GIT Pathology.pdf

 Gastrointestinal Tract Gastrointestinal tract Dr. Thusharie Liyanage Oesophagus - Objectives Oesophagus List: Congenit...

 Gastrointestinal Tract Gastrointestinal tract Dr. Thusharie Liyanage Oesophagus - Objectives Oesophagus List: Congenital abnormalities Common symptoms Motor dysfunctions Causes of oesophagitis Heart burn Dysphagia Pain Describe: Pathogenesis oesophagitis Haematemesis Morphology– Barrett’s oesophagus Tumours Clinical features of tumours Congenital abnormalities 1. Agenesis : absence Oesophageal atresia and 2. Atresia: thin, non-canalized cord TOF 3. Fistulas (TOF): connection with trachea Associated with other congenital abnormalities CVS, GUT, CNS  Lesions of motor dysfunction Tracheo-oesophageal fistula (TOF) 1. Achalasia Discovered shortly after birth (failure to relax) Feeding problems - Aperistalsis Need prompt correction - LES tone - relaxation of LES Aspiration Suffocation Dilated oesophagus Pneumonia Fluid electrolyte imbalances - Progressive dysphagia - Nocturnal regurgitation - Aspiration Achalasia Microscopy Primary Secondary Absence of myenteric ganglia – in the body of - Majority - Chagas disease oesophagus Trypanosoma cruzi Complications - Diabetic neuropathy - Infiltrative disorders aspiration pneumonia malignancy squamous cell carcinoma amyloidosis Candida oesophagitis sarcoidosis Lower oesophageal diverticula 2. Hiatal Hernia Complications of hiatal hernias Ulceration Bleeding Perforation Reflux oesophagitis Paraoesophageal hernia Strangulation Obstruction  4. Lacerations 3. Diverticula Out pouching of GIT that (Mallory – weiss syndrome) contain all visceral layers Linear superficial lacerations at the 2 types gastro-esophageal junction Traction Pulsion After excessive vomiting -Inflammatory -luminal processes pressure In alcoholics -weakened wall 5-10% upper GIT bleeding Oesophagitis 3. Other causes of oesophagitis 1. Reflux oesophagitis alcohol / hot fluids chemicals (acids / alkali) 2. Infectious oesophagitis smoking rare uremia (CRF) Immuno compromised patient’s (AIDS) autoimmune diseases Candida albicans cytotoxic anti-cancer therapy Herpes simplex virus GVHD CMV radiation therapy skin diseases Pathogenesis Oesophageal stenosis Infections Narrowing of oesophagus Severe acute inflammation Fibrous thickening of submucosa Mucosal injury Superficial necrosis Often due to inflammation and scarring Ulceration Caused by – acid reflux Chemicals – caustic injury (gastric reflux) – irradiation Granulation tissue Fibrosis (strictures)  Reflux oesophagitis Clinical Features Heartburn Reflux of gastric contents into lower esophagus Dysphagia Haematemesis Causes LES tone : pregnancy, hypothyroidism, Complications alcohol, tobacco, NG tube Bleeding Ulceration gastric volume Strictures Delayed gastric emptying Barrett esophagus sliding hiatal hernia Barrett oesophagus Normal stomach macro Prolong reflux distal squamous mucosa replaced by metaplastic columnar epithelium. Endoscopy red velvety mucosa located between smooth pale squamous mucosa. Normal endoscopy Barrett esophagus  Normal esophagus microscopy Barrett oesophagus Barrett esophagus with intestinal metaplasia Complications - local ulceration - bleeding - strictures - dysplasia adeno CA x 30 (distal esophagus) Low grade high grade Chronic Barrett esophagus with dysplasia inflammatory diseases Tuberculosis Crohn’s disease  Esophageal varices Tumours Dilated tortuous veins within submucosa Benign Malignant – Portal hypertension – Cirrhosis Leiomyomas Squamous cell – Hepatic schistosomiasis carcinoma Fibromas Lipomas Adenocarcinoma Massive haematemesis Haemangiomas Death Papillomas Squamous cell carcinoma Clinical Features Progressive dysphagia Commonest malignant tumour – gradual obstruction Late diagnosis – diet (solid to liquids) Adults > 50 years Extreme weight loss Poor prognosis Male > Female Debilitation