(Mnemonic::: B1T2)

class I (bc has heavy and light chains)

(Mnemonic::: B1T2)

CLASS II because has 2 similar size chains (alpha and beta)

1) NECESSARY for B cell activation

2) Growth factor for Th2 T Cells

3) Isotype switching - IgG and IgE

4) Prevents diff. of naive CD4 T cells into Th1 T cells

5) With IL-10 and IL- 13 down regulates NK cell activity

6) With IL-10 and IL-13 down regulations CD8 T cell activity

1)Necessary for B cell activation

2)Absolutely necessary to activate eosinophils that defend against parasites

3)Isotype switching to IgE

1)Necessary for B cell activation

2) Increases antibody production in activated B cells

1) With TGFbeta, causes isotype switching to IgA in humans

2)Suppresses macrophage respiratory burst and cytokine secretion 3) Suppresses development of new Th1 T cells.

1)Growth factor for B cells

2) With IL-4 down regulations NK cell activity

3) With IL-4 down regulates CD8 T cell activity.

1) Inhibits growth of B cells

2) With IL-10 isotypes switches to IgA

3)Inhibits macrophage activation

4)Activates neutrophils.

1) T cell growth factor

2) Can induce apoptosis in armed effector T cells

1) Activates vascular endothelium

2) Shuts down venous return to increase fluid drainage to lymph nodes

3) Acts systemically to produce fever

4) Mobilizes metabolites

5) Can cause shock

• cytotoxic chemotherapy
• radiation therapy
• graft-versus-host disease (GVHD)

• HSV
• CMV
• fungal infections (Candida)

• Reflux of gastric contents into the lower esophagus
• Causes: Esophagitis
• Found in:
  • adults over 40 
  • infants and children

• sliding hiatal hernia
• alcohol
• cigarette smoking
• obesity
• CNS depressants
• pregnancy
• delayed gastic emptying
• increased gastric volume

• leukoplakia
• ulcers
•  fibrosis
• esophageal stricture which lead to dysphagia.

• Due to: 
  • Change of squamous cell to intestinal goblet cells in lower third of esophagus
• Predisposes to:
  • adenocarcinoma
• Common in:
  •  white males between 40 and 60

• transient mucosal inflammatory process
• can be be asymptomatic 
• can cause variable degrees of 
  • epigastric pain
  • nausea
  • vomiting

• aspirin
• NSAIDs
• alcohol
• cigarettes
• Helicobactter (H. pylori) infection

• presence of neutrophils in acute gastritis above the basement membrane in direct contact with epithelial cells is abnormal in all parts of the GI tract and signifies active inflammation. 
• With more severe mucosal damage, erosions and hemorrhage develop.

• loss of the superficial epithelium, generating a defect in the mucosa that is limited to the lamina propria, a thin layer of vascular connective tissue beneath the epithelium
• Hemorrhage may occur and cause dark punctae or spots like coffee grains.

Bleeding  

• Most frequent complication ; May be life-threatening; May be the first indication of an ulcer 

Perforation 

• Accounts for two thirds of ulcer deaths ; Is rarely first indication of an ulcer 

Obstruction 

• Mostly in chronic ulcers ; Secondary to edema or scarring; associated with pyloric channel ulcers ;May occur with duodenal ulcers 
• Causes incapacitating, crampy abdominal pain; rarely cause total obstruction and intractable vomiting

• Cause: H.pylori inf or Autoimmune gastritis
  • Clinical of H. pylori
    • less severe but more persistent than acute
    • Nausea 
    • upper abdominal discomfort
    • sometimes with vomiting
    • hematemesis is uncommon
  • Atrophic gastritis
  •  
    • Due to autoimmune gastritis, with a loss of parietal cell mass.
    • Clinical:
      • Leads to pernicious anemia

