Lect 4- gastric disorder


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Lect 4- gastric disorder

  1. 1. SMS 2044
  2. 2. Mucous: Mucus, Pepsinogen IiChief: Pepsinogen I, IiParietal: AcidEnteroendocrine: Histamine, Somatostatin,Endothelin
  3. 3. StomachCondition CommentPyloric stenosis 1 in 300 to 900 live births   Male to female ratio 3:1 Pathology: muscular hypertrophy of pyloric smooth muscle   wall Symptoms: persistent, nonbilious projectile vomiting in   young infantDiaphragmatic hernia Rare Pathology: herniation of stomach and other abdominal   contents into thorax through a diaphragmatic defect   Symptoms: acute respiratory embarrassment in newbornGastric heterotopia Uncommon Pathology: a nidus of gastric mucosa in the esophagus or   small intestine ("ectopic rest") (The Latin word for "nest“) Symptoms: asymptomatic, or an anomalous peptic ulcer in   adult
  4. 4. Gastric heterotopia 6
  5. 5. In keeping with the limited sensory apparatus of the  alimentary tract, gastric disorders give rise to  symptoms similar to esophageal disorders, primarily  heartburn and vague epigastric pain.Gastric mucosa and bleeding, hematemesis or  melena may ensue. Unlike esophageal bleeding, however, blood quickly  congeals and turns brown in the acid environment  of the stomach lumen.Vomited blood hence has the appearance of coffee grounds.
  6. 6. Gastritis: includes a myriad of disorders that involve  inflammatory changes in the gastric mucosa, including:Gastritis: is  simply  defined  as  inflammation  of  the  gastric  mucosa.  By  far  the  majority  of  cases  are chronic gastritis, but  occasionally,  distinct  forms  of  acute gastritis are encountered. 1. Erosive gastritis caused by a noxious irritant   2. Reflux gastritis from exposure to bile and pancreatic  fluids 3.  Hemorrhagic gastritis 4.  Infectious gastritis5.  Gastric mucosal atrophy 
  7. 7. Acute Gastritis Acute gastritis is an acute mucosal inflammatory process, usually of a transient nature. The inflammation may be accompanied by hemorrhage into the mucosa and, in more severe circumstances, by sloughing of the superficial mucosal epithelium (erosion).Pathogenesis: The pathogenesis is poorly understood, in part because normal mechanisms for gastric mucosal protection are not totally clear.
  8. 8.  H pylori (most common cause of ulceration) NSAIDs, aspirin Gastrinoma (Zollinger-Ellison syndrome) Severe stress (eg, trauma, burns), Curling ulcers Alcohol Bile reflux Pancreatic enzyme reflux Radiation Staphylococcus aureus exotoxin Bacterial or viral infection
  9. 9. 11
  10. 10.  Suicide attempts with acids and alkali Mechanical trauma (e.g., nasogastric intubation) One or more of the following influences are thought to be  operative in these varied settings:   disruption of the adherent mucous layer,   stimulation of acid secretion with hydrogen     ion back-diffusion into the superficial epithelium,   decreased production of bicarbonate buffer by superficial  epithelial cells,   reduced mucosal blood flow, and direct damage to the  epithelium. 
  11. 11. 13
  12. 12.  There  is  a  spectrum  of  severity  ranging  from  extremely  localized  (as  occurs  in  NSAID-induced  injury) to diffuse and from superficial inflammation to  involvement  of  the  entire  mucosal  thickness  with  hemorrhage and focal erosions. Concurrent erosion and hemorrhage is readily visible  by  endoscopy  and  is  termed  acute erosive gastritis.  14
  13. 13. MORPHOLOGYAll variants are marked by :Mucosal edema Inflammatory infiltrate of  neutrophils and possibly by  chronic inflammatory cells.Regenerative replication of  epithelial cells in the gastric pits is  usually prominent.Provided that the noxious event is  short lived, acute gastritis may  disappear within days with  complete restitution of the normal  mucosa.
