GIT #1Congenital Anomolies

(A) Tracheao-Esophageal Atresia(B) Lower Esophageal FistulaMost Common(C) Tracheo-Esophageal FistulaDiaphragmatic Hernia

failure of abdom wall to form

Omphalocele Memb. Sac w/ IntestinesGastroschisis exposed intestines w/o Sac covering the IntestinesMorgagni hernia

defect is through the front of the diaphragm towards the heart

Meckel Diverticulum

(Rule of 2’s: 2ft from Iliocecal Valve, appears at 2yrs old, 2M>F,) “Current Jelly colored stool”

Pyloric Stenosis “Projectile, Non-Bilious Vomiting” “Gastric Peristaltic Wave”, “Olive Shaped Mass” low Cl & low K

Small BowelAtresia & Stenosis

Billious vomiting, 1st wk, no passage of meconium “double-bubble” sig on Abd- X ray Assoc w/ Down Syndrome

Hirschsprung Disease“Congenital Aganglionic Megacolon”

Migration of neural crest cells arrested prematurely or undergo death à lack of Meissner and Auerbach plexus in distal intestinal segm (aganglionosis) à functional obstruction à dilation proximal to affected segm

Assoc w/ Down Syndrome Complications: enterocolitis, fluids and electrolytes disturbances, perforation and

peritonitis. Chagas associated with loss of Ganglia

Esophageal ObstructionNutcracker Esophagus

Lack of coordination

Stenosis Congenital or Acquired from: Inflammation Scarring, Irradiation, GER, caustic Inj.Achalasia Failure of Lower Esphageal Sphinctor to relax, ↑ LES tone

Primary (Idiopathic) Failure of distal esophag inhib neuron. Secondary (Chaga’s disease) à damages the Ganglions May have absent myenteric plexi (mega esoph/ureter/colon ) DX: “Beaked Tapering” “Bird Beak” w/ Barium Swallow TX: Botox

Esophageal Mucosal Web

Semi circumferential protusions of mucosa Webs (Upper): When accompanied by Iron-deficiency anemia, glossitis, and cheilosis

(Paterson Brown-Kelly syndrome or Plummer-Vinson syndrome) Esophageal rings or Schatzki rings (Lower): circumferencial and thicker. (A and B rings)

DysphagiaDifferential Diagnosis

Diseases of skeletal muscle such as Myasthenia gravis, Dermatomyositis and Polymyositis Scleroderma causes dysphagia because of extensive fibrosis mostly in the lower portion of the

esophagus Clinical manifestations : dysphagia, heartburn /GERD. Mask-like, leathery facies. CREST

(calcinosis, Raynaud, esoph dysmotility, sclerodactyly, telangiectasia) Diagnosis : Screening test: ANA

anticentromere Ab (CREST), anti-topoisomerase (anti-SCL70) (scleroderma)Hiatal Hernia Cardia of the stomach slides up into the esophagus, “Hour Glass” appearanceDiverticula Zenker’s Diverticulum

False Diverticulum Outpouching of the Mucosa, the lumen is not usually affected

Eosinophilic Esophagitis

Dysphagia (adults), feeding intolerance or GERD-like symp (children) Associated with atopic dermatitis, allergic rhinitis, asthma, modest peripheral eosinophilia Dx: GERD, other esophagitis Micro: ↑ intraepith eos TX: dietary restriction (cow’s milk). Steroids

Esophageal Varices

Dilated submucosal esophageal veins d/t portal hypertension can result in upper GI hemorrhage (hematemesis) (peptic ulcer, Mallory-Weiss synd)

Assoc w/ Liver Cirrhosis & Portal HTN – Alcohol & hepatic schistosomiasis MC cause of death in cirrhosis: ruptured EV Often asymptomatic, but can have Hematemesis May rupture: (inflamm erosion, ↑ venous pressure, vomiting). 50% die in 1st episode. TX: balloon tamponade, rubber band ligation, sclerother

Barrett’s Esophagus

Glandular cell Metaplasia due to GERD à causes Adenocarcinoma Occurs in the Lower 1/3 of esophagus DX: Goblet cell metaplasia & Inc Mucus production

EsophagitisMallory-Weiss syndrome

Longitudinal tears usually shallow in the esophago-gastric junction Predisposing factors: alcoholics due to episodes of excessive vomiting & Bulimia Hematemesis can occur but not as severe as varices Esophageal rupture is known as Boerhaave’s syndrome Vasoconstrictive measures, transfusions and balloon tamponade may be required Gross- shows multiple esophageal tears which has extended from the stomach Most often associated with severe retching and vomiting d/t acute alcohol intoxication Dx: endoscopy

Chemical & Infectious Esophagitis

Alcohol Corrosive (acids / alkalis) Hot fluids Heavy smoking Pill-induced esophagitis

Iatrogenic (chemo, radioth) GVHD HSV, CMV, candida, aspergillosis Bullous pemphigoid, epidermolysis bullosa, Crohn disease