• H. pylori organisms are present
  • duodenal ulcers *most
  • gastric ulcers 
  • chronic gastritis (antrum- 90% of cases)
• Complications of H. Pyloris Gastritis:
  • Peptic Ulcer disease (also seen in chronic)
  • increases the risk of gastric cancer
• In US
  • associated with poverty, household crowding, limited education, African-American or Mexican-American ethnicity, residence in rural areas, and birth outside of the United States

• characterized by 
  • (1) antibodies to parietal cells + loss of intrinsic factor +  achlorhydria 
  • (2) vitamin B 12 def - pernicious anemia. May cause atrophic glossitis and peripheral neuropathy
• Pernicious anemia and autoimmune gastritis are associated with other autoimmune diseases:
  •  Hashimoto thyroiditis
  • insulin-dependent (type 1) diabetes mellitus
  • Addison disease
  • Graves disease
  • vitiligo
  • myasthenia gravis
• Spares the antrum + hypergastrinemia

• associated with H. pylori-induced chronic gastritis + NSAIDs use
• Location:
  • Anywhere but most common in duo than gastric antrum 
• Path-phys-
  • The imbalances of mucosal defenses and damaging forces that cause chronic gastritis 
  • develops on a background of chronic gastritis
  • cigarette smoking (impairs blood flow to the gastric mucosa) 
  • high dose corticosteroid therapy (suppresses prostaglandin synthesis and impairs healing)
• Clinical
  • perforation, hemorrhage, and pyloric stricture (due to fibrosis)
  • epigastric pain, or aching pain
  • iron deficiency anemia may result

• Causes: nonbacterial infectious gastroenteritis
• Get it by:
  • Contaminated food or water, schools, hospitals, nursing wards, and cruise ships. 
• Clinical
  • Nausea, vomiting, watery diarrhea, and abdominal pain.

• Transmural inflammation on any part of GI
• due to-not clear: bacterial, dietary factors, stress
• Clinical
  • early lesion- aphthous ulcer
  • transmural inflammation - leathery
  • edema
  • nodular lymphoid aggregates
  • non-caseating granulomas in submucosa
  • “skip lesions” - cobblestone appearance
  • abdominal pain, diarrhea, fever, malabsorption 
  • if in small intestine, bleeding intestinal obstruction, fistulae
  • creeping fat - mesenteric fat extends around the serosal surface 
• complication 
  • stricture due to fibrosis and obstruction 
  • inc risk to intestinal cancer

• Inflammation limited to the mucosa of colon and the superficial submucosa
• Due to: genetic factors
• Clinical
  • Crypt abscesses
  • bleeding, cramps, blood diarrhea
  • moderate anemia with moderate colitis
  • dehydration, electrolyte depletion, massive hemorrhages
• Increased risk for:
• colon cancer. 

• Embolism or thrombosis 
• hernia intussusception
• volvulus

• Marked dilation or varicosity of hemorrhoidal venous plexus
• very common
• less common cause is obstruction of portal circulation in liver cirrhosis.

• Squamous cell carcinoma
• in the USA - low incidence, more in males, Caspian sea area, Iran, Central Asia, Mongolia No. China-esophageal cancer belt with incidence 30-70 x greater
• distribution suggests environmental factors 
• Clinical
  • alcohol, cigarette smoking, nitrosamines, 
  • Plummer Vinson syndrome, chronic esophagitis, achalasia, esophageal stricture
  • dysphagia, cachexia, anorexia, poor survival

• In Japan, Chile, Costa Rica, and Eastern Europe the incidence = 20x higher. US rates dropped.
• Dietary and environmental factors:
  • N-nitroso compounds used w/ smocked meats or fish, pickled vegetables
• Risk inc w/:
  • H. pylori infection in chronic gastritis
  • Barrett esophagus and may reflect the increased incidence of GERD and obesity
  • individuals with multifocal mucosal atrophy and intestinal metaplasia
• Clinical
  • early symptoms include: dyspepsia, dysphagia, and nausea. 
  • Loss of E-cadherin

• signet-ring cell morphology
  • contain vacuoles mucin that expand the cytoplasm and push the nucleus to the periphery
• desmoplastic reaction 
  • fibrous CT that stiffens the gastric wall
• linitis plastica
  • Leather bottle appearance due to diffuse rugal thick. + rigid thick wall (from large areas of infiltration) 
• most powerful prognostic indicators for gastric cancer
  • depth of invasion + extent of nodal and distant metastasis 
• Local invasion:
  •  duodenum, pancreas, and retroperitoneum 
• Five year survival- adv gastric cancer <20 %.