Blacks > Whites Increase incidence : Iran, China, S. Africa Early diagnosis : Endoscopy & biopsy Squamous cell carcinoma SCC oesophagus  Factors associated with SCC 3. Dietary : vitamin deficiency (A,C,B) trace metal deficiency (zn) 1. Lifestyle : betel chewing smoking nitrosamines / nitrates alcohol fungal contamination hot beverages or food 4. Genetic factors : racial predisposition 2. Oesophagial diseases : Celiac disease oesophagitis Ectodermal dysplasia Plummer Vinson Syndrome Epidermolysis bullosa achalasia Morphology Squamous cell carcinoma macroscopy Site : Upper 1/3 20% Middle 1/3 50% Lower 1/3 30% Small grey-white plaques (In situ carcinoma) Invasive carcinoma polypoidal excavated/ ulcer flat/ diffusely infiltrative Squamous cell carcinoma macroscopy Microscopy : Most SCC : moderate or well differentiated  Squamous cell carcinoma Squamous cell carcinoma SCC spread Adenocarcinoma oesophagus Submucosal lymphatic spread Distal oesophagus – M>F Local spread mediastinal structures – Whites > Blacks (pleura, trachea) – 40 - 60yrs Lymph node metastases Majority arise from Barrett mucosa – Upper 1/3 cervical nodes – Middle 1/3 mediastinal, paratracheal Dysplasia – Lower 1/3 gastric and celiac nodes adenocarcinoma Adenocarcinoma oesophagus Adenocarcinoma oesophagus  Objectives List causes of gastritis Briefly describe each type of gastritis Pathology of stomach Describe morphological features of acute and chronic gastritis Dr. Thusharie Liyanage List causes of peptic ulcer Describe briefly etiology, pathogenesis, morphology and complications of peptic ulcer Stomach Gastritis Inflammation of the gastric mucosa Mucosal protective mechanisms Classification - mucus secretion 1. Acute gastritis - HCO3 secretion 2. Chronic gastritis - epithelial barrier 3. Special forms of gastritis - mucosal blood flow - eosinophilic - prostaglandin synthesis - lymphocytic - granulomatous Acute gastritis Microscopy Acute mucosal inflammation of transient Acute superficial inflammation of mucosa nature – hemorrhages - Lamina propria oedematous – mucosal erosions congested bld vessels neutrophils - No glandular loss or atrophy - Loss of superficial epithelium “Gastric erosions” ( limited by MM)  Acute gastritis microscopy Acute gastritis microscopy Causes of acute gastritis Clinical features NSAID’s (aspirin) Asymptomatic alcohol smoking Epigastric pain uremia severe stress(trauma, surgery, burns) Nausea, vomiting ischemia shock systemic infections (salmonellosis) Haemorrhage acids/ alkali – Haematemesis fatal irradiation – Malena cancer chaemotherapy Chronic gastritis Classification Definition Type A : Auto-immune Presence of chronic mucosal inflammatory Type B : Helicobacter pylori changes, Leading to mucosal atrophy and intestinal Others : Toxic: alcohol, smoking, metaplasia, usually in the absence of Mechanical, erosions. Radiation, May become dysplastic, and constitute the Post surgical (antrectomy), background for development of carcinoma. Granulomatous, uremia, GVHD, amyloidosis  Chronic Gastritis Anti-parietal cell antibody Auto Immune (Type A) Gastritis < 10% Body and fundus affected Auto antibodies to Parietal cells IF B12 absorption pernicious anaemia Microscopy Diffuse mucosal atrophy Dysplasia Intestinal metaplasia Carcinoma in situ Lymphocytes, plasma cells in LP Carcinoma Lymphoid aggregates Helicobacter pylori (Type B) Gastritis Associated with other autoimmune diseases – Diabetes mellitus type 1 Commonest type 90% – Hashimoto thyroiditis Lesions : antrum – Addison’s disease Lymphocytes, plasma cells in LP Neutrophils in LP Increased risk of developing No / minimal glandular atrophy – Gastric carcinoma – Endocrine tumours (carcinoid) Dysplasia Ca in situ CA  Organisms Gram (-) ve, non sporing rod in luminal surface , no tissue invasion Helicobacter pylori Diseases associated with H. Pylori Most common infection worldwide – Chronic gastritis Colonization rates increases with age. – Peptic ulcers ( 50% asymptomatic American adults > 50 yrs) – Gastric carcinoma – Gastric MALT lymphoma In endemic areas acquired in childhood Persists for decades Granulomatous gastritis Lymphocytic gastritis Epithelioid cell granulomas – Lymphoid aggregates – Intra epithelial lymphocytes – Crohn’s disease – Associated with Celiac disease – Infections (TB, syphilis, fungi) – Sarcoidosis Eosinophilic gastritis – Vasculitis – Eosinophilic enteritis – Foreign body reactions – Allergic gastroenteropathy – Idiopathic  Peptic Ulcer Disease Peptic Ulcers: Ulcer: breach in the mucosa of GIT, which Chronic, solitary lesion that occur in any extends through the MM into the portion of GIT exposed to the action of submucosa or deeper. acid / peptic juices. - Duodenum (1st) 98% - Stomach (antrum) - Gastro-esophageal junction - Gastrojejenostomy margins Pathogenesis Imbalance between mucosal defenses and the damaging forces Impaired mucosal defenses: – Ischemia – shock – delayed gastric emptying – epithelial regeneration Damaging forces: Clinical features H. pylori duodenal ulcers 100% Epigastric pain gastric ulcers 70% night 1-3 hrs after meals NSAID’s / Aspirin reduced by alkali / food Smoking Alcohol Chronic / recurrent disease 15 yrs. Hyperacidity Corticosteroids With therapy heals within weeks  Morphology Peptic ulcer macroscopy Round to oval Punched-out defect Straight walls Margins level with mucosa Base: smooth and clean thrombosed vessels Scarring Peptic ulcer microscopy mucosal folds radiating from ulcer Adjacent mucosa (gastritis) red oedematous Size cannot differentiate from a Location malignant ulcer Complications Microscopy 1. Bleeding 15-20% Necrotic fibrinoid debris 2. Perforation 5% Inflammatory cells 3. Obstruction 2% Granulation tissue Pyloric channel ulcers & duodenal ulcers Fibrous / 4. Iron deficiency anaemia collagenous scar 5. Malignancy rare, not in DU  Acute gastric ulceration Acute stress ulcers NSAID therapy Multiple lesions Mainly stomach, occasionally duodenum Physiologic stress Mucosal erosions – Shock Small ulcers – Severe burns – Dark brown (acid digestion of blood) – Sepsis – Normal gastric rugal pattern – Trauma – Raised intracranial pressure Complete healing with re-epithelialization  Objectives List the infective diseases affecting intestine INFECTIOUS DISEASES OF INTESTINE Describe the pathogenesis and morphological features of typhoid fever List the complications of typhoid fever Dr. Thusharie Liyanage Describe intestinal TB with morphological features Diarrhoea Infectious enterocolitis An increase in stool mass, stool frequency, and / or stool fluidity. Global problem > 250g stools / day 12,000 deaths / day among children in developing countries 70 – 95% water constitute one half of all deaths before age 5 Dysentery 2 nd only to common cold Low volume, painful bloody diarrhoea. Viral gastroenteritis Destroys mature enterocytes Replaced by immature secretory cells Acute / self limited Infectious diarrhoea - Absorption lead to dehydration and metabolic acidosis Watery diarrhoea, vomiting - Secretion Rota virus children Adeno virus ( 6 -24 months) Calici virus Dehydration Astro virus Metabolic acidosis  Bacterial Enterocolitis 2. Toxigenic organisms 1. Ingestion of preformed toxin IP hrs explosive Proliferate release diarrhoea diarrhoea enterotoxins Staphylococcus aureus Vibrio cholera Bacillus cereus E.coli Traveler's Clostridium perfringens diarrhoea Clostridium botulinum Salmonellosis 3. Entero invasive organisms Salmonella Gram (-)ve rod IP proliferate invade and S.enteritidis S.typhi destroy mucosal cells S.typhimurium S.paratyphi TYPHOID FEVER dysentery life threatening Shigella self limited diarrhoea systemic illness Salmonella no systemic disease humans only host E coli chickens spread due to poor cows sanitation Pathogenesis