stomach Flashcards
robbins
differentiate between acute gastritis and gastropathy
acute gastritis= acute gastric mucosal inflammation with neutrophils present
gastropathy= mucosal injury without inflammatory cells (or rare inflammatory cells)
what are the two examples of hypertrophic gastropathy
ménétrier ds
zollinger-ellison syndrome
what factors will cause gastropathy
NSAIDs, alcohol, bile, and stress induced injusry
ulcers, lesions s/p decreased perfusion, portal HTN –> gastropathy –> gastritis
list the protective and damaging factors that effect gastric mucosa
protective=
mucus secretions, bicarb, blood flow, epithelial barrier + regeneration capacity, prostaglandins
damaging=
acidity, peptic enzymes, H. Pylori, NSAIDs, tobacco, alc, duodenal-gastric reflux, ischemia, shock
what is the function of foveolar cells
secrete mucin, bicarb
complete replacement of the surface foveolar cells every 3-7 days is essential for the maintenance of the epithelial layer
what is the function of parietal cells
secrete HCl into the gastric lumen and bicard into the mucosal vasculature
= capillary ‘alkaline tide”
what are the two functions of mucosal vasculature in the stomach
delivers O2 and nutrients while washing away acid that has back diffused into the lamina propria and delivering bicarb
relate the use of NSAIDS to gatritis
NSAIDs inhibit COX–> inhibit synthesis of prostaglandins E2+ I2
greatest injury with nonselective COX inhibitors= aspirin, ibuprofen, naproxen
also injurious to have COX2 specific inhibition= celecoxib
how does H. Pylori cause injury leading to gastritis
urease secreting H. Pylori can inhibit gastric bicarb transporters by ammonium ions
reduced mucin and bicarb secretion in ______ patients predisposes them to developing gastritis
older
relate high altitudes to developing gastritis
decreased O2= decreased protective factors produced
foveolar cell hyperplasia, slight vasculature congestion, corkscrew profiles and epithelial proliferation
mucosal infiltrate and fibrin containing purulent exudate int he lumen, with possible hemorrhage and dark punctae in hyperemic mucosa
gastropathy and mild acute gastritis
(in stomach) the presence of _____ above the basement membrane and in direct contact with epithelial cells signifies active gastritis
neutrophils
describe the clinical presentation of NSAID-induced gastropathy
asymptomatic or persistent epigastric pain that responds to antacids or PPIs
describe the clinical presentation associated with bile reflux induced gastropathy
pain is refractory to therapy and may be accompanied by occasional bilious vomiting
more than 75% of critically ill patients develop endoscopically visible ___ _____ during the first 3 days of their illness
gastric lesions
___ ____ are the most common in people with shock, sepsis, or severe trauma
stress ulcers
______ are ulcers associated with severe burns and trauma, that occur in the ____ ____
curling ulcer, proximal duodenal
________ are ulcers associated with intracranial disease that arise in the ____, _____, and ____. they carry a ____ incidence of perforation
cushing ulcers
stomach, duodenum, esophagus
high
describe the etiology of how stress ulcers form
stress from systemic hypotension or reduced blood flow
upregulation of inducible NO synthase and endothelin 1–> ischemic gastric mucosal injury
intracranial injury–> direct stimulation of vagal nuclei–> hypersecretion of gastric acid –> lowering intracellular pH of mucosal cells
found anywhere in the stomach, rounded and less than 1 cm. stained brown/black by acid digestion at the base, can be associated with transmural inflammation and local serositis, sharply demarcated next to normal adjacent mucosa
acute STRESS ulcer (not a peptic ulcer)
differentiate between the morphology of an acute and chronic stress ulcer in the stomach
chronic do not have scarring and blood vessel thickenings that are in acute stress ulcers
____ _____ may blunt the impact of stress ulceration in critically ill patients, but the most important determinant of clinical outcome is the ability to _____________
prophylactic PPIs
correct the underlying condition
what are the two non-stress related causes of gastric bleeding
dieulafoy lesions and gastric antral vascular ectasia (GAVE)
what is the etiology of a dieulafoy lesion
= a submucosal A that doesn’t branch properly within the wall of the stomach, resulting in an A up to 10x the size of mucosal capillaries
bleeding is self-limited and can be associated with NSAID use (recurrent)
where are dieulafoy lesions most commonly found
the lesser curvature of the stomach
near the GE junction
(in the stomach) ‘longitudinal stripes of edematous erythematous mucosa that alternate with less severely injured, paler mucosa” “watermelon stomach”
GAVE (gastric antral vascular ectasia)
in the stomach, histology of antral mucosa shows reactive gastropathy with dilated capillaries containing fibrin thrombi
GAVE (gastric antral vascular ectasia)
while most often ___, GAVE can be associated with ___ and ______. patients usually present with ________ or _________
idiopathy
systemic sclerosis
occult fecal blood
iron deficiency anemia
the most common cause of chronic gastritis
H. Pylori
the most common cause of diffuse atrophic gastritis
autoimmune gastritis
clinical presentation of H. Pylori
