Peptic ulcer.pdf

○ Decreased dietary fiber makes the forward propulsion of feces at normal transmural pressures more difficult. ○ The increased muscle contraction, which contributes to the development of diverticular disease and also causes the abdominal pain (the c...

○ Decreased dietary fiber makes the forward propulsion of feces at normal transmural pressures more difficult. ○ The increased muscle contraction, which contributes to the development of diverticular disease and also causes the abdominal pain (the cardinal symptom of uncomplicated diverticular disease) ○ The pain may last hours to days, with sudden relief on passing flatus or feces ○ Constipation or diarrhea and flatulence are common findings during such episodes, leading to the suggestion that there is a relationship between IBS and the development of diverticulosis Clinical Manifestation: ○ About one-fifth of all individuals with diverticular disease develop one of the two major complications: Diverticulitis Diverticular bleeding Acute Diverticulitis: ○ Affects ~5% of patients with diverticulosis ○ Develops when a focal area of inflammation occurs in the wall of a diverticulum in response to irritation by fecal material ○ The patient develops symptoms of abdominal pain and fever with a risk of progression to abscess with or without perforation ○ These symptoms mimic acute appendicitis (however, pain localizes typically to the left (rather than the right) lower abdominal quadrant) ○ Perforations are usually self-contained, but the potential for subsequent fistula formation and intestinal obstruction is high ○ Stops spontaneously in 80% of cases, but can be life threatening ○ Approximately 15-25% of patients who develop diverticulitis will require surgery. ○ Hemostasis can be attempted by endoscopic methods (cautery, injection, or clips) or by interventional radiology Diverticular Bleeding: ○ Diverticula are a source of bleeding in 3-5% of patients with diverticulosis ○ This is the most common cause of massive lower GI bleeding in the elderly ○ Branches of the colonic intramural arteries (vasa recta) are closely associated with the diverticular sac, presumably leading to occasional rupture and bleeding. ○ Diverticular bleeding is typically painless and not believed to be associated with a focus of inflammation ○ The differential diagnosis of painless bleeding per rectum also includes internal hemorrhoids (dilated venous channels in the anal canal) and angiodysplasia Lecture 14: Disorders of the esophagus, stomach, duodenum. Zollinger-Ellison syndrome. Esophageal Achalasia:  Motor disorder in which the LES fails to relax properly in response to swallowing LES more tightly contracted and loss of normal peristalsis in the esophageal body Failure of a hypertensive LES to relax and the absence of esophageal peristalsis The result is a functional obstruction at the gastro-esophageal junction: ○ Dysphagia (inability to swallow) ○ Regurgitations ○ Chest pain Clinical manifestations: ○ Tremendous enlargement of esophagus ○ Esophagus can hold as much as 1 L of putrid, infected material → risk of aspiration pneumonia ○ Progressive severe weight loss ○ Mucosal ulceration ○ Infections ○ Esophageal rupture ○ Death Etiology: ○ Degeneration of the myenteric plexus: Defective innervations of smooth muscle of the esophagus and lower sphincter Improper relaxation of the LES in response to swallowing Loss of normal peristalsis in the esophageal body ○ Loss of inhibitory enteric neurons that release VIP, nitric oxide Defective LES dilation with its more tightly contraction Diagnosis: ○ Diagnosis is based on a failure of the LES to completely relax with swallowing, confirmed via esophageal manometry (criterion standard), a contrast esophagram, or esophagoscopy ○ Classical description radiologically is a “bird’s beak” narrowing of the esophagus observed during a contrast esophagram Differentiation: ○ Chagas’ disease: damage to the neural plexuses of the esophagus by parasite Trypanosoma cruzi ○ Malignancies Treatment: ○ The approach to treatment is to reduce the pressure at the lower esophageal sphincter ○ Therapy may involve: Medications: Long-acting nitrates