Mononuclear phagocytic involvement (2nd week) - enlarged lymph nodes Organism enters body via food / water - splenomegaly - enlarged payers patches Penetrate intestinal mucosa & enter into blood Bacteremia (1st week) Ulceration of Payer patches (3rd week) fever, rose spots, - linear oval ulcers headache, myalgia - long axes along axes of SI leucopenia - bleeding and shock  Enlarged mesenteric lymph nodes Complications Ulceration Bleeding Shock Perforation Peritonitis Intestinal stenosis Gallbladder colonization chronic carrier ( reservoir of infection ) Intestinal TB Secondary Tuberculosis More common primary secondary Mycobacterium tuberculosis Primary TB Swallowing of infected material (cough) Mycobacterium bovis drinking milk Ileocaecal area Palpable mass “ Tuberculoma” primary lesion inconspicuous. mesenteric lymph nodes enlarged. Small nodules on serosa (Tubercles) Macroscopy Intestinal Ulceration tuberculosis ragged undermined transverse ulcers with nodular margins Fibrosis stenosis / intestinal obstruction Fistulous tracts between bowel loops Tuberculous peritonitis  Microscopy Tuberculosis Granulomatous inflammation Caseous necrosis Chronic inflammatory cell infiltrate Fibrosis AFB (+) DD: Crohn's disease Fungal infections (actinomycosis) Tuberculosis Intestinal tuberculosis Intestinal tuberculosis Intestinal tuberculosis  Pseudomembranous colitis Macroscopy (Antibiotic associated colitis) Yellow mucosal plaques (adherent fibrino-purulent necrotic debris) Broad spectrum antibiotic treatment Alteration of normal intestinal flora Clostridium difficile Toxin elaborated Damage colonic mucosa Microscopy Amoebiasis Denuded surface epithelium Entamoeba histolytica Mushroom like mass ( pseudo membrane) ( Protozoan parasite) - mucus - neutrophils Cause amoebic dysentery - adherent to surface Fecal oral transmission Most are asymptomatic healthy carriers Pathogenesis Caecum, ascending & sigmoid colon Infectious form (cysts) resist gastric acid Flask shaped ulcer Within the colonic mucosa Narrow neck amoebic trophozoites are released Broad base Invade colonic crypts burrow into the LP, submucosa Limited by muscularis spread laterally creating propria flask shaped ulcers  Microscopy Complications Sloughing of mucosa 1. Amoebic liver abscess - zones of necrosis of hepatocytes Liquifactive necrosis - scant inflammatory reaction - hemorrhage into cavities Little cellular reaction “chocolate cyst” Amoeba in inflammatory - secondary infections purulent abscess exudate - lungs / heart / kidney / brain 2. Pan colonic ulceration necrotizing colitis 3. Megacolon 4. Perforation with peritonitis 5. Colonic strictures 6. Amoeboma (Granulation tissue & fibrous tissue) Pseudo tumour 7. Amoebiasis of skin (anus and vulval region)  Objectives List premalignant lesions of stomach Tumours of the Stomach List tumours of stomach List clinical features of gastric carcinoma Dr. Thusharie Liyanage Describe morphological features of gastric carcinoma Describe the spread of gastric carcinoma Tumours of Stomach WHO Histological classification of gastric tumours Epithelial tumours Benign Malignant Adenomas, Intra epithelial neoplasia Adenocarcinomas Epithelial Non- epithelial Carcinoid Tumours Small cell carcinomas Gastric Polyps Non epithelial tumours Polyp: any nodule or mass that projects above the level of surrounding mucosa. Leiomyoma Schwannoma GIST (Gastro intestinal stromal tumours) Lymphomas Leiomyosarcomas Kaposi sarcomas  Hyperplastic polyps Gastric Polyps Non-neoplastic Neoplastic > 75% gastric polyps hyperplastic polyp most are small & sessile * adenomas * carcinomas multiple polyps 20-25% 75% * lipomas * leiomyomas associated with chronic gastritis Gastric adenomas Microscopy - hyperplastic Constitute 10 % of gastric polyps epithelium - cystically dilated Contains proliferative dysplastic epithelium glands (pre-malignant) - no