Gastroenterology and Liver Disease 2023 Part 1 PDF

Structure and Function of the Digestive System Learning Objectives ▪ Describe the pathophysiologic alterations that lead to diarrhea, constipation, and abdominal pain. ▪ Differentiate between parietal pain, visceral pain, and referred pain. ▪ Discuss the signs and symptoms and physiologic respons...

Structure and Function of the Digestive System Learning Objectives ▪ Describe the pathophysiologic alterations that lead to diarrhea, constipation, and abdominal pain. ▪ Differentiate between parietal pain, visceral pain, and referred pain. ▪ Discuss the signs and symptoms and physiologic response to acute gastrointestinal bleeding. ▪ List and briefly explain the various disorders of motility of the gastrointestinal tract – GERD, Intestinal obstruction ▪ Describe the causes, manifestations, treatments, outcomes, and complications of gastritis. ▪ Compare the three main types of peptic ulcers: duodenal, gastric, and stress. ▪ Compare and contrast ulcerative colitis and Crohn disease. ▪ Discuss the pathophysiology, clinical manifestations, and treatment of appendicitis, and irritable bowel syndrome ▪ Discuss the five major complications of liver dysfunction: portal hypertension, ascites, hepatic encephalopathy, jaundice, and hepatorenal syndrome. ▪ Discuss the pathophysiology of viral hepatitis and fulminant hepatitis. ▪ Discuss the causation, treatment options, and prognosis for alcoholic and biliary cirrhosis. ▪ Discuss the pathophysiology of cholelithiasis and cholecystitis. ▪ Compare and contrast acute and chronic pancreatitis. ▪ Discuss the risk factors, incidence, manifestations, treatment, morbidity, and mortality of the various cancers of the digestive system.  The Gastrointestinal Tract The gastrointestinal tract (alimentary canal) consists of the mouth, esophagus, stomach, small intestine, large intestine, rectum, and anus A network of intrinsic nerves that controls mobility, secretion, sensation, and blood flow is located solely within the gastrointestinal tract and controlled by local and autonomic nervous system stimuli through the enteric (intramural) plexus located in different layers of the gastrointestinal walls ▪ Wall of the Gastrointestinal Tract Is made up of four layers with a network of nerves between the layers. Note that the serosa is continuous with a fold of serous membrane called the mesentery. Digestive glands may empty their products into the lumen of the gastrointestinal tract by way of ducts.  Anorexia Anorexia is lack of a desire to eat despite physiologic stimuli that would normally produce hunger. This nonspecific symptom is often associated with nausea, abdominal pain, diarrhea, and psychologic stress. Side effects of drugs and disorders of other organ systems, including cancer, heart disease, and renal disease, are often accompanied by anorexia.  Vomiting (emesis) ▪ is the forceful emptying of stomach and intestinal contents (chyme) through the mouth ▪ The vomiting center lies in the medulla oblongata ▪ Nausea is a subjective experience associated with various conditions, including abnormal pain and labyrinthine stimulation (i.e., spinning movement) hypersalivation and tachycardia are common associated symptoms ▪ Retching is the muscular event of vomiting without the expulsion of vomitus. ▪ Spontaneous vomiting not preceded by nausea or retching is called projectile vomiting. caused by direct stimulation of the vomiting center by neurologic lesions (e.g., increased intracranial pressure, tumors, or aneurysms) involving the brainstem or can be a symptom of gastrointestinal obstruction (pyloric stenosis). ▪ The metabolic consequences of vomiting fluid, electrolyte, and acid-base disturbances including hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis Constipation  Pathophysiology Primary constipation : Normal transit (functional) constipation involves a normal rate of stool passage but there is difficulty with stool evacuation. ▪ is associated with a sedentary lifestyle, low-residue diet or low fluid intake. Slow-transit constipation involves impaired colonic motor activity with infrequent bowel movements, straining to defecate, mild abdominal distention, and palpable stool in the sigmoid colon. Secondary constipation can be caused by diet, medications, or neurogenic disorders (e.g., stroke, Parkinson disease, spinal cord lesions) in which neural pathways or neurotransmitters are altered and colon transit