Viral Esophagitis

CMV - infected endothelial cells with nuclear and cytoplasmic inclusions HSV - nuclear inclusions in Multinucleate squamous cells (Multinucleated Giant Cells,

Margination, Molding, “Ground-Glass” appearance)GERD MCC of Esophagitis

Reflux of gastric juices, and bile from duodenum ↓ LES tone, or ↑ abdominal pressure. Also (caffeine, etoh, tobacco, obesity, pregnancy, CNS

depressantshiatal hernia, delayed gastric emptying) DX: 24-hour esophageal pH monitoring TX: ↑ head of bed, avoid (coffee, etoh, tobacco, chocolate, spicy and fatty foods, anticholinergic

med). Antacid, H blockers, PPI, and Surgery (Nissen fundoplication)

Neoplasms of EsophagusSquamous cell CAw/ Keratin Pearls

4M : F Risk factors: etoh, tobacco, poverty, caustic injury, achalasia, tylosis, Plummer-Vinson synd,

freq consump of hot beverages, and previous radiation Other Risk Factors: - Western hemisphere – Smoking & Alcohol - Asia – Dietary role - Fungal contamination - Lack of Vitamin & Trace elements - Nitrites & Nitosamines Pathogenesis: incompletely defined but loss of p53 and p16 are involved Location – 50% Middle third 30% lower third 20% upper third Presents as: - Polypoid exophytic growth - Diffuse infiltrative encircling growth - Excavated (Ulcerative growth) Clinical features:

Progressive dysphagia Weight loss and anorexia Blood loss Hoarseness and cough Aspiration of food due to TE fistula 9% five-year survival rate (overall) Dysphagia first to solids and then with liquids

AdenocarcinomaInc in Mucin

Risk Factor: dysplasia, tobacco, obesity, radiation therapy Often involves the Gastric Cardia. High incidence in U.S. UK, Canada, Australia, Brazil Low incidence Korea, Thailand, Japan, Ecuador Pathogenesis: chromosomal abnormalities and genetic mutations have been involved (p53,

c-ERB-B2, cyclin D1, cyclin E, and p16) Morphology: distal third. Flat, raised, infiltrative, ulcerated Micro: well to poorly differentiated. Infiltra signet-ring cell Clinical features: discovered in evaluation of GERD or BE. Dysphagia, chest pain, weight

loss, hematemesis, vomiting

Stomach Mucosal Protection:

Mucus secretion, Bicarbonate secretion, Epithelial barrier, and Rich mucosal blood flow

Mechanisms of gastric injury and protection. This diagram illustrates the progression from more mild forms of injury to ulceration that may occur with acute or chronic gastritis. Ulcers include layers of necrosis (N), inflammation (I), and granulation tissue (G), but a fibrotic scar (S), which takes time to develop, is only present in chronic lesions.

Acute Gastritis Definition: acute mucosal inflammatory process, usually transient and self-limited, in which there is focal necrosis of the mucosa, in an otherwise normal stomach

Cause: Loss of gastric defenses allowing back diffusion of H+ ions Associated conditions:

Use of non-steroidal drugs and corticosteroids Alcohol abuse Cigarette smoking Shock Uremia

Morphology: Mild (only edema of lamina propria) à active inflammation à erosion à acute erosive hemorrhagic gastritis

Clinical: may be asymptomatic painless bleeding, occasionally massive & fatal,- Variable epigastric pain, nausea & vomiting- One of the major causes of hematemesis (AEG)

Acute Gastric Ulcer

Focal, acutely developing mucosal defects Well known complication of NSAIDs Stress ulcers (shock, sepsis, severe trauma). Curling ulcers (proximal duodenum): assoc with burns or trauma Cushing ulcers (gastric, duoden, esopha): intracranial disease Morphology: rounded, , 1-cm, brown/black, anywhere, more often multiple, not indurated

margins or base Prophylaxis: with H2 histamine blockers, PPI. Correct the underlying condition

Pyloric Stenosis Projectile Vomiting, Delayed onset (6wks)

GIT #2Chronic Gastritis

Chronic Inflammation of the stomach mucosaCauses: H. Pylori (MCC), NSAIDs, Autoimmunity, Allergic response

also Smoking, Alcohol, Psychological stressDx: usually asymptomatic but may manifest as epigastric pain or, rarely, with nausea, vomiting, anorexia, or

significant weight loss. Symptoms may occur with the development of complications (peptic ulcers, gastric adenocarcinoma, and MALT lymphoma)- serologic tests for Ab to HP, fecal bact detection, urea breath test.- Gastric Bx for micro, stain, rapid urease test, culture, PCR

H.Pylori Gastritis

Effects the Antrum of the StomachFeatures linked to H. Pylori virulence:

- Non-sporing, curvilinear gram-negative rod- Flagella,- Urease + à ammonia from urea- Adhesins (blood group “O”),- Cytotoxin-associated gene A (CagA) (assoc ↑ risk Ca)- Vacuolating toxin A (VacA) are more likely to develop peptic ulcers

Tx: Antibiotics & PPIComplications: if untreated… Peptic Ulcer, Gastric Cancer, and MALT Lymphoma

Autoimmune Gastritis

Typically spares the antrum and includes hypergastrinemiaCharacterized by:

- Ab to parietal cells and Intrinsec factor- ↓ serum pepsinogen concentration- G-cell hyperplasia- Vit B12 deficiency- Achlorhydria

Parietal cell destruction à dec Intrinsic Factor à dec Vit-B12 à Pernicious AnemiaParietal cell destruction à dec Gastric Acid à inc Gastrin à G-cell HyperplasiaPathogenesis:

“It was initially thought that the autoantibodies to parietal cell components, most prominently the H+,K+-ATPase, were involved in the pathogenesis of autoimmune gastritis. However, this is unlikely because passive transfer of these antibodies does not produce gastritis in experimental animals”.

“It is more likely that CD4+ T cells directed against parietal cell components, including the H+,K+-ATPase, are the principal agents of injury”.

“This is supported by the observation that transfer of H + ,K + -ATPase-reactive CD4+ T cells into naive mice results in gastritis and production of H + ,K + -ATPase autoantibodies”.

Clinical features: median age of diagnosis at 60. Symptoms of anemia. Vit B12 def à atrophic glossitis, malabsorptive diarrhea, peripheral neuropathy

Reactive Gastropathy

Foveolar hyperplasia, glandular regenerative changes, and mucosal ededma.Causes: NSAIDs, chemical injury, bile reflux, and mucosal trauma d/t prolapse. After gastric

surgery.Gastric antral vascular ectasia (GAVE) associated with antral trauma. Reactive GP with

dilated capillaries containing fibrin thrombiReactive gastropathy. Gastric mucosa, showing hyperplasia of foveolar surface epithelial cells,

glandular regenerative changes, and smooth muscle fibers extending into lamina propria.Gastric antral vascular ectasia (GAVE): uncommon cause of chronic GI Bleeding or iron

deficiency anemia. The condition is associated with dilated small blood vessels in the antrum. Called watermelon stomach because streaky long red areas that are present in the stomach may resemble the markings on watermelon

Eosinophilic Gastritis

Dense infiltrate of eos in mucosa and muscularisAntral and pyloric regions involvedAlso in other areas of GI. Peripheral eosinophilia. ↑ IgECauses: allergic reactions (cow’s milk, soy protein), drugs, systemic collagen vasc diseases,

parasitic infections, H pyloriLymphocytic Gastritis (Varioliform)

Idiopathic. 40% assoc with celiac diseaseEntire stomach is involvedMarked increase in intraepithelial lymphocytes mostly CD8+

Granulomatous Gastritis

Crohn disease, and sarcoidosis. Mycobacteria, fungi, CMV, H pylori

Peptic Ulcer A chronic ulcer with a breach in mucosa extending to submucosa or deeperMC associated to HP chronic gastritisHP present in 85% to 100% with DU, and 65% with GUCommon sites: In order of decreasing frequency

Duodenum: 1st portion (4x more common in Prox Duodenum > Stomach) Stomach – usually Antrum (due to H.Pylori) Gastro-esophageal junction (with GERD) Within the margins of gastro-jejunostomy Multiple site in patients with Zollinger-Ellison syndrome

Within the ectopic gastric mucosa of Meckel diverticulumPathogenesis: Imbalances of mucosal defenses & damaging forces are responsible for PUD

H. pylori and NSAIDs primary underlying causes Cigarrette, alcohol, psychologic stress, COPD

Gastric Peptic Ulcer

Location: Lesser curvature, antrumUp to 50% of those with gastric peptic ulcer have concurrent duodenal ulcerCauses: H.Pylori, NSAIDs, and GERDGross Appearance:

Less than 4 cms in diameter Round to oval in shape Punched-out area with clean base Margins are usually level with surrounding mucosa or slightly elevated due to edema

(heaped up margins should arouse the suspicion of Ca) Rugosal folds radiate from ulcer in a spoke like fashion

Hypertrophic Gastropathies

Giant cerebriform enlargement of the rugal folds d/t epithelial hyperplasia without significant inflammation

Menetrier disease (Giant fold disease): diffuse hyperplasia of foveolar epithelium (body/fundus) with overexpression of TGF-alpha with protein loss, malabsorption & risk for adeno ca in adults.

- In children is self limited and second to CMV, HSV, giardia, H pylory.Clinical manifestations: upper abd pain, n/v, diarrhea, and weight lossDx: endoscopy, Bx

Zollinger-Ellison syndrome – Gastric gland hyperplasia secondary to excessive gastrin secretion by gastrinoma (small intestine and pancreas).

↑ parietal, mucous, and endocrine cells. Risk for peptic ulcers (often multiple and resistant to treat).