  14. 14. Free powerpoint template: www.brainybetty.com 16
  15. 15. Histopathology usually demonstratesincreased numbers of eosinophils 17
  16. 16.  Depending on the severity of the anatomic changes, acute  gastritis may be entirely asymptomatic,  Epigastric to left upper quadrant Frequently described as burning May radiate to the back Usually occurs 1-5 hours after meals May be relieved by food, antacids (duodenal), or vomiting (gastric) Typically follows a daily pattern specific to patient vomiting, or may present as overt hematemesis, melena,  and potentially fatal blood loss.
  17. 17.  Often, a diagnosis can be made based on the patients  description of his or her symptoms, but other methods may be  used to verify: Blood tests:  Blood cell count  Presence of H. pylori  Pregnancy  Liver, kidney, gallbladder, or pancreas functions Urinalysis Stool sample, to look for blood in the stool X-rays Endoscopy, to check for stomach lining inflammation and  mucous erosion Stomach biopsy, to test for gastritis and other conditions 19
  18. 18.  Malignancy Hemorrhage Perforation Obstruction 
  19. 19. Chronic Gastritis is  defined  as  the  presence  of  chronic  mucosal  inflammatory  changes  leading  eventually  to  mucosal  atrophy and epithelial metaplasia. In  the  western  world,  the  prevalence  of  histologic  changes  indicative  of  chronic  gastritis  exceeds  50%  in  the later decades of adult life. 
  20. 20. Schematic presentation of the presumed action of H. pylori in thedevelopment of chronic gastritis and peptic ulceration. The histologicfeatures of the two disease conditions are depicted
  21. 21.  A – autoimmune B – bacterial (helicobacter) C - chemical Autoimmune chronic gastritisAutoantibodies to gastric parietal cellsHypochlorhydria/achlorhydriaLoss of gastric intrinsic factor leads to malabsorption of vitamin B12 with macrocytic, megaloblastic anaemia
  22. 22.  Commonly seen with bile  reflux (toxic to cells) Prominent hyperplastic  response (inflammatory  cells scanty)
  23. 23. Common infection10% of men, 4% women develop PUD *1st Part of duodenum > antrum > G-E junction.H.pylori related disorders:  Chronic gastritis – 90%  Peptic ulcer disease – 95-100%  Gastric carcinoma – 70%  Gastric lymphoma  Reflux Oesophagitis.  Non ulcer dyspepsia
  24. 24.  The most important etiologic  association is chronic infection by the  bacillus Helicobacter pylori . This organism is a worldwide  pathogen.  Prevalence of infection among adults  maybe reached to 80% it seems to be acquired in childhood  and persists for decades.  Most individuals with the infection also  have the associated gastritis but are  asymptomatic.
  25. 25.  H. pylori is a noninvasive,  non-spore-forming,S-shaped  gram-negative rod  measuring approximately  3.5 × 0.5 μm. Causes cell damage and  inflammatory cell infiltration In most countries the  majority of adults are  infected
  26. 26.  Peptic ulcer disease (Helicobacter) Adenocarcinoma (all types)
  27. 27. Histological F.    Regardless  of  the  cause  or  histological  distribution  of  chronic  gastritis,  the inflammatory changes consist of  a lymphocytic and plasma cell infiltrate in the lamina propria,  occasionally accompanied by  neutrophilic inflammation of the neck  region of the mucosal pits. A Steiner silver stain The inflammation may be  demonstrates the numerous darkly stained H. pylori organisms along accompanied by variable gland loss  the luminal surface of the gastric and mucosal atrophy.  epithelial cells. Note that there is no tissue invasion by bacteria.  
  28. 28.  In  the  autoimmune  variant,  loss  of  parietal  cells  is  particularly prominent.  Intestinal metaplasia refers to the replacement of gastric  epithelium  with  columnar  and  goblet  cells  of  intestinal  variety. Gastrointestinal-type carcinomas appear to arise from  dysplasia of this metaplastic epithelium. Second, H. pylori-induced proliferation of lymphoid tissue  within the gastric mucosa has been implicated as a  precursor of gastric lymphoma Free powerpoint template: www.brainybetty.com 30
  29. 29. Chronic inflammatory cell  infiltrationMucosal atrophyIntestinal (goblet cell) metaplasia Seen in Helicobacter and autoimmune gastritis (not chemical)
  30. 30. Chronic gastritis with lymphoid follicle formation in the gastric mucosa(arrow)Some gastric glands are still found (arrowhead). 32
  31. 31. Chronic gastritis with chronic inflammatory cell infiltration and lymphoidfollicle formation (arrowhead) in the gastric mucosa.Atrophy of the gastric glands is seen.(arrow). (M: mucosa, and SM:submucosa) 33
  32. 32. Clinical Features Chronic gastritis usually causes few or no symptoms; upper abdominal discomfort,  nausea and vomiting.  Hypochlorhydria or achlorhydria (referring  to  levels  of gastric luminal hydrochloric acid) Hypergastrinemia are characteristically present. Most  important  is  the  relationship  of  chronic  gastritis  to  the development of peptic ulcer and gastric carcinoma.