dysplasia Carcinoma not pre-malignant - 40% harbor CA - 30% adjacent CA Gastric adenomas Gastric adenomas  Gastric adenomas Gastric commonest site: antrum adenomas sessile or pedunculated usually a single lesion Associated with – autoimmune gastritis – chronic gastritis with intestinal metaplasia – colonic polyposis syndromes Gastric Carcinoma Clinical Features - 2 nd most common tumour in the world Insidious disease asymptomatic until late - leading cause of cancer death in the world weight loss, - Incidence varies widely. abdominal pain, Japan, Chile, Columbia, China anorexia, vomiting, anemia. Late diagnosis - Japan: mass endoscopy screening programs Poor prognosis 35% early gastric carcinomas Factors associated with gastric carcinoma Host factors Environmental Chronic gastritis Partial gastrectomy Helicobacter pylori Gastric adenomas Diet Barrett oesophagus nitrites / nitrates smoked/ salted/ preserved foods Genetic fresh fruits / vegetables Family history HNPCC Smoking Blood group A Low socio economic status Familial gastric carcinoma syn.  Morphology Gastric carcinoma is classified on the : – depth of invasion – macroscopic growth pattern – histologic subtype Depth of invasion Nodal metastases Distant metastases Has the greatest impact on the clinical outcome Gastric Carcinoma Carcinoma – in – situ carcinoma confined to the surface epithelial Early Late layer. Early gastric carcinoma lesion confined to the mucosa or sub- mucosa regardless of lymph-nodes. Advanced gastric carcinoma neoplasm that has extended below sub- mucosa into the muscular wall. Macroscopy Normal stomach Exophytic Flat or depressed Excavated – mimics peptic ulcers – heaped up margins – necrotic base – not in level with adjacent mucosa Linitis plastica – rigid, thickened stomach wall – diffuse infiltration of carcinoma  Gastric carcinoma Gastric carcinoma Microscopy Gastric carcinoma Lauren classification Adenocarcinoma Intestinal type Diffuse type high risk areas * No precursor lesion * No 55 years *Younger (48 y) M:F 2:1 * M=F commoner * less common incidence Histologic subtypes Gastric carcinoma - intestinal type Intestinal type – neoplastic intestinal glands – resemble colonic adenocarcinoma – arise from precursor lesions  Gastric carcinoma - intestinal type Diffuse type – gastric type mucus cells – do not form glands – infiltrate as scattered individual cells – mucin vacuole pushes the nucleus to a periphery Signet ring cells Gastric carcinoma - diffuse type Gastric carcinoma - diffuse type Spread Regional lymph nodes Penetrate wall Distant lymph nodes Serosa * Virchow’s node Adjacent (supra clavicular lymph nodes) tissues duodenum * Sister Mary Joseph nodule pancreas (Subcutaneous nodule peri umbilical retroperitoneum region) peritoneal metastases  Prognosis Metastases Depth of invasion - Peritoneal nodules Nodal involvement - Liver Metastases TN - Lung M - Ovaries 5 yr survival “Krukenberg tumour” early gastric carcinoma 90-95% advanced gastric CA 15% (Stomach, colon, breast, pancreas, GB) Gastric lymphomas GIST: Gastro intestinal stromal Tumours MALT lymphoma ( B cell lymphoma) Mesenchymal neoplasm Composed of spindle cells 5% gastric tumours CD 117 positive tumour cells Helicobacter pylori Chronic gastritis  4/7/2022 Objectives Describe ulcerative colitis and Crohn disease INFLAMMATORY BOWEL in relation to etiology, pathogenesis, DISEASE morphology and clinical features including complications Compare and contrast ulcerative colitis and Crohn disease Dr. Thusharie Liyanage Inflammatory Bowel Disease Normal intestine * Crohn disease * Ulcerative colitis Steady state of inflammation - chronic - relapsing Factors activating immune system - inflammatory diseases (microbes, dietary antigens) - extra intestinal manifestations Factors down regulating inflammation - persistent activation of mucosal immune system Maintains integrity of