or calcium channel blockers Can be used to relax the lower esophagus sphincter Injection with botulinum toxin (Botox) May help relax sphincter muscles Any benefit wears off within a matter of weeks or months  Widening (dilation) of the esophagus at the location of the narrowing Done during esophagogastroduodenoscopy Pneumatic dilation involves forceful balloon dilation of the LES Reduces LES pressure by 50-70% Not a permanent cure → in many patients it has to be repeated (up to 50%) Surgery more permanent than treatment (repeated in 10% of cases) Risk of esophageal perforation: about 5% If patient does not respond to two dilation procedures, then surgery is indicated Surgery (esophagomyotomy): May be needed to decrease the pressure in the lower sphincter Cuts the LES and circular smooth muscle of the distal esophagus to the level of aortic arch Effective in 80-90% of patients In 10% of cases has to be repeated Only long-term complication → GERD ○ Surgeons do a loose antireflex procedure at the time of myotomy to decrease this complication Reflux Esophagitis: Gastroesophageal Reflux Disease (GERD) Chronic symptoms or mucosal damage produced by the abnormal reflux in the esophagus ○ Backflow of gastric or duodenal contents or both into the esophagus Due to: ○ Incompetence of the LES ○ Transient LES relaxation ○ Impaired expulsion of gastric reflux from the esophagus ○ A hiatus hernia LES provides an effective barrier to reflux of acid from the stomach back into the esophagus ○ Effectiveness of the barrier can be altered by: Increased frequency of transient LES relaxations Loss of secondary peristalsis after transient LES relaxations (impairment of reflexes) Loss of LES tone Hiatal hernia: a portion of the proximal stomach slides into the chest cavity with upward displacement of the LES Increased stomach volume or pressure Increased production of acid Alkaline injury: pancreatic juice reflux (incompetent pyloric sphincter and LES)  ○ Factors influencing the rate of spontaneous transient LES relaxation: increase or decrease in LES pressure Hormones: Increase: Gastrin, Motilin, Substance P Decrease: Secretin, Cholecystokinin, Glucagon, Somatostatin, Progesterone, Gastric inhibitory peptide, Vasoactive intestinal peptide Neural agents: Increase: α-adrenergic agonists, β-adrenergic antagonists, Cholinergic agonists Decrease: β-adrenergic agonists, α-adrenergic antagonists, Anticholinergic agents Foods: Increase: protein meals Decrease: Fat, Chocolate, Ethanol, Peppermint Other: Increase: Histamine, Antacids, Metoclopramide, Domperidone Decrease: Theophylline, Caffeine, Smoking, Pregnancy, PGE2, I2, Serotonin, Dopamine Clinical presentation: ○ Burning chest pain (heartburn) Resulting from mucosal injury Worse: At night When lying supine After consumption of food or drugs that diminish LES tone ○ Dysphagia: Progressive obstruction to solid/liquid food Caused by stricture in the distal esophagus ○ Hemorrhage, perforation ○ Hoarseness ○ Coughing ○ Wheezing ○ Aspiration pneumonia ○ Barrett’s esophagus (duodenal metaplasia of the distal esophagus more resistant to HCl) Cigarette smoking + alcohol abuse + recurrent reflux In 2-5% leads to adenocarcinoma Diagnosis: ○ Barium swallow radiograph: Uses x-rays to help spot abnormalities such as a hiatal hernia and other structure or anatomical problems of the esophagus  ○ Upper endoscopy: Sometimes with biopsy More accurate than barium swallow radiograph ○ pH monitoring examination: Inserting a small tube into the esophagus or clipping a tiny device to the esophagus that will stay there for 24-48 hours Measures when and how much acid comes up into the esophagus ○ Completely accurate diagnostic test for GERD does not exist Tests have not consistently shown that acid exposure to lower esophagus directly correlates with damage to the lining Treatment: ○ Drugs: Antacids: alka-Seltzer, Maalox, Mylanta Usually the first drugs recommended to relive heartburn and other mild GERD symptoms Side effects: ○ Magnesium salt can lead to diarrhea ○ Aluminum salt may cause constipation H2 blockers: Cimetidine, Famotidine, Ranitidine Decrease acid production Provide short-term relief and are