Dyspepsia

CHRONIC DYSPEPSIA

Seminar Prepared by :-
Ali Abdulazeem
Shilan Adnan Abdulrahman
Alaa Shamil
Guldan Hameed


Internal Medicine
College of Medicine - University of Kirkuk

1. CHRONIC DYSPEPSIA supervised by: Dr. Summer Shilan Adnan Abdulrahman Alaa Shamil Guldan Hameed Ali Abdulazeem

2. D efinition : *# is not a disease *# is group of symptoms rather than one predominant symptom Dyspepsia (indigestion): is a collective term* for any symptoms thought to originate from upper GIT . It composes many causes and symptoms like ; heartburn , upper abdomen discomfort , nausea , regurgitation , bloating , fullness …etc And the cause are:

3. Causes of dyspepsia Upper gastrointestinal disorders Peptic ulcer disease Acute gastritis Gallstones Oesophageal spasm Non-ulcer dyspepsia Irritable bowel syndrome Other gastrointestinal disorders Pancreatic disease (cancer, chronic pancreatitis) Colonic carcinoma Hepatic disease (hepatitis, metastases) Systemic disease Renal failure Hypercalcaemia Drugs NSAIDs Corticosteroids Iron and potassium supplements Digoxin Others Psychological (anxiety, depression) Alcohol

4. Differential diagnosis

5. Differential diagnosis Gastroesophageal reflux disease Peptic ulcer Gastroparesis Gastritis (NSAIDs & H.pylori ) Non ulcer dyspepsia (functional dyspepsia ) malignancy

6. a.Organic dyspepsia

7. Risk factors of dyspepsia

8. b.Functional dyspepsia is defined as ≥3 months of bothersome postprandial fullness, early satiety, or epigastric pain or burning with symptom onset at least 6 months before diagnosis in the absence of organic cause.

9. Rome criteria The Rome criteria were originally developed to understand functional gastrointestinal disorders (FGIDs), which are conditions that are based on symptoms that cluster as opposed to conditions that are defined by organ pathology (microscopic or macroscopic), such as inflammatory bowel disease and celiac disease, or by altered motility, such as gastroparesis or achalasia . The Rome IV diagnostic criteria are the most recent iteration of symptom-based criteria for FGIDs and were developed in a collaborative effort between 126 experts representing 26 countries. The process to update Rome III criteria, which were published in 2006, began in 2008 with the creation of working teams to acquire knowledge. Between 2010 and 2015, committee members collected, evaluated, presented, and modified clinical trial data in various areas of interest, including different ages patient populations with irritable bowel syndrome (IBS) and FGIDs. 

10. pathophysiology The pathophysiology of dyspepsia not well understood so the researchers are focused on several key factors :

11. P athophysiology of functional dyspepsia N onmotility disorder M otility disorder psychosocial

12. Motility and nonmotility disorders the diseases that can affect the motility of GIT like : GERD ( decrease th lower esophageal sphincter tone ), Impaired gastric fundus relaxation after eating… visceral afferent hypersensitivity (These individuals with functional heartburn are believed to have heightened perception of normal esophageal pH and volume) With motility disorders there is little correlation between symptoms and severity of duodenitis , and no relation between treatment and improvement of mucosal appearance on endoscopy .

13. Abnormal fundic relaxationin response to meal in functional dyspepsia Motility disorder

14. Altered motility in dyspepsia

15. P sychosocial factors Patients with nonulcer dyspepsia are more likely to have symptoms of anxiety and depression than are healthy patients with ulcers. Multiple somatic complaints also more common in patients who have nonulcer dyspepsia. A history of child abuse also has been linked with symptoms of nonulcer dyspepsia Stress life events .

