Acute & Chronic Gastritis, Autoimmune & Chemical Gastritis PDF

Acute&chronic gastritis,autoimmune& chemical gastritis. AP Dr.Rajendra Choubey BOT Batch 1 Sem 2 Learning objectives Acute and chronic gastritis 1. Describe the aetiology and morphology of acute gastritis (C2) 2. Differentiate "erosion" and "ulcer" of the stomach. (...

Acute&chronic gastritis,autoimmune& chemical gastritis. AP Dr.Rajendra Choubey BOT Batch 1 Sem 2 Learning objectives Acute and chronic gastritis 1. Describe the aetiology and morphology of acute gastritis (C2) 2. Differentiate "erosion" and "ulcer" of the stomach. (C4) 3. Explain the pathogenesis and morphology of Helicobacter pylori associated gastritis. (C2) Autoimmune and chemical gastritis 1.Describe the aetiopathogenesis and morphology of autoimmune gastritis. (C2) 2.Compare autoimmune, Helicobacter pylori associated and chemical gastritis on the basis of: (C4) a)Pathogenic mechanisms b)Microscopic findings Manipal University College Malaysia 2 Histology of stomach Manipal University College Malaysia 3  Acute gastritis Inflammation of gastric mucosa in various conditions with presence of neutrophils is acute gastritis. When neutrophils are rare or absent it is gastropathy. Irritants of NSAIDs,alcohol& bile are most common cause for both. Both conditions have symptoms like gastric pain,nausea and vomiting. They may become severe with hematemesis,haemorrhage,melena & severe blood loss. Manipal University College Malaysia 4 Manipal University College Malaysia 5 Acute Gastritis Aetiology (Causes ) 1.Diet and habits Alcohol Increased aggressive forces Smoking Impairment of defense mechanisms Hot spicy food Impairment of defense mechanisms 2.Infections - Helicobacter pylori due to urease formation, inhibition of bicarbonate secretion. Impairment of defense mechanisms 6 Aetiology (causes ) of acute gastritis…continued 3.Drugs - NSAIDS (aspirin) by COX 1 inhibiting synthesis of prostaglandins. Impairment of defense mechanisms 4.Chemical injury- Ingestion of strong acids/bases Increased aggressive forces 5.Stress - shock, ischemia, trauma, burns Stress ulcers Impairment of defense mechanisms Curling ulcers in burns Cushing ulcers in CNS disorders. 7  Acute Gastritis This is a more typical acute gastritis with a diffusely hyperemic gastric mucosa. There are many causes for acute gastritis: alcoholism, drugs, infections, etc. Manipal University College Malaysia (MUCM) 8 Difference between Erosion & Ulcer of stomach -An erosion is defined as the loss of superficial epithelial layers of the mucosa. - An ulcer is the loss of all epithelial cell layers, extending through to the submucosa. -Erosions can occur anywhere in the gastrointestinal tract, but the stomach is a relatively common location. -Erosions often occur in areas of preexisting epithelial hyperplasia. Alternatively, the presence of an erosion can induce epithelial cell proliferation (as a healing response), which can result in epithelial hyperplasia. Inflammation is common in tissues around erosions. -Erosion of the stomach can be spontaneous, secondary to the lavage procedure, or treatment related (especially when the test article is an irritant), but in many cases, the exact cause of erosions is not known. Manipal University College Malaysia 9  Erosion Manipal University College Malaysia 10 Ulcer in Stomach…. Gastric peptic ulcers are solitary in more than 80% of cases & form round to oval sharply punched out defect. Mucosal margin is usually in level with surrounding mucosa but may overhang the base mostly on proximal side. In contrast heaped up margin are more typical of cancer. Depth of ulcer correlates with diameter& deep extension may be limited by thick muscular propria,adherent Pancreas,omenal fat or Liver. Peritoneum in peptic ulcer is smooth& clean as vented by peptic digestion of exudate. Active ulcer may be lined by a thin layer of fibrinoid debris with neutrophilic inflammatory infiltrate. Beneath the granulation tissue with immature vesels,mononuclear leucocytes & a fibrous collageneous scar forms the base of ulcer. Manipal University College Malaysia 11  Gastric erosion Here are some larger areas of gastric hemorrhage that could best be termed "erosions" because the superficial mucosa is eroded away. Such erosions are typical for the pathologic process termed