DISEASE

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Evaluation of the patient with GI disease begins with a careful history and physical examination. Special additional investigations to test the structure or function of the gut are indicated in selected cases. Some patients exhibit normal findings on diagnostic testing. In these individuals a functional bowel disorder can be suspected.

HISTORY

The history of the patient with suspected GI disease has several components. Symptom timing can suggest specific etiologies. Symptoms of short duration commonly result from acute infection, toxin exposure, or abrupt inflammation or ischemia. Long-standing symptoms point to an underlying chronic inflammatory or neoplastic condition or a functional bowel disorder. Symptoms from mechanical obstruction, ischemia, IBD, and functional bowel disorders are worsened by eating. Conversely, ulcer symptoms may be relieved by eating or antacids. The symptom pattern and duration may suggest underlying etiologies. Ulcer pain occurs at intermittent intervals lasting weeks to months, biliary colic has a sudden onset and lasts up to several hours. Pain from acute inflammation, as with acute pancreatitis, is severe and persists for days to weeks. Meals call diarrhea in some cases of IBD and IBS, while defecation relieves discomfort in these conditions. Functional bowel disorders are exacerbated by stress. Sudden awakening from sleep suggests organic disease rather than a functional bowel disorder. Diarrhea from malabsorption usually improves with fasting, while secretory diarrhea persists without oral intake.

Symptom relation to other factors narrows the list of diagnostic possibilities. Obstructive symptoms with prior abdominal surgery raise concern for adhesions, whereas loose stools after gastrectomy or gallbladder excision suggest dumping syndrome or post-cholecystectomy diarrhea. Symptom onset after travel allows to think about enteric infection. Medications produce pain, changed bowel habits, or GI bleeding. Lower GI bleeding likely results from neoplasm, diverticula, or vascular lesions in an older person and anorectal abnormalities or IBD in a younger individual. Celiac disease is prevalent in people of Irish descent; IBD is more common in certain Jewish populations. A sexual history may raise concern for sexually transmitted diseases or immunodeficiency.

Over the past two decades, working groups worked to collect symptom criteria to improve the diagnosis of the functional bowel disorders and to minimize the number of unnecessary diagnostic tests performed. The most widely accepted symptom-based criteria are the Rome criteria.

PHYSICAL EXAMINATION

The physical examination complements information from the history. Abnormal vital signs provide diagnostic variants and determine the need for acute intervention. Fever suggests inflammation or neoplasm. Orthostasis is found with significant blood loss, dehydration, sepsis, or autonomic neuropathy. Skin, eye, or joint findings may point to specific diagnoses. Neck examination with swallowing assessment evaluates dysphagia. Cardiopulmonary disease may present with abdominal pain or nausea; thus lung and cardiac examinations are important. Pelvic examination tests for a gynecologic source of abdominal pain. Rectal examination may detect blood, indicating gut mucosal injury or neoplasm, or a palpable inflammatory mass in appendicitis. Metabolic conditions and gut motor disorders have associated peripheral neuropathy.

Inspection of the abdomen may reveal distention from obstruction, tumor, or ascites or vascular abnormalities with liver disease. Ecchymoses develop with severe pancreatitis. Auscultation can detect bruits or friction rubs from vascular disease or hepatic tumors. Loss of bowel sounds signifies ileus, while high-pitched, hyperactive sounds characterize intestinal obstruction. Percussion assesses liver size and can detect shifting dullness from ascites. Palpation assesses for hepatosplenomegaly as well as neoplastic or inflammatory masses. Abdominal examination is helpful in evaluating unexplained pain. Intestinal ischemia shows severe pain but little tenderness. Patients with visceral pain may exhibit generalized discomfort, while those with parietal pain or peritonitis have directed pain often with involuntary guarding, rigidity, or rebound. Patients with musculoskeletal abdominal wall pain may note tenderness exacerbated by Valsalva or straight leg lift maneuvers.