• Lesions pedunculated or flat base (sessile)
• Found: 
  • colon* most
  • can be seen in esophagus, stomach, SI
• Neoplastic polyp
  • adenoma (can progress into cancer)
• Non-neoplastic polyps 
  • inflammatory
  • hamartomatous
  • hyperplastic

• benign tumor-like nodule 
• It is an overgrowth of mature cells + tissues normally present in the affected part, but with disorganization and with one element predom
• occur 
  • sporadically 
  • genetically determined
  • acquired syndromes

• focal malformations of the mucosal epithelium + lamina propria
• Clinical
  • sporadic or in clinical syndromes
  • Typically pedunculated
  • Most in the rectum
  • Most with rectal bleeding
  • Dysplasia occurs in a small proportion of juvenile polyps

 
Autosomal dominant juvenile polyposis syndrome = increased risk of colon adenocarcinoma.

• Auto dominant syndrome  
• multiple GI hamar polyps + mucocutaneous pigmentation
• Who: 
  • median age of 11
• Clinical
  • SI and pedunculated
  • Brown macules around the mouth, eyes, nostrils, buccal mucosa, palmar surfaces of the hands, genitalia, and perianal region. 
• Complictions:
  • increased risk of wide variety of cancers 
  • The GI adenocarcinomas arise independently of the hamartomatous polyps

• Epithelial proliferations that represent a "piling up" of goblet cells and absorptive cells
• found in:
  • People in their 60s, 70s
•  Lesions = without malignant potential

• Most clinically important neoplastic polyps:
  • colonic adenomas, benign polyps that are precursors to colorectal adenocarcinomas.

• intra-epithelial neoplasms 
• Range: small, pedun polyps to large, sessile 
• Found in: 
  • 50% of Western world by age 50 
  • no gender preference
• Three types
  • Colorectal adenomas 
• • presence of epithelial dysplasia. 
  • the majority of adenomas do not progress to become adenocarcinoma
  • Most adenomas are clinically silent, with the exception of large polyps that produce occult (hidden) bleeding and anemia. 
  • A positive guaiac test detects occult blood in the stool
  • 50% of all polyps are found in the rectosigmoid region
  • 50% are evenly distributed throughout the rest of colon
  • Tubular adenomas 
• • 2/3 of all benign adenomas;
  • less than 2cm in diameter 
  • attached to a stalk (pedunculated)
  • Large tumors show a range of dysplastic changes
  • Villous adenomas 
• • predominantly in the rectosigmoid colon. 
  • large
  • (sessile)
  • elevated lesions
  • 60 % are larger than 2 cm in diameter; 
  • commonly 1/3 of villous adenomas contain foci of carcinoma 
  • higher potential for malignant transformation to colorectal carcinoma than tubular adenomas

• Men and women equal affected
•  Peaks at 60 to 70; 20 % of cases before age 50
• Etiology 
  • low fiber diet, high fat diet, high anaerobic bacterial content, genetic predisposition, Crohn disease
• Protective measures include 
  • colonoscopy, cruciferous vegetables, calcium, selenium, and aspirin (as COX-2 inhibitor)
• distributed equally over the entire length of the colon
• Colon cancer can metastasize to the lymph node, lung, liver, and brain
• Elevated carcinoembryonic antigen (CEA) is seen in about 25% of patients.

• Size 
  • ie, while cancer is extremely rare in adenomas less than 1 cm in diameter, some studies suggest that nearly 40 % of lesions larger than 4 cm in diameter contain foci for cancer
• high-grade dysplasia is a risk factor for progression to cancer.