less severe and more persistent compared to acute gastritis
nausea, upper abd pain, vomiting
RARELY hematemesis
H. Pylori is a __-shaped or ____bacilli and is present in almost all patients with ____ ulcers
spiral, curved
duodenal
acute H. Pylori does not produce _____ _____ to be caught. in most cases, it is the ___ ___ that causes individuals to seek trx
sufficient sx
chronic gastritis
what epidemiological factors are associated with H. Pylori
poverty, household crowding, limited education, African Americans+ Mexican Americans, rural areas, birth outside of the US
H. Pylori is transmitted via the _____ route and is typically acquired in ______ and persists throughout life _____
fecal-oral
childhood, without trx
H. Pylori most often presents as …
a predominantly antral gastritis with normal or increased acid production
As in the case of H. Pylori, when ____ is limited to the antrum, increased ____ production results in a greater disk for duodenal ulcers
inflammation
acid
H. Pylori gastritis spreading to the body and fundus is called ___ ____ ____. In this condition, there is an ____ risk of gastric adenocarcinoma. thus, there is an ___ relationship between duodenal ulcer and gastric adenocarcinoma
multifocal atrophic gastritis
increased
inverse
the virulence of H. Pylori is linked to what factors
flagella
urease, elevating local gastric pH to allow for survival
adhesins, adhese to foveolar cells
toxins = CagA
Cag A, produced by _____, leads to an increased risk of _______
H. Pylori,
gastric adenocarcinoma
(in the context of H. Pylori infection) genetic mutations that lead to increased production of __ and ___ or decreased expression of ____ are associated with increased risk of pangastritis, atrophy, and gastric CA. __ ___ may also be risk factor of H. Pylori associated-gastric C
TNF, IL-1B
IL-10
iron deficiency
where in the stomach are H. Pylori most often found, which is directly related to the increased risk of ___ ____
antrum
duodenal ulcers
gastric antrum viewed endoscopically is erythematous and has a coarse/nodular appearance, with neotrophils within the lamina propria accumulating in the lumen to create abscesses
H. Pylori infected antrum
the presence of what two cell types is characteristic of H. Pylori infection
intraepithelial neutrophils
subepithelial plasma cells
long standing H. pylori gastritis can spread to the body and fundus, causing a loss in ___ and ___ cells, causing the oxyntic mucosa to take on the appearance of antral mucosa
parietal , chief
what are the diagnostic tests for H. Pylori infection
noninvasive serologic tests for Ab against H. Pylori
fecal bacterial detection
urea breath test
gastric biopsy–> rapid urease test, bacterial culture, PCR
what are the effective trx for H. Pylori
abx and PPIs for at least 10-14 days
in contrast to H. Pylori associated, autoimmune gastritis typically spares the __ and is associated with _____
antrum
hypergastrinemia
autoimmune gastritis is associated with Ab against \_\_\_\_\_\_ and \_\_\_\_ \_\_\_\_ levels of serum pepsinogen I endocrine cell \_\_\_\_\_ Vit \_\_\_ deficiency \_\_\_\_ gastric acid secretion ( \_\_\_\_\_)
parietal cells, intrinsic factors reduced hyperplasia B12 defective, achlorhydria
what are the inflammatory infiltrates for H. Pylori associated and autoimmune gastritis
H. Pylori = Nø, subepithelial plasma cells
autoimmune= lymphocytes, Mø
describe acid production in H. Pylori associated and autoimmune gastritis
H. Pylori= increased to slightly decreased
autoimmune= decreased
describe gastric levels in H. Pylori associated and autoimmune gastritis
h pylori= normal to decreased
autoimmune= increased (neuroendocrine hyperplasia)
describe the gastric mucosa lesions associated with H. Pylori associated and autoimmune gastritis
h pylori –> hyperplastic/inflammatory polyps
autoimmune= neuroendocrine hyperplasia
describe the serology results in H. Pylori associated and autoimmune gastritis
h pylori= ab against h pylori
autoimmune= ab against parietal cells (H/K ATPase, intrinsic factor)
what are the sequelae of H. Pylori associated and autoimmune gastritis
h pylori = peptic ulcer, adenocarcinoma, MALToma
autoimmune= atrophy, pernicious anemia, adenocarcinoma, carcinoid tumor
what conditions are associated with autoimmune gastritis
thyroiditis, DM, Graves disease
describe how autoimmune gastritis results in pernicious anemia
Ab-parietal cells –> x parietal cells –> decreased intrinsic factor –> decreased B12 absorbed in intestine –> pernicious anemia
describe how autoimmune gastritis results in hypergastrinemia
Ab-parietal cells –> x parietal cells –> decreased gastric acid –> increased gastrin production + hyperplasia of G cells in antrum –> super increased gastrin production = hypergastrinemia
_______ are considered to be the principal agents of injury in autoimmune gastritis, attacking parietal cell components like the _______
CD4 T cells
H/K ATPase
in autoimmune gastritis, reduced ______ results from chief cell destruction, which is achieved through ___________ during the autoimmune attack on parietal cells
serum pepsinogen 1 concentration,
gastric gland destruction
Ab are not thought to be pathogenic in autoimmune gastritis because
neither secreted IF nor luminally oriented PPIs are accessible to circulating Abs
oxyntic mucosa appears markedly thinned and rugal folds are lost.