time delayed. Aging may result in decreased mobility, changes in neuromuscular function, use of medications, and comorbid medical conditions causing constipation. Constipation as a notable change in bowel habits can be an indication of colorectal cancer  Opiates (particularly codeine), Antacids containing calcium carbonate or aluminum hydroxide Iron Bismuth tend to inhibit bowel motility. Pelvic hiatal hernia Pregnancy  Pathophysiology of Diarrhea It generally is caused by excessive amounts of water or secretions or both in the intestines. The three major mechanisms of diarrhea ❖ Osmotic diarrhea ▪ A nonabsorbable substance in the intestine draws excess water into the intestine and increases stool weight and volume, producing large-volume diarrhea. ▪ Causes include: lactase and pancreatic enzyme deficiency; excessive ingestion of synthetic nonabsorbable sugars; full-strength tube-feeding formulas ❖ Secretory diarrhea Excessive mucosal secretion of fluid and electrolytes produces large-volume diarrhea. Infectious causes include: viruses (e.g., rotavirus), bacterial enterotoxins (e.g., Escherichia coli and Vibrio cholerae), exotoxins from overgrowth of Clostridium difficile following antibiotic therapy or small bowel bacterial overgrowth. Motility diarrhea Excessive motility decreases transit time and opportunity for fluid absorption, resulting in diarrhea caused by: Resection of the small intestine (short bowel syndrome) Surgical bypass of an area of the intestine Irritable bowel syndrome; Hyperthyroidism; Laxative abuse. Small-volume diarrhea is usually caused by an inflammatory disorder of the intestine, such as ulcerative colitis, Crohn disease, or microscopic colitis, but also can result from colon cancer or fecal impaction.. cAMP blocks the absorption of sodium and chloride by the microvilli and promotes the secretion of chloride and water by the crypt cells. The result is watery diarrhea with electrolyte concentrations isotonic to those of plasma.  Abdominal Pain The causal mechanisms: Mechanical, Inflammatory, or Ischemic Generally, the abdominal organs are not sensitive to mechanical stimuli, such as cutting, tearing, or crushing. These organs are, however, sensitive to stretching and distention, which activate nerve endings in both hollow and solid structures. ▪ Abdominal pain may be generalized to the abdomen or localized to a particular abdominal quadrant. ▪ The nature of the pain is often described as sharp, dull, or colicky. ▪ Abdominal pain can be parietal (somatic), visceral, or referred  Referred Pain Quadrants Of the Abdomen Causes of Gastrointestinal Bleeding Acute Bleeding Hematemesis Bloody vomitus; either fresh, bright red blood or dark grainy digested blood with “coffee grounds” appearance that has been affected by stomach acids Melena Black, sticky, tarry, foul-smelling stools caused by digestion of blood in gastrointestinal tract; should be distinguished from black stools caused by dietary iron supplements, blackberries, or bismuth (e.g., Pepto-Bismol) Hematochezia Fresh, bright red blood passed from rectum Occult Bleeding Trace amounts of blood in normal-appearing stools or gastric secretions; detectable only with positive fecal occult blood test (guaiac test). usually caused by slow, chronic blood loss that is not obvious and results in iron deficiency anemia as iron stores in the bone marrow are slowly depleted  Gastroesophageal reflux disease (GERD) is the reflux of acid and pepsin or bile salts from the stomach into the esophagus that causes esophagitis. Risk factors for GERD include: Older age Obesity Hiatal hernia Drugs Chemicals that relax the LES (anticholinergics, nitrates, calcium channel blockers, nicotine) GERD may be a trigger for asthma or chronic cough. Gastroesophageal reflux that does not cause symptoms is known as physiologic reflux.  