60% to 90% are malignant.75% sporadic. 25% MEN I (parathyrroid H/A, pancreatic endocrine tumor G/I, pituitary adenoma)

Clinical manifestations: related to peptic ulcers or chronic diarrheaDx: high gastrin level. Endoscopic U/S, Bx, somatostatin receptor scintigraphy.

Gastric TumorsFundic Gland Polyps

Sporadic and in Familial adenomatous polyposis (FAP)5F : MWell circumscribed. Single or multipleMicros: cystically dilate, irregular glands lined by parietal and chief cellsNo association with adenoCa

Gastric 10% of all gastric polyps

Adenoma 50 to 60 y/o. 3M : FHigh incidence in FAPIn a background of atrophy, and IMRisk for adenoCa related to size (>2-cm)Usually solitary. In antrum. < 2-cmIntestinal type columnar epithelium, and dysplasia

Gastric AdenoCA

The MC malignancy of stomach (90%)High incidence in Japan, Chile, China, Portugal, Russia (up to 20 fold higher than USA)M:F = 2:1Age: >50 yrs“It still exceeds lung cancer as the leading cause of cancer death worldwide”Overall incidence is ↓, but gastric cardia is↑20% 5 year survivalRisk Factors: H.Pylori, Nitrates, Smoked food, Pickled veggies, Excessive Salt intake, Menetrier

disease, Adenomatous polyps, Chronic atrophic gastritis, Pernicious anemiaLocation - Pylorus & AntrumSignet-ring cells can be recognized by their large cytoplasmic mucin vacuoles and peripherally

displaced, crescent-shaped nuclei.Krukenberg Tumour à Metastasis to Ovaries bilaterallySister Mary Joseph Nodules à metastasis to skin around umbilicus producing nodules

Mesenchymal Neoplasms“GIST”

GIST (Gastro-Intestinal Stromal Tumor)Presentation: Incidental. BleedingPathology:

Sheets of spindle cells Previously mistaken for leiomyoma Origin cell – interstitial cell of Cajal C-kit + and CD34+

Small IntestineIntestinal Obstruction

Adhesion of Small Intestine is MCCMCC’s:

Adhesions (Adults Intussusception or invagination (3mo-6yrs) Incarcerated inguinal hernia & Meckel div (child)

Clinical: Abd pain, Vomiting, constipation, and failure to pass flatus

Adhesions: after surgical procedures, peritoneal infections, endometriosis

Volvulus: complete twisting of an intestinal loop. Affects sigmoid, cecum, SB, stomach

Intussusception: segment of intestine, constricted by a wave of peristalsis, telescopes into the immediate distal segment. Location Illieocecal Junction Causes: anatomic defect or Rotavirus , Lymphoid Hyperplasia (child), or Tumors (adults)

Ischemic Bowel Disease

Nonocclusive (Low flow states)- more common than occlusive Vasoconstriction, due to decreased cardiac output Hypovolemia Dehydration Hypotension

Transmural InfarctionAngiodysplasia Vascular Ectasia

Dilations of peri-crypt vascular plexuses, with dilation of submucosal veinsMost commonly, >55 y/o, cecum / R sided colon20% of major episodes of lower intestinal bleeding

Pathogenesis: mechanical / congenital?Diagnosis: difficult, usually requires selective angiography or colonoscopyRx: resection is curative

Malabsorption SyndromesCeliac Sprue Gluten-sensitive Enteropathy, “Non-Tropical Sprue”

Pathogenesis: Antibodies against Gliadin Gliadin is presented by APCs via MHC II cells), T-helper cells mediate the tissue damage

Exposure to gliadin, a component of gluten causes mucosal injury à in loss of villi and absorptive surface area

Duodenum* is the most affected areaCan be Immune Mediated or Genetic (HLA-DQ2 or DQ8)Also Assoc w/: DM 1, Hashimoto’s Thyroiditis, Sjogren syndTypes:Silent CD: pos serology and villous atrophy w/o symptomsLatent CD: pos serology w/o villous atrophy

Chronic diarrhea, anemia, bloating, weight loss Children: typical start 6 to 24 months Dermatitis Herpetiformis (itchy, blistering) – due to IgA deposition on Dermal Papillae Lymphocytic gastritis or colitis Enteropathy-associated T-cell lymphoma, SB adenoCa

Dx / Clinical manifestations: IgA anti-tissue transglutamionase or IgA/IgG anti-Gliadin in blood IgA against-Endomysial (more specific, less sensitive) HLA-DQ2 or HLA-DQ8 (high neg predictive value) Flattening of Villi & Hyperplasia of Crypts Bx Duodenal/jejunal)

Prognosis: most do well with gluten free diet. If not, consider non compliance, refractory celiac or cancer Dermatitis herpetiformis (itchy, blistering) in 10% Lymphocytic gastritis or colitis Enteropathy-associated T-cell lymphoma, SB adenoCa

Tropical Sprue Same symps as ^ but due to ParasiteJejunium & Ileum* are most affected areas

Disaccharidase (Lactase) def.