  33. 33. Normal  Acute gastritis  Atrophic gastritis Chronic  gastritis Intestinal   Dysplasia Cancer metaplasia
  34. 34. GASTRIC ULCERATION Ulcers  are  defined  as  a  breach  in  the  mucosa  of  the  alimentary  tract  that  extends  through  the  muscularis  mucosa into the submucosa or deeper. This  is  to  be  contrasted  to  erosions,  in  which  there  is  a  breach in the epithelium of the mucosa only. Erosions  may  heal  within  days,  whereas  healing  of  ulcers  takes much longer. Although ulcers may occur anywhere in the alimentary tract,  none are as prevalent as the peptic ulcers that occur in the  duodenum and stomach. 
  35. 35.  Focal,  acutely  developing  gastric  mucosal  defects  may  appear  after  severe  stress  and  are  designated  stress ulcers. Generally,  there  are  multiple  lesions  located  mainly  in  the  stomach and occasionally in the duodenum  Severe trauma, including major surgical procedures, sepsis,  or grave illness of any type   Extensive  burns  (the  ulcers  are  then  referred  to  as  Curling ulcers)   Traumatic or surgical injury to the central nervous system  or  an  intracerebral  hemorrhage  (the  ulcers  are  then  called Cushing ulcers)   Chronic  exposure  to  gastric  irritant  drugs,  particularly  NSAIDs and corticosteroids 
  36. 36. Neurogenic or catecholamine-induced vasoconstriction Mucosal ischemiaDamage the mucosal Directly injure mucosal cells bybarrier oxygen or metabolic deprivation
  37. 37. Free powerpoint template: www.brainybetty.com 40
  38. 38. MORPHOLOGY Acute stress ulcers are usually circular and small (less than 1 cm in diameter). The ulcer base is frequently stained a dark brown by the acid digestion of extruded blood. They may occur singly, but more often they are multiple, located throughout the stomach and duodenum Multiple stress ulcers of the Microscopically, acute stress ulcers are stomach, highlighted by the abrupt lesions, with essentially dark digested blood in their unremarkable adjacent mucosa. bases.
  39. 39. An ulcer is distinguished from an erosion by its  penetration through the muscularis mucosa or the  muscular coating of the gastric or duodenal wall occurring  as a result of acid and pepsin attackThe lesion of peptic ulcer disease (PUD) is a disruption  in the mucosal layer of Sites: Duodenum (DU) Stomach (GU) Oesophagus Gastro-enterostomy stoma Related to ectopic gastric mucosa (e.g. in Meckel’s  diverticulum)
  40. 40. Etiology of PUDNormalIncreased AttackHyperacidity, ZollingerEllison syndrome.Weak defenseStress, drugs, smokingHelicobacter pylori*
  41. 41.  Peptic ulcer disease results from the imbalance  between defensive factors that protect the mucosa  and offensive factors that disrupt this important barrier.  Mucosal protective factors include the water-insoluble  mucous gel layer, local production of bicarbonate,  regulation of gastric acid secretion, and adequate  mucosal blood flow.  Aggressive factors include the acid-pepsin  environment, infection with Helicobacter pylori, and  mucosal ischemia Free powerpoint template: www.brainybetty.com 44
  42. 42. Peptic ulcers are remitting, relapsing lesions that are most  often diagnosed in middle-aged to older adults, but they  may first become evident in young adult life.They often appear without obvious precipitating influences  and  may  then  heal  after  a  period  of  weeks  to  months  of  active disease.Even  with  healing,  however,  the  propensity  to  develop  peptic ulcers remains.Genetic or racial influences appear to play little or no role in the causation of peptic ulcers. Duodenal  ulcers  are  more  frequent  in  patients  with  alcoholic  cirrhosis,  chronic  obstructive  pulmonary  disease,  chronic  renal  failure, and hyperparathyroidism.
