Acid Peptic Disorders of the Stomach and SB

gastric body
-mucous neck cells
-parietal cells
-chief cells
-ECL cells

gastric antrum
-mucous cells
-G cells

Hydrochloric Acid- kills microorganisms, cleaves pepsinogen to pepsin at pH<4

Intrinsic Factor- binds cit B12 which allows absorptionin the terminal ileum.

B12 is liberated from dietary proteins by pepsin/acid
B12 binds to salivary/gastric R factor
B12 is cleaved from R factor by pancreatic proteases
B12 binds to Intrinsic Factor
B12-IF complex binds to ileal receptor

autoimmune gastritis
antibodies directed against:
parietal cells
intrinsic factor
mucosal damage is greatest in body and fundus
gland destruction leads to:
achlorhydria
vitamin B12 deficiency
gastritis - metaplasia - dysplasia - carcinoma

Pepsinogens: cleaved to active from by HCL, pepsin is a proteolytic enzyme.

Histamine: stimulates parietal cell to secret HCL
Histamine release by ECL cells is stimulated by gastrin, acetylcholine (vagus) and is inhibited by somatostatin

Gastrin-stimulates ECL cells to release Histtamine, stimulates oxyntic glands to secrete:HCL, pepsinogens
has a trophic effect on parietal cell mass and ECL cell mass

Gastrin release stimulated by:
gastric distention
amino acids
Gastrin release inhibited by:
somatostatin
gastric acid

Somatostatin-inhibits histamine release by ECL cells, inhibits gastrin release by G cells, and inhibits HCL secretion by parietal cells

Somatostatin release is stimulated by acid, CCK and gastrin. Inhibited by ACh (vagus)

histamine*gastrinACh

somatostatin, prostaglandins, epidermal growth factor EGF

Elicited by sight, smell, and taste of food entirely mediated by the vagus nerve directly stimulates parietal cell
stimulates ECL cells to release histamine
stimulates antral G cell to release gastrin
inhibits D cell release of somatostatin.
feedback inhibition: low gastric pH evokes
direct inhibition of parietal cells and G cells
inhibitory neural reflexes

gastric distension-mechanoreceptors in the gastric wall initiate vasovagal reflexes
amino acids and peptides- stimulate antral G cells to secrete gastrin

Stimulation:
duodenal distention initiates vagovagal reflex.
peptides and AA stimulate duodenal G cells.
Inhibition**:
acid in duodenum -
inhibits vagovagal reflex
releases secretin, which inhibits acid secretion
through inhibition of g cell gastrin release
fat and protien in the duodenum-
release CCK, which inhibits acid secretion
through stimulation of D cell somatostatin release

mucus secretion
bicarbonate secretion
epithelial barrier
mucosal blood flow

H. Pylori, NSAIDS, Stress, Gastrinoma

small gram negative rod with flagella
colonizes the mucous layer (not invasive)
elaborates urease
produces ammonia and thereby neutralizes acid
strains expressing cagA and vacA genes are the most ulcerogenic and carcinogenic
induces chronic gastritis through the elaboration of cytotoxins and bacterial lipopolysaccharide
inflamed gastric mucosa produces less mucus and bicarbonate, hindering mucosal protection

The most common cause of gastritis is H. pylori
Chronic inflammation leads to:
intestinal metaplasia > dysplasia > carcinoma
H. pylori has been associated with a 6-fold increase in the incidence of gastric cancer.
H. pylori may cause up to 40% of all cases of gastric adenocarcinoma.
H. pylori may cause up to 90% of all cases of MALT (mucosa-associated lymphoid tissue) lymphoma.

serology
urea breath test
stool antigen assay
biopsy urease test (CLO)
histology
culture

older people have more- but they have more bc of the primitive sanitation when they were growing up

clarithromycin 500 mg PO bid    amoxacillin 1 gm PO bid    omeprazole 20 mg PO bid2 antibiotics plus PPI

Cyclo-oxygenase (COX) exists in 2 formsCOX-1  constitutive isoform of COXproduces prostacyclin      (cytoprotective in gastric mucosa)COX-2inducible isoforminduced by inflammation, cytokines

increase mucosal blood flowstimulate the secretion of   mucus and bicarbonateincrease mucosal cell restitutioninhibit acid secretion

decrease mucosal blood flowdecrease mucus productiondecrease bicarbonate productionmay increase secretion of acid and pepsintopical toxicity probably not related to PG

inhibition of COX-2 results in desired effects of decreased inflammationinhibition of COX-1 results in undesired effects of gastrointestinal toxicitytherefore, a selective COX-2 inhibitor could theoretically provide all the benefit of an NSAID without the adverse effects

Seen only in extremely sick patientstraumaburnshead injuriesventilator patientsrelated to alpha-adrenergic mediated decrease in mucosal blood flow

endocrine tumors of the duodenum or pancreas (rarely stomach,liver, spleen)
1/3 patients have MEN-1
dramatic gastrin production
drives acid production by parietal cells
increases parietal cell and ECL cell mass
90% of patients have PUD
50% of patients have diarrhea
diagnosis is based on serum gastrin level
tumor localization
endoscopic ultrasound, octreotide scan, CT scan
surgical resection is the only curative therapy
> 50% are locally invasive or metastatic at dx
PPI therapy provides best symptom palliation

pain
bleeding
perforation
gastric obstruction

acetylcholine
anticholinergics
vagatomy
histamine
H2 receptor antagonists
gastrin
antrectomy
proton pump inhibitors

Cimetidine (Tagamet) 400 mg PO bidRanitidine (Zantac) 150 mg PO bidFamotidine (Pepcid) 40 mg PO qHSNizatidine (Axid) 150 mg PO bid

Omeprazole (Prilosec) 20 mg PO daily
Lansoprazole (Prevacid) 30 mg PO daily
Dexlansoprazole (Kapidex) 30 mg PO daily
Pantoprazole (Protonix) 40 mg PO daily
Rabeprazole (Aciphex) 20 mg PO daily
Esomeprazole (Nexium) 40 mg PO daily

Misoprostol (Cytotec) 200 mcg PO qid
a synthetic prostaglandin E1 analog
increases mucus and bicarbonate production
also inhibits acid production
Sucralfate (Carafate) 1 gm PO qid
adheres to ulcer base, forming a protective barrier
also inhibits pepsin activity