47 Gastrointestinal Disorder II Flashcards
H.pylori can be detected 100% in GU and 95% in DU.
Which of the below describes H.Pylori?
A. Gram-negative
B. Non-invasive spiral bacterium
C. spread infection via oral transmission
All of the above
C. Infected via oral transmission (e.g. contaminated endoscopy/ chopticks)
How H.pylori survive in low pH?
- Urease is highly expressed on cell wall of H.pylori, which causes H+ + urea to become HCO3- and NH4+
- With HCO3- leak out of the cell, cause neutralisation
How pylori cause epithelial mucosal cell damage, leading to PUD? (3 points)
- NH4+ is a cytotoxic agent that increases gastric mucosal damage.
- NH4+ produces endotoxin and exotoxin that increases mucosal ulceration
- Chemotactic factors recruit and activate inflammatory cells to increase mucosal inflammation.
What is the difference in location of H.pylori in GU and DU?
GU: gastric body, acid-secreting area by parietal cells (therefore it is due to diminishing gastric mucosal barrier rather than increased acid secretion)
DU: gastric antrum, hormone-secreting area (damage to D-cells, somatostatin decreased, no inhibitory effect on acid secretion)
Invasive tests for diagnosis of H.Pylori infected PUD:
Antral biopsy, requires tissue sample via endoscopy.
Name the 2 tests.
- Gram’s stain
2. Urease test
Name the 2 non-invasive tests for diagnosis of H.Pylori infected PUD. Briefly describe the 2nd one.
- Serological testing for antibody to H.Pylori (but positive test doesn’t imply active infection)
- Urea breath test
- high sensitivity and specificity for H.pylori
- 13C or 14C labelled urea (capsule/liquid). 13C is radioactive: health problem; 14C is expensive
- Swallowed together with ascorbic acid (citric acid), thus delay gastric emptying (acid is a potent gastric emptying inhibitor) for increasing contact time of urea and the H.pylori if present
- Collect samples and check isotope activity
***The bacteria contains urease to turn urea to HCO3- (and NH4+)
Briefly state the target of treating
A. GU
B. DU
A. Mucosal defence enhancement
B. Acid suppression
Name all the 5 treatments to suppress acid secretion.
Give examples.
- Antacids
- Al(OH)3, Mg(OH)2
- Nonspecific, side effects like Mg-induced diarrhea and Al induced constipation - H2 receptor antagonists
- cimetidine, ranitidine, famotidine
- inhibition of histamine-dependent acid secretion - PPI/ H+/K+-ATPase inhibitors
- omeprazole, iansoprazole
- inhibition of proton pump thus acid secretion
- more potent and long lasting (acts on the ATPase, need to wait for 24 hours after new ATPase are synthesized ) - Muscarinic receptor antagonists
- Pirenzepine, atropine
- Inhibition of Acetylcholine-stimulated acid secretion - Vagotomy/Antrectomy
- remove vagal nerve/ antrum
- Removal of Ach- or gastrin mediated acid secretion
Name the treatment to enhance mucosal defense.
Prostaglandin agonists
- misoprostol
- Inhibition of acid secretion; direct cytoprotection (mucous and HCO3- secretion)
Name the 2 treatments to eradicate H.Pylori directly.
- Triple therapy:
use of PPI (omeprazole) or H2 receptor antagonist (Ranitidine)
+ 2-3 antibiotics (Amoxycillin, metronidazole, clarithromycin)
- enhance healing rate and decrease recurrence - Bismuth salts
- toxic to H.Pylori
- Coat ulcer base
- adsorb pepsin
- enhance PG synthesis
- Stimulate HCO3- secretion
Side effects: Black tongue and stool
Balance between intestinal absorption and secretion (A>S = normal)
State 3 features of diarrhea.
- Absorption decreased
- Secretion increased
- GI motility increased
(Hypersecretion and Hypermotility)
What cells are responsible for absorption in GI?
In what scenario will these cells cause diarrhea?
Absorptive villus cells;
Villus cell damaged by inflammation and infection > also glucose/AA/Peptide carrier system
A
What cells are responsible for secretion in GI?
In what scenario will these cells cause diarrhea?
Crypt cells
- Overstimulation by bacteria (endotoxins), increased liquidity of luminal contents
S>A, causing diarrhrea
What are the neural and hormonal agents that stimulate intestinal secretion?
Briefly describe when each agent causes an “oma”.