effective for about half of those who have GERD symptoms Proton pump inhibitors: Omeprazole, Lansoprazole, Pantoprazole Prokinetics: Bethanechol, Metoclopramide Help strengthen the LES and make the stomach empty faster Frequent side effects that limit their usefulness: ○ Fatigue ○ Sleepiness ○ Depression ○ Anxiety ○ Problems with physical movement ○ Surgery: When medicine and lifestyle changes do not help to manage GERD symptoms Fundoplication (Nissen): standard surgical treatment for GERD Upper part of the stomach is wrapped around the LES to: ○ Strengthen the sphincter ○ Prevent acid reflux ○ Repair a hiatal hernia Classic operation or using a laparoscope ○ Instrument that is inserted through tiny incisions in the abdomen ○ Safe and effective in people of all ages  ○ People can leave the hospital in 1-3 days and return to work in 2-3 weeks Acid-Peptic Disease: (APD) Disorder of GIT which results from superficial or deep lesion of GI mucosa as a consequence of imbalance between protective and aggressive factors Different forms of APD: ○ Duodenal ulcer ○ Gastric ulcer ○ Gastritis Etiology: ○ Bacterium Helicobacter pylori Predisposition to a number of forms of APD Duodenal ulcer Gastric ulcer Gastritis Livers in mucous layer of the stomach which secretes urease ○ Converts urea to CO2 and ammonia ○ Ammonia buffers HCl and protects H. pylori from acid Altered signal transduction → increased inflammation Increased acid secretion Decreased mucosal defenses → apoptosis in the GI tract H. pylori infection: In 50% of the world’s population Rates of infection higher in the poorest countries Route of spread from person to person: fecal - oral 90% of infected individuals show signs of inflammation (gastritis or duodenitis) Only 15% of infected individuals ever develop a clinically significant ulcer ○ Other factors account for individual variations Genetic Environment Cigarette smoking Treatment without eradication of H. pylori is associated with rapid recurrence of APD in most patients Gastric ulcer: ○ Penetrates through mucosa Deep lesion → distinguish from gastritis which is superficial lesion ○ Ulcer crater often surrounded by an area of intact but inflamed mucosa Gastritis is predisposing lesion to development of gastric ulcer ○ Most occur on the lesser curvature of stomach ○ Some related to impaired mucosal defenses Acid or pepsin secretion: normal / below normal  ○ Gnawing or burning hypergastric pain ○ Occurring just after meals ○ Food exaggerates pain: patient avoids eating ○ Affects: Middle-aged / elderly men Chronic users of NSAIDs, alcohol, tobacco ○ H. pylori infection in 75% ○ Results from decrease in protective factors (impaired mucosal defenses) ○ Acid and pepsin secretion: normal/low ○ Etiology: Motility defects: Duodenal reflux: incompetent pyloric sphincter ○ Tendency of duodenal contents to reflux back to the stomach ○ Bile acts as an irritant → diminishes mucosal barrier against acid and pepsin Delayed emptying of gastric contents into duodenum ○ Delayed gastric emptying → food retention → increased gastric secretion and gastric acid production Mucosal ischemia: (stress: shock, burn, operation) PG increase mucosal blood flow, bicarbonate, and mucus secretion PG stimulate mucosal cell repair and renewal PG deficiency (after NSAID or other agents) may predispose to gastritis and gastric ulcer NSAID ingestion, smoking, psychological stress, H. pylori infection: Diminished bicarbonate and mucus secretion Gastritis (inflammation of gastric mucosa): Caused by aspirin and other NSAID, bile salts, alcohol ○ Attenuate the barrier created by the epithelial cells or the mucus and bicarbonate they secrete ○ Reduce the quantity of PG produced by epithelial cells Duodenal ulcer: ○ Consequence of H. pylori infection Mucosal inflammation Altered defenses ○ Secondary role of excessive acid secretion ○ Other factors: Diet  Smoking Alcohol abuse Genetic factors: heritable component in duodenal ulcer distinct from that involved in gastric ulcer Psychological stress ○ Sometimes painless ○ 80%: Gnawing or burning epigastric pain Occurring 1-3 hours after meals Often waking patient at night With antacids or food producing