  43. 43. Pathogenesis  There are two key facts.   First,  the  fundamental  requisite  for  peptic  ulceration  is  mucosal exposure to gastric acid and pepsin.   Second,  there  is  a  very  strong  causal  association  with  H. pylori infection. Despite  the  clarity  of  these  two  statements,  the  actual  pathogenesis of mucosal ulceration remains murky.
  44. 44. The  array  of  host  mechanisms  that  prevent  the  gastric  mucosa from being digested like a piece of meat include  the following:   Secretion of mucus by surface epithelial cells  Secretion of bicarbonate into the surface mucus, to create a buffered surface microenvironment  Secretion of acid- and pepsin-containing fluid from the gastric pits as "jets" through the surface mucus layer, entering the lumen directly without contacting surface epithelial cells Rapid gastric epithelial regeneration  Robust mucosal blood flow, to sweep away hydrogen ions that  have  back-diffused  into  the  mucosa  from  the  lumen  and  to  sustain the high cellular metabolic and regenerative activity  Mucosal  elaboration  of  prostaglandins,  which  help  maintain  mucosal blood flow. 
  45. 45.  Among the "aggressive forces," H. pylori is very  important, because this infection is present in 70% to  90% of patients with duodenal ulcers and in about 70%  of those with gastric ulcers.The possible mechanisms are as follows:  Although H. pylori don’t invade the tissues, it induces  an intense inflammatory and immune response.
  46. 46. Bacteria overepithelial cells
  47. 47. H. pylori  secretes  a  urease  that  breaks  down  urea  to  form toxic compounds such as ammonium chloride and  monochloramine. The  organisms  also  elaborate  phospholipases  that  damage surface epithelial cells.Bacterial  proteases  and  phospholipases  break  down  the  glycoprotein-lipid  complexes  in  the  gastric  mucus,  thus weakening the first line of mucosal defense.Epithelial  injury  is  also  caused  by  a  vacuolating  toxin  (VacA).  Another  toxin  encoded  by  the  cytotoxin- associated gene A (CagA) is a powerful stimulus for the  production of IL-8 by the epithelial cells. 
  48. 48.  H. pylori  enhances  gastric  acid  secretion  and  impairs  duodenal  bicarbonate  production,  thus  reducing  luminal pH in the duodenum. The B lymphocytes aggregate to form follicles.  The role of T and B cells in causing epithelial injury is  not established,  but  T-cell-driven  activation  of  B  cells  may  be  involved  in the pathogenesis of gastric lymphomas.
  49. 49.  Gram negative, Spirochete. Does not invade cells  Colonize Gastric mucosa only *  Common cause of Duodenal ulcer  * ? Urease  Breakdown urea  ammonia  high  pH  reflex acid prod… Protease  Break down mucosa  expose  epithelium for digestion. Chronic infl.  Gastric Metaplasia Ulceration. Complications: Bleeding, perforation, stenosis,    Carcinoma.
  50. 50. NSAIDs are the major cause of peptic ulcer disease in patients who do not have H. pylori infection. The gastroduodenal effects of NSAIDs range from acute erosive gastritis and acute gastric ulceration to peptic ulceration in 1% to 3% of users. Thus, those who take these drugs for chronic rheumatic conditions are at particularly high risk.
  51. 51.  Inhibition of prostaglandin synthesis increases secretion of hydrochloric acid and reduces bicarbonate and mucin production. Loss of mucin degrades the mucosal barrier that normally prevents acid from reaching the epithelium. Some NSAIDs can penetrate the gut mucosal cells as well. By mechanisms not clear some NSAIDs also impair angiogenesis, thus impeding the healing of ulcers.
  52. 52.  All peptic ulcers, whether gastric or duodenal, have an  identical gross and microscopic appearance. 1. defects in the mucosa that penetrate at least into the submucosa, and often into the muscularis propria or deeper.2. Most are round, sharply punched-out craters 2 to 4 cm in diameter.3.   Those  in  the  duodenum  tend  to  be  smaller,  and  occasional  gastric lesions are significantly larger.4.  Favored sites are the anterior and posterior walls of the first  portion  of  the  duodenum  and  the  lesser  curvature  of  the  stomach.
