Lecture On Gastroenterology And Hepatology (1).pptx

Discusses general approach patients with acid peptic disorders with paryicular emphasis od H.pyelori and NSAID mediated pud. Additionall4discusses on IBD.

1. Lecture On Gastroenterology And Hepatology for Clinical I students Dr.Tadele Sahlemariam ( MD,MBA,internist ) @ yekatit 12 hospital medical college

2. Acid Peptic Diseases & Bleeding PUD September/2025 @ yekatit 12 hospital medical college

3. Gross anatomy of the stomach

4. Acid peptic disorders (APD) refer to a group of conditions resulting from an imbalance between aggressive factors—like stomach acid and pepsin—and the stomach’s protective mucosal defenses. This imbalance can cause damage to the lining of the stomach, duodenum, and esophagus.

5. Common diseases under this umbrella APD include: Peptic Ulcer Disease (PUD) Gastroesophageal Reflux Disease (GERD) Stress-related mucosal injury, in severely ill or hospitalized patients

6. A peptic ulcer is : “ disruption of the mucosal integrity of the stomach and/or duodenum leading to a local defect or excavation due to active inflammation . “ Dyspepsia(burning epigastric pain exacerbated by fasting and improved with meals) is a symptom complex associated with PUD >90% patients with this symptom complex do not have ulcers (Functional dyspepsia) The majority of patients with peptic ulcers may be asymptomatic. Ulcers occur within the stomach and/or duodenum and are often chronic in nature.

7. The mucosal defense system -three-level barrier Pre-epithelial Mucus-bicarbonate-phospholipid layer , which serves as a physicochemical barrier Epithelial Mucus production, ionic transport, bicarbonate production, and intracellular tight junctions Generate heat shock proteins Sub-epithelial elements Microvascular system within the gastric submucosal providing HCO3, which neutralizes the acid generated by the parietal cell.

8. Prostaglandins : Play a central role in gastric epithelial defense/repair. Regulate the release of mucosal bicarbonate and mucus, Inhibit parietal cell secretion, and are important in maintaining mucosal blood flow and epithelial cell restitution

9. PATHOPHYSIOLOGIC BASIS OF PUD PUD encompasses both gastric ulcers (GUs) and duodenal ulcers (DUs). Ulcers are defined as breaks in the mucosal surface >5 mm in size, with depth to the submucosa . H. pylori and NSAIDs are the most common risk factors for PUD Additional risk factors include chronic obstructive lung disease , Chronic renal insufficiency , tobacco use older age, coronary heart disease obesity and diabetes A rise in idiopathic PUD has also been noted.

10. H. PYLORI AND ACID PEPTIC DISORDERS Gastric infection with the bacterium H. pylori accounts for the majority of PUD . This organism also plays a role in the development of Gastric mucosa-associated lymphoid tissue ( MALT ) lymphoma and Gastric adenocarcinoma .

11. Transmission of H. pylori occurs from person to person, following an oral-oral or fecal-oral route. The prevalence of H. pylori varies throughout the world and depends largely on the overall standard of living in the region. In developing parts of the world, 80% of the population may be infected by the age of 20, whereas the prevalence is 20–50% in industrialized countries.

12. Factors that are essential determinants of H. pylori–mediated pathogenesis and colonization are The outer membrane protein (Hop proteins), Urease, catalase, lipase, adhesins , platelet-activating factor, and pic B (induces cytokines). The vacuolating cytotoxin ( Vac A).

13. NSAID-INDUCED DISEASE Side effects and complications due to NSAIDs are considered the most common drug-related toxicities. The spectrum of NSAID-induced morbidity ranges from nausea and dyspepsia (50–60%) to peptic ulceration (15–30%). Over 80% of patients with serious NSAID-related complications did not have preceding dyspepsia.

14. No dose of NSAID is completely safe. Established risk factors include Advanced age, History of ulcer, Concomitant use of glucocorticoids, High dose NSAIDs or multiple NSAIDs, Concomitant use of anticoagulants or clopidogrel , Serious or multisystem disease. Concomitant infection with H. pylori, Cigarette smoking, and alcohol consumption.

15. Clinical Features History Abdominal pain is common to many GI disorders, including DU and GU, but it has a poor predictive value for the presence of either DU or GU. NB: Approximately two-thirds of patients with PUD do not have abdominal pain. Up to 87% of patients with NSAID-induced mucosal disease can present with a complication without antecedent symptoms.

16. The typical pain pattern in DU occurs 90 min to 3 h after a meal Is frequently relieved by antacids or food. Awakes the patient from sleep (between midnight and 3 a.m.) The pain pattern in GU Precipitated by food. Nausea and weight loss

17. Dyspepsia that becomes constant, is no longer relieved by food or antacids, or radiates to the back may indicate a penetrating ulcer (pancreas ). Sudden onset of severe, generalized abdominal pain may indicate perforation . Pain worsening with meals, nausea, and vomiting of undigested food suggest gastric outlet obstruction. Tarry stools or coffee-ground emesis indicate bleeding .

18. Coffee-ground vomitus Melena (tarry stool)

19. Physical Examination Epigastric tenderness is the most frequent finding in patients with GU or DU. Tenderness may be found to the right of the midline in 20% of patients. Physical examination is critically important for discovering evidence of ulcer complication. Tachycardia and orthostasis suggest dehydration secondary to vomiting or active GI blood loss. A severely tender, board-like abdomen suggests a perforation. Presence of a succussion splash indicates retained fluid in the stomach, suggesting gastric outlet obstruction.

