D 2 Academic Elevator General Pathology Systemic effects
- Slides: 9
D 2 Academic Elevator General Pathology: Systemic effects Kanvar Panesar 10/27/15
general effects: fever ✤ fever - IL-1, IL-6, TNF-a ✤ resident M 0 and recruited m 0 through PAMPs and DAMPs activate NFk. B to stimulate cytokines ✤ IL-1 stimulates PGE 2 synthesis in hypothalamus increasing basal body temperature ✤ IL-6 and TNF-a directly stimulate hypothalamus
general effects: shock ✤ massive trauma/sepsis stimulates TNF-a release ✤ result: generalized vasodilation, h. TN, shock
general effects: leukocytosis ✤ increased #’s of leukocytes from neoplastic diseases such as leukemia ✤ stimulate by IL-6 and TNF-a ✤ neutrophilia - assoc. with bacterial inf, left shift ✤ lymphocytosis - assoc. with viral inf ✤ eosinophilia - assoc. with allergic rxn or parasitic inf
acute phase response ✤ very primitive ✤ includes ✤ altered lipid metabolism - INC total cholesterol, LDL, TG’s, DEC HDL ✤ gluconeogenesis - Sk/Ad tissue to INC blood sugar ✤ induction of acute phase proteins - [serum] INC/DEC by ~25% synthesized in liver and regulated by IL-1, IL-6, TNF-a ✤ INC - CRP, SAA, fibrinogen, haptoglobin ✤ DEC - albumin, transferin
CRP ✤ structure similar to Ig. M - pentameric ✤ binds to - phosphotidyl choline, phosphatidylethanolamine, chromatin, laminin, fibronectin ✤ complement activation via classical pathway ✤ CRP receptors expressed on M 0, m 0, and PMNs facilitate opsonization
CRP and atherosclerosis/MI ✤ Framingham study - INC HDL reduces CVD ✤ Ridker study - RCT, half of group assigned 325 mg ASA qd ✤ risk of MI increased 4 x higher in highest CRP quartile ✤ 1 tab of ASA cut risk more than half ✤ CVD accounts for 1/3 rd of all deaths
CRP and atherosclerosis/MI
CRP and periodontitis ✤ NHANES III - in severe PD ( > 10% of sites with > 4 mm pocket) mean CRP was greatest ✤ mean serum Ig. G Ab - increased with P. gingival ✤ INC cholesterol, LDL, TG’s and DEC HDL - acute phase response ✤ mechanism - anachoresis - seeding of oral bacteria