GI Disorders Flashcards
what gastroduodenal disorders is H pylori indicated in?
- acute and chronic gastritis 2. gastric and duodenal ulceration 3. gastric cancer 4. gastric MALT lymphoma
where is h pylori found
present in gastric antrum and lives beneath mucus layer, can secrete urease
how does urease help H pylori?
environmental modulator, protects microorganism from toxic effects of the gastric acidity by raising the pH of its microenvironment OR maintains intracellular nitrogen balance in H pylori (excess nitrogen inside cells produced by fast catabolism of AA could be disposed of by excretion via urea cycle)
what does urease do
hydrolyses urea to carbonic acid/bicarbonate and ammonia/ammonium; contributes to buffering the acidic pH around the bacteria
what does the presence of arginase suggest?
that H pylori has a complete urea cycle which acts as an effective mechanism to extrude excess nitrogen from cells
what is the urea cycle that h pylori does
arginase converts water and arginine to urea, which is then broken down by urease to ammonium and CO2
what are 2 roles fore urease?
- hydrolysis of urea by urease outside of cells avoids the formation of a concentration gradient that may drive urea/metabolic product back into the cytosol
- compatible with an acid-protection function
sources of urea?
- H pylori produces its own urea from arginine as part of its own urea cycle
- host urea formed in the liver from protein deamination. carried to kidneys for renal use and excretion. urea carried by circulatory system from liver to kidneys
- urea is present in saliva and gastric secretions
what is BUN
blood urea nitrogen – measures amount of urea nitrogen found in blood. normal is 6-20mg/dL of BUN, high BUN indicates kidney problem bc kidneys are not able to remove urea from the blood normally
what is the purpose of a highly acidic gastric environment
kill microorganisms and activate pepsinogen
how can h pylori survive in a ph 1-3 environment?
- lives in the alkaline mucous produced by gastric mucosa
- generates ammonium ion through urease on urea from itself and the host
- helical body shape not used to corkscrew, but H modifies its microenvironment
describe how h pylori modifies its microenvironment
mucin is the main protein in mucus.
mucin is in gel form at acidic pH near the gastric lumen.
at neutral pH, mucin is a viscous liquid, allows h pylori to swim near cell surface.
H pylori then binds to different mucins on cell surface.
ammonium ion production via ureas damages the plasma membrane facilitating cell penetration.
what does mucin look like at acidic ph
gel like at gastric lumen to form barrier
what does gastrin look like at neutral ph
viscous liquid, so allows h pylori to swim near cell surface. damages cells via ammonium ion
what causes zollinger ellison syndrome?
gastrin producing tumors release abnormal amounts of gastrin, leading to excess gastric acid in the stomach and duodenum. this causes multiple peptic ulcers to form in the lining of the duodenum.
1 or more tumors in pancreas, duodenum or both.
who is most commonly affected by zollinger ellison syndrome?
30-50yo males and those with the MEN-1 gene
possible indicators of ZES
peptic ulcers in the absence of H pylori infections or NSAID use
OR
severe peptic ulcers that bleed or cause perforations
ZES symptoms
burning abdominal pain
n/v/d
weight loss
severe gastroesophageal reflux
how to treat ZES
H2 receptor antagonists
PPI
surgical resection or removal
what is peptic ulcer disease
ulcer (greater than 0.5cm) of an area of the GI tract that is usually acidic and painful
how are ulcers made worse?
caused or worsened by drugs like aspirin or other NSAIDS
where do most ulcers arise?
more in the duodenum than the stomach
what are 3 common causes of ulcers?
- stress
- diet
- h pylori
- (4% caused by malignant tumor like ZES)
difference between IBS and IBD
IBS is a cluster of symptoms without a tangible cause.
IBD is a heterogenous group of disorders with a tangible cause.
what is IBS
irritable bowel syndrome, functional bowel disorder with a characteristic cluster of symptoms in the ABSENCE OF DETECTABLE STRUCTURAL ABNORMALITIES
what causes IBS
unknown, intangible cause.
common theory of IBS cause
disorder of the interaction between the brain and the GI tract
(interstitial cells of cajal? myenteric plexus?)
may be abnormalities in gut glora or immune system
what is IBD
heterogeneous group of disorders characterized by various forms of chronic mucosal and/or transmural inflammation of the intestine (all or part of digestive tract)
what does IBD include?
ulcerative colitis and crohn’s disease
what characterizes IBS
spastic colon
chronic abdominal pain
discomfort
bloating
alteration of bowel habits in the absence of any detectable organic cause
how can IBS be classified further?