20. Complications of PUD Bleeding- (to be adressed by seminar/tutorial) Perforation- to be adressed at your surgical atteachement Gastric outlet obstruction- to be adressed at your surgical attachment

21. Differential diagnosis Functional dyspepsia/essential dyspepsia Proximal GI tumors, Gastro-esophageal reflux, Vascular disease, Pancreatico -biliary disease Biliary colic, Chronic pancreatitis, Gastroduodenal-Crohn’s disease.

22. Diagnostic evaluation-PUD Documentation of an ulcer requires either a radiographic (barium study ) or an endoscopic procedure). Test for H. pylori Serologic testing, Urea breath test, Fecal H. pylori ( Hp ) antigen

23. The sensitivity of older single-contrast barium meals for detecting a DU is as high as 80%, with a double-contrast study providing detection rates as high as 90%. A DU appears as a well-demarcated crater, most often seen in the bulb

24. A GU may represent benign or malignant disease. Typically, a benign GU also appears as a discrete crater with radiating mucosal folds originating from the ulcer margin. Ulcers >3 cm in size or those associated with a mass are more often malignant.

25. Endoscopy provides the most sensitive and specific approach for examining the upper GI tract. Permits direct visualization of the mucosa, Facilitates photographic documentation of a mucosal defect Facilitates tissue biopsy to rule out malignancy (GU) or H. pylori. Helpful in identifying lesions too small to detect by radiographic examination, Helpful for evaluation of atypical radiographic abnormalities, Helpful to determine if an ulcer is a source of blood loss.

26. Duodenal ulcer-endoscopy Duodenal ulcer with visible vessel

27. Gastric ulcer-endoscopy

28. TREATMENT-Peptic Ulcer Disease Goal of treatment To provide relief of symptoms Promote ulcer healing, prevent ulcer recurrence and complications. Although acid secretion is still important in the pathogenesis of PUD, eradication of H. pylori and therapy/prevention of NSAID-induced disease is the mainstay of treatment .

29. 1. Antacids Are often used by patients for symptomatic relief of dyspepsia. The most commonly used agents are mixtures of aluminum hydroxide and magnesium hydroxide. Calcium carbonate and sodium bicarbonate are potent antacids with varying levels of potential problems.

30. 2. H2 Receptor Antagonists All will significantly inhibit basal and stimulated acid secretion to comparable levels when used at therapeutic doses. Similar ulcer-healing rates are achieved with each drug when used at the correct dosage. Often used for treatment of active ulcers (4–6 weeks) in combination with antibiotics directed at eradicating H. pylori

31. Proton Pump (H+,K+-ATPase) Inhibitors covalently bind and irreversibly inhibit H+,K+-ATPase.

32. THERAPY OF H. PYLORI Documented eradication of H. pylori in patients with PUD is associated with a dramatic decrease in ulcer recurrence to <10–20% as compared to 59% in GU patients and 67% in DU patients when the organism is not eliminated.

33. Who of the many individuals with H. pylori infection should be treated?. Patients with documented PUD. Patients with a history of documented PUD Patients with gastric MALT lymphoma Patients who will be using NSAIDs on a long-term basis. Patients who have undergone resection of early gastric cancer. First-degree relatives of family members with gastric cancer; Individuals with a risk of gastritis (severe pangastritis or body-predominant gastritis) Individuals with strong environmental risk factors for gastric cancer (heavy smoking; high exposure to dust, coal, quartz, or cement; and/or work in quarries) Patients with unexplained iron deficiency anemia Patients with idiopathic thrombocytopenic purpura

34. Upper gastrointestinal bleeding (UGIB) Upper gastrointestinal bleeding (UGIB): Refers to bleeding that originates proximal to the ligament of Treitz (i.e., from the esophagus, stomach, or duodenum).

35. Major Causes of UGIB 1. Esophageal Causes Esophageal varices (from portal hypertension, e.g., cirrhosis) Esophag itis (reflux, pill-induced, infectious in immunocompromised ) Mallory–Weiss tear (longitudinal mucosal tear at gastroesophageal junction, usually after retching/vomiting) Esophageal ulcers (peptic, medication-induced, infectious) Esophageal cancer (rare cause)

36. 2.Gastric Causes Peptic ulcer disease (gastric ulcers) – one of the most common causes Gastritis (NSAIDs, alcohol, stress-related mucosal disease, H. pylori) Gastric varices (due to portal hypertension, splenic vein thrombosis) Gastric cancer (bleeding tumor) Dieulafoy lesion (large caliber artery in gastric wall erodes and bleeds massively) GAVE (Gastric antral vascular ectasia) – “watermelon stomach” 3. Duodenal Causes Peptic ulcer disease(duodenal ulcers, also a leading cause) Erosive duodenitis Hemobilia (bleeding into biliary tract, presenting as UGIB) Vascular malformations( angiodysplasia , AVMs)

37. 4. Iatrogenic / Trauma Post–endoscopic procedure bleeding (e.g., post- polypectomy , after sphincterotomy ) Nasogastric tube trauma Post-surgical anastomotic ulcer or bleeding Most Common Causes in Practice Peptic ulcer disease (gastric or duodenal) Esophageal varices Mallory–Weiss tear Gastritis/ duodenitis

38. CLINICAL PRESENTATION Hematemesis (either red blood or coffee-ground emesis) , Suggests bleeding proximal to the ligament of Treitz . Melena (black, tarry stool) In 90 % of patients, bleeding originates proximal to the ligament of Treitz , though it may also originate from the oropharynx or nasopharynx or lower GI sources such as small bowel or proximal colon As little as 50 mL of blood may produce melena. It takes at least 14 hours for bleeding to manifest as melena, and melena may persist for up to five days after bleeding has stopped.

