Alterations of Digestive Function Chapter 39 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2 Clinical Manifestations of Gastrointestinal Dysfunction  Anorexia  A lack of desire to eat despite physiologic stimuli that would normally produce hunger  Vomiting  The forceful emptying of the stomach and intestinal contents through the mouth  Several types of stimuli initiate the vomiting reflex

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Clinical Manifestations of Gastrointestinal Dysfunction  Nausea  A subjective experience associated with a number of conditions  Common symptoms: hypersalivation and tachycardia  Retching  Nonproductive vomiting  Projectile vomiting  Spontaneous vomiting that does not follow nausea or retching

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Clinical Manifestations of Gastrointestinal Dysfunction  Constipation  Infrequent or difficult defecation  Pathophysiology Neurogenic disorders, functional or mechanical conditions, low-residue diet, sedentary lifestyle, excessive use of antacids, changes in bowel habits Neurogenic disorders, functional or mechanical conditions, low-residue diet, sedentary lifestyle, excessive use of antacids, changes in bowel habits

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Clinical Manifestations of Gastrointestinal Dysfunction  Diarrhea  Increased frequency of bowel movements  Increased volume, fluidity, weight of the feces May be protective May be protective  Major mechanisms of diarrhea Osmotic diarrhea Osmotic diarrhea Secretory diarrhea Secretory diarrhea Motility diarrhea Motility diarrhea

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Clinical Manifestations of Gastrointestinal Dysfunction  Systemic effects of GI dysfunction  Manifestations of diarrhea Dehydration, electrolyte imbalance, metabolic acidosis, and weight loss Dehydration, electrolyte imbalance, metabolic acidosis, and weight loss  Manifestations of acute bacterial or viral infection Fever, with or without cramping pain Fever, with or without cramping pain  Manifestations of inflammatory bowel disease Fever, cramping pain, bloody stools Fever, cramping pain, bloody stools  Manifestations of malabsorption syndromes Steatorrhea (fat in the stools) and diarrhea Steatorrhea (fat in the stools) and diarrhea

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Clinical Manifestations of Gastrointestinal Dysfunction  Abdominal pain  A symptom of a number of GI disorders  Parietal pain  Visceral pain  Referred pain  Biochemical mediators of the inflammatory response (histamine, bradykinin, and serotonin) stimulate organic nerve endings producing abdominal pain

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Clinical Manifestations of Gastrointestinal Dysfunction  GI bleeding  Upper GI bleeding Esophagus, stomach, or duodenum Esophagus, stomach, or duodenum  Lower GI bleeding Below the ligament of Treitz, or bleeding from the jejunum, ileum, colon, or rectum Below the ligament of Treitz, or bleeding from the jejunum, ileum, colon, or rectum  Hematemesis  Hematochezia  Melena  Occult bleeding

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Disorders of Motility  Dysphagia  Difficulty swallowing  Types Mechanical obstructions Mechanical obstructions Functional obstructions Functional obstructions  Achalasia Denervation of smooth muscle in the esophagus and lower esophageal sphincter relaxation Denervation of smooth muscle in the esophagus and lower esophageal sphincter relaxation

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Disorders of Motility  Gastroesophageal reflux disease (GERD)  The reflux of chyme from the stomach to the esophagus  If GERD causes inflammation of the esophagus, it is called reflux esophagitis  A normal functioning lower esophageal sphincter maintains a zone of high pressure to prevent chyme reflux

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Disorders of Motility  Gastroesophageal reflux disease (GERD)  Conditions that increase abdominal pressure can contribute to GERD  Manifestations Heartburn, regurgitation of chyme, and upper abdominal pain within 1 hour of eating Heartburn, regurgitation of chyme, and upper abdominal pain within 1 hour of eating

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Disorders of Motility  Pyloric obstruction  The blocking or narrowing of the opening between the stomach and the duodenum  Can be acquired or congenital  Manifestations Epigastric pain and fullness, nausea, succussion splash, vomiting, and with a prolonged obstruction, malnutrition, dehydration, and extreme debilitation Epigastric pain and fullness, nausea, succussion splash, vomiting, and with a prolonged obstruction, malnutrition, dehydration, and extreme debilitation

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Disorders of Motility  Intestinal obstruction and ileus  An intestinal obstruction is any condition that prevents the flow of chyme through the intestinal lumen or failure of normal intestinal motility in the absence of an obstructing lesion  An ileus is an obstruction of the intestines  Manifestastions Colicky pain, vomiting, distention, hypovolemia, metabolic acidosis Colicky pain, vomiting, distention, hypovolemia, metabolic acidosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Disorders of Motility  Intestinal obstruction and ileus  Simple obstruction  Functional obstruction  Small intestinal obstruction  Large bowel obstruction