16. I nvestigation

17. Alarming signs

18. Specific investigation Depend on causes and history for example: Peptic ulcer with hx of smoking and NSAIDs (endoscopy) Gastric duodenal ulcer with hx of unexplained weight loss , dysphagia and smoking (endoscopy) Gastric cancer (endoscopy) H.pylori (urea breath , stool antigen ,whole blood antibody , serum IgG antibody tests)

19. GERD with hx of heartburn aggrevated when supine , chronic cough ( omperazole test , endoscopy and 24hrs pH monitoring )

20. endoscopy Endoscopy is a nonsurgical procedure used to examine a person's digestive tract Types : flexible and rigid Uses : diagnostic ( e.g biopsy taking) and therapeutic ( e.g polyp remove)

21. HELICOBACTER PYLORI

22. HISTORY Dr. Robin Warren , a pathologist from Perth, Australia, observed small curved bacteria colonizing the lower part of the stomach in about 50% of patients who had their stomachs biopsied. He observed that signs of inflammation were always present in the gastric mucosa close to where he saw the bacteria.

23. Barry Marshall , a colleague, became interested in Warren’s findings and together they initiated a study of biopsies from 100 patients. Marshall succeeded in cultivating a previously unknown bacterial species – later named  Helicobacter pylori  – from several of these biopsies. They found that the organism was present in almost all patients with gastric inflammation, duodenal ulcer, or gastric ulcer. Based on these results, they proposed that this newly identified bacterium caused these diseases. Until that time, so entrenched was the belief that lifestyle caused ulcers that, even with their evidence, it was difficult for these two researchers to convince the world of  H. pylori ’s role in ulcer disease.” To provide even more conclusive evidence, in 1985 Marshall deliberately infected himself with the bacterium and established his own stomach illness. Eradication therapy was then employed with mixed success, but both received the Nobel Prize for Medicine and Physiology in 2005..

24. Helicobacter pylori a gram-negative bacillus that has naturally colonized humans for at least 100,000 year and probably throughout human evolution. It lives in gastric mucus, with a small proportion of the bacteria adherent to the mucosa and possibly avery small number of the organisms entering cells or penetrating the mucosa Its spiral shape and flagella render H. pylori motile in the mucus environment. The organism has several acid-resistance mechanisms , most notably a highly expressed urease that catalyzes urea hydrolysis to produce buffering ammonia. H. pylori is microaerophilic (i.e., requires low levels of oxygen), is slow-growing, and requires complex growth media in vitro

25. Prevalence and Risk Factors The prevalence of H. pylori among adults is <30% in most parts of the United States and in other developed countries >80% in most developing countries. In the United States, prevalence varies with age: up to 50% of 60-year-old persons, ~20% of 30-year-old persons, and fewer than10% of children are colonized. H

26. Transmission Humans are the only important reservoir of H. pylori. Children may acquire the organism from their parents (most often the primary caregiver) or from other children Whether transmission takes place more often by the fecal-oral or the oral-oral route is unknown , but H. pylori is easily cultured from vomitus and gastroesophageal refluxate and is less easily cultured from stool

27. Most H. pylori–colonized persons do not develop clinical sequelae . That some persons develop overt disease whereas others do not is related to a combination of factors: bacterial strain differences, host susceptibility to disease, and environmental factors

28. CLINICAL MANIFESTATIONS

29. Peptic Ulcer Disease Worldwide, >80% of duodenal ulcers and >60% of gastric ulcers are related to H. pylori colonization However, in particular, the proportion of gastric ulcers caused by aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) is increasing, and in many developed countries these drugs have overtaken H. pylori as a cause of gastric ulceration. The main lines of evidence supporting an ulcer-promoting role for H. pylori are that (1) the presence of the organism is a risk factor for the development of ulcers, (2) non-NSAID-induced ulcers rarely develop in the absence of H. pylori, (3) eradication of H. pylori virtually abolishes long-term ulcer relapse, and (4) experimental H. pylori infection of gerbils can cause gastric ulceration .