mucosa. Pathogenesis Normal gut flora (commensals) Normal gut mucosal immune system - responsive to ingested pathogens Unregulated / exaggerated - unresponsive to normal intestinal flora local immune response (CD4 T cells) Key abnormalities in IBD : - Strong local immune response against normal flora Genetically susceptible individuals - Defects in epithelial barrier function - 15% pt’s have affected relatives - monozygotic twins 30 – 50% 1  4/7/2022 CROHN DISEASE Clinical Features Other names - mild diarrhoea – Terminal ileitis (1932) - abdominal pain chronic course - fever – Regional enteritis - anaemia – Granulomatous colitis - weight loss asymptomatic periods Any part of gut may be involved (mouth to anus) any age (peak ages: 2nd – 3rd decades) Common in western developed countries whites > blacks F>M Smoking is a strong exogenous risk factor Macroscopy Long serpentine linear ulcers Lesions are with adjacent mucosal swelling discontinuous, patchy with normal “cobblestone intervening gut appearance” “skip lesions” Serosa: granular & Intestinal wall dull gray rubbery and thick Mesentery: swollen, narrowed lumen fibrotic, thickened proximal gut Mesenteric fat wraps distension around the bowel surface Enlarged LN’s 2  4/7/2022 Microscopy : Transmural inflammation Mucosa – distorted architecture villus blunting (SI) irregular, branching glands (LI) – lymphoplasma cell infiltration basal plasmacytosis – cryptitis – crypt abscesses – superficial ulceration – gastric metaplasia – granulomas Crohn disease microscopy Crohn disease microscopy Muscularis mucosa - thickening , reduplication Granulomas - irregularity Non-caseating granulomas Fibrosis - all tissue layers - mucosa - areas of active disease - submucosa - uninvolved bowel - muscularis propria - absence of granulomas does not exclude Crohn disease stricture formation 3  4/7/2022 Crohn disease - granulomas Fissures Complications Extensive SI involvement Fibrosing strictures - protein loosing enteropathy - generalized malabsorption Fistulas - pernicious anaemia (B12) – bowel loops, bladder, vagina - steatorrhoea (bile salts) – perianal skin Carcinoma X 5-6 fold Peritoneal abscess less than UC Bowel perforation / adhesions Renal diseases - ureteric involvement Amyloidosis ULCERATIVE COLITIS Epidemiology Limited to colon and rectum Western countries Whites > Blacks Extends in a continuous fashion Female > Male Peak age : 20 -25 years Affects only mucosa & submucosa UC is a systemic disorder with extra intestinal Well formed granulomas absent manifestations 4  4/7/2022 Clinical features Macroscopy Rectum extends proximally in a Relapsing disorder of retrograde fashion to colon Bloody mucoid diarrhoea PAN COLITIS Lower abdominal pain Chronic course No skip lesions Disease of continuity Flare ups precipitated by emotional or physical stress Mucosa - Initially reddened / granular / friable Can spread to distal ileum - 10% patients - Ulceration - within 25cm of ileoceal valve broad based ulcers - diffuse ileitis along axis of colon BACKWASH ILEITIS - Pseudo polyps Appendix can be involved regenerating mucosa Ulcerative colitis active disease Ulcerative colitis active disease 5  4/7/2022 Ulcerative colitis active disease With chronic disease with healing - mucosal atrophy - flattened / attenuated mucosa Macroscopy cont….. Toxic megacolon No mural thickening Severe disease Serosa is normal Damage to neural plexus Toxic megacolon WHY ? Risk of perforation Microscopy Active disease Affects only the mucosa and submucosa distorted glandular architecture cryptitis crypt abscesses Active disease Healed disease lymphoplasma cell infiltration - Atrophy basal plasmacytosis - Glandular architectural no granulomas disarray ulceration (superficial) - Submucosal fibrosis 6  4/7/2022 UC microscopy UC cryptitis and crypt abscesses UC with dysplasia Dysplasia Nuclear atypia Loss of