Congenital (hereditary) lack of enzymes in infants in the Brush Border cellsAquired Lactase deficiency occurs commonly in Native Americans and African AmericansSymps: Osmotic diarrheaBacterial fermentation of unabsorbed sugar leads to increased hydrogen production---

measured by gas chromatography of exhaled air (hydrogen breath test)Abetalipoprote-inemia

Inborn error of metabolism – AR, inability to synthesize Apolipoprotein-BTGL gets stored in the cells causing lipid vacuolation. There is complete absence of

chylomicrons, VLDL, LDL in the plasma.Clinical: infancy present w/ failure to thrive, diarrhea and steatorrheaDx: Peripheral blood smear- Burr cells ***(Acantholytic erythrocytes)

GIT #3Infectious Enterocolitis

Cholera Vibrio cholera , G(-) comma-shaped (India, Gulf of Mexico). V parahemoliticus (the MCC of sea-food assoc gastroenteritis in US)

Cause: Eating raw sea-food***Clinical features: Most are asymptomatic or mild diarrhea.In severe cases: watery diarrhea (rice water, fishy odor) /vomiting after IP of 1-5 days.

Dehydration, hypotension, shock

Dx: stool cultures. Rapid test kitsTx: Oral or IV fluids. Doxixyclin

Campylobater Enterocolitis

The MC bacterial enteric pathogen in developed countries, and important cause of traveler diarrhea

Symp: Bloody Diarrhea***Dysentery with crypt abscesses and ulcer resembling Ulcerative colitisIncubation period: up to 8 daysAssoc w/ Reactive Arthritis (HLA-B27)***, erythema nodosum, Guillain-Barre synd15% to 50% of pts with G-B synd have stool culture (+) for Campylobacter J.Only 0.1% of Camp J + in stool à G-B synDx: watery diarrhea, flu-like prodrome, dysent(15%). Stool for culture

Campylobacter jejuni

infection produces acute, self-limited colitis. Neutrophils can be seen within surface and crypt epithelium and a crypt abscess is present at the lower right.

Shigellosis Humans the only known reservoirThe MCC of bloody diarrhea.Daycares, travelers to developing countries, nursing homesMicro similar to Campylobacter. If aphtous ulcers present, may mimic Crohn disIP of 4d. Self-limited about 6d with diarrhea, fever, abd painDx: stool cultureComplications: Reiter synd (arthritis, urethr, conjuntivitis), Hemolytic uremic synd (S.

dysenteriae with shiga toxin) “Cant See, Cant Pee, Cant climb a Tree” describes the Symps

Treat: antibiotics. NO antidiarrhealSalmonellosis Infections caused by salmonella spp. Typhi, (Typhoid fever) Paratyphi (TP), and non-

typhoid (S. enteritidis: food poisoning)Clinical features: mild to profuse watery diarrhea to dysentery. Fever resolves within 2d,

but diarrhea can persists for 1wk (stool cult +)Antibiotic therapy NOTa recommended in most cases (can prolong carrier state or

relapse). Most are self limited but complications can occur mainly in pts with malign, alcoholic, sickle cell, and hemolyitic anemia

Typhoid Fever Caused by S. typhi (endemic) and paratyphi (travelers to India, Mexico, El Salvador, Pakistan, Haiti, Philippines)

- Wk 1: invades Peyer’s patches and à bacterem (blood cult best for Dx. > 90% + during febrile phase)

- Wk 2: diarrhea (pos stool cult); classic triad of bradycardia, neutropenia, splenomegaly. Chronic carrier state d/t gallbladder colonization

Clinical features: anorexia, abd pain, N/V, bloody diarrhea à short asymptomatic phase , bacteremia, fever with flu-like symp

-Rose spots: small erythematous maculopapular lesion in chest and abd. May mimic appendicitis

Treat: antibioticsComplications: encephalopathy, meningitis, seizures, endocarditis, myocarditis,

pneumonia,Pts with sickle cell are particula/ susceptible to Salmonella osteomyelitis

Yersinia Enterocolitica & Pseudotuberculosis

Enterocolitica more common than pseudotuberculosis.Source: Seafood, FishPreferencially ileum, appendix, R colonLymph node and Peyer’s patch hyperplasiaWhen aphtous ulcers are present can be confused with Crohn disWhen regional lymph node involvement, can mimic appendicitisExtraintestinal manifest: arthralgias, pharyngitis, and erythema nodosumComplications: arthritis, Reiter synd, myocarditis, glomerulonephritis

Escherichia Coli G neg bacilli that colonize the healthy GI tractMost are nonpathogenicSubgroups with clinical relevance:

Enterotoxigenic E. coli (ETEC): ppal cause of traveler’s diarrhea. Produces Heat-labile (LT) and Heat stable toxin (ST). Secretory noninflammatory diarrhea, dehydration, and shock in severe cases

Enterohemorrhagic E. coli (EHEC): O:157:H7 (developed countries. Fast foods. undercooked beef). Non-O157:H7 serotypes. Both produce shiga-like toxin. Morphology and clinical like shigella (dysentery and hemolytic-uremic synd)

Enteroinvasive E. coli (EIEC): no toxins. Acute self-limited colitis, most common in children in developing countries.