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Gastritis  Inflammatory disorder of the gastric mucosa  Acute gastritis  H. pylori, NSAIDs  Chronic gastritis  Chronic fundal gastritis  Chronic antral gastritis Signs and symptoms of chronic gastritis often do not correlate with the severity of the disease Signs and symptoms of chronic gastritis often do not correlate with the severity of the disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Peptic Ulcer Disease  A break or ulceration in the protective mucosal lining of the lower esophagus, stomach, or duodenum  Acute and chronic ulcers  Superficial  Erosions  Deep  True ulcers

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Peptic Ulcer Disease  Duodenal ulcers  Most common of the peptic ulcers  Developmental factors H. pylori infection H. pylori infection  Toxins and enzymes that promote inflammation and ulceration Hypersecretion of stomach acid and pepsin Hypersecretion of stomach acid and pepsin Use of NSAIDs Use of NSAIDs High gastrin levels High gastrin levels Acid production by cigarette smoking Acid production by cigarette smoking

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 32 Gastric Ulcer  Tends to develop in the antral region of the stomach, adjacent to the acid-secreting mucosa of the body  Pathophysiology  The primary defect is an increased mucosal permeability to hydrogen ions  Gastric secretion is normal or less than normal

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 35 Stress Ulcer  Stress ulcer is a peptic ulcer that is related to severe illness, neural injury, or systemic trauma  Ischemic ulcers  Cushing ulcers Ulcers that develop as a result of a burn injury Ulcers that develop as a result of a burn injury  Manifestastions Bleeding most common Bleeding most common

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 36 Dumping Syndrome  Rapid emptying of chyme from surgically created residual stomach into small intestine  A clinical complication of partial gastrectomy or pyloroplasty surgery  Developmental factors  Loss of gastric capacity, loss of emptying control, and loss of feedback control by the duodenum when it is removed  Late dumping syndrome

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 37 Postgastrectomy Syndromes  Alkaline reflux gastritis  Afferent loop obstruction  Diarrhea  Weight loss  Anemia

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 38 Malabsorption Syndromes  Inadequate digestion  Pancreatic insufficiency  Lactase deficiency  Bile salt deficiency  Gluten-sensitive enteropathy

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 39 Malabsorption Syndromes  Pancreatic insufficiency  Insufficient pancreatic enzyme production Lipase, amylase, trypsin, or chymotrypsin Lipase, amylase, trypsin, or chymotrypsin  Causes: pancreatitis, pancreatic carcinoma, pancreatic resection, and cystic fibrosis  Fat maldigestion is the main problem, so the person will exhibit fatty stools and weight loss

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 40 Malabsorption Syndromes  Lactase deficiency  Inability to break down lactose into monosaccharides and thus prevent lactose digestion and monosaccharide absorption  Fermentation of lactose by bacteria causes gas (cramping pain, flatulence, etc.) and osmotic diarrhea

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 41 Malabsorption Syndromes  Bile salt deficiency  Conjugated bile salts needed to emulsify and absorb fats  Conjugated bile salts are synthesized from cholesterol in the liver  Result from liver disease and bile obstructions  Poor intestinal absorption of lipids causes fatty stools, diarrhea, and loss of fat-soluble vitamins (A, D, E, K)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 42 Malabsorption Syndromes  Fat-soluble vitamin deficiencies  Vitamin A Night blindness Night blindness  Vitamin D Decreased calcium absorption, bone pain, osteoporosis, fractures Decreased calcium absorption, bone pain, osteoporosis, fractures  Vitamin K Prolonged prothrombin time, purpura, and petechiae Prolonged prothrombin time, purpura, and petechiae  Vitamin E Uncertain Uncertain

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 43 Inflammatory Bowel Diseases  Chronic, relapsing inflammatory bowel disorders of unknown origin  Genetics  Alterations of epithelial barrier functions  Immune reactions to intestinal flora  Abnormal T-cell responses

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 47 Ulcerative Colitis  Chronic inflammatory disease that causes ulceration of the colonic mucosa  Sigmoid colon and rectum  Suggested causes  Infectious, immunologic (anticolon antibodies), dietary, genetic (supported by family studies and identical twin studies)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 49 Ulcerative Colitis  Symptoms  Diarrhea (10-20/day), bloody stools, cramps  Treatment  Broad-spectrum antibiotics and steroids  Immunosuppressive agents  Surgery  Increased colon cancer risk demonstrated

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 50 Crohn Disease  Granulomatous colitis, ileocolitis, or regional enteritis  Idiopathic inflammatory disorder; affects any part of the digestive tract, from mouth to anus  Difficult to differentiate from ulcerative colitis  Similar risk factors and theories of causation