gastropathy, which describes gastric mucosal injury without significant inflammation. Manipal University College Malaysia (MUCM) 12 Acute peptic ulcer Acute Peptic ulcer A 1 cm acute gastric ulcer is shown here in the upper fundus. The ulcer is shallow and sharply demarcated, with surrounding hyperemia and some smaller ulcers. Manipal University College Malaysia (MUCM) 13 Peptic ulcer( diagrammatic microscopic view) Manipal University College Malaysia (MUCM) 14 Pathogenesis of acute gastritis The gastric mucosa has ph of 1 million time less than blood.This contributes for digestion but can cause damage as well. The protection mechanism: Foveolar cells secretion form thin layer of mucus of mucosa & phospholipids,which helps in protecting big food particles as they don’t touch the gastric mucosa. Bicarbonate of mucus provides neutral ph. Beneath gastric mucus epithelial cells prevent diffusion of acid &leakage of other luminal material like digestion enzymes into lamina propria. Gastritis induced by alcohol consumption,NSAIDs,radiation therapy, cancer chemotherapy may cause generalised mucosal damage by inhibiting epithelial renewal.These are the main damaging factors. Foveolar cells are replaced every 3-7 days…..cntd.. Manipal University College Malaysia 15 Pathogenesis…cntd. Rich mucosal vasodilation provides oxygen and nutrients& diffuse gastric acid from lamnia propria. Gastritis& gastropathy results, when damaging forces overwhelm the protective factors. i.Inhibition of cyclooxygenase(Cox) by NSAIDs.They inhibit the cox dependent synthesis of Prostaglandins(E2&I2)which contribute to all defence mechanisms like mucus bicarbonate& phospholipid secretion. ii.NSAID injury is greater than aspirin,ibuprofen & naproxen. Iii. Inhibition of gastric bicarbonate transporters by ammonium ions can cause gastric injury in uremic pts.&those infected with urease secreting H.Pylori. Manipal University College Malaysia 16 Acute Gastritis(HP view) Infiltration of neutrophils in acute Gastritis. Manipal University College Malaysia (MUCM) 17 Pathogenesis…cntd. Reduced oxygen delivery can lead to higher incidence of gastritis at higher altitudes. Ingestion of harsh chemical acid or base(accidentally or suicide),can cause gastropathy. Radiation or chemotherapy or radiation therapy can cause sever gastric damage. Manipal University College Malaysia 18  Morphological features of ac.gastritis Difficult to differentiate gastropathy & gastritis histologically. Lamnia propria shows only moderate edema or slight congestion. Surface epithelium is intact but epithelial proliferation with cocscrew pattern is seen. Neutrophils can be seen in epithelial cells.Lamnia propria shows lymphocytes& plasma cells. Presence of neutrophils alone on basement membrane all over GIT shows active inflammation. As injury progresses there are erosions,superficial mucosal defects and haemorrhage are termed as acue erosion haemorrhagic gastritis. Manipal University College Malaysia 19 What is Helicobacter pylori? Gram negative ,Vibrio like bacilli Colonise in GASTRIC MUCOSA (close to surface epithelium) H pylori causes the following lesions in the stomach. Gastritis- Acute , Chronic Gastric ulcer Duodenal ulcer Gastric carcinoma Lymphoma Manipal University College Malaysia 20 Pathogenesis of H.Pylori infection H.Pylori infection presents as antral gastritis. When infection is limited to antrum it modestly increases local gastrin production and can augument parietal cells within gastric body and increase acid secretion leading to gastric or duodenal ulcers.Ultimately long standing H.Pyori gastritis may involve gastric body & fundus. This leads to atrophic gastritis with reduced parietal cell mass & intestinal metaplasia. Loss of parietal cell leads to reduced acid secretion stimulating gastrin production. Remainig surviving parietal cells stimulate limited gastrin secretion thereby reducing risk of gastric & duodenal ulcers…….cntd.. Manipal University College Malaysia 21 Morphological features of H.Pylori infn.cntd. Gastric biopsy specimen generally show H.Pylori in infected people. Organism is concentrated with superficial mucus on epeth.cells.They are demonstrated with immunostains& histochemical stains. Antram is a profound site. In dense colonisation organisms may be found in oxyntic(acid