Enteroaggregative E. coli (EAEC): non bloody prolonged diarrhea in AIDS ptsWhipple’s disease Multisystemic infectious disease due to Gram-positive bacilli called Tropheryma whippelii,

which belongs to actinomycetes- Macrophages, packed w/ PAS (+) bacilli are seen in the small intestine, mesenteric lymph

nodes, synovial membranes, heart, and other organs.- Affects whites in their 30s. Diarrhea, weight loss, malabsorption, polyarthalgia, generalized

lymphadenopathy- M:F = 10:1Differential includes Mycobacterium avium intracellulare infectionsElectron micrograph of one lamina propria macrophage shows these bacilli within the

cell (top) and at higher magnification (inset).

Pseudomemb. Colitis

AKA antibiotic associated colitis or antibiotic associated diarrheacaused by the toxin from Clostridium difficile. Also Salmonella, C perfringes, Staph aureus

(food poisoning, the latter 2))Cause: treatment with broad-spectrum antibiotics, 3rd generation cephalosporins,

clindamycin , and ampicilinMicroscopic featuresPseudomembrane is composed of fibrin, mucin, inflammatory cells, and cellular debrisSymps: Fever, toxicity, and diarrheaLaboratory: C. difficile toxin assayTx: Metronidazole (Flagyl)

Viral GastroenteritisNorovirus (previously known as Norwalk-like V). Causes half of all gastroenteritis worldwide and is a

common cause of sporadic gastroent in developed countries. Self-limited diseaseRotavirus MCC of severe childhood diarrhea, and diarrhea mortality worlwide. > 6m < 2y/o.

Vaccine now availableAdenovirus 2nd MCC of pediatric diarrhea. Symptoms resolve in 10d

Parasitic EnterocolitisAscaris lumbricoides

infects over a billion individuals worldwide d/t oral-fecal contaminationIngested eggs hatch in the intestine and larvae penetrate intest mucosa à splanchnic circul

à syst circulac à liver abscess or peumonitis à larvae migrate trachea à swallowed and mature in intest into adult. Worm masses induce eosinophilic response à intest or biliary obstruc

Dx: detection of eggs in stoolEnterovius vermicularis (pinworm)

In industrialized and developing countries.Adult worms migrate to the anal orifice at night. Female deposits eggs. Perianal pruritus.

Finger contamination. Human to human transmissionDx: applying cellophane tape to the perianal skin and looking for eggs under a microscope.

Schistosomiasis granulomatous reaction in intest, with bleeding and obstruction. Assoc with Bladder Sq cell Ca in Middle East and Africa (S. hematobium)

Intestinal CestodosDiphyllobthrium latum

fish tapeworm. Abd symptoms and vit B12 deficiency

Taenia solium pork tapeworm. Encysted larvae. Enlarges by formation of eggs-filled segement (proglottids). Adult worms can grow several meters

Seizures with ring-enhancing brain lesions on CT or MRI (cysticercosis)

Hymenolepsis nana

one of the most common cestodes of humans in the world, only cestode that does not require intermediate host to develop into its infective stage

Protozoal causes for diarrheaGiardia lamblia Initially described by van Leeuwenhoeck, inventor of microscope, who discovered it in his

own stool- A cause of Traveler’s diarrhea. Also in campers, after hiking or drinking from a stream- Resistant to chlorine.malabsorption syndrome; diarrhea, abdominal painDx: cysts and trophozoites in feces

Amoebiasis “Flask-shaped ulcer” in cecum or ascending colonBiopsy- Erythrophagocytosis by trophs is diagnosticDx: cysts or trophozoites in stool

Cryptosporidium Acute self-limited diarrhea in immunologically normal pts.Chronic diarrhea in AIDS Pt’s***Worldwide except AntarticaDx: by finding the oocysts in the stoolorganisms are seen as small blue spheres that appear to lay on top of the brush border but

are actually enveloped by a thin layer of host cell cytoplasm. Most concentrated in terminal ileum and proximal colon

IBSIrritable Bowel Synd

Common cause of GI complainsMore common in femaleUndefined pathogenesisClinical features: classic pt is anxious/neurotic, symptoms aggravated by stress, alternating

D/C, bloating, abd pain relieved by defecation, and or mucous in the stool. Clinical criteria: abd pain or discomfort 3d/m over 3m, improvement with defecation, and change in stool frequency or form. Also fibromyalgia, depression,

Dx: of exclusionTreat: avoid triggering subst( caffeine, lactose), med, and reassurance