ADDITION EXAMINATIONS

Laboratory, radiographic, and scintigraphic tests can assist in diagnosis of suspected GI disease. The GI tract can be investigated with internal evaluation - upper and lower endoscopy, and examination of luminal contents. Histopathologic examinations of gastrointestinal tissues complement these tests.

Laboratory

Selected laboratory tests facilitate the diagnosis of GI disease.

Blood test.

Iron-deficiency anemia suggests mucosal blood loss, whereas vitamin B₁₂ deficiency results from small-intestinal, gastric, or pancreatic disease. Either can also result from inadequate oral intake.

 Leukocytosis and increased erythrocyte sedimentation rates are found in inflammatory conditions, while leukopenia is seen in viremic illness.

Biochemical serum tests.

Severe vomiting or diarrhea elicits electrolyte disturbances, acid-base abnormalities, and elevated blood urea nitrogen.

Pancreaticobiliary or liver disease is suggested by elevated pancreatic or liver chemistries.

 Thyroid chemistries, cortisol, and calcium levels are obtained to exclude endocrinologic causes of GI symptoms. Hormone levels are obtained for suspected endocrine neoplasia.

Pregnancy testing is considered for young women with unexplained nausea.

Serologic tests are available for rheumatologic diseases such as systemic lupus erythematosus or scleroderma.

Intraabdominal malignancies produce tumor markers including carcinoembryonic antigen, while paraneoplastic dysmotility is associated with antineuronal antibodies.

Ascitic fluid is analyzed for infection, malignancy, or findings of portal hypertension.

Cerebrospinal fluid is obtained for suspected central nervous system causes of vomiting.

Urine samples screen for carcinoid, porphyria, and heavy metal intoxication.

Luminal Contents

Stool samples are cultured for bacterial pathogens or examined for leukocytes or parasites.

Duodenal aspirates can be examined for parasites or cultured for bacterial overgrowth.

Fecal fat is quantified in possible malabsorption.

Stool electrolytes and osmolarity can be measured in diarrheal conditions.

Gastric acid is quantified to rule out Zollinger-Ellison syndrome.

Pancreatic juice is analyzed for enzyme or bicarbonate content to exclude pancreatic exocrine insufficiency.

Instrumental

S5. Esophageal and intragastral pH testing are done for refractory symptoms of acid reflux, acid gastral secretion.

S6. Endoscopy

Endoscopy can provide the diagnosis of the causes of bleeding, pain, nausea and vomiting, weight loss, changed bowel function, and fever. Table 2 lists the most common indications for the major endoscopic procedures.

S7. Upper endoscopy evaluates the esophagus, stomach, and duodenum, while colonoscopy assesses the colon and distal ileum. Upper endoscopy is advocated as the initial structural test performed in patients with upper GI bleeding, suspected ulcer disease, esophagitis, neoplasm, malabsorption, and Barrett's metaplasia because of its ability both to visualize the abnormality directly and to biopsy it.

Colonoscopy is the procedure of choice for colon cancer screening and observation; diagnosis of colitis secondary to infection, ischemia, radiation, and IBD; and characterization of causes of lower GI bleeding.

Sigmoidoscopy examines the colon up to the splenic flexure and is currently used to exclude distal colonic inflammation or obstruction in young patients not at significant risk for colon cancer. For GI bleeding secondary to arteriovenous malformations or superficial ulcers, small-intestinal examination is performed with push enteroscopy or capsule endoscopy.

Endoscopic retrograde cholangiopancreaticography (ERCP) provides diagnoses of pancreatic and biliary disease.

Endoscopic ultrasound is useful for evaluating the extent of disease in GI malignancy as well as exclusion of choledocholithiasis, evaluation of pancreatitis, drainage of pancreatic pseudocysts, and assessment of anal continuity.