when incomplete can get a nodular appearance, or intestinal metaplasia characterized by the presence of goblet cells and columnar absorptive cells
diffuse gastric atrophy related to autoimmune gastritis
in autoimmune gastritis, if Vit B12 loss is extensive, it can lead to what kind of change
megaloblastic change= nuclear enlargment
describe the clinical presentation of autoimmune gastritis
because it takes decades to progress, the median age of diagnosis is 60, with more women than men
have sx of anemia,
atrophic glossitis secondary to Vit B12 deficiency,
epithelial megaloblastosis,
malabsorptive diarrhea,
peripheral neuropathy, spinal cord lesions, and cerebral dysfunction, parasthesias and numbness
in autoimmune gastritis, the demyelination of the ___ and ___ spinal tracts can give rise to ___ ____ ____ __ ____ ____, resulting in the following clinical signs: ____
dorsal, lateral, subacute combined degeneration of the cord
loss of vibration and position sense, sensory ataxia with a + Romberg sign, limb weakness, spasticity, extensor plantar responses, mild personality changes and memory loss to psychosis
in autoimmune gastritis, unlike anemia, neurologic changes are _____ by Vit B replacement
not reversible
(stomach) tissue damage associated with dense infiltrates of eosinophils in the mucosa and muscularis, in the antrum or pyloris
eosinophilic gastritis
what are the most common causes of eosinophilic gastritis
allergies to dairy and soy
in what population is lymphocytic gastritis most common
women, those with celiac ds
in stomach= thickened folds covered by small nodules with central aphthous ulceration, marked increase in the number of intraepithelial T lymphocytes
lymphocytic gastritis/ varioliform gastritis
what are the most common causes of granulomatous gastritis
Crohn ds, sarcoidosis, infections
what are risk factors of PUD
PUD is a complication of chronic gastritis
risk with H. Pylori, cigarettes, CV disease, COPD, illicit drugs, NSAIDs, alcoholic cirrhosis, psych stress, zollinger ellison, vital infection with CMV, herpes
the most common form of PUD occurs within the gastric ____ or _____ as a result of chronic ______-associated gastritis associated with increased ______ and decreased _________ secretions
atrum, duodenum
H. Pylori
gastric acid, duodenal bicard
PUD within the gastric ____ or ____ are generally protected form ___ and ____ because, which they have increased acid production, they don’t make enough
fundus, body
antral and duodenal ulcers
growing incidence of PUD is seen in patients _______ because of increased ____ use
older than 60 y.o
NSAID
because PUD results from an imbalance between mucosal protection and damage, it usually develops on a background of ______, though they are most common in the _____
chronic gastritis,
proximal duodenum
gastric peptic ulcers are mostly located _____, near the interface of the ___ and ____
lesser curvature, body and antrum
(in the stomach) usually solitary lesions. round-oval, sharply punched out defect and usually level with the surrounding mucosa
peptic ulcers
perforation of peptic ulcers is a ___ ___, and may be identified by ____
surgical emergency,
detection of free air under the diaphragm on upright radiographs of the abdomen
malignant transformation of peptic ulcers is
very rare
the majority of peptic ulcers come to clinical attention because of ____, though some also come in because of
epigastric burning or aching pain
iron deficiency anemia, hemorrhage, or perforation
describe clinical sx of PUD
pain occurs 1-3 hours after meals during the day, worse at night, relieved by alkali or food
N/V, bloating, belching
trx of PUD
H. Pylori eradication, neutralization of gastric acid with PPIs, withdraw offending agents
2/3 of deaths due to PUD occur because
perforation
H Pylori gastritis induces _____ that can give rise to B cell lymphomas ( __ )
MALT
MALTomas
the risk of adenocarcinoma is greatest in _____ gastritis
autoimmune
epithelial exposure to ___ and ____ with chronic gastritis can lead to dysplasia
free radicals and proliferative stimuli
hyperchromasia and nuclear enlargement of histologic changes associated with
dysplasia
reactive epithelial cells ____ as they reach the mucosal surface, while dysplastic lesions remain ___. this shows as normal growth becoming ___ to the basement membrane, while dysplasia stays ___