producing) mucosa of fundus & body. H.Pylori has a coarse or nodular mucosa. Inflammatory infiltrate includes large number of Plasma cells,lymphocytes,macrophages & neutrophils within lamnia propria. Thick rugal folds appearing like early cancer may be seen…….cntd… Manipal University College Malaysia 22 Morph.features of H.Pylori infn…cntd Lymphoid aggregates,some with germinal centres, frequently represent induced mucosa associated lymphoid tissue(MALT). MALT can transform to Lymphoma. Thus chronic H.Pylori gastritis has high risk of both gastric carcinoma & Lymphoma. Manipal University College Malaysia 23 H.Pylori in Methylene blue stain Chronic gastritis and peptic ulcer disease are often accompanied by infection with Helicobacter pylori. This small curved to spiral rod-shaped bacterium is found in the surface epithelial mucus of most patients with active gastritis. The rod-shaped bacteria are seen here with a methylene blue stain. Manipal University College Malaysia (MUCM) 24  Stress related Mucosal disease This occurs in pts with severe trauma,extensive burn,intracranial -disease,major surgery or serious medical conditions..Stress ulcers are most common in settings of shock,sepsis or severe trauma. Curling ulcers occur in proximal duodenum becoz of severe burn or trauma. Manipal University College Malaysia 25  Pathogenesis Stress related gastric mucosal injury is related to local ischeamia. This is caused by stress related splanchnic vasoconstriction. Increased release of vasoconstrictor endothelin-1 which also contributes to ischeamic gastromucosal injury. Those in intracranial injuries are caused by direct stimulation of vagal nuclei. It also causes hypersecretion of gastric juice. Systemic acidosis also contributes by lowering intracellular ph of mucosal cells. Manipal University College Malaysia 26 Morphological features of stress related gastritis Stress related gastric mucosal injuries range from shallow erosions to deep mucosal ulcers. Ulcers are rounded,less than 1 cm in diameter. Base of ulcers are brown or black becoz of acid digestion of blood. Unlike peptic ulcers which are solitary & found in antrum,stress ulcers are found anywhere in stomach and are often multiple. Microscopically stress ulcers are sharpely demarcated & have normal adjacent mucosa. Healing with complete re-epetheliaisation occurs within days or wks. after successful treatment. Manipal University College Malaysia 27  Clinical features Critically ill pts., have histological evidences of gastric mucosal damage. Blood transfusion is required. Perforation can occur. Non stress related gastric bleeding includes following 2 conditions: i.Dieulafoy lesion-consists of an abnormal submucosal arteriol found within lesser curvature of stomach near gastroesophageal junction.Its erosion can cause severe gastritis or severe bleeding.NSAIDs are main cause. ii.Gastric antral vascular atrasia-It is seen endoscopically as…cntd. Manipal University College Malaysia 28  Clinical features….cntd...as longitudinal stripes of oedematous erythematous mucosa, & can be termed as WATERMELON STOMACH.These stripes are created by ectatic mucosal vessels. Histologically mucosa shows reactive gastropathy with dilated capillaries containing fibrin thrombi. Mostly idiopathic ,GAVE can be found in Cirrhosis & systemic sclerosis. Recurrent bleeding can cause blood in stool and Iron deff. Anaemia. Manipal University College Malaysia 29 Watermelon stomach(endoscopic view) Multiple Superficial gastric injury Heal rapidly Manipal University College Malaysia (MUCM) 30 Chronic Gastritis & its causes Its mostly caused by H.Pylori infection. Other causes can be autoimmune gastritis or radiation injury. Chronic bile reflux,mechanical injury,nasogatric tube,Crohn’s disease,Amyloidosis and graft Vs host reaction can be other causes. It is less severe than acute gastritis. Hematemesis is less common. Manipal University College Malaysia 31  Autoimmune atrophic gastritis It accounts for less than 10% cases of chr. Gastritis. 2% prevalence above 60 yrs. Of age. Unlike H.pylori infection it typically spares Antrum and has marked hypergastrineamia. It is characterised by i.-antibodies to parietal cells and intrinsic factor that can be detected and gastric secretions. ii.Reduced serum Pepsinogen1 concentration. iii.Endocrine cell hyperplasia iv.Vitamin B12 deff. Defective gastric acid secretion.