polarity low grade high grade infiltrative CA Risk of cancer pancolitis >10 yrs x 20 – 30 Screening programs : colonoscopic biopsies Extra intestinal manifestations of UC and Crohn disease Migratory polyarthritis Sacroilitis Ankylosing spondylitis Erythema nodosum Primary sclerosing cholangitis Uveitis Clubbing of finger tips Systemic amyloidosis 7  4/6/2022 Learning outcomes Malabsorption and At the end of this lecture students will be able to, Appendicitis List the malabsorption syndromes Describe the important malabsorption syndromes in relation to Dr k.b.rojika, aeitiology, pathogenesis, morphology, and clinical features Department of pathology, Describe the macroscopic appearance of the appendix in appendicitis faculty of medicine ruhuna Describe the microscopic features of appendicitis. Clinical features Malabsorption syndromes characterized by, Defective absorption of fat Vitamins Chronic diarrhea Proteins Steatorrhea Charbohydrates Abdominal pain Electrolytes and ,minerals and water LOW Anaemia Peripheral neuropathy Failure to thrive Major malabsorption syndromes Malabsorption results from disturbance in at least one of the four phases of nutrient absorption. 1.Reduced intestinal surface area Intraluminal digestion Crohn disease Terminal digestion coeliac diease Transepithelial transport 2. Infections Lymphatic transport of absorbed lipids acute infectious enteritis parasitic infestation tropical sprue whipple disease 1  4/6/2022 3. Defective intraluminal digestion 4. Mucosal cell abnormality -pancreatic disease chronic pancreatitis defective terminal digestion cystic fibrosis disaccharidase deficiency-lactase deficiency -Zollinger Ellison syndrome defective epithelial transport inactivation of enzymes -Defective bile secretion abetalipoproteinemia hepatic dysfunction bile acid malabsorption -Defective bile flow 5. Lymphatic obstruction bile duct obstruction lymphomas TB Celiac disease/celiac sprue/glueton sensitive enteropathy 5. Iatrogenic Immune mediated enteropathy gastrectomy Triggered by ingestion of gluten containing diet eg; wheat, rye,barley short gut syndrome Genetic predisposition is recognized distal ileal resection Pathogenesis ingestion of gluten containing diet Trigger activation and proliferation of CD8 intraepithelial lymphocytes These lymphocytes have NKG2D a natural killer cell marker and MIC –A Gluten is digested by luminal and brush border receptor enzymes in to amino acids and peptides Expression of MIC-A in enterocytes in relation to stress Gliadin is a peptide which is resistant to enzymatic degradation. These enterocytes are attacked by above lymphocytes epithelial damage enhance passage of further gliadin in to the LP Induce epithelial cells to express IL-15 2  4/6/2022 Stimulate CD4 T cells to produce cytokines Microscopy Changes evident in second portion of the duodenum and proximal chronic inflammatory reaction ,tissue damage jejunum Villous atrophy, crypt hyperplasia ,crypt elongation Villous atrophy Intraepithelial lymphocytes Increased lymphocytes, plasma cells, eosinophils, mast cells Reduced surface area malabsorption Clinical features often asymptomatic chronic diarrhea bloating chronic fatigue weight loss anaemia dermatitis herpitiformis small children – failure to thrive Environmental enteropathy/tropical sprue Complications T cell lymphoma Coeliac like disease in tropics underlying cause is unknown Likely involved etiologies are defective intestinal barrier Chronic exposure to fecal pathogens repeated bouts of diarrhea within 2-3years of age 3  4/6/2022 Autoimmune enteropathy No accepted clinical, laboratory or histopathologic criteria to diagnose Histologic features are more similar to severe coeliac disease than infectious X-linked disorder enteritis. Characterized by Severe persistent diarrhea and autoimmune disease that occurs most often in young adults A severe familial