W.10: Pathophys. of GI tract Flashcards
Enzymes that are secreted by the chief cells?
- Pepsinogen
- Lipase
Hormones that are secreted by the endocrine cells?
- Gastrin
- Sertotonin
- Somatostatin
What does parietal cells secrete?
- HCl
- IF
Pathways of Vagus n. stimulation of parietal cells (3)?
Vagus n. –> M3 (Acetylcholine receptor)
–> Stimulation of parietal cell secretion of HCl
Vagus n. –> ECL cell (enterochromaffin- like cell) –> H2 (Histamin receptor) –> Stimulation of parietal cell secretion of HCl
Vagus n. –> G cell –> CCK3 (Gastrin receptor) –> Stimulation of parietal cell secretion of HCl
Which other cell type acts on H2 receptor?
Mast cells
Where are ECL cells found?
In corpus and fundus.
Which other pathway fo G- cells stimulate?
ECL- cell pathway.
Pathway of G- cell?
G cell –> CCK3 (Gastrin receptor) –> Stimulation of parietal cell secretion of HCl
Pathway of ECL- cells?
ECL cell (enterochromaffin- like cell) –> H2 (Histamin receptor) –> Stimulation of parietal cell secretion of HCl
Mode of action of Aspirin (NSAID)
Inhibition of COX2, thereby inhibition of AA binding to PGE2 receptor –> lack of inhibition mode of action of H2 receptor.
Mode of action of somatostatin?
Inhibition of gastric acid secretion by action upon inhibition of gastrin.
Possible reactions to an H. pylori infection (6)?
- Symtom free carrier 80%
- Duodenal ulcer 12%
- Chronic atrophic gastritis 4%
- Gastric ulcer 2%
- Gastric adenocaricnoma 1%
- MALT lymphoma <1%
Mode of action of bicarbonate?
pH of bicarbonate is 7, while that of gastric acid is 2. HCO3- protects the mucous layer by making it harder for H+ to penetrate the mucous layer which protect the gastric epithelium.
Main cause of duodenal cancer?
H. pylori infection.
Two main causes of formation of gastric ulcer?
- H. pylori
2. NSAID
One method used for detection of H. pylori?
Measurement of urease activity.
How does H. pylori colonosation affect gastric acid secretion?
NH4+ will increase the pH –> decrease of Somatostatin –> Increase of Gastrin –> Stimulation of parietal cells –> Increased HCl
Which pathogenetic factors lead to increased accidity?
- Urease
- OMP and outer membrane proteins
Pathogenetic factors leading to gastritis?
- Flagella
- Adhesion (adhesion fimbriae)
- Porins
- Toxins
- CagA (Cytotoxin Associated Gene) 50- 70%
- Vac (VACuolising toxin=
- LPS (Lipopolysaccharide = endotoxin)
Pathway of H. pylori by CagA
H. pylori –> CagA –> IL-8 –> Neutrophils –> Neutrophil/ macrophage –> ROIs –> Type IV secretion system
By which pathway does H. pylori lead to alterations in mucous glycoproteins which leads to epithelial damage? (2)
H. pylori –> PLA2 –> Alterations in mucous glycoproteins –> Epithelial damage
H. pylori –> Urase, LPS, Porin –> Macrophage –> IL-1beta, TNFalfa
–> Alterations in mucous glycoproteins –> Epithelial damage
H. pylori with its pathogenetic factors will lead to hyperacidity which will lead to? (2)
- Reflux (GERD)
- Duodenal cancer
Genetic predisposition eg. cytokine polymorphism will cause?
Mucosal atrophy (atrophic gastritis)
Mucosal atrophy (atrophic gastritis) may cause what? (2)
- Gastric ulcer
- Gastric carcinoma
Pharmacologic inhibition of gastric acid secretion? (4)
H2 antagonist (Cimetidin, Ranitidin).
Prostaglandin analoges (Misoprostol) --> PGE/I-2 receptor --> Inhibition of H2
Proton- pump- inhibitors (Omeprazol, Losec) –> Inhibition of H+/ K+ pump.
Antacids (Al(OH)3, Mg(OH)2, CaCO3, NaHCO3) –> Bind HCl
Mode of action of Bizmut on H. pylori?
Bacteriostatic
Effect of Bizmut combined with Amoxicillin on H. pylori?
Bacteriocid
Bizmut + Amoxicillin is combinde with?
Proton- pump- inhibitor (PPI)
Problems in treatment of H. pylori?
- Resistance
- Costs
GERD
Gastro- Esophageal- Reflux- Disease
Percentage of GERD that lead til serious complications?