Neural: VIP ○ Stimulate intestinal secretion ○ VIPoma results in pancreatic cholera (watery diarrhea) Mediator: cAMP (2nd messenger)
Hormonal:
Gastrin
Gastrinoma (excessive gastrin, act on parietal cells to produce HCl and IF) results in persistent watery diarrhea
What are the 3 broad categories of diarrhea? State the definition of each diarrhea.
Can they occur simultaneously?
- Malabsorptive diarrhea
- diarrhea due to impaired absorption by intestine
(e. g. infection, inflammation) - Osmotic diarrhea
- diarrhea due to accumulation of non-absorbable solutes in intestines - Secretory diarrhea
- diarrhea due to over stimulation of secretory crypt cells in villi by enteric pathogens/toxins.
Yes.
What is Celiac disease?
Which diarrhea is it related to ?
Celiac disease is a gluten (gliadin) -sensitive enteropathy (degeneration of villus cells)
Gluten, a wheat protein activates immunological reaction in GALT, causing inflammation and then loss of villous architecture (blunted/flattened villi)
Malabsorptive diarrhea.
Give examples of causes of osmotic diarrhea.
Glucose malabsorption (genetic defect of SGLT 1 in neonates)
Lactase deficiency (lactose intolerance in adults)
Explain the mechanism of osmotic diarrhea resulting from lactase deficiency.
Lactase deficiency > accumulation of lactose in bowel lumen, increased luminal osmolality in lumen > fluid accumulation in lumen (hypersecretion) > luminal distension > enhanced peristalsis (hypermotility) > watery diarrhea (lactose free diet helps)
Secretory diarrhea can be further subdivided into inflammatory and non-inflammatory diarrhea. What are the differences in nature of the two?
Inflammatory:
- Pathogens invade intestinal mucosa, elaborate toxins resulting in loss of mucosal integrity & inflammation
- E.g. invasive & cytotoxin-producing Salmonella
Non-inflammatory diarrhea:
- Pathogens colonize intestinal lumen/ produce toxins with intact mucosal integrity & no inflammation
- e.g. Enterotoxins from Vibrio cholerae or enterotoxigenic E. coli
Briefly state the effects of Vibrio cholerae on stimulating cholera toxin receptor (GM1-ganglioside) located on the crypt cell.
- When cholera toxin receptor is activated, cAMP increases, which activates protein phosphorylation and therefore cAMP-dependent CFTR channels (Cl- channels).
- Anion secretion (Na+ and Cl-)
Excessive loss of water and ions
e.g. K+ and HCO3-
Briefly state the effects of heat stable enterotoxigenic E.Coli on stimulating STa receptor and guanylate cyclase located on the crypt cell.
- Activation of heat stable enterotoxin receptor, cGMP increase > G kinase increases > protein phosphorylation increases Therefore cGMP-dependent CTFR channels
- Anion secretion (Na+ and Cl-)
State the differences of inflammatory and non-inflammatory diarrhea in terms of stool.
Inflammatory: bloody, mucoid
Non-inflammatory: watery
State the differences of inflammatory and non-inflammatory diarrhea in terms of volume.
Inflammatory: small volume, frequent bowel movements, dehydration is unusual
Non-inflammatory: Large, dehydration possible
State the differences of inflammatory and non-inflammatory diarrhea in terms of fecal leukocytes.
Inflammatory: many, frequently occult blood
Non-inflammatory: absent
State the differences of inflammatory and non-inflammatory diarrhea in terms of clinical symptoms.
Inflammatory: tenesmus, fever, severe abdominal pain
Non-inflammatory: no blood, no pus, no tenesmus, no fever, abdominal pain usually not prominent
State the differences of inflammatory and non-inflammatory diarrhea in terms of causes.
Inflammatory: Invasive and cytotoxin-producing microorganisms
e.g. Salmonella, Shigella, Invasive E.Coli
Non-inflammatory: Enterotoxin-producing bacteria, minimally destructive viruses
e.g. Vibro cholarae (cAMP dependent),
Enterotoxingenic E. coli (cGMP depedent),
Rotavirus (Gastroenteristis_
Why is oral rehydration therapy is not suitable for inflammatory type of diarrhea, but only non-inflammatory?
Villous cells are damaged and thus the glucose/AA/Peptide carrier system (e.g. SGLT 1) too, no effect when oral rehydration therapy is given,