39. Hematochezia (red or maroon blood in the stool) is usually due to lower GI bleeding, but may also occur in rapid, large volume upper GI bleeding. Occult upper GI bleeding – Patients with GI bleeding may also present without overt signs of bleeding, but rather with symptoms of anemia. If there are no alternate explanations,standard endoscopic evaluation for upper and lower GI bleeding begins.

40. The initial evaluation in acute upper GI bleeding includes Ascertaining upper GI bleed symptoms, Evaluating hemodynamic stability and bleeding severity, Determining the presence of comorbidities or medications ( eg , antithrombotics ) NB: The information gathered from the initial evaluation is used to guide decisions regarding triage, hemodynamic resuscitation, empiric medical therapy, and diagnostic testing.

41. Evaluate hemodynamic stability Resting tachycardia (>100 beats per minute) Orthostatic hypotension Supine hypotension Lightheadedness, confusion, angina, palpitations, and cold/clammy extremities. NB: The absence of severe anemia does not rule out a severe upper GI bleed. A decline in hemoglobin values can lag one to three days after a bleeding episode (called equilibration).

42. Past Medical History History of cirrhosis or liver disease – Varices or portal hypertensive gastropathy History of Helicobacter pylori (H. pylori) infection or nonsteroidal anti-inflammatory drug (NSAID) use – Peptic ulcer disease, gastroduodenal erosions History of gastroenteric anastomosis – Marginal ulcer History of aortic stenosis or hereditary hemorrhagic telangiectasia – Gastrointestinal angiodysplasia . History of abdominal aortic aneurysm or aortic graft – Aorto -enteric fistula Tobacco use – Peptic ulcer disease, malignancy Excess alcohol use – Gastric erosions or subepithelial hemorrhages, prolapse gastropathy , malignancy, cirrhosis or liver disease

43. Comorbid illnesses Coronary artery disease or myocardial ischemia – May increase susceptibility to adverse effects of anemia. Such patients may need to be maintained at higher hemoglobin levels than patients without these disorders. Chronic kidney disease or heart failure – May predispose to volume overload in the setting of vigorous fluid resuscitation or blood transfusions. Such patients may need more invasive hemodynamic monitoring during resuscitation. (See 'Fluid resuscitation' below.) Coagulopathies or thrombocytopenia – May result in bleeding that is more difficult to control. Such patients may require correction of coagulopathy and/or need additional hemostatic therapies. Dementia or hepatic encephalopathy – May predispose to aspiration of GI contents into the lungs. Such patients may benefit from aspiration precautions and monitoring for development of pneumonia.

44. Medication history should be obtained, with particular attention paid to drugs that: Increase the risk of bleeding, such as anticoagulants (including direct oral anticoagulants and warfarin) and antiplatelet agents ( eg , P2Y12 inhibitors and aspirin). Predispose to peptic ulcer formation, such as aspirin and other NSAIDs, including COX-2 selective NSAIDs. Are associated with pill esophagitis, eg , antibiotics (especially tetracycline and doxycycline), bisphosphonates, and NSAIDs. May alter the clinical presentation, such as iron, bismuth, charcoal, and licorice, which can turn the stool black.

45. Associated symptoms and signs that suggest specific causes of upper GI bleeding: Emesis, retching, or coughing prior to hematemesis – Mallory-Weiss tear Jaundice, abdominal distention (ascites) – Variceal hemorrhage or portal hypertensive gastropathy Upper abdominal pain – Peptic ulcer Odynophagia, gastroesophageal reflux, dysphagia – Esophageal ulcer Dysphagia, early satiety, unintentional weight loss, cachexia – Malignancy

46. Laboratory data — Complete blood count, Serum chemistries Coagulation studies. ECG and serial cardiac enzymes may be indicated in patients who are at risk for a myocardial infarction.

47. Initial Management Of UGIB

48. Glasgow-Blatchford score (GBS)

49. Values range from 0 to 23. It is estimated that ≥99 percent of patients with a score of 0 or 1 do not die or require transfusion or hospital-based intervention within 30 days

50. Intravenous access: Patients who are hemodynamically unstable should have two large-caliber 16-gauge peripheral IV catheters and/or a large-bore ( eg , 6 to 9 French), single-lumen central catheter. For hemodynamically stable patients, at least one, but ideally two, large caliber (18 gauge or larger) peripheral IV catheters should be inserted.

51. Fluid resuscitation Patients with hemodynamic instability or active bleeding should receive bolus intravenous crystalloid fluids ( eg , at least 500 to 1000 mL of normal saline or lactated Ringer's solution over 30 minutes), with reassessment of blood pressure and volume status, while being typed and cross-matched for blood transfusion.

52. NPO status and pre-endoscopic medications NPO A PPI( Esomeprazole, pantoprazole) Pre-endoscopic PPIs modestly reduce the need for endoscopic hemostatic treatment.

53. Bleeding peptic ulcer disease ---management Stigmata of recent hemorrhage — Certain endoscopic findings, known as stigmata of recent hemorrhage, are associated with an increased risk of recurrent bleeding (up to 90 percent depending on the finding)

54. Endoscopy shows an actively bleeding gastric ulcer (Forrest classification Ia ) along the lesser curvature.

55. A duodenal ulcer with a non-bleeding visible vessel (arrow) in a large circumferential ulcer (Forrest classification IIa )

56. Upper endoscopy showing a gastric ulcer with an adherent clot (Forrest classification IIb ).

57. Ulcers with a flat pigmented spot (Forrest classification IIc ; panel A) or a clean base (Forrest classification III, panel B)

58. Inpatient or outpatient management? Hospitalization is required for Patients at high-risk for further bleeding, Patients with evidence of severe upper gastrointestinal (UGI) bleeding (hemodynamic instability, blood transfusion requirement), Patients at increased risk for complications should bleeding recur Significant coronary artery or cerebrovascular disease, Age over 65 years, patients taking antiplatelet or anticoagulant medications.