relief Affects mostly men, ages 20-50 Results from increase in aggressive factors: H. pylori: primary cause (95%) Excessive acid secretion: secondary role Chronic Atrophic Gastritis: ○ Inflammatory cell infiltration ○ Gastric mucosal atrophy ○ Loss of glands ○ Chronic disease without endoscopic abnormalities ○ Progressively reduced capacity to secret gastric acid → hypochlorhydria, achlorhydria ○ Elevated serum gastrin levels ○ Presence of autoantibodies to parietal cells, and intrinsic factor ○ Associated with: H. pylori infection Development of pernicious anemia Vit. B12 deficiency: impaired synthesis of purines and thymine Gastric adenocarcinoma GI endocrine hyperplasia with carcinoids Neuroendocrine tumors of the GI tract producing serotonin metabolites Associated with dramatic symptoms of flushing and diarrhea Zollinger-Ellison Syndrome: Caused by gastrin-secreting tumor (gastrinoma) ○ Stimulates the acid-secreting cells of the stomach to maximal activity ○ Hyperproliferation of gastric glands and parietal cells ○ Excess secretion of gastric acid Consequently: gastrointestinal mucosal ulceration May occur: ○ Sporadically ○ As part of an autosomal dominant familial syndrome Multiple Endocrine Neoplasia type I (MEN I)  Primary tumor is usually located in: ○ Duodenum ○ Pancreas ○ Abdominal lymph nodes Ectopic locations: Heart, Ovary, Gallbladder, Liver, Kidney Symptoms: ○ Secondary to hypergastrinemia Gastrin stimulates acid secretion → direct mucosal damage by: Acid Inactivation of pancreatic enzymes Precipitation of bile salts Gastrointestinal mucosal ulceration Diarrhea (fatty stool) Malabsorption ○ Sporadic in 75% of patients ○ 25%: associated with MEN I (autosomal dominant condition) Pancreatic endocrine tumor (gastrinoma) Hyperparathyroidism (tumor of parathyroid glands) Pituitary tumors ○ Abdominal pain (75% of patients) Typically located in upper abdomen Mimics that of peptic ulcer disease ○ Diarrhea (73%) MEN I / ZES Female patients Combination of diarrhea and abdominal pain (>50%) ○ Heartburn: mimics GERD ○ Other symptoms: Nausea Vomiting GI bleeding (due to ulceration in duodenum, 25%) Weight loss ○ Patients with MEN I / ZES: History or family history of nephrolithiasis, hypercalcemia, pituitary disorders Physical examination: ○ May be normal ○ Paleness in GI bleeding ○ Jaundice: if tumor compresses common bile duct (very rare) ○ Epigastric tenderness ○ Dental erosions (if symptoms consistent with GERD) ○ Hepatomegaly (in liver metastasis) Diagnosis: ○ Fasting serum gastrin (best single screening test)  Normal levels of serum gastrin in untreated ZES → extremely rare (1%) ○ Gastric acid secretory tests: suggestive of ZES Basal acid output (BAO): > 15 mEg/h Or > 5 mEg/h in patients with prior vagotomy and partial gastrectomy Basal gastric secretary volume: > 140 mL in patients with no prior gastric acid-reducing surgery (ex: vagotomy) Gastric pH: < 2.0 in presence of large gastric volume (>140 mL) over 1 hour in patients without prior gastric acid-reducing surgery Complications: ○ Abdominal perforation secondary to ulceration Most common sites: duodenum and jejunum ○ Esophageal stricture with reflux ○ Obstruction ○ GI bleeding ○ Gastric carcinoids Hypergastrinemia: especially in patients with MEN I Prognosis: excellent in patients without metastatic disease Goals of treatment: ○ Medical control of gastric acid hypersecretion IV proton pump inhibitors (PPI) IV pantoprazole was approved recently by US FDA Proton pump inhibitor superior to H2 blockers for control of gastric acid hypersecretion ○ Surgical resection of the tumor ○ Chemotherapy with interferon and octreotide (in metastatic disease) ○ Liver transplantation in hepatic metastasis ○ Surgical resection or thermoablation in single confined liver metastatic lesion Lecture 15: Hyperbilirubinemias. Jaundice. Cholestatic liver diseases. Gallbladder diseases. Alcoholic and non-alcoholic fatty liver diseases. Liver Diseases: Hyperbilirubinemias (including inherited hyperbilirubinemias) and jaundice Cholestatic liver disease Acute and chronic hepatitis Liver cirrhosis Alcoholic liver disease Nonalcoholic fatty liver disease Gallbladder disease