10%
Possible cause to reflux?
Disfunction of LES (Lower Esophageal Sphincter) due to:
- Weakness
- Sponatenous relaxation
At which age does maturration of LES occur?
6 months
Physiologic form of G to E reflux may be caused by:
- Loose LES
- Too much:
- Eating
- Swallowing of too much air (–> burping)
GERD may lead to?
- Vomiting
- Foreful
- Painful
- Persistent, not onlu after eating
Complications of GERD?
Inflammation: Reflux esophagitis
–> Barrets esophagus –> Esophageal cancer
Strictures –> Axhalasie or nutcracker esophagus
Definition of Barrets esophagus?
Cuboidal epithelial metaplasia of the lower esophagus
normal type of epithelium of esophagus is sqamous non- keratinized ep.
Which complications may be seen due to Barrets metaplasia?
- Barrets ulcer
- Esophageal adenocarcinoma
Definition of Achalasia?
Narrowing of esophagus.
(possible complaints: difficulty of swallowing solid food).
Percentage that GERD lead to complications?
25%
Which TLR is expressed by the flagellum of H. pylori?
TLR5
Which TLR is expressed by endotoxin (LPS)?
TLR4
How can TLR signaling be inhibited?
By miRNAs.
H. pylori –> Inflammation –>
miRNA activation –> Inhibition of inflammatory signaling (negative feedback)
Which interleukins are produced by the H. pylori?
IL-1 and IL-6.
Which genetic syndromes may have a role in development of colorectal cancer in the 10% of the population?
- Familiar adenomatous polyposis (FAP) = Multiple papillary adenoma
- Hereditary non- polyposis colorectal cancer (HNPCC)
What may lead to HNPCC?
DNA micro satellite instability (MSI)
What is a micro satellite?
2- 5 nucleotide which repeats 5- 50X. Has high mutation rate.
Ususally DNA mismatch repair (MMR) enzyme corrects errors caused by DNA polymerase. In case of MMR deficiency, what might develop?
Micro satellite deficiency.
4 different mutations of MMR cause HNPCC.
What is the patomechanism behind development of Polyposis coli?
Patomechanism is unknown. H. pylori eradication may cure it.
Untreated FAP may lead to?
Increased risk of developing colon carcinoma by 100%, before the age of 40.
Cause of FAP?
APC mutation.
APC: Adenomatous polyposis coli-= Tumour supressor gene.
Diagnosis of colorectal carcinoma is done by?
- Colonoscopy
- Videocapsule endoscopy
- Virtual endoscpoy
Percentage of mortality in pancreatic cancer?
85%
What might be the underlying cause of development of pancreatic cancer?
- Chronic pancreatitis
- Cytokine polymorphism
Underlying causes in development of IBD?
- Inflammation
- Autoimmunity
Difference in Crohn’s disease (CD) and Ulcerative colitis (US)?
Crohn’s disease: Illeitis terminalis - anywhere discontinous.
Ulcerative colitis (UC): Only colon - continous, ascending.
What may Crohn’s disease lead to in the small intestine?
Stenosis of the small intestine and formation of fistulas.
What is the endoscopic image in Crohn’s disease?
Cobbelstone pattern
Which may be the causes leading to Crohn’s disease?
Genetic defects:
- Family history
- > 70 genes (intestinal immune system)
- NOD2- CARD mutation, 205 of Crohn’s patients
Damage to the intestinal- barrier function:
- NSAIDs
- Intestinal- infections (Salmonella, E.coli)
- Immune response against normal flora
Abbreviation NOD2- CARD stands for?
Nucleotide- binding Oligomerization Domain containing 2- CAspase Recruitment Domain family member 15.
Therapy of Crohn’s focuses on?
Inhibition of inflammatory (Th1) cytokines with antibodies.
- TNF- alfa
- IFN- gamma
- IL- 2, 12
Pathology Colitis ulcerosa
- Only superficial mucosal damage
- Chronic disease –> Interstinal wall scarring, shortening of the colon.
Pathomechanism of Colitis ulcerosa?
- Autoimmunity
- Intestinal bacteria: H2S, red meat/ alcohol sulfur content
- Cigarette smoke: HCN (may be protective)
Leading symptoms of Colitis ulcerosa?
- Fever
- Flatulence
- Anemia
Diagnosis of Colitis ulcerosa is made by?
- Colonoscopy
- Histology
Therapy for Colitis ulcerosa?
- Anti- inflammatory drugs
- Immunosuppression
- Biologicals (antibodies: TNF- alfa, IFN- gamma, IL-2, 12)