(Achorhydria). Manipal University College Malaysia 32 Pathogenesis Autoimmune atrophic gastritis has loss of Pareital cells,which secrete gastric acid & intrinsic factor. Lack of acid leads to gastric release leading to hypergastrinemia. Lack of intrinsic factor leads to defective Vit. B12 absorption from ileum thereby causing Vit.B12 defficiency & Purnicious Anaemia. Associated intestinal metaplasia leads to autoimmune metaplastic atrophic gastritis. CD4+T cells (reactive) cause H+K+AT pase autoantibodies.They impact on proton pump. Contd… Manipal University College Malaysia 33 Pathogenesis.. There may be gastric gland destruction during autoimmune attack on Parietal cells. They are not pathogenic proven by their passive transfer to animals. Manipal University College Malaysia 34 A, Chronic atrophic gastritis (right) contrasted with normal pyloric mucosa (left). There is marked gastric atrophy with disappearance of gastric glands and appearance of goblet cells (intestinal metaplasia). B, Photomicrograph showing chronic atrophic gastritis with intestinal metaplasia. Morphological features of Autoimmune atrophic gastritis. Autoimmune atrophic gastritis is characterised by oxyntic(acid producing) mucosa within the body & fundus.Antrum & cardia are fully spared. Mucosa & body show diffuse atrophy. Fundus is very thin with rugal folds lost. If Vit.B12 deficiency is severe, nuclear enlargement occurs in epithelial cells(megaloblastic change). Neutrophils may be present but the inflammatory infiltrate contains lymphocytes,macrophages,plasma cells with lymphoid aggregate & follicles. ……………cntd……. Manipal University College Malaysia 36 Morphological features…cntd. Inflammation is centred in gastric glands. Loss of parietal cells & chief cells is extensive. Small surface elevation may represent intestinal metaplasia with goblet cells. Rarely endocrine cell hyperplasia may form low grade neuroendocrine(carcinoid) tumor. Manipal University College Malaysia 37  Autoimmune gastritis. (A) Low-magnification image of gastric body demonstrating deep inflammatory infiltrates, primarily composed of lymphocytes, and glandular atrophy. (B) Intestinal metaplasia, recognizable as the presence of goblet cells within gastric foveolar epithelium.  Clinical features More common in women than men. Purnicious anaemia and autoimmune atr.gastritis are often associated with autoimmune disease like Hashimotos Thyroiditis,Addison’s disease etc. There is megaloblastic anaemia & malabsorption diarrhoea. Vit.B12 deff.in bone. Subacute degeneration of spinal cord. Manipal University College Malaysia 39  Chemical gastritis Alcohol and certain drugs can cause acute chemical gastritis, depending on how much and how often people use them. They can cause chemical erosion of stomach mucosa (erosive gastritis). Overuse of NSAIDS(nonsteroidal anti-inflammatory drugs), such as aspirin and ibuprofen, is one of the most common causes of acute chemical gastritis. Some recreational drugs, like cocaine, may also cause it. Bile reflux can also lead to chemical gastritis.Pt. feels extreme burning sensation on the epigastric region. Manipal University College Malaysia 40 Compare autoimmune, Helicobacter pylori associated and chemical gastritis. 41 Uncommon forms of Gastritis…Eosinophilic gastritis. It is characterised by dense infiltrate of Eosinophils in mucosa & muscularis of antral & pyloric region. They may be present in other parts of GIT as well. Common cause is Soy milk or cow’s milk allergy in children. Immune disorders like systemic sclerosis, inflammatory myopathy,parasitic infestation or even H.Pylori infection. LYMPHOCYTIC GASTRITIS- Affects mostly women& cause nonspecific abdominal symptoms. Its idiopathic & associated with Coeliac disease suggesting immune mediated etiology………..cntd… Manipal University College Malaysia 42 Lymphocytic gastritis……cntd It affects entire stomach termed as Variola gastritis. Endoscopy shows thickened folds covered by small nodules. Histologially shows marked increase in intra epithelial T.lymphocytes. GRANULOMATOUS GASTRITIS- Applied to all granulomatous conditions. Example of Crohn’s dis.is most specific. Cause of granulomatous gastritis –Sarcoidosis,tuberculosis,fungal infections,CML& H.pylori