  53. 53. 5.  The  base  of  the  crater  appears  remarkably  clean,  owing  to  peptic  digestion  of  the  inflammatory  exudate  and  necrotic  tissue.6.  Infrequently,  an  eroded  artery is  visible  in  the  ulcer  (usually  associated with a history of significant bleeding).7. If the ulcer crater penetrates through the duodenal or gastric  wall,  a  localized  or  generalized  peritonitis  may  develop  and  adjacent  structure  such  as  adherent  omentum,  liver,  or  pancreas could be affect.
  54. 54. Histologic Appearanceo The  histologic appearance varies with the activity, chronicity, and  degree of healing.o  In a chronic, open ulcer, four zones can be distinguished:o (1) the base and margins have a thin layer of necrotic fibrinoid debris o (2) a zone of active nonspecific inflammatory infiltration with neutrophils  predominating, o (3) granulation tissue, deep to which is-------------------------- o (4) fibrous, collagenous scar that fans out widely from the margins of the  ulcer.  o Vessels trapped within the scarred area are characteristically thickened and occasionally thrombosed, but in some instances they are widely patent. o With healing, the crater fills with granulation tissue, followed by re- epithelialization from the margins and more or less restoration of the normal architecture (hence the prolonged healing times). o Extensive fibrous scarring remains.
  55. 55. FIgure 2).        ( Four zones of active peptic ulcer. The necrotic fibrinoid debris and nonspecific inflammatory infiltrate are labeled by arrowhead. Figure 3). Necrotic fibrinoid debris Beneath the necrotic and inflammatory zones, and inflammatory infiltrate in the there is granulation tissue (arrow). Below the granulation tissue, fibrotic tissue is ulcer base. seen (F).
  56. 56. Figure 4). Granulation tissue in the ulcerbase. New blood vessels lined by plump (Figure 5). Fibrotic tissue beneathendothelial cells (arrow). Edema and the ulcer baseinflammatory infiltrate are also seen.
  57. 57. (Figure 7) Chronic gastritis with (Figure 8) Intestinal metaplasia in chronicintestinal metaplasia (arrow) seen in gastritis. The gastric foveolar epitheliumthe mucosa around the peptic ulcer. (arrowhead) is replaced by intestinal typeThe mucinous gastric foveolar of epithelium (arrow). The intestinalepithelium (arrowhead) is replaced epithelium has goblet cells. Chronicby intestinal type of epithelium inflammatory cell infiltration is also
  58. 58.  Most peptic ulcers cause epigastric gnawing, burning, or boring pain but a significant minority first come to light with complications such as hemorrhage or perforation. The pain tends to be worse at night and occurs usually 1 to 3 hours after meals during the day. Classically, the pain is relieved by alkalis or food, but there are many exceptions. Nausea, vomiting, bloating, belching, and significant weight loss (raising the specter of some hidden malignancy) are additional manifestations. Bleeding is the chief complication, occurring in up to one third of patients, and may be life-threatening.
  59. 59. Pain or discomfortA feeling of fullness -- people with severe dyspepsia  are unable to drink as much fluid as people with mild or  no dyspepsiaHunger and an empty feeling in the stomach, often 1 -  3 hours after a mealMild nausea (vomiting may relieve symptoms)Regurgitation (sensation of acid backing up into the  throat)Occasionally, symptoms of GERD are presentObstruction of the pyloric channel is rare. 67
  60. 60. Diagram of aggravating causes of, and defense mechanisms against, peptic ulceration.
  61. 61. Sharp edges, converging folds of mucosa in the upper half. The ulcer bed is covered by fibrinopurulent exudate. 
  62. 62. Free powerpoint template: www.brainybetty.com 70
  63. 63. (Figure 1) Peptic ulcer of stomach (arrow). The whole mucosa and part ofsubmucosa are denuded.(M: mucosa, SM: submucosa, MP: muscularis propria)
  64. 64. as as a re re ucos nc nc Pa PaM r lce U
  65. 65. I wish to eat nacy lemak noooooooooooooooooooow lah Free powerpoint template: www.brainybetty.com 75