IBS-D (diarrhea predominant)
IBS-C (constipation predominant)
IBS-A (alternating stool pattern, pain predominant)
relationship with IBD and CRC
IBD people with crohn’s disease or ulcerative colitis are at higher risk for developing CRC than the general population
incidence of cRC
147000 new CRC are diagnosed
57000 die
second leading cause of cancer related deaths in the country
what causes crohn’s disease
inherited genes
autoimmune repsonses
environmental factors
symptoms of crohn’s disease
persistent diarrhea
abdominal cramps and pain
fever
fatigue
rectal bleeding
loss of appetite
could impact joints, eyes, skin, liver
complications of Crohn’s disease
obstruction due to swelling and formation of scar tissue.
development of fissures
abscesses
fistulas (abnormal tunnel between 2 structures)
what is the valsalva maneuver
closure of the glottis, contraction of the abdominal and thoracic muscles causes transient increase in blood pressure. helps defecation.
why is everyone supposed to be lactose intolerance but isn’t
we are genetically programmed to become lactose intolerant, but the body continues to produce lactase as long as we consume dairy products.
what happens in lactose intolerance
lactose (normally digested in SI) is passed to large intestine where E coli breaks it down into monosaccharides. this causes large volumes of methane, H2 gas and lactic acic = flatus!!
flatus distension of the colon causes pain.
ecoli breaking into monosaccharides into FA which causes water movement into Li causing diarrhea.
what causes diarrhea in lactose intolerance?
E coli breaks down lactose into FA which osmotically causes water movement into the LI
what causes pain in lactose intolerance?
flatus distension of the colon
what serum hormones regulate appetite
leptin, ghrelin, growth hormone, neuropeptide Y
what secretes neuropeptide Y?
paraventricular nucleus of the hypothalamus
what is the most abundant peptide of the CNS?
neuropeptide Y
actions of neuropeptide Y
- most potent orexigenic peptide in the brain (increases food intake)
- increases proportion of energy stored as fat
- blocks nociceptive signals to the brain (pain)
- augments vasoconstrictor effects of noradrenergic neurons
3 actions of ghrelin
- stimulation of growth hormone secretion
- increase hunger
- suppress fat utilization in adipose tissue
APPETITE REGULATING FACTOR
how does ghrelin stimluate growth hormone secretion?
binds growth hormone secretagogue receptor (GHSR1a) in the anterior pituitary resulting in release of GH
how does ghrelin increase hunger?
- acts on hypothalamic appetite regulation receptors
- hippocampal receptors and regions with reward systems
what circuits does ghrelin activate?
some of the same circuits that are involved in drug reward
what produces ghrelin?
P/D1 cells lining fundus of stomach
AND
epsilon cells of the pancreas
synthesize preprohormone then is proteolytically processed to yield 28-AA peptide when its in the right place
generally, what does ghrelin stimluate
food intake, promotes body weight gain, and adipogenesis
describe ghrelin levels before and after meals
ghrelin levels increase before meals and decrease after meals
what produces leptin?
adipose tissue
how does leptin provide satiety?
leptin binds to neuropeptide Y neurons in the arcuate nucleus so that it decreases the activity of the neuropeptide Y neurons. signals the brain that the body has had enough to eat.
what is the most potent orexigenic peptide in the body
neuropeptide Y
what 4 neuropeptides play essential roles in regulation of food intake and energy homeostasis?
- the agouti related protein (AgRP)
- neuropeptide Y (NP-Y)
- proopiomelanocortin (POMC)
- cocaine and amphetamine regulated transcript (CART)
what is CART
cocaine and amphetamine regulated transcript
a neuropeptide that plays roles in reward, feeding, and stress that also serves as a NT
what is POMC
proopriomelanocortin
a 241aa hormone precursor that cleaves in 8 places to give rise to 10 active compounds with roles in pain and energy homeostasis, melanocyte stimulation, and immune modulation
what is one of the most potent and long lasting appetite stimulators in humans
AgRP (agouti related protein)
how does ghrelin act on the body
- is relased from P/D1 cells in fundus of stomach or epsilon cells in pancreas. acts on arcuate nucleus to make NP-T and AgRP coexpression. this leads to a strong orexigenic signal to the paraventricular nucleus in the hypothalamus to stimulate ultradian and rhythmic patterns
what does leptin inhibit
leptin released by adipocytes inhibts arcuate nucleus (NP-Y and AgRP) AND ghrelin release by fundus of stomach
how does leptin work on the body
released from adipocytes to activate POMC and CART cells in the arcuate nucleus to send anorexigenic negative signals to the paraventricular nucleus.