30. Pathogenesis of duodenal ulceration Gastric colonization causes duodenal ulceration is now becoming more clear. H. pylori–induced inflammation of the gastric antrum diminishes the number of somatostatin producing D cells. Because somatostatin inhibits gastrin release, gastrin levels are higher than in H. pylori– ve , and these higher levels lead to increased meal-stimulated acid secretion from the relatively spared gastric corpus.

31. How this situation increases duodenal ulcer risk remains controversial, but the increased acid secretion may contribute to the formation of the potentially protective gastric metaplasia found in the duodenum of duodenal ulcer patients. Gastric metaplasia in the duodenum may become colonized by H. pylori and subsequently inflamed and ulcerated .

32. Gastric Adenocarcinoma and Lymphoma Prospective nested case-control studies have shown that H. pylori colonization is a risk factor for adenocarcinomas of the distal ( noncardia ) stomach . Long-term experimental infection of gerbils also may result in gastric adenocarcinoma . Moreover, H. pylori may induce primary gastric lymphoma, although this condition is much less common. Many low-grade gastric B-cell lymphomas are dependent on H. pylori for continuing growth and proliferation, and these tumors may regress either fully or partially after H. pylori eradication . However, they require careful short- and long-term monitoring, and some necessitate additional treatment with chemotherapeutic agents.

33. Pathogenesis of gastric ulceration and gastric adenocarcinoma The pathogenesis of these conditions is less well understood, although both arise in association with pan- or corpus predominant gastritis . The inflammation in the gastric corpus means that it produces less acid ( hypochlorhydria ) despite hypergastrinemia . Gastric ulcers usually occur at the junction of antral and corpus-type mucosa, an area that is often particularly inflamed. Gastric cancer probably stems from progressive DNA damage and the survival of abnormal epithelial cell clones. The DNA damage is thought to be due principally to reactive oxygen and nitrogen species arising from inflammatory cells, perhaps in relation to other bacteria that survive in a hypochlorhydric stomach. Longitudinal analyses of gastric biopsy specimens taken years apart from the same patient show that the common intestinal type of gastric adenocarcinoma follows stepwise changes from simple gastritis to gastric atrophy, intestinal metaplasia , and dysplasia. A second, diffuse type of gastric adenocarcinoma found more commonly in younger adults may arise from chronic gastritis without atrophic changes .

34. Functional Dyspepsia Many patients have upper gastrointestinal symptoms but have normal results on upper gastrointestinal endoscopy (so-called functional or nonulcer dyspepsia ). Because H. pylori is common, some of these patients will be colonized with the organism. H. pylori eradication leads to symptom resolution a little more commonly (from 0 to 7% in different studies) than does placebo treatment.

35. DIAGNOSIS

36. TREATMENT

37. Treatment FIRST LINE THERAPY PPI taken simultaneously with two antibiotics (from amoxicillin, clarithromycin and metronidazole ) for at least 7 days Success is achieved in 80–90% of patients SECOND LINE THERAPY quadruple therapy regimen, consisting omeprazole (or another PPI), bismuth subcitrate , metronidazole and tetracycline (OBMT) for 10–14 days , recommended. In areas of clarithromycin resistance AND second-line therapy to those who remain infected after initial therapy

38. THIRD LINE THERAPY antimicrobial sensitivity testing, rescue therapy ( levofloxacin , PPI and clarithromycin ) or long-term acid suppression .

39. Eradication of the infection has proven benefits in several extragastric disorders, including unexplained B12 deficiency and iron deficiency anaemia , once sources of gastrointestinal bleeding have been looked for and excluded. Platelet counts improve and may normalise after eradication therapy in patients with idiopathic thrombocytopenic purpura The mechanism for this is unclear

40. Use of Tests to Assess Treatment Success The urea breath test, the stool antigen test, and biopsy-based tests can all be used to assess the success of treatment However, because these tests are dependent on H. pylori load , their use <4 weeks after treatment may yield falsenegative results. Furthermore, these tests are unreliable if performed within 4 weeks of intercurrent treatment with antibiotics or bismuth compounds or within 2 weeks of the discontinuation of proton pump inhibitor (PPI) treatment. In the assessment of treatment success, Noninvasive tests are normally preferred;

41. However, after gastric ulceration ,endoscopy should be repeated to ensure healing and to exclude gastric carcinoma by further histologic sampling. Serologic tests are not used to monitor treatment success, as the gradual drop in titer of H. pylori specific antibodies is too slow to be of practical use.