mature
immature
perpendicular
parrallel
(in the stomach) reactive epithelial proliferation in responde to trauma, can mimic invasive adenocarcinoma
gastritis cystica
giant “cerebriform” enlargement of the rugal folds due to epithelial hyperplasia without inflammation
hypertrophic gastropathies
what are the two examples of hypertrophic gastropathies
menetrier ds and zollinger ellison syndrom
what is the etiology and histologic change associated with menetrier ds
-excessive secretionof TGFα,
diffuse hyperplasia of the foveolar epithelium of the body and fundus of the stomach, irregular enlargement of teh gastric rugae with the antrum generally spared
glands elongated in corkscrew appearance and cystic dilation
what are the clinical sx of menetrier ds
weight loss, diarrhea, and peripheral edema (due to hypoproteinemia
menetrier ds in children is different than in adults in that in children the ds is usually ____ and often follows a _____
self-limited, respiratory infection
which hypertrophic gastropathies and gastric polyps are associated with adenocarcinoma
menetrier ds
gastric adenoma
FAP syndrome (fundic gland polyps)
what are the main sx of zollinger ellison ds
peptic ulcers
what is the clinical presentation of inflammatory and gastric polyps
look like chronic gastritis
what is the clinical presentation of gastric adenoma
presents like chronic gastritis
what is the inflammatory infiltrate in menetriere ds
limited, if any they’re lymphocytes
what is the inflammatory infiltrate in zollinger-ellison syndrome
neutrophils
what sx present with zollinger ellison syndrome
peptic ulcers (duodenal) chronic diarrhea
what is the inflammatory infiltrate in inflammatory and hyperplastic polyps
neutrophils and lymphocytes
what is the inflammatory infiltrate in gastric cystica
neutrophils and lymphocytes
what inflammatory infiltrates are present in fundic gland polyps
NONE
in what hypertrophic gastropathies/gastric polyps is mucous cells the predominant cell type
menetriere ds
inflammatory and hyperplastic polyps
gastritis cystica
in what hypertrophic gastropathies/gastric polyps is parietal cells the predominant cell type
zollinger ellison syndrome
in what hypertrophic gastropathies/gastric polyps is parietal and chief cells the predominant cell type
fundic gland polyps
what is the mean patient age for menetrier ds
30-60
what is the mean patient age for zollinger ellison syndrome
50
what is the mean patient age for inflammatory and hyperplastic polyps
50-60
what is the mean patient age for fundic gland polyps
50
what is the population most commonly seen with gastric adenomas
50-60, men
what is the treatment for menetriere ds
IV albumin and parenteral nutritional supplementation
agents that block TGF a mediated activation of epidermal GF
what is the cause of zollinger ellison syndrome
gastrin secreting tumors
doubling of oxyntic mucosal thickness due to 5x increase in the number of parietal cells,
zollinger ellison syndrome
____ induces hyperplasia of mucous neck cells, mucin hyperproduction, and proliferation of endocrine cells in ___ syndrome
gastrin
zollinger-ellson
what is the treatment of zollinger ellison syndrome
blockade of acid hypersecretion- PPIs
treatment of the gastrinoma is the main determinant of long-term survival
in zollinger ellison syndrome, though slow growing, most gastrinomas are ____. 1/4 of them are associated with _____
malignant
MEN1
what risk factors lead to presence of fundic gland polyps
FAP= familial adenomatous polyposis
increased use of PPIs
risk of adenocarcinoma in gastric adenomas is related to the _____ of the lesion, and is particularly increased in lesions _____
size, >2 cm in diameter
risk of gastric adenomas
gastric adenomas (>/=) intestinal adenomas
>
the most common malignancy of the stomach
adenocarcinoma
most common sites of gastric CA metastasis
supraclavicular sentinal LN (virchow node) periumbilical LN L axillary LN ovary pouch of Douglas
what are risk factors for gastric CA
lower SES
multifocal mucosal atrophy, intestinal metaplasia
white PUD does not increase risk for gastric CA, those who have partial ____ have a higher risk of developing CA in the ____
gastrectomies
residual gastric stump
