5 GI Path Chronic Gastritis, Gastric Ca – Flashcards
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What's the most common cause of chronic gastritis?
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H.pylori
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What's the most common cause of atrophic gastritis?
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autoimmune gastritis
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What is the most common form of chronic gastritis in pts w/o H.pylori infection?
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autoimmune gastritis
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Which portion of the stomach does H.pylori gastritis typically affect?
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antrum
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Risk of which type of ulcer is increased in pts w/ H. pylori gastritis?
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duodenal
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Which cancer is associated w/ pangastritis?
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adenocarcinoma
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H.pylori is found in pts with gastric and _______ ulcers.
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duodenal
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Which demographics are associated w/ H.plylori infection/
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low socioeconomic status, large, crowded households, uneducated
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What's the likely transmission of H.pylori?
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oral-oral, fecal-oral, environmental spread
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What are the 4 virulence factors of H.pylori?
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1. flagella 2. urease 3. adhesins 4. toxins
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Does H. pylori inc or dec acid production?
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inc
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What might H. pylori gastritis progress to?
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pangastritis resulting in multifocal atrophic gastritis
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Which gene is linked with development of pangastritis after H. pylori infection?
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IL-1B
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How does H.pylori chronic gastritis usually present?
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asymptomatic (sx's include: non-ulcer gastric pain, nasuea, anorexia, bloating or weight loss)
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What's the colonization of H.pylori like?
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w/i the superficial mucous of the antrum, distribution is patchy
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What is the diagnostic test for H.pylori chronic gastritis?
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antral biopsy
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What does antral mucosa look like on endoscopy w/ h pylori chronic gastritis?
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erythmatous
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Where are the neutrophils in h pylori chronic gastritis?
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in lamina propria, gastric pits creating pit abscesses, plasma cells in
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Intraepithelial neutrophils & subepithelial plasma cells are characteristic of which dz?
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H. pylori
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What is the only way chronic gastritis can be established?
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on histologic grounds
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How can you i.d. hypolori non-invasively?
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*1. serologic test for AB's to H. pylori* 2. fecal bacterial detection *3. urea breath test* 4. rapid urease test 5. bacterial DNA detection by PCR
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What 2 things are measured to determine gastric secretory function?
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1. serum pepsinogen I 2. gastrin
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What are serum PGI & gastrin levels like in h pylori chronic gastritis?
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PGI is inc gastrin is normal (parietal cell & intrinsic factor AB's & pernicious anemia are absent)
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What is usually associated w/ autoimmune gastritis?
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adult pernicious anemia @ 60 yo
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loss of parietal cells & therefore absence of acid production stimulating gastrin release & hypergastrinemia & hyperplasi of antral gastrin-producing G cells.
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Autoimmune gastritis
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Why is pernicious anemia associated w/ autoimmune gastritis?
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lack of intrinsic factor disables ileal B12 absorption, causing B12 deficiency & slow-onset memgaloblastic anemia (pernicious anemia).
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Are chief cells lost in addition to parietal cells in autoimmune gastritis?
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yes
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What does the loss of chief cells result in?
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dec serum pesinogen I & achlorydria
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What attacks the parietal cells in autoimmune gastritis?
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CD4+ T cells (attack at the H+K+ ATPase (proton pump).
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What part of the stomach is damaged in autoimmune gastritis?
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body & fundus
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loss of parietal & chief cells loss of rugae, thin fundus fibrosis of lamina propria atrophy of acid-producing mucosa
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autoimmune gastritis
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does hyperplasia of antral G (enterochromaffin-like) cells develop in autoimmune gastritis?
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yes
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In autoimmune gastritis, which comes first, hypergastrinemia, or G cell hyperplasia?
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hypergastrinemia (G cell hyperplasia results from chronic hypergastrinemia)
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Inflammatory infiltrate consists of lymphocytes, macs, & plasma cells. Is this h pylori or autoimmune gastritis?
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autoimmune
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inflammatory reaction is deep & centered on gastric glands:
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autoimmune gastritis
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Are AB's to parietal cells & intrinsic factor part of the pathogenesis of autoimmune gastritis?
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no
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When do AB's to parietal cells & intrinsic factor present in the disease course?
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early
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How long does it take to see gastric atrophy in autoimmune gastritis?
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2-3 decades
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What's the median age of dx in autoimmune gastritis?
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60 yo
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Is autoimmune gastritis associated w/ other autoimmune dz?
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often times, yes
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What are signs of B12 deficiency?
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atrophic glossitis - smooth beefy red subacute combined degeneration of spinal cord causing myelopathy
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What part of the spinal cord is affected in subactue combined degeneration d/t B12 deficiency?