42. Common causes of Dyspepsia

43. Causes of dyspepsia Upper gastrointestinal disorders Peptic ulcer disease Acute gastritis Gallstones Oesophageal spasm Non-ulcer dyspepsia Irritable bowel syndrome Other gastrointestinal disorders Pancreatic disease (cancer, chronic pancreatitis) Colonic carcinoma Hepatic disease (hepatitis, metastases) Systemic disease Renal failure Hypercalcaemia Drugs NSAIDs Corticosteroids Iron and potassium supplements Digoxin Others Psychological (anxiety, depression) Alcohol

44. Gastric and duodenal ulcer The prevalence of peptic ulcer (0.1–0.2%) The male-to female ratio for DU varies from 5 : 1 t o 2 : 1, GU is 2 : 1 or less. Chronic GU is usually single; 90% are situated on the lesser curve within the antrum or at the junction between body and antral mucosa. Chronic DU usually occurs in the first part of the duodenum and 50% are on the anterior wall .

45. Pathophysiology H. pylori NSAIDs: Treatment with NSAIDs is associated with peptic ulcers due to impairment of mucosal defences Smoking: Smoking confers an increased risk of gastric ulcer and, to a lesser extent, duodenal ulcer.

46. NSAIDs

47. Risk factors for NSAID-induced ulcers Age > 60 yrs Past history of peptic ulcer Past history of adverse event with NSAID Concomitant corticosteroid use High-dose or multiple NSAID High-risk NSAID (Indometacin, Ketoprofen, Piroxicam, Azapropazone)

48. Commonly used NSAIDs and their relative risk of gastrointestinal bleeding and perforation Very low risk Celecoxib, Etoricoxib Low risk Ibuprofen, Etodolac, Meloxicam, Nabumetone Medium risk Ibuprofen, Naproxen, Diclofenac High risk Indometacin, Ketoprofen Highest risk Piroxicam, Azapropazone

49. Functional dyspepsia This is defined as chronic dyspepsia in the absence of organic disease. Other commonly reported symptoms include early satiety, fullness, bloating and nausea. ‘Ulcer-like’ and ‘dysmotility-type’ subgroups are often reported, but there is overlap between these and with irritable bowel syndrome. The cause is poorly understood but probably covers a spectrum of mucosal, motility and psychiatric disorders.

50. clinical features P t. are usually young (< 40 years) and women are affected as twice as men. Abdominal discomfort is associated with other ‘dyspeptic’ symptoms ( nausea, early satiety and bloating after meals ) . Morning symptoms are characteristic and pain or nausea may occur on waking. Direct enquiry may elicit symptoms suggestive of IBS . Peptic ulcer disease must be considered, whilst in older subjects intra-abdominal malignancy is a prime concern.

51. clinical features There are no diagnostic signs, apart perhaps from inappropriate tenderness on abdominal palpation. Symptoms may appear disproportionate to clinical well-being and there is no weight loss. Patients often appear anxious. A drug history should be taken and the possibility of a depressive illness should be considered. Pregnancy should be ruled out in young women before radiological studies are undertaken. Alcohol misuse should be suspected when early morning nausea and retching are prominent

52. investigation All patients should be checked for H. pylori infection . patients over the age of 55 years should undergo endoscopy to exclude mucosal disease.