Pathophysiology ▪ Abnormalities in lower esophageal sphincter function, esophageal motility, and gastric motility or emptying can cause GERD. ▪ The resting tone of the LES tends to be lower than normal from either transient relaxation or weakness of the sphincter. ▪ Vomiting, coughing, lifting, bending, obesity, or pregnancy increases abdominal pressure, contributing to the development of reflux esophagitis ▪ Hiatal hernia can weaken the LES. ▪ Delayed gastric emptying (1) lengthening the period during which reflux is possible and (2) increasing gastric acid content ▪ The refluxate causes mucosal injury and inflammation with hyperemia, increased capillary permeability, edema, tissue fragility, and erosion. ▪ Fibrosis and thickening may develop  Gastritis is an inflammatory disorder of the gastric mucosa It can be acute or chronic and affect the superficial mucosa of the fundus or antrum, or both. Acute gastritis is caused by injury of the protective mucosal barrier caused by drugs, chemicals, or Helicobacter pylori infection. Nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen, indomethacin, and aspirin) NSAIDs inhibit the action of cyclooxygenase-1 (COX-1) and cause gastritis because they inhibit prostaglandin synthesis, which normally stimulates the secretion of mucus. Alcohol, histamine, digitalis, and metabolic disorders, such as uremia, are contributing factors. The clinical manifestations of acute gastritis can include vague abdominal discomfort, epigastric tenderness, and bleeding. Healing usually occurs spontaneously within a few days. Chronic gastritis tends to occur in older adults and causes chronic inflammation, mucosal atrophy, and epithelial metaplasia.  Peptic Ulcer is a break or ulceration in the protective mucosal lining of the lower esophagus, stomach, or duodenum. Ulcers develop when mucosal protective factors are overcome by erosive factors commonly caused by NSAIDs and H. pylori infection. Peptic ulcers can be single or multiple, acute or chronic, and superficial or deep. ❖ Superficial ulcerations are called erosions because they erode the mucosa but do not penetrate the muscularis mucosae ❖ True ulcers extend through the muscularis mucosae and damage blood vessels, causing hemorrhage, or perforate the gastrointestinal wall. Peptic Ulcer Disease Duodenal ulcers ▪ Most common of the peptic ulcers ▪ Developmental factors: Helicobacter pylori infection Toxins and enzymes that promote inflammation and ulceration Hypersecretion of stomach acid and pepsin Use of NSAIDs High gastrin levels Acid production by cigarette smoking Gastric Ulcer Gastric ulcers tend 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 tends to be normal or less than normal  Stress ulcer A stress-related mucosal disease is an acute form of peptic ulcer that tends to accompany the physiologic stress of severe illness or major trauma. Usually multiple sites of ulceration are distributed within the stomach or duodenum. Classified as: ❖ Ischemic ulcers develop within hours of an event such as hemorrhage, multisystem trauma, severe burns, heart failure, or sepsis. Shock, anoxia, inflammation, and sympathetic responses cause ischemia of the stomach and duodenal mucosa, disrupting the mucosal barrier. Stress ulcers that develop as a result of burn injury are often called Curling ulcers. ❖ Cushing ulcer associated with severe brain trauma or brain surgery. Decreased mucosal blood flow and hypersecretion of acid caused by overstimulation of the vagal nuclei damage the mucosal barrier, causing erosions and ulceration. Pathophysiology of Gastric Ulcer Formation Characteristics Gastric Ulcer Duodenal Ulcer Age at onset 50-70 years 20-50 years Family history Usually negative Positive Gender (prevalence) Equal in women and men Greater in men S tress factors Increased Average Ulcerogenic drugs Normal use Increased use Cancer risk Increased Not increased Clinical Manifestation Pain Located in upper abdomen Located in upper abdomen Intermittent Intermittent Pain-antacid-relief pattern Pain-antacid/food-relief pattern Food-pain pattern (when food in Pain when stomach empty stomach) Nocturnal pain common Chronic ulcer without pattern of Clinical course Pattern of remissions and exacerbation for remission and exacerbation Years Heals more quickly Heals more slowly  Intestinal Obstruction and Paralytic Ileus Intestinal obstruction can be caused by any condition that prevents the normal flow of chyme through the intestinal lumen Obstructions can occur in either the small or the large intestine The small intestine is more commonly obstructed because of its narrower lumen. Classified by cause as: ❖ Simple obstruction - mechanical blockage of the lumen by a lesion and it is the most common type of intestinal obstruction. ❖ Paralytic ileus, or functional obstruction, is a failure of intestinal motility often occurring after intestinal or abdominal surgery, acute pancreatitis, or hypokalemia. ▪ Acute obstructions usually have mechanical causes, such as adhesions or hernias ▪ Chronic or partial obstructions are more often associated with tumors