59. Patients who are otherwise healthy and who are at low risk for recurrent UGI bleeding may be safely allowed to eat and be discharged from the hospital on oral antisecretory therapy once the effects of procedural sedation have worn off, provided that the patient is reliable and can promptly get medical care should bleeding recur.

60. Pharmacotherapy-bleeding PUD Acid suppression Treatment with PPIs leads to elevation of gastric pH levels, which stabilizes blood clots and improves clinical outcomes. PPIs are recommended for all patients with peptic ulcer bleeding. IV PPI every 12 hours or a continuous infusion. In patients with high-risk stigmata of recent hemorrhage, a high-dose continuous infusion of a PPI ( eg , esomeprazole 8 mg per hour) should be started and continued for 72 hours.

61. The high-dose IV PPI may be switched to a high-dose oral PPI ( eg , omeprazole 40 mg twice daily) 72 hours after endoscopy, provided there is no evidence of recurrent bleeding Oral formulations are a reasonable alternative if IV formulations are not available Oral potassium-competitive acid blockers(PCABs), such as vonoprazan , may be another alternative to IV PPIs.

62. Patients who do not have active bleeding or other high-risk stigmata may be switched to a standard-dose oral PPI ( eg , omeprazole or esomeprazole 20 mg once daily, pantoprazole 40 mg once daily) immediately following endoscopy. The goal of treatment in low-risk patients should be directed at healing the ulcers and eliminating precipitating factors (such as Helicobacter pylori and nonsteroidal anti-inflammatory drugs).

63. High-dose oral PPIs in patients with high-risk stigmata of recent hemorrhage are continued for a total of two weeks and then changed to a once daily dose H2 receptor antagonists (H2RAs) in bleeding peptic ulcers have produced mixed but generally disappointing results and are not recommended for patients with acute upper gastrointestinal bleeding

64. Somatostatin and octreotide : Somatostatin and its long-acting analogue octreotide Have a theoretical benefit in bleeding ulcer disease because They reduce splanchnic blood flow, Inhibit gastric acid secretion, and May have gastric cytoprotective effects. Because of the effectiveness of PPI and endoscopic therapy, its role is generally limited to settings in which endoscopy is unavailable or as a means to help stabilize patients before definitive therapy can be performed.

65. A typical dose of somatostatin was 250 mcg given as a bolus followed by an infusion of 250 mcg per hour for three to seven days, A typical dose of octreotide was 50 to 100 mcg given as a bolus followed by an infusion of 25 mcg per hour for up to three days.

66. Prokinetic agents Erythromycin(250 mg intravenously over 20 to 30 minutes)may be used before endoscopy to improve gastric visibility and diagnostic yield of endoscopy. Endoscopy is performed 20 to 90 minutes after the infusion is complete.

67. Endoscopic Therapy In Bleeding PUD Endoscopic therapy is indicated for the treatment of most ulcers with stigmata of recent hemorrhage that increase the risk of recurrent bleeding. Endoscopic therapy should only be performed following adequate resuscitation and hemodynamic stabilization. Standard approaches to treatment include thermal coagulation and endoscopic clip placement . In addition, both of these modalities can be combined with injection therapy, an approach known as combination therapy.

68. 1. Injection therapy Epinephrine Injection therapy should be used in conjunction with other forms of therapy, such as thermal coagulation or endoscopic clip placement. Injection therapy should not be used as monotherapy because it is associated with higher rates of recurrent bleeding . Injection therapy with dilute epinephrine results in local tamponade and vasospasm Saline Injection of saline also causes local tamponade , which can be effective in achieving temporary hemostasis. Saline injection alone is associated with higher recurrent bleeding rates compared with other standard therapies

69. 2.Thermal coagulation Thermal coagulation with contact probes achieves acute hemostasis and prevents recurrent bleeding by coaptive coagulation of the underlying artery in the ulcer base . An alternate form of thermal coagulation uses argon plasma coagulation (APC).

70. 3. Endoscopic clips The application of endoscopic clips is an alternative to thermal coagulation. Once applied, the clips achieve hemostasis in a manner similar to surgical ligation. Placement of an endoscopic clip can be of value even if an ulcer is not amenable to endoscopic therapy since it may serve as a radiopaque marker for subsequent interventional angiographic or surgical intervention.

71. Alternative approaches Alternatives to standard endoscopic therapy that are being studied include the use of tissue adhesives and agents that promote hemostasis. Fibrin sealant Endoscopically injected fibrin sealant to achieve initial hemostasis and decrease the rate of recurrent bleeding.

72. Topical hemostatic agents(THAs), Such as hemostatic sprays , can be used to control active GI bleeding in a variety of contexts, particularly when traditional endoscopic techniques fail to control massive GI bleeding THAs are temporizing measures to stop bleeding when conventional modalities to control bleeding fail or are not available THAs may be deployed in patients with bleeding from a GI malignancy, which may be from multiple sites and can be difficult to control with standard techniques.