____, caused by loss of function of ___, is the key step to developing diffuse gastric CA
other genetic mutations that increase risk of diffuse gastric CA are ___ and ____
loss of E-cadherin, CHD-1
x BRCA2, xTP53
genetic mutations that lead to sporadic intestinal type gastric CA
increase Wnt pathway signalling
LOF of APC gene,
GOF of B-catenin encoding genes
LOF of TGFB, BAX, CDKN2A
most adenocarcinoma of the stomach exist in the ___, along the ____ curvature
antrum
lesser
due to _____, some gastric adenocarcinomas will not form glands but rather have large mucin vacuoles that push the nucleus to the periphery, called ____ morphology
E-cadherin loss
signet-ring cell
diffuse gastric infiltrative tumors often evoke a desmoplastic reaction that ____, cause diffuse rugal ___ and caused thick walls with leather bottle like appearance called ___ ____
stiffens
flattening
linitis plastica
intestinal type gastric CA, as opposed to antral type, predominates in what populations
high risk areas, those with precursor lesons
males over 55 yo
what is the most powerful prognostic indicator in gastric CA
depth of invasion and extent of nodal and distal metastases
what is the trx and prognosis of gastric CA
surgical resection
5 year survival rate= 90%
what is the most common inducer of MALTomas in the stomach
H. Pylori
what genetic translocations are commonly associated with MALTomas
t(11;18)(q21;q21) –> create chimeric AP12-MLT fusion gene
t)1;14)(p22;q32) –> increased expression of MALT1 and BLC-10 proteins
both –> constituitively activate NFKB–> promot B cell growth and survival
describe the connection between H Pylori trx and the trx of MALToma
if MALToma is caused by H Pylori–>eradication slashes recurrence rates and allows durable remission
if MALToma caused by genetic translocation–> eradication does nothing
what are the most common presenting sx of MALTomas
dyspepsia and epigastric pain
hematemesis, melena, weight loss
what are the most common sites of carcinoid tumors
small intestine, tracheobronchial tree, lungs
what conditions are associated with carcinoid tumors
endocrine cell hyperplasia
autoimmune chronic atrophic gastritis
MEN-1
zollinger, ellison gastritis
in what population are carcinoid tumors seen in
patients > 60 yo
what are the sx of carcinoid tumor
depends on what hormones are being elaborated
make gastrin? –> zollinger-ellison syndrome
ileal tumor —> carcinoid syndrome (too many vasoactive substances being secreted into systemic circulation)
what is the most important prognostic factor for GI carcinoid tumors- elborate
location
foregut (before the ligament of treitz) = rarely metastasize, cured by resection
midgut= aggressive, greater depth of local invasion, increased size, have necrosis and mitoses and associated with worse prognosis
hindgut= (appendix and colorectal) = incidental findings, almost always benign, usually found when small
what is the most common mesenchymal tumor of the abd
GI stromal tumor
in what population will you find GISTs
peak age= 60 y.o
what is a Carney triad
uncommon presentation in which you have GIST in children
in young females
=GIST , paraganglioma, and pulmonary chondrome
what genetic mutations are common in GISTs
what does it result in
most have gain of function of receptor tyrosine kinase KIT
another mutation is of PDGFRA, both increase intracellular signals for proliferation and survival
also have mutations in genes coding for succinate dehydrogenase comples (SDH_) = inherited in Carney-Stratakis syndrome
=dysregulation of HIF-1a–> increased transcription of VEGF and IGF1R
deletion of ch 9p, less of cell cycle regulator ____, is involved in many gastric CAs
CDKN2A
what is the most useful diagnostic marker of GIST
KIT gene
(in the stomach)a large fleshy mass with a whorled appearance, either spindle cell type or epithelioid type
GIST
where do GISTs metastasize to?
peritoneal cavity
liver
what are the clinical sx of GISTs
mucosal ulceration–? blood loss, anemia
can be an incidental finding
what is the trx and prognosis of GIST
trx= surgical resection
GISTs with KIT/PDGFRA mutations usually respond to trx with imatinib, though resistance is common
prognosis depends on size, mitotic index, and location
-gastric GISTs are less aggressive than intestinal GISTs