TABLE 2 Common Indications for Endoscopy

Upper Endoscopy Colonoscopy Endoscopic Retrograde Cholangiopancreatography Endoscopic Ultrasound Dyspepsia despite treatment Dyspepsia with signs of organic disease Refractory vomiting Dysphagia Upper bleeding Anemia Weight loss Malabsorption Biopsy radiologic abnormality Polypectomy Place gastrostomy Barrett's metaplasia surveillance Palliate neoplasm Sample duodenal tissue/fluid Remove foreign body Cancer screening Lower bleeding Anemia Diarrhea Polypectomy Obstruction Biopsy radiologic abnormality Cancer surveillance:   Family history, prior polyp/cancer, colitis Palliate neoplasm Remove foreign body Jaundice Postbiliary surgery complaints Cholangitis Gallstone pancreatitis Pancreatic/biliary/ampullary tumor Unexplained pancreatitis Pancreatitis with unrelenting pain Fistulas Biopsy radiologic abnormality Pancreaticobiliary drainage Sample bile Sphincter of Oddi manometry Staging of malignancy Characterize and biopsy submucosal mass Bile duct stones Chronic pancreatitis Drain pseudocyst Large gastric folds Anal continuity

S8. IMAGING

Radiographic tests evaluate diseases of the gut and extraluminal structures. Oral or rectal contrast agents such as barium provide mucosal definition from the esophagus to the rectum. Contrast radiography also assesses gut transit and pelvic floor dysfunction. Barium swallow is the initial procedure for evaluation of dysphagia to exclude subtle rings or strictures and assess for achalasia, whereas small-bowel contrast radiology reliably diagnoses intestinal tumors and Crohn's ileitis. Contrast enemas are performed when colonoscopy is unsuccessful or contraindicated.

Ultrasound and computed tomography (CT) evaluate regions not accessible by endoscopy or contrast studies, including the liver, pancreas, gallbladder, kidneys, and retroperitoneum. These tests are useful for diagnosis of mass lesions, fluid collections, and organ enlargement. Ultrasound is the initial test to evaluate for gallstone disease. Virtual CT colonoscopy is being evaluated as a method of colon cancer screening.

Magnetic resonance imaging assesses the mesenteric circulation to screen for arterial exclusion; the pancreaticobiliary ducts to exclude neoplasm, stones, and sclerosing cholangitis; and the liver to characterize benign and malignant tumors.

Angiography excludes mesenteric ischemia and determines spread of malignancy. Angiographic techniques also access the biliary tree in obstructive jaundice.

Positron emission tomography may become useful in distinguishing malignant from benign pancreatic disease.

Scintigraphy both evaluates structural abnormalities and quantifies luminal transit.

Radionuclide bleeding scans localize bleeding sites in patients with brisk hemorrhage so that therapy with endoscopy, angiography, or surgery may be directed.

Radiolabeled leukocyte scans can show the intraabdominal abscesses not visualized on CT.

Biliary scintigraphy is complementary to ultrasound in the assessment of cholecystitis.

Scintigraphy to quantify esophageal and gastric emptying are well established, while techniques to measure small-intestinal or colonic transit are less widely used.

Histopathology

Gut mucosal biopsies obtained at endoscopy evaluate for inflammatory, infectious, and neoplastic disease. Deep rectal biopsies assist with diagnosis of Hirschsprung's disease or amyloid. Liver biopsy is indicated in cases with abnormal liver chemistries, unexplained jaundice, following liver transplant to exclude rejection, and to characterize the degree of inflammation in patients with chronic viral hepatitis prior to initiating antiviral therapy. Biopsies obtained during CT or ultrasound can evaluate for other intraabdominal conditions not accessible by endoscopy.

Functional Testing

Tests of gut function provide important data when structural testing is nondiagnostic. In addition to gastric acid and pancreatic function testing, functional testing of motor activity is provided by regional manometric techniques.

S9. Esophageal manometry is useful for suspected achalasia, whereas small-intestinal manometry tests for pseudoobstruction.

Anorectal manometry is employed for unexplained incontinence or constipation from outlet dysfunction.

Biliary manometry tests for sphincter of Oddi dysfunction with unexplained biliary pain.

Electrogastrography measures gastric electrical activity in individuals with nausea and vomiting, whereas electromyography assesses anal function in fecal incontinence.