73. Second-look endoscopy Refers to the practice of performing a planned follow-up endoscopy, generally within 24 hours of the initial endoscopy. If there is active bleeding or a nonbleeding visible vessel, endoscopic therapy is performed

74. Treatment-related complications Complications that may occur before endoscopy include Aspiration (especially in a sedated, combative, or encephalopathic patient), Hypoventilation (related to oversedation ), or Hypotension (due to inadequate volume replacement or transfusions, in addition to sedation with opiates Complications of endoscopic therapy include Perforation and precipitation (or worsening) of bleeding Tachycardia and arrhythmias(related to epinephrine ).

75. Aggressive initial treatment or repeated applications of thermal or injection therapy may improve hemostasis, but also increase the risk of treatment-induced complications. Predetermined limits (volume of injection solution, total treatment pulses, and total energy delivered) should be set and not exceeded for each technique, in order to minimize the risk of complications.

76. Treatment Of Persistent And Recurrent Bleeding Persistent bleeding : refers to active bleeding that does not stop despite endoscopic therapy or bleeding that develops during endoscopic therapy of a non-bleeding lesion that cannot be controlled endoscopicaly . Recurrent bleeding : refers to bleeding that occurs following spontaneous hemostasis or after successful endoscopic hemostasis.

77. The presence of one or more of the following criteria has been proposed for defining recurrent bleeding. Hematemesis or bloody nasogastric aspirate more than six hours after endoscopy Melena after normalization of stool color Hematochezia after normalization of stool color or after melena Development of tachycardia (heart rate ≥110 beats per minute) or hypotension (systolic blood pressure ≤90 mmHg) after at least one hour of hemodynamic stability in the absence of an alternative explanation for hemodynamic instability, such as sepsis, cardiogenic shock, or medications

78. Criteria for recurrent bleeding …. cont Hemoglobin drop of 2 g/ dL or more after two consecutive stable hemoglobin values (less than a 0.5 g/ dL decrease) obtained at least three hours apart Tachycardia or hypotension that does not resolve within eight hours after index endoscopy despite appropriate resuscitation (in the absence of an alternative explanation), associated with persistent melena or hematochezia Persistently dropping hemoglobin of more than 3 g/ dL in 24 hours, associated with persistent melena or hematochezia

79. Factors associated with persistent or recurrent bleeding include Ulcer location, The patient's presentation, The appearance of the ulcer at the time of endoscopy, Size of the ulcer, and Presence of comorbid illnesses.

80. A meta-analysis of 10 studies found that predictors of recurrent bleeding included Active bleeding at endoscopy, Large ulcers (>1 to 2 cm), Posterior duodenal ulcers(posterior gastroduodenal artery) Gastric ulcers on the lesser curvature(left gastric artery). End-stage kidney disease may also increase the risk of recurrent bleeding

81. Inflammatory bowel disease( ibd )

82. Please revisit your anatomy and physiology courses!!!!

83. Definition : Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disease of the gastrointestinal tract . Ulcerative colitis (UC) and Crohn’s disease (CD) are the two major types of IBD.

84. Epidemiology-IBD Peak incidence of IBD is in the second to fourth decades,with 78% of CD studies and 51% of UC studies reporting the highest incidence among those aged 20–29 years old . A second modest rise in incidence occurs between the seventh and ninth decades of life. IBD is not gender-specific.

85. Although the greatest prevalence of IBD is among Whites, the prevalence of IBD in Latino, Black, and Asian people is increasing. Urban areas have a higher prevalence of IBD than rural areas. High socioeconomic classes have a higher prevalence than lower socioeconomic classes.

86. Etiology And Pathogenesis Homeostasis normally exists between th e commensal microbiota , intestinal epithelial cells and immune cells within the tissues. Each of these three major components are affected by specific environmental (e.g., smoking, antibiotics, enteropathogens ) and genetic factors Disruption of this homeostasis culminate in a chronic state of dysregulated inflammation;i.e ., IBD. IBD is currently considered an inappropriate immune response to the endogenous commensal microbiota within the intestines, with or without some component of autoimmunity.

87. PATHOLOGY-IBD Ulcerative Colitis: Macroscopic Features UC is a mucosal disease that usually involves the rectum and extends proximally to involve all or part of the colon. 40–50% of patients have disease limited to the rectum and rectosigmoid , 30–40% have disease extending beyond the sigmoid but not involving the whole colon, 20% have a pancolitis . Proximal spread occurs in continuity without areas of uninvolved mucosa. Although variations in macroscopic activity may suggest skip areas, biopsies from normal appearing mucosa are usually abnormal.

88. In mild inflammation , the mucosa is erythematous and has a fine granular surface that resembles sandpaper . In more severe disease, the mucosa is hemorrhagic, edematous, and ulcerated. In long-standing disease , inflammatory polyps ( pseudopolyps ) may be present as a result of epithelial regeneration. In patients with many years of disease, the mucosa appears atrophic and featureless, and the entire colon becomes narrowed and shortened. Patients with fulminant disease can develop a toxic colitis or megacolon w here the bowel wall becomes thin and the mucosa is severely ulcerated.

89. Diffuse ( nonsegmental ) mucosal disease, with broad areas of ulceration

90. Ulcerative Colitis: Microscopic Features The process is limited to the mucosa and superficial submucosa , with deeper layers unaffected except in fulminant disease. The two major histologic features suggest chronicity and help distinguish it from infectious or acute self-limited colitis. The crypt architecture of the colon is distorted; crypts may be bifid and reduced in number, often with a gap between the crypt bases and the muscularis mucosae. Some patients have basal plasma cells and multiple basal lymphoid aggregates. Mucosal vascular congestion,with edema and focal hemorrhage, and an inflammatory cell The neutrophils invade the epithelium, usually in the crypts, giving rise to cryptitis and, ultimately, to crypt abscesses .