IBDIrritable Bowel Dis

Chronic inflammatory disorders of the gut.Crohn's disease and ulcerative colitis are the best known forms of IBDboth fall into the category of "idiopathic”Primary Symptom: Bloody diarrhea of > 6 months often relapsing and remittingLab Testing : pANCA – 75% of UC, and 11% in CD pANCA (perinuclear antineutrophil cytoplasmic antibody)

Crohn's Disease There is a bimodal incidence (teens& twenties, 50’s & 60s)increased incidence in women and persons of Caucasian race.Morphology: any part of the GI tract, but most frequently involves the terminal ileum,

ileocecal valve, and cecum. (Terminal Ileitis & Regional ileitis)4 Important Features;

The transmural inflammation of the bowel Presence of non-caseating granulomas Inflammation leading to the development of fissures & fistulas between loops of bowel

and other structures. Inflammation is typically segmental with uninvolved bowel separating areas of involved

bowel. Skip Lesions***, “Cobblestone” appearanceDiseased bowel - The serosa is granular and dull gray with mesentric fat wrapping the bowel

“Creeping fat”Intestinal wall is rubbery and thick due to edema, inflammation and fibrosis.Lumen is narrowed and X-ray shows “string sign”Early disease – focal mucosal ulcers “Apthous ulcers”Later form longitudinal ulcersLab Testing : anti-Saccharomyces cerevisiae antibody (ASCA) are often present in CDClinical Presentations:

Cramping abdominal pain Watery Diarrhea (SI involvement), Bloody (Large intestine involvement) Fever Weight loss Perinicious Anemia (B12 deficiency b/c illium involvement) Generalized malabsorbtion Enterocutaneous Fistula - Perirectal disease (fistula, fissure, abscess) Extraintestinal manifestations of arthritis, uveitis, erythema nodosum, and ankylosing

spondylitis. PSC and pericholangitis Increased risk for intestinal cancer (5-6 fold increase)

Ulcerative colitis (UC)

UC is more common in persons of Caucasian race, in women, and in young persons (peak incidence at ages 20 - 25 years).

Morphology: involves the colon as a diffuse mucosal disease with distal predominance. Rectum is virtually always involved. Pancolitis. Backwash ileitis Mucosa surface: Broad-base ulcers, pseudopolyps, and mucosal bridges

Microscopic Feature: Crypt Abscesses*** Muscularis propria and serosa are unaffected*** Overall thickness of the bowel wall is within normal limits

Increased risk of: Colon Cancer, Sclerosing cholangitis, & bile duct carcinomaMicroscopic Colitis

Chronic , nonbloody, watery diarrhea without weight lossB-Collagenous colitis: in middle age women. Dense subepith collagen layer, intraepith

lymph, mixed infl infilt LPC-Lymphocytic colitis: strong assoc with celiac dis and autoimmune dis (lymphocytic

gastritis)Diverticulosis Colonic diverticuli are protrusions of mucosa and submucosa through a defect in the

musculature of the colon.PathogenesisHigh incidence in W countries: environmental, not geneticLow fiber diet results in small stools which require high intraluminal pressures for

propulsion. Highest pressure occurs in the sigmoid colon. This disordered motility results in herniations of mucosa through muscularis propria

90% Left colon (Sigmoid, )Crampy pain, usually LLQ , have a sense of incomplete defecationDx: CT scan with Barium contrast (best test to confirm)

Melanosis Coli “melanotic” pigment is felt to be a breakdown product of laxatives and is a strong indicator of laxative abuse.

Dx: use Prusian Blue to stain the Iron

PolypsHyperplastic Polyps

These are the most common colonic polyps occuring predominantly in rectum. Age: After 60’s & 70’s They are small (1 to 5mm.) ,typically dome shaped (Dew drop size) Their histology is that of well formed glands with prominent infoldings giving a serrate or

saw tooth appearanceHamartomatous - Juvenile Polyp

(juvenile, retention) polyps: They are hamartomatous (Haphazard Growth)These occur more often in children below 5 yrsSMAD4 and BMPR1A gene mutations< 3-cm in ф. Peduncul. Cystic on sectionMicro: cystic gland with mucin and inflamm debris↑ risk thyroid, breast, lung, panc adenoca

Peutz-Jeghers Polyps/syndrome

Autosomal DominantSTK11/LKB1 gene mutationMultiple hamartamatous polyps through out GIT (Small bowel, most) and melanotic mucosal

& cutaneous pigmentation – Mouth, genitalia, palmLarge and pedunculatedMicro: Disorganized growth pattern with branching network of connective tissue and

smooth muscle lined by normal intestinal epithelium↑ risk for extra-intestinal carcinoma (colon, panc, thyroid, breast, lung, gonadal, bladderAssoc Clinical Symps: Mucocutaneous Hyperpigmentations (Lip Pigmentation

Inflammatory Polyps

Result from chronic cycles of injury and healingThe classical example: IP that form as part of the solitary rectal ulcer syndPts often present with rectal bleeding, mucus discharge, and inflammatory lesion of the

anterior rectal wallMicro: Granulation tissue-like capillary proliferation within the lamina propria caused by

repeated erosion and re-epithelialization.