form associated with; germ line mutation in foxp3 immune dysregulation – defective CD4+ T cells polyendocrinopathy autoantibodies against enterocytes, goblet cells, parietal cells Lactase/disaccharidase deficiency Intestinal biopsy: intra epithelial lymphocytes Two types lamina propria inflammation with inflammatory cells Congenital lactase deficiency Acquired lactase deficiency Neutrophils often present Congenital lactase deficiency Acquired lactase deficiency Autosomal recessive Seen in both children and adults adults Mutation in gene encoding lactase Down regulation of lactase gene expression Seen in children Symptoms occurs upon introducing milk Seen after enteric viral or bacterial infection 4  4/6/2022 Pathogenesis Lactase present in brush border membrane of villous absorptive epithelial cells lactase deficiency incomplete breakdown of lactose Bacterial fermentation of sugars production of lactate, H+ ion Abetalipoprotenemia Osmotic Diarrhea, frothy stools, abdominal distension Rare autosomal recessive disease Unable to secrete triglyceride rich lipoproteins Occurs due to mutation in the microsomal triglyceride transfer protein (MTP). It catalyzes transfer of lipids to apolipoprotein B. Defect in MTP causes intracellular accumulation of lipids Deficiency of fat soluble vitamins Vacuolization of epithelial cells lipid membrane defects presence as acanthotic red cells Failure to absorb lipids Diarrhea, steatorrhea ,failure to thrive 5  4/6/2022 Whipple disease Rare systemic infection Cytoplasmic vacuoles in enterocytes Due to Tropheryma whippelli Proliferate within macrophages No significant immune reaction Systemic disease Intestine- malabsorption Morphology Joint – arthropathy Edematous mucosa Foamy macrophages within the lamina propria containing PAS CNS involvement positive diastase resistant granules CVS – cardiac abnormalities Hyperpigmentation APPENDICITIS Pathogenesis Progressive increase of luminal pressure Acute inflammation of the appendix. due to fecolith - common Normal true diverticulum of the cecum Gall stone/ true calculus Common to get inflamed Tumour Common among young adults and adolescents Mass of warms Difficult to made the diagnosis pre operatively Can cause death if not manage properly increase in intra luminal pressure venous obstruction 6  4/6/2022 ischemic injury and stasis of luminal content Morphology Macroscopy Enlarged edematous appendix favour bacterial proliferation Congested serosal vessles Dull granular appearing serosal surface trigger inflammatory response May be ruptured and exudate over the serosal surface May be normal in early disease tissue edema , neutrophil infiltration of the lumen Macroscopy ct….. Cut surface – luminal pus , fecolith Microsopy Surface mucosal ulceration Microscopy ct….. Neutrophil infiltration of the wall / Muscularis propria (diagnostic) Focal disruption of muscularis propria with spillage of neutrophils if Focal abscess formation (neutrophil collection) may be peri ruptured appendicular Granulomas – if associated with Crohn’s disease , TB Hemorrhages Look for atypical cell clusters at the tip – as neuroendocrine tumours are common at the tip 7  4/6/2022 Clinical features Early diagnosis and timely management is important to prevent complications Symptoms are not always classic Sometimes subtle, difficult to diagnose Initial periumbilical pain radiating to right lower quadrant/right iliac fossa Latter localized to right iliac fossa complications Guarding and rebound tenderness at McBurney’s point Atypical presentation with generalized abdominal pain /non localizing pain Periappendicular abscess formation Nausea, vomiting, Rupture Low grade fever Suppurative peritonitis If ruptured features of acute abdomen due to peritonitis – guarding, rigidity and Appendicular mass formation high fever Septicemia Death if not diagnosed and intervene timely 8