or inflammatory disorders, particularly of the large intestine Cause Pathophysiology Hernia Protrusion of intestine through weakness in abdominal muscles or through inguinal ring Intussusception Telescoping of one part of intestine into another; this usually causes strangulation of blood supply; more common in infants 10-15 months of age than in adults Torsion Twisting of intestine on its mesenteric pedicle, with occlusion of blood supply; often (volvulus) associated with fibrous adhesions; occurs most often in middle-aged and elderly men Diverticulosis Inflamed saccular herniations (diverticuli) of mucosa and submucosa through tunica muscularis of colon; diverticuli are interspersed between thick, circular, fibrous bands; most common in obese individuals older than 60 years Tumor Tumor growth into intestinal lumen; adenocarcinoma of colon and rectum is most common tumoral obstruction; most common in individuals older than 60 years Paralytic Loss of peristaltic motor activity in intestine; associated with abdominal surgery, (adynamic) ileus peritonitis, hypokalemia, ischemic bowel, spinal trauma, or Pneumonia Fibrous Peritoneal irritation from surgery, trauma, or Crohn disease leads to formation of fibrin adhesions and adhesions that attach to intestine, omentum, or peritoneum and can cause obstruction; most common in small intestine Criteria for Classification Intestinal Obstruction Extent of Obstruction Partial - Incomplete obstruction of intestinal lumen Complete - Complete obstruction of intestinal lumen Location of Obstructing Lesion Intrinsic Obstruction develops within intestinal lumen; examples: gut wall edema or hemorrhage, foreign bodies (gallstones), tumors, or gut wall fibrosis Extrinsic Obstruction originates outside intestine; examples: tumors, torsion, fibrosis, hernia, intussusception  Effects on Intestinal Wall ▪ Simple Luminal obstruction without impairment of blood supply ▪ Strangulated Luminal obstruction with occlusion of blood supply ▪ Closed loop Obstruction at each end of a segment of intestine Causal Factors ❖ Mechanical Blockage of intestinal lumen by intrinsic or extrinsic lesions; usually treated surgically ❖ Functional (paralytic ileus) Paralysis of intestinal musculature caused by trauma, peritonitis, electrolyte imbalances, or spasmolytic agents; usually treated by decompression with suction or surgery if death of tissue  Inflammatory Bowel Disease Ulcerative colitis (UC) and Crohn disease (CD) are chronic relapsing inflammatory bowel diseases (IBDs). The disease is more prevalent among white populations and Ashkenazi Jews Risk factors and theories of causation include: ▪ Susceptibility genes ▪ Environmental factors ▪ Alterations in epithelial cell barrier functions ▪ Altered immune response to intestinal microflora Features Ulcerative Colitis Crohn Disease Age at onset Any age; 10-40 years most common Any age; 10-30 years most common Family history Less common More common Gender Prevalence equal in women and men Prevalence about equal in women and men Cancer risk Increased Increased Nicotine use Later and less severe disease; nicotine Increases disease risk and greater disease withdrawal may cause exacerbation severity Pathophysiology Large intestine, continuous lesions Mouth to anus, “ skip” lesions common Location of lesions Left side more common Right side more common Inflammation Mucosal layer involved Entire intestinal wall involved Rare Transmural granulomata common; cobblestone Granulomata Appearance Ulceration Friable mucosa, superficial ulcers, Deep fissuring ulcers and fistulae common crypt abscesses common Anal and perianal Common; abscesses Rare fistulae Narrowed lumen and Rare Common; obstruction  Chron’s Disease Clinical Manifestations Ulcerative Colitis Abdominal pain Mild to severe Moderate to severe Diarrhea Common; 4 times/day May or may not be present Bloody stools Common Less common Weight loss Less common Common Abdominal mass Rare Common Small intestine None Common malabsorption Clinical course Remissions and exacerbations Remissions and exacerbations Comorbidities Extra intestinal manifestations Extra-intestinal manifestations  Environmental factors or infections are thought to alter the barrier function of the mucosal epithelium, leading to loss of immune tolerance to normal intestinal antigens. The risk of colon cancer increases significantly after 30 to 35 years of inflammatory bowel disease, particularly in untreated disease The End