PATOFISIOLOGI

PERITONITIS EDCAUSA TB

Hormonal regulation Gastrin, CCK, Gihrelin, Growth factor and cytokynes adrenal Corticosteroids

1. 2.

3.

4. 5.

6.

7. Prostaglandins ( PGE2 and PGI2) maintain and enhance all mucosa defensive mechanism working synergistically with nitric oxide.

Unstirred layer of mucus And bicarbonate Surface epitelial cells secrete mucus, bicarbonate, generate prostaglandins, heat shock proteins, tretoil, peptides, and antimicrobial cathelicidins Cells renewal from mucosa progenitor cells is stimulated by growth factors (e.g. TGF and IGF-1) utilizing EGF receptor. Alkaline tide Microcirculations trough capillaries is maintained by continous generations of prostaglandins, nitric oxide, etc. Sensory nerves gastric mucosa and sub mucosa vessels are innervated by primary afferent sensory neurons and nerves forming a dense pluxus at the mucosa based.

Gastric Ulcers
GUs can represent a malignancy should be biopsied upon discovery Benign GUs :
most often found distal to the junction between the antrum and the acid secretory mucosa quite rare in the gastric fundus associated with H. pylori are also associated with antral gastritis.

Gastric Ulcers
Majority of GUs can be attributed to either H. pylori or NSAID-induced mucosal damage Gastric acid output (basal and stimulated) tends to be normal or decreased in GU patients
When GUs develop in the presence of minimal acid levels, impairment of mucosal defense factors may be present.

NSAID-Induced PUD
The spectrum of NSAID-induced morbidity :
5060%: nausea and dyspepsia 1530%: serious GI complication endoscopydocumented peptic ulceration 1.5% : complicated by bleeding or perforation

NSAID-Induced PUD
Established risk factors: advanced age, history of ulcer, concomitant use of glucocorticoids, high-dose NSAIDs, multiple NSAIDs, concomitant use of anticoagulants, clopidogrel, and serious or multisystem disease Possible risk factors: concomitant infection with H. pylori, cigarette smoking, and alcohol consumption.

Pathophysiology
Prostaglandins play a critical role in maintaining gastroduodenal mucosal integrity and repair. Interruption of prostaglandin synthesis impair mucosal defense and repair facilitating mucosal injury via a systemic mechanism

Pathophysiology
Animal studies: neutrophil adherence to the gastric microcirculation plays an essential role in the initiation of NSAID-induced mucosal injury The interplay between H. pylori and NSAIDs in the pathogenesis of PUD is complex
Meta-analysis: these aggressive factors is independent and synergistic risk factors for PUD and its complications such as GI bleeding.

 Aspirin and many NSAIDs are weak acids

that remain in a nonionized lipophilic form when found within the acid environment of the stomach.

alter the surface mucous layerpermitting back diffusion of H+ and pepsin leading to further epithelial cell damage

 Injury to the mucosa also occurs as a result of the topical encounter with NSAIDs
migrate across lipid membranes of epithelial cells trapped intracellularly in an ionized form leading to cell injury

Enteric-coated or buffered preparations are also associated with risk of peptic ulceration.

MECHANISMS BY WHICH NSAIDs MAY INDUCE MUCOSAL INJURY.

Endothelial effects Stasis Ischemia Direct toxicity ion trapping Ephithelial effects ( due to prostaglandin depletion) HCI secretion Mucin secretion HCO3secretion Surface active phospholipid secretion Epithelial cell proliferation

ULCER

Acid

HEALING (spontaneous or therapeutic)

EROSIONS