53. M angment The most important elements are explanation and reassurance , Possible psychological factors should be explored. restrictive diets are of little benefit, but smaller portions And fat restriction may help. Up to 10% of patients benefit from H. pylori eradication therapy also removes a major risk factor for gastric cancer but at the cost of a small risk of side effects and worsening symptoms of underlying gastrooesophageal reflux diseases

54. M angment Antacids, such as hydrotalcite, are sometimes helpful. Prokinetic drugs, such as metoclopramide (10 mg 3 times daily) or domperidone (10–20 mg 3 times daily), may be given before meals if nausea, vomiting or bloating is prominent. H2-receptor antagonist drugs may be tried if night pain or heartburn is troublesome. Low-dose tricyclic agents, such as amitriptyline, are of value in up to two-thirds. Some patients need behavioural or other formal psychotherapy

55. Gastric ca .

56. Clinical features Asymptomatic Two-thirds of patients with advanced cancers have weight loss. 50% have ulcer-like pain. Anorexia and nausea occur in one-third. Early satiety, haematemesis, melaena and dyspepsia alone are less common Dysphagia Anaemia

57. Clinical features Weight loss Anaemia Palpable epigastric mass Jaundice or ascites tumour spread occurs to the supraclavicular lymph nodes (Troisier’s sign), umbilicus (Sister Joseph’s nodule) or ovaries (Krukenberg tumour). Paraneoplastic phenomena, such as acanthosis nigricans, thrombophlebitis (Trousseau’s sign) and dermatomyositis, occur rarely

58. Endoscopic image of a small superficial pre-pyloric cancer

59. Appearance after endoscopic mucosal resection (EMR)

60. Irritable bowel syndrome Is characterised by recurrent abdominal pain in association with abnormal defecation in the absence of a structural abnormality of the gut. About 10–15% of the population are affected at some time but only 10% of these consult their doctors because of symptoms. Young women are affected 2–3 times more often than men. Coexisting conditions, such as non-ulcer dyspepsia, chronic fatigue syndrome, dysmenorrhoea and fibromyalgia, are common.

61. Pathophysiology The cause of IBS is incompletely understood but biopsychosocial factors are thought to play an important role, along with luminal factors, such as diet and the gut microbiota. Behavioural and psychosocial factors About 50% of patients referred to hospital have a psychiatric illness, such as anxiety,depression, somatisation and neurosis. Acute psychological stress and overt psychiatric disease are known to alter visceral perception and gastrointestinal motility. These factors contribute to but do not cause IBS.

62. Clinical feature The most common presentation is that: Recurrent abdominal discomfort , colicky or cramping in nature,felt in the lower abdomen relieved by defecation. Abdominal bloating worsens throughout the day The cause is unknown but it is not due to excessive intestinal gas. Most patients alternate between episodes of diarrhoea and constipation, but it is useful to classify patients as having predominantly constipation or predominantly diarrhoea.

63. Clinical feature Those with constipation tend to pass infrequent pellety stools, usually in association with abdominal pain or proctalgia. Those with diarrhoea have frequent defecation but produce low-volume stools and rarely have nocturnal symptoms . Passage of mucus is common but rectal bleeding does not occur. Patients do not lose weight and are constitutionally well.

64. Diagnosis The diagnosis is clinical in nature. Full blood count and faecal calprotectin, with or without sigmoidoscopy,are usually done and are normal in IBS. Colonoscopy should be undertaken in; (over 40 years of age) to exclude colorectal cancer. report rectal bleeding to exclude colon cancer and IBD.

65. Diagnosis Those who present atypically require investigations to exclude other gastrointestinal diseases. Diarrhoea predominant patients justify investigations to exclude : coeliac disease microscopic colitis lactose intolerance , bile acid malabsorption, thyrotoxicosis, parasitic infection.