infn.Histologically narrowing& rigidity of gastric wall due to granulomatous inflammation maybe seen. Manipal University College Malaysia 43 Other complications of chronic gastritis:Mucosal atrophy &Intestinal metaplasia Chr. Gastritis leads to significant loss of parietal cell mass. This oxyntic atrophy leads to intestinal metaplasia recognised by presence of Goblet cells which is strongly associated risk of Adenocarcinoma. Risk of Adenoma is maximum in autoimmune metaplastic atrophic gastritis. This is so becoz achlorhydria of gastric mucosal atrophy permits growth of bacteria which produces cinogenic nitrosamines. Intestinal metaplasia also occurs in chr.H.Pylori gastritis, but may regress after regression of organisms. Manipal University College Malaysia 44  Dysplasia Chr. Gastritis exposes the epithelium of inflammation related free radical damage & proliferative stimuli that include regenerative response thereby production of gastrin,a gastric epithelial hitogen. Overtime this combination of stressors lead to amplifications of genetic alterations causing carcinoma. Preinvasive lesion can be recognised by change like dysplasia,variation in epithelial size,shape,orientation along with chromatin texture,hyperchromasia & nuclear enlargement. Pathologist can be confused but modern methods help. Manipal University College Malaysia 45  Gastritis cystica This is an exuberant reactive epithelial proliferation associated with entrapment of epithelial lined cysts. These may be formed within submucosa(gastric cystic polyposa)or deeper layers of gastric wall(Gastritis cystica profounda). Being associated with chr.gastritis and partial gastrectomy,it is concluded that gastrica cystica is trauma induced but why cysts are formed,is not clear. Regenerative changes can be prominent in entrapped epithelium therefore gasica cystica is mistaken for Adenocarcinoma. Manipal University College Malaysia 46  Hypertrophic Gastritis They are uncommon conditions characterised by giant cerebriform enlargement of the rugal folds due to epithelial hypertrophy without inflammation. These are related with excessive growth factor release. There are two examples of such condition. i.Menetrier’s disease ii.Zollinger ellison syndrome Manipal University College Malaysia 47  Menetrier’s disease It’s a disorder associated with excessive secretion of transforming growth factor(TGF) which is an EGFreceptor(EGFR)ligand. Hyperactivation of epidermal growth factor receptor on gastric epithelial cells.Some case occur with viral or H.Pylori infection. Diffuse hypertrophy of foveolar epetheium within the body of fundus+hypoprotieneamia due to albumin loss(10G/day) across gastric mucosa characterises Menetrier’s dis. Secondary symptoms like wt.loss,diarrhoea& peripheral edema are seen. …cntd.. Manipal University College Malaysia 48 Ménétrier disease. (A) Marked hypertrophy of rugal folds. (B) Foveolar hyperplasia with elongated and focally dilated glands.)  Menetrier’s dis….cntd. -Children also have same symptoms are like adults. Also systemic effects of TGF , including hyperplasia of Liver,Panreas,GIT(beyond stomach),muscle,fat loss & Psoriasis may be present. Risk of gastric Adenoma is more in adults. Manipal University College Malaysia 50  Morphological features Irregular enlargement of gastric rugae in body & fundus. Histologically most important feature is hyperplasia of foveolar mucus cells. Glands are enlarged with cockscrew like appearance of cystic dilation. Inflammation in nodes except in some cases marked intraepithelial lymphocytosis.Diffuse or patchy glandular atrophy besides hypoplasia of parietal & chief cells.,intermixed with epithelial hyperplasia. Manipal University College Malaysia 51 Zollinger Ellison syndrome It is caused by gastrin secreting neuroendocrine tumors. They are always found in small intestines & Pancreas. Pt.presents with duodenal ulcers or Pancreatitis. It also presents with duodenal ulcer & chr. Diarrhoea. In stomach there is a marked increase in oxyntic mucosal thickness due to massive parietal cell hyperplasia. Gastrin also causes hyperplasia of mucous neck and endocrine cells with oxyntic mucosa. Treatment is done by blockade of acid hypersecretion with proton pump inhibitors. Manipal University College Malaysia 52  Thank you!! Manipal University College Malaysia 53