91. Crohn’s Disease: Macroscopic Features CD can affect any part of the gastrointestinal (GI) tract from the mouth to the anus. 30–40% of patients have small-bowel disease alone, 40–55% have disease involving both the small and large intestines, 15–25% have colitis alone. In the 75% of patients with small-intestinal disease, the terminal ileum is involved in 90%. Unlike UC, which almost always involves the rectum, the rectum is often spared in CD. CD is often segmental with skip areas throughout the diseased intestine

92. Perianal disease, manifesting as perirectal fistulas,fissures , abscesses, and anal stenosis, is present in one-third of patients with CD. Rarely, CD may also involve the liver and the pancreas. Unlike UC, CD is a transmural process. Endoscopically , Aphthous or small superficial ulcerations characterize mild disease; In more active disease, stellate ulcerations fuse longitudinally and transversely to demarcate islands of mucosa that frequently are histologically normal i,.e “cobblestone” appearance

93. Active CD is characterized by focal inflammation and formation of fistula tracts , which resolve by fibrosis and stricturing of the bowel. The bowel wall thickens and becomes narrowed and fibrotic, leading to chronic, recurrent bowel obstructions. Projections of thickened mesentery known as “creeping fat” encase the bowel, and serosal and mesenteric inflammation promotes adhesions and fistula formation.

94. Crohn’s disease of the colon showing thickening of the wall, with stenosis, linear serpiginous ulcers , and cobblestoning of the mucosa

95. Crohn’s Disease: Microscopic Features The earliest lesions are aphthoid ulcerations and focal crypt abscesses with loose aggregations of macrophages, which form noncaseating granulomas in all layers of the bowel wall. Granulomas are a characteristic feature of CD and are commonly found on surgical resection specimens than on mucosal biopsies. Other histologic features of CD include Submucosal or subserosal lymphoid aggregates, Gross and microscopic skip areas, Transmural inflammation Fissures that penetrate deeply into the bowel wall and sometimes form fistulous tracts or local abscesses.

96. CLINICAL PRESENTATION-IBD ULCERATIVE COLITIS Signs and Symptoms The major symptoms of UC are diarrhea, rectal bleeding, tenesmus , passage of mucus, and crampy abdominal pain . The severity of symptoms correlates with the extent of disease. Although UC can present acutely, symptoms usually have been present for weeks to months.

97. Patients with proctitis Usually pass fresh blood or blood-stained mucus, either mixed with stool or streaked onto the surface of a normal or hard stool. They also have tenesmus , or urgency with a feeling of incomplete evacuation, but rarely have abdominal pain. Patients with proctitis or proctosigmoiditis : Proximal transit slows, which may account for the constipation commonly seen in patients with distal disease.

98. When the disease extends beyond the rectum: Blood is usually mixed with stool or grossly bloody diarrhea may be noted. Colonic motility is altered by inflammation with rapid transit through the inflamed intestine. When the disease is severe: Patients pass a liquid stool containing blood, pus, and fecal matter. Diarrhea is often nocturnal and/or postprandial. Severe cramping and abdominal pain. Anorexia,nausea , vomiting, fever, and weight loss.

99. Physical signs Physical signs of proctitis include a tender anal canal and blood on rectal examination . With more extensive disease, patients have tenderness to palpation directly over the colon . Patients with a toxic colitis have severe pain and bleeding. Patients with megacolon have hepatic tympany . Both may have signs of peritonitis if a perforation has occurred.

100. Laboratory, Endoscopic, and Radiographic Features Active disease can be associated with a rise in acute-phase reactants (C-reactive protein [CRP]), platelet count, and erythrocyte sedimentation rate (ESR) and a decrease in hemoglobin . Fecal lactoferrin , a glycoprotein present in activated neutrophils, is a highly sensitive and specific marker for detecting intestinal inflammation. Fecal calprotectin is present in neutrophils and monocytes, and the levels correlate well with histologic inflammation, predict relapses, and detect pouchitis . Both fecal lactoferrin and calprotectin are an integral part of IBD management and are used frequently to rule out active inflammation versus symptoms of irritable bowel or bacterial overgrowth.

101. In severely ill patients, the serum albumin level will fall rather quickly. Leukocytosis may be present but is not a specific indicator of disease activity. Diagnosis relies on The patient’s history, clinical symptoms, Negative stool and/or tissue examination for bacteria, C. difficile toxin, ova and parasites, and viruses depending on epidemiologic considerations and clinical presentation; Sigmoidoscopic appearance;and Histology of rectal or colonic biopsy specimens.

102. Endoscopic assessment of severity of UC Mild disease : is characterized by erythema, decreased vascular pattern, and mild friability. Moderate disease is characterized by marked erythema, absent vascular pattern, friability, and erosions. Severe disease : is characterized by spontaneous bleeding and ulcerations. Histologic features change more slowly than clinical features but can also be used to grade disease activity. Intestinal ultrasound is a newer tool to assess UC activity and mucosal healing and correlates well with endoscopy and inflammatory markers.

103. Complications - UC Only 15% of patients with UC present initially with severe disease. Massive hemorrhage occurs in 1% of patients, and treatment for the disease usually stops the bleeding. Toxic megacolon Defined as a transverse or right colon with a diameter of >6 cm, with loss of haustration in patients with severe attacks of UC . It occurs rarely and can be triggered by electrolyte abnormalities and narcotics . About 50% of acute dilations will resolve with conservative management alone, but urgent colectomy is required for those who do not improve.