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dorsal columns of lower cervicals & upper thoracics, later axonal degeneration & neuronal death
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numbness, weakness, paresthesia of extremities, affectin legs more than arms
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B12 deficiency
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unsteady gait, poor coordination, bowel/bladder dysfunction:
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b12 deficiency
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Loss of position & vibration sense ataxia, vision changes & change of mental state:
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B12 deficiency
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What are the lab studies for autoimmune gastritis?
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1. antiparietal and anti-intrinsic factor (IF) antibodies in the serum 2. achlorhydria, both basal and stimulated 3. low serum pepsinogen I concentrations and low pepsinogen I/pepsinogen II ratio; 4. hypergastrinemia which reflects G cell hyperplasia 5. low serum cobalamin (vitamin B12) levels (< 100 pg/mL)
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is risk of gastric adenocarcinoma higher in ppl w/ pernicious anemia?
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yes
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Are gastric fundic gland polyps (FGP's) benign and exclusive to the fundus?
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yes, yes
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FGP's can be sporadic, familial or caused by ________.
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proton pump inhibitors
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numerous adenomatous polyps in the colon that predispose to colon cancer
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familial adenomatous polyposis (FAP)
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germ line mutation in APC gene
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FAP
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B-catenin mutation
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sporadic FGP
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What are gastric hyperplastic polyps associated w/?
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H. pylori & autoimmune gastritis
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sessile & pedunculated
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hyperplastic polyps
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develop in apparently normal, non-atrophic mucosa
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gastric adenomas of gastric phenotype
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APC gene inactivation
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Gastric adenoma
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What is the strongest risk factor for stomach cancer?
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Chronic bacterial infection w/ H. pylori
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How does H. pylori favor the development of stomach cancer?
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mutagenic substances are formed by mutagenic stubstances through inflammatory mediators by inducing DNA methylation or by impairing the mismatch repair pathway
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nitrosamines
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gastric cancer
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what are some hereditary syndromes that have a predisposition for stomach cancer?
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hereditary nonpolyposis colorectal ca, Li-fraumeni syndrome, familial adenomatous polyposis, Peutz-Jeghers syndrome
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Which part of the stomach does gastric cancer favor?
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distal stomach, lesser curvature of antrum & prepyloric region (rare in fundus)
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What are the 3 major macroscopic types of gastric cancer?
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1. polypoid/fungating 2. ulcerating 3. diffuse schirrous
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solid mass, several cm's in diameter that projects into stomach lumen, 1/3 of gastric ca
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polypoid gastric carcinoma
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shallow ulcers, lateral margins are irregular & base is ragged,surrounding tissue is raised & nodular, 1/3 of gastric ca
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ulcerating gastric carcinoma
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no true tumor mass seen, diffuse thickening & firmness, 10% of gastric ca
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scirrhous gastric carcinoma (aka diffuse or infiltrating adenocarcinoma)
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*linitis plastica tumor*
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entire stomach involved in scirrhous/diffuse gastric carcinoma
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*desmoplastic reaction* (fibrosis of submucosa & muscularis) & leather bottle-like appearance
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scirrhous/diffuse gastric carcinoma
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Where does well-differentiated adenocarcinoma arise from?
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intestinalized gastric mucosa
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What is the most common site of metastasis from well-differentiated adenocarcinoma?
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liver
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How do poorly-differentiated carcinoma appear?
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*signet-ring cells* diffusely infiltrate gastric wall
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Where are metastases of poorly-differentiated carcinoma appear?
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serosa or lymph nodes
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What is the most common type of metastatic spread of gastric carcinoma?
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lymph nodes along greater & lesser curvature of stomach, & occasionally supraclavicular nodes (Virchows nodes) via the thoracic duct
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periumbilical region nodes that gastric carcinoma can metastasize to:
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Sister Mary Joseph nodule
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What 2 structures are commonly involved in peritoneal metastatic spread?
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b/l ovaries (*Krukenberg's tumor*) & rectal shelf (Bllumer's tumor)
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loss of E-cadherin (and silencing of CDH1 promoter by hypermethylation) is associated with what?
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gastric cancer
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How does gastric cancer present?
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weight loss, abdominal pain, epigastric, vague, nausea, early satiety, gastric outlet obstruction, occult gastrointestinal bleeding w/ or w/o iron deficiency anemia
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Which antigen is elevated in gastric cancer?
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carcinoembryonic antigen (CEA) (45-50%) Cancer antigen (CA) (20%)
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What is the preferred treatment for gastric adenocarcinoma?
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resection, if metastatic, chemo or radiation