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 53 Crohn Disease  Causes “skip lesions”  Ulcerations can produce longitudinal and transverse inflammatory fissures that extend into the lymphatics  Anemia may result due to malabsorption of vitamin B 12 and folic acid  Treatment is similar to ulcerative colitis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 56 Diverticular Disease of the Colon  Diverticula  Herniations of mucosa through the muscle layers of the colon wall, especially the sigmoid colon  Diverticulosis  Asymptomatic diverticular disease  Diverticulitis  The inflammatory stage of diverticulosis  Manifestations  Low abdominal pain, diarrhea, constipation, fever, leukocytosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 57 Appendicitis  Inflammation of the vermiform appendix  Possible causes  Obstruction, ischemia, increased intraluminal pressure, infection, ulceration, etc.  Manifestations  Epigastric and right lower quadrant pain, rebound tenderness  Nausea, vomiting, fever, leukocytosis  Most serious complication is peritonitis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 62 Vascular Insufficiency  Blood supply to the stomach and intestine  Celiac axis  Superior and inferior mesenteric arteries  Two of three must be compromised to cause ischemia  Mesenteric venous thrombosis  Acute occlusion of mesenteric artery blood flow  Chronic mesenteric insufficiency

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 65 Obesity  Obesity is an increase in body fat mass  Body fat index >30  A major cause of morbidity, death, and increased health care costs  Risk factor for many diseases and conditions

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 66 Obesity  Hypothalamus  Hormones that control appetite and weight  Insulin, ghrelin, peptide YY, leptin, adiponectin, and resistin  Leptin resistance  Hyperleptinemia

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 67 Anorexia Nervosa and Bulimia Nervosa  Characterized by abnormal eating behavior, weight regulation, and disturbed attitudes toward body weight, body shape, and size

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 68 Anorexia Nervosa and Bulimia Nervosa  Anorexia nervosa  Person has poor body image disorder and refuses to eat  Person can lose 25% to 30% of ideal body weight due to fat and muscle depletion  Can lead to starvation-induced cardiac failure  In females, characterized by absence of three consecutive menstrual periods  Binge eating/purging

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 69 Anorexia Nervosa and Bulimia Nervosa  Bulimia nervosa  Body weight remains near normal but with aspirations for weight loss  Findings Recurrent episodes of binge eating Recurrent episodes of binge eating Self-induced vomiting Self-induced vomiting Two binge-eating episodes per week for at least 3 months Two binge-eating episodes per week for at least 3 months Fasting to oppose the effect of binge eating, or excessive exercise Fasting to oppose the effect of binge eating, or excessive exercise

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 70 Anorexia Nervosa and Bulimia Nervosa  Bulimia nervosa  Continual vomiting of acidic chyme can cause pitted teeth, pharyngeal and esophageal inflammation, and tracheoesophageal fistulae  Overuse of laxative can cause rectal bleeding

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 71 Anorexia Nervosa and Bulimia Nervosa  Starvation  Decreased caloric intake leading to weight loss  Short-term starvation Glycogenolysis Glycogenolysis Gluconeogenesis Gluconeogenesis  Long-term starvation Marasmus Marasmus Kwashiorkor Kwashiorkor

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 72 Manifestations of Liver Disease  Portal hypertension  Ascites  Hepatic-encephalopathy  Jaundice  Hepatorenal syndrome

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 73 Liver Disorders  Portal hypertension  Abnormally high blood pressure in the portal venous system due to resistance to portal blood flow Prehepatic Prehepatic Intrahepatic Intrahepatic Posthepatic Posthepatic

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 77 Liver Disorders  Portal hypertension  Consequences Varices Varices  Lower esophagus, stomach, rectum Splenomegaly Splenomegaly Ascites Ascites Hepatic encephalopathy Hepatic encephalopathy

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 79 Hepatic Encephalopathy  Accumulation of toxins related to liver failure cause disruption of neurotransmission  Ammonia-bacterial urease acting on gut proteins  Neurotoxins: result from hepatic failure  Symptoms  Personality changes  Confusion  Memory loss  Stupor, coma, death

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 80 Liver Disorders  Jaundice (icterus)  Obstructive jaundice Extrahepatic obstruction Extrahepatic obstruction Intrahepatic obstruction Intrahepatic obstruction  Hemolytic jaundice Prehepatic jaundice Prehepatic jaundice Excessive hemolysis of red blood cells or absorption of a hematoma Excessive hemolysis of red blood cells or absorption of a hematoma

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 82 Hepatorenal Syndrome (HRS)  Renal failure demonstrating oliguria, sodium and water retention, hypotension, and peripheral vasodilation due to advanced liver disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 83 Hepatorenal Syndrome  Renal failure associated with liver failure  Hypovolemia  Hypotension  Decreased renal blood flow  Intrarenal vasoconstriction  Decreased GFR and urine output