104. Perforation Is the most dangerous of the local complications. Physical signs of peritonitis may not be obvious, especially if the patient is receiving glucocorticoids. The mortality rate for perforation complicating a toxic megacolon is ~15%. Toxic colitis Severe ulcerations that the bowel may perforate without first dilating.

105. Strictures Occur in ~5% of patients and are always a concern in UC because of the possibility of underlying neoplasia . Strictures that are impassable with the colonoscope should be presumed malignant until proven otherwise. Anal fissures, perianal abscesses, or hemorrhoids NB: Extensive perianal lesions should suggest CD.

106. CROHN’S DISEASE Signs and Symptoms CD usually presents as acute or chronic bowel inflammation. The inflammatory process evolves toward one of two patterns of disease: A fibrostenotic obstructing pattern or A penetrating fistulous pattern, Each with different treatments and prognoses.

107. The site of disease influences the clinical manifestations ILEOCOLITIS A chronic history of recurrent episodes of right lower quadrant pain and diarrhea. The initial presentation mimics acute appendicitis with pronounced right lower quadrant pain, a palpable mass, fever, and leukocytosis. Pain is usually colicky; it precedes and is relieved by defecation. A low-grade fever is usually noted. High-spiking fever suggests intraabdominal abscess formation. Weight loss typically10–20% of body weight is common —and develops as a consequence of diarrhea, anorexia, and fear of eating.

108. An inflammatory mass may be palpated in the right lower quadrant of the abdomen. Bowel obstruction. Severe inflammation of the ileocecal region may lead to localized wall thinning, with microperforation and fistula formation to the adjacent bowel, the skin, or the urinary bladder, or to an abscess cavity in the mesentery .

109. JEJUNOILEITIS Extensive inflammatory disease results in malabsorption and steatorrhea . Nutritional deficiencies Anemia, hypoalbuminemia , hypocalcemia , hypomagnesemia , coagulopathy. Vertebral fractures are caused by a combination of vitamin D deficiency, hypocalcemia , and prolonged glucocorticoid use. Pellagra from niacin deficiency can occur in extensive small-bowel disease, Malabsorption of vitamin B12 can lead to megaloblastic anemia and neurologic symptoms. Other important nutrients to measure and replete if low are folate and vitamins A, E, and K. Most patients should take daily multivitamin, calcium, and vitamin D supplements.

110. COLITIS AND PERIANAL DISEASE Patients with colitis present with low-grade fevers, malaise, diarrhea, crampy abdominal pain, and sometimes hematochezia . Gross bleeding is not as common as in UC.Only 1–2% exhibit massive bleeding. Pain is caused by passage of fecal material through narrowed and inflamed segments of the large bowel. Stricturing can occur in the colon in 4–16% of patients and produce symptoms of bowel obstruction . If the endoscopist is unable to traverse a stricture in Crohn’s colitis, surgical resection should be considered.

111. Colonic disease may fistulize into the stomach or duodenum, causing feculent vomiting, or to the proximal or mid-small bowel, causing malabsorption . 10% of women with Crohn’s colitis will develop a rectovaginal fistula . Perianal disease affects about one-third of patients with Crohn’s colitis and is manifested by incontinence, large hemorrhoidal tags, anal strictures, anorectal fistulas, and perirectal abscesses . NB:Not all patients with perianal fistula will have endoscopic evidence of colonic inflammation

112. GASTRODUODENAL DISEASE Symptoms and signs of upper GI tract disease include nausea, vomiting, and epigastric pain . Patients usually have a Helicobacter pylori–negative gastritis. The second portion of the duodenum is more commonly involved than the bulb. Patients with advanced gastroduodenal CD may develop a chronic gastric outlet obstruction .

113. aL4 is a modifier and can be added to L1–L3 when there is concomitant foregut disease. b P is added to B1–B3 when there is concomitant perianal disease.

114. Laboratory, Endoscopic, and Radiographic Features Laboratory abnormalities: Elevated ESR and CRP. In more severe disease, findings include hypoalbuminemia , anemia, and leukocytosis. Fecal calprotectin and lactoferrin levels have been used to Distinguish IBD from irritable bowel syndrome (IBS), Assess whether CD is active, Detect postoperative recurrence of CD.

115. Endoscopic features of CD include Rectal sparing, aphthous ulcerations, fistulas, and skip lesions . Colonoscopy Allows examination and biopsy of mass lesions or strictures and biopsy of the terminal ileum. An ileal or colonic stricture may be dilated with a balloon introduced through the colonoscope . Upper endoscopy is useful in diagnosing gastroduodenal involvement in patients with upper tract symptoms.

116. CT/MRI CT enterography and MR enterography have been shown to be equally accurate in the identification of active small-bowel inflammation. MRI is thought to offer superior soft tissue contrast and has the added advantage of avoiding radiation exposure changes. Pelvic MRI is superior to pelvic CT for demonstrating pelvic lesions such as ischiorectal abscesses and perianal fistulas. ULTRASOUND SBUS(small bowel ultrasound) is at least as sensitive as MR enterography and CT enterography for detecting small-bowel CD, with a sensitivity of 94%, specificity of 97%, positive predictive value of 97%, and negative predictive value of 94%.

117. Complications –CD Fistula formation Because CD is a transmural process, serosal adhesions develop that provide direct pathways for fistula formation and reduce the incidence of free perforation. Perforation Perforation occurs in 1–2% of patients, usually in the ileum but occasionally in the jejunum or as a complication of toxic megacolon . The peritonitis of free perforation, especially colonic, may be fatal.

118. Intraabdominal and pelvic abscesses Occur in 10–30% of patients with CD at some time in the course of their illness. CT-guided percutaneous drainage of the abscess is standard therapy. Despite adequate drainage, most patients need resection of the offending bowel segment. Other complications include Intestinal obstruction in 40%, Massive hemorrhage, Malabsorption , Severe perianal disease.

119. Differential diagnosis- ibd Infectious Non-infectious

120. Extraintestinal Manifestations Up to one-third of IBD patients have at least one extraintestinal disease manifestation. 1.Disorders that usually parallel ( ie , wax and wane with) IBD flare-ups : Peripheral arthritis, Episcleritis , Aphthous stomatitis, Erythema nodosum . Arthritis tends to involve large joints and be migratory and transient

121. 2. Disorders that are clearly associated with IBD but appear independently of IBD activity : Ankylosing spondylitis, Sacroiliitis , Uveitis, Pyoderma gangrenosum , Primary sclerosing cholangitis. 3. Disorders that are consequences of disrupted bowel physiology: These disorders occur mainly in severe Crohn disease of the small bowel. Malabsorption may result from extensive ileal resection and cause deficiencies of fat-soluble vitamins, vitamin B12, or minerals. Results in anemia, hypocalcemia , hypomagnesemia , clotting disorders, and bone demineralization.

122. Erythema nodosum Pyoderma gangrenosum

123. Sweet syndrome Psoriasis

124. episcleritis

125. TREATMENT Inflammatory Bowel Disease Approach considerations The two goals of therapy are The achievement of remission (induction) and the prevention of disease flares (maintenance). The care of a patient with IBD can be either Medical Surgical in nature or, A combination of both(in many patients). The management algorithm is also dependent on whether the diagnosis is Crohn disease or ulcerative colitis.

126. The medical approach for patients with IBD is both symptomatic care ( ie , relief of symptoms) and mucosal healing . Mild disease can follow a stepwise approach to medication, with escalation of the medical regimen until a response is achieved. Moderate to severe disease , however, warrants more aggressive initial treatment for the prevention of intestinal complications.

127. The concept of deep mucosal healing , particularly in Crohn disease, is becoming routine care. The elimination of inflammation (as demonstrated by endoscopic and histologic criteria) results in a decrease in The rate of surgery, The use of corticosteroids, and The rate of hospitalization. This supports the use of immune-modifying agents ( mercaptopurine or azathioprine) or one of the anti-TNF agents earlier in the course of IBD

128. Treatment of IBD Symptomatic treatment Supportive care Pharmacotherapy 5-Aminosalicylic acid Corticosteroids Immunomodulating drugs Biologic agents ( anticytokine drugs) Antibiotics ( eg , metronidazole, ciprofloxacin) and probiotics Surgical treatment

129. Symptomatic therapy Antidiarrheal agents ( loperamide or diphenoxylate /atropine) Particularly when their symptoms are not related to active inflammation Should generally be avoided in patients with active inflammation, as these drugs can precipitate toxic megacolon Similarly, other agents that may have anticholinergic effects should be avoided. Bile-binding resins( cholestyramine ) May be helpful in managing the diarrhea (that may be due to bile salt malabsorption ) in patients with Crohn disease who have significant ileal disease or who have had an ileal resection.

130. Supportive Immunization Yearly H.influenza,pneumococcal -before starting immunosuppressive therapy when possible. Routine vaccinations such as tetanus-diphtheria, hepatitis A, hepatitis B, and human papillomavirus. Screening tests For cervical cancer every 3 years For Skin cancer annually(All patients who are taking or plan to take immunomodulating drugs or biologic agents ) Patients at risk of osteoporosis should have a dual-energy x-ray absorptiometry (DXA) scan

131. Overview of pharmacotherapy A stepwise approach The step-up approach may be taken in mild inflammatory bowel disease (IBD).  Moderate to severe IBD should be treated more aggressively up front to prevent permanent damage. Aminosalicylates The first step in medication therapy for mild IBD. There are several different aminosalicylates , but none have been consistently demonstrated to be superior to the others for all patients. Have greater efficacy for the treatment of ulcerative colitis than for Crohn disease. Antibiotics For Crohn disease, metronidazole or ciprofloxacin is occasionally used, particularly for perianal disease or an inflammatory mass.

132. Corticosteroids The second step if the patient's condition fails to respond to an adequate dose of aminosalicylates . Provide rapid relief of symptoms and a significant decrease in inflammation. They work quickly and are effective for acute flares. They are not effective for maintenance of remission. Once a clinical response is seen, the dose is tapered. Inability to taper down the steroids without recurrence of symptoms should trigger discussion regarding the use of alternative drugs ( immunomodulators or anti-TNF therapy).

133. The immune-modifying agents (azathioprine, 6-mercaptopurine, and methotrexate ) Are used if corticosteroids fail or are required for prolonged periods for milder disease. They can be used up front for moderate and severe disease. Anti-TNF monoclonal antibody therapies (Infliximab, certolizumab ,  adalimumab , and  golimumab ) Are also effective in both Crohn disease and ulcerative colitis. Patients who are intolerant or have lost their initial response to any one of the aforementioned TNF inhibitors may respond to a different anti-TNF medication. NB: The early introduction of the above agents in conjunction with immunosuppressants in those with an increased risk of a complicated, severe, or possibly aggressive IBD has the potential to modify the disease course and is commonly pursued.

134. References Uptodate Harrisons principles of internal medicine 22 nd ed.