GIT #4Colon Cancer

Neoplastic Polyps (Adenomatous polyps)

malignant risk is correlated with size, histologic architecture, and severity of dysplasiaTubular adenomas – pedunculated or sessile (Low Ca risk. Ca is rare in TA < 1-cm))Tubulo-villous adenomas (Intermediate Ca risk)Villous adenomas – often sessile (High Ca risk. ≈ 40% in SVA > 4-cm)

Familial Adenomatous Polyposis (FAP) / Familial Polyposis Coli (FPC)

chromosome 5q21, APC (Adenomatous Polyposis Coli) tumor suppressor genePrecancerous: virtually 100% will develop cancer within 10 to 15 yearsVariants:oGardner’s Syndrome

AD. High risk for colon cancer In addition to intest polyps, osteomas of mandible/skull/long bones, desmoid

tumors, epidermal cysts, thyroid Ca.oTurcot’ Syndrome – AR. Familial adenomatous Polyposis with CNS neoplasms, 2/3

medulloblastoma, 1/3 glioblastomaoAttenuated FAP : delayed polyp development, less than 100 adenomas,and delayed

appearance of colon cancer

Hereditary Non-Polyposis Colorectal Cancer (HNPCC) “Lynch Syndrome”

AD.Missmatch repair defect. MSH2 / MLH1 gene mutationsColorectal cancer with fewer polyps than FAPIn younger pts than sporadicsOften located in R colon

AdenoCA of Colon Colorectal Adenocarcinoma

Most Common Malignancy of GITPeak age of incidence: 60 – 79 years (in younger person, its due to FAP or UC)Pathogenesis:

APC/β-catenin pathway (classic adenoma-carcinoma sequence), and the microsatellite instability pathway

↑ CpG methylation w/o instability also exists. May have KRAS mutationsRisks:

Low intake of unabsorbable vegetable fiber High content of refined carbohydrates Decrease intake of protective micronutrients (particularly vitamin A, C & E) Aspirin or other NSAIDs have protective effects

Clinical Features: Right Colonic cancers – brought to attention (early) because these bulky tumors

bleed; they also produce fatigue, weakness & iron def. Anemia Left Colonic cancers - usually detected (Late) even though they produce prominent

changes in bowel habits (diarrhea, constipation, melena). They also cause crampy abdominal pain & occult bleeding. Obstruction

Important tumour marker – CEA Liver the MC site of met. Also reg LN, lungs, bones

Astler-Coller Staging

Duke Staging: Duke's A - spread into submucosa but not through muscle Duke's B - spread through muscle but nodes negative Duke's C - lymph node metastases present

Advantages of the Dukes classification are that it Is simple and reproducible Accurately reflects prognosis Accepted nationally and internationally

Five year survival - 90%, 70% and 30% for Stages A, B and C respectively The two most important prognostic factors are depth of invasion and the presence or absence of lymph node metastases

Carcinoid TumorAppendicial Carcinoid Metastasizes to LiverCarcinoid Syndrome Inc Serotonin:

Urinary excretion of 5-HIAA*** – The most useful initial diagnostic test for the carcinoid syndrome is to measure 24-hour urinary excretion of 5-hydroxyindoleacetic acid (HIAA), which is the end product of serotonin metabolism

Skin – Flushing, Telengectasia, and cyanosis GIT – Diarrhea, cramps, vomiting Asthmatic attacks – With wheezing & dyspnea Hepatomegaly Systemic fibrosis Heart-Valvular thickening, Endocardial fibrosis (Rt Ventricle) Rertoperitoneal fibrosis Collagenous pleural & intimal plaques

G.I. LymphomasSporadic lymphoma(western type)– “Maltomas”

Arise from B-cells of gut MALT, assoc w/ t(11;18)

Sprue associated Usually lymphoma of T-cell type

lymphoma Prognosis is poor Age – 30-40 yrs Tend to arise from jejunum and forms ulcerative plaques and mass

Mediterranean lymphoma

Gastric Lymphoma: The MC site of extranodal lymphomas The MC extra-nodal marginal zone B-cell lymphoma ( MALTomas). Low grade B-cell

lymphoma B-cell Markers: CD19(+), CD20(+), CD5(-), CD10(-) The MC “pro-lymphomatous” inflammation in stomach: chronic H. pylori infection

Acute Appendicitis Differential Dx:

Mesenteric lymphadenitis PID Ectopic pregnancy Meckel’s diverticulitis

Mucocoele of Appendix may occur simply by blockage of the lumen of the appendix with inspissated mucus.

Other causes - mucin secreting cystadenoma or carcinomaPseudomyxoma Peritonei