66. Rome III criteria for diagnosis of irritable bowel syndrome Recurrent abdominal pain or discomfort at least 3 days/mth in the last 3 months, associated with two or more of the following: Improvement with defecation Onset associated with a change in frequency of defecation Onset associated with a change in form (appearance) of stool

67. Features supporting a diagnosis of IBS Symptoms > 6 mths Frequent consultations for non-gastrointestinal problems Previous medically unexplained symptoms Stress worsens symptoms Alarm features Age > 50 yrs; male gender Weight loss Nocturnal symptoms Family history of colon cancer Anaemia Rectal bleeding

68. Chronic pancreatitis 80% of cases in West from alcohol misuse. severe chronic calcific pancreatitis occurs in non-alcoholics, possibly as a result of malnutrition and cassava consumption.

69. Chronic pancreatitis Abdominal pain, i n 50%, this occurs as episodes of ‘acute pancreatitis’ . Slowly progressive chronic pain without acute exacerbations affects 35% of patients, whilst the remainder have no pain but present with diarrhoea. Pain may be relieved by leaning forwards or by drinking alcohol. Steatorrhoea : > 90% of the exocrine tissue is destroyed 30% of patients are diabetic, 70% in those with chronic calcific pancreatitis. erythema ab igne

70. Pancreatic carcinoma 90% are adenocarcinomas from the ducts. Many p t. are asympt . until an advanced stage . They present with central abdominal pain, weight loss and obstructive jaundice The pain results from invasion of the coeliac plexus and is characteristically incessant and gnawing. It often radiates from the upper abdomen through to the back and may be eased a little by bending forwards.

71. Pancreatic carcinoma Almost all patients lose weight and many are cachectic . 60% of tumours in head of the pancreas, and involvement of the CBD results in obstructive jaundice, with severe pruritus. A few patients present with diarrhoea, vomiting from duodenal obstruction, diabetes mellitus, recurrent venous thrombosis, acute pancreatitis or depression. Weight loss, An abdominal mass, a palpable gallbladder or hepatic metastasis, A palpable gallbladder in a jaundiced patient is usually the consequence of distal biliary obstruction by a pancreatic cancer (Courvoisier’s sign).

72. Viral hepatitis H eadache, myalgia, arthralgia, nausea and anorexia usually precedes the development of jaundice by a few days to 2 weeks. Vomiting and diarrhoea may follow, and abdominal discomfort is common. Dark urine and pale stools may precede jaundice. The liver is often tender but only minimally enlarged. Occasionally, mild splenomegaly and cervical lymphadenopathy are seen.

73. G allstones Only 10% of individuals with gallstones develop clinical evidence of gallstone disease. Symptomatic stones within the gallbladder manifest as either biliary pain (‘biliary colic’) or cholecystitis. The term ‘biliary colic’ is a misnomer because the pain does not rhythmically increase and decrease in intensity like other forms of colic. Combinations of fatty food intolerance, dyspepsia and flatulence ‘gallstone dyspepsia’.

74. Pain is usually felt in the epigastrium (70% of patients) or right upper quadrant (20%) . R adiates to the interscapular region or the tip of the right scapula,the left upper quadrant and the lower chest . It occurs suddenly and persists for about 2 hours .

75. C olorectal cancer L eft colon : fresh rectal bleeding is common with early obstruction. R ight colon : anaemia from occult bleeding or with altered bowel habit, but obstruction is a late feature. Colicky lower abdominal pain is present in twothirds of patients and rectal bleeding occurs in 50%. Some present with either obstruction or perforation, leading to peritonitis, localised abscess or fistula formation. Ca . of the rectum usually causes early bleeding, mucus discharge or a feeling of incomplete emptying.

76. Thank you

77. T hanks for attending and listening What do you think about the first part? What did you learn or if you have Any note, advise or question? What do you think about the second part? What did you learn or if you have any note, advise or question? What do you think about the third part? What did you learn or if you have any note, advise or question? What do you think about the fourth part? What did you learn or if you have any note, advise or question? ?