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 84 Viral Hepatitis  Systemic viral disease that primarily affects the liver  Hepatitis A Formally known as infectious hepatitis Formally known as infectious hepatitis  Hepatitis B Formally known as serum hepatitis Formally known as serum hepatitis  Hepatitis C, D, E, G

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 85 Hepatitis A  Can be found in the feces, bile, and sera of infected individuals  Usually transmitted by the fecal-oral route  Risk factors  Crowded, unsanitary conditions  Food and water contamination

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 87 Hepatitis B  Transmitted through contact with infected blood, body fluids, contaminated needles  Maternal transmission if the mother is infected during the third trimester  Hepatitis B vaccine prevents transmission and development of hepatitis B

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 89 Hepatitis C  Responsible for most cases of post- transfusion hepatitis  Also implicated in infections related to IV drug use  50% to 80% of hepatitis C cases result in chronic hepatitis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 90 Hepatitis  Hepatitis D  Depends on hepatitis B for replication  Hepatitis E  Fecal-oral transmission  Developing countries  Hepatitis G  Recently discovered  Parenterally and sexually transmitted

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 91 Hepatitis  Sequence  Incubation phase  Prodromal (preicteric) phase  Icteric phase  Recovery phase  Chronic active hepatitis  Fulminant hepatitis  From impairment or necrosis of hepatocytes  Acute hepatic failure  Acetaminophen overdose

92 Hepatic fibrosis is the wound-healing response of the liver to many causes of chronic injury, of which viral infection, alcohol and non-alcoholic steatohepatitis (NASH) are the most common. Regardless of the underlying cause, iterative injury causes inflammatory damage, matrix deposition, parenchymal cell death and angiogenesis leading to progressive fibrosis. The scar matrix typically accumulates very slowly (the median time to cirrhosis in chronic hepatitis C is 30 years) but once cirrhosis is established the potential for reversing this process is decreased and complications develop.

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 93 Cirrhosis  Irreversible inflammatory disease that disrupts liver function and even structure  Decreased hepatic function from nodular and fibrotic tissue synthesis (fibrosis)  Biliary channels become obstructed and cause portal hypertension; due to the hypertension, blood shunted away from the liver, and a hypoxic necrosis develops

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 94 Cirrhosis  Alcoholic  Oxidation of alcohol damages hepatocytes  Biliary (bile canaliculi)  Cirrhosis begins in bile canaliculi and ducts  Primary biliary cirrhosis (autoimmune)  Secondary biliary cirrhosis (obstruction)  Postnecrotic  Consequence of chronic disease

95 Cirrhosis is a condition of the liver. It is marked by scarring of liver tissues that results in blocked blood flow and impaired liver function. Cirrhosis is one of the leading causes of death by disease. Sadly, it kills more than 25,000 people per year.

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 98 Disorders of the Gallbladder  Cholecystitis  Gallstones  Cholesterol stones form in bile that is supersaturated with cholesterol. Theories: Enzyme defect; increases cholesterol synthesis Enzyme defect; increases cholesterol synthesis Decreased secretion of bile acids to emulsify fats Decreased secretion of bile acids to emulsify fats Decreased resorption of bile acids from the ileum Decreased resorption of bile acids from the ileum Gallbladder smooth muscle hypomotility, stasis Gallbladder smooth muscle hypomotility, stasis Genetic predisposition Genetic predisposition Combination of any or all of the above Combination of any or all of the above

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 102 Cholecystitis can be seen on a cholangiogram. Radio-opaque dye is used to enhance the X-ray. Multiple stones are present in the gallbladder (PTCA).

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 103 Disorders of the Pancreas  Pancreatitis  Inflammation of the pancreas  Associated with several clinical disorders (alcohol intake and cholelithiasis) Caused by injury or damage to pancreatic cells and ducts, causing a leakage of pancreatic enzymes into the pancreatic tissue Caused by injury or damage to pancreatic cells and ducts, causing a leakage of pancreatic enzymes into the pancreatic tissue  These enzymes cause autodigestion of pancreatic tissue and leak into the bloodstream to cause injury to blood vessels and other organs

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 106 Disorders of the Pancreas  Pancreatitis  Manifestations and evaluation Epigastric pain radiating to the back Epigastric pain radiating to the back Fever and leukocytosis Fever and leukocytosis Hypotension and hypovolemia Hypotension and hypovolemia  Enzymes increase vascular permeability Characterized by an increase in a patient’s serum amylase level Characterized by an increase in a patient’s serum amylase level  Chronic pancreatitis Related to chronic alcohol abuse Related to chronic alcohol abuse

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 107 Cancer of the Gastrointestinal Tract  Esophagus  Stomach  Colon and rectum  Liver  Gallbladder  Pancreas

Alterations of Digestive Function Chapter 39 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

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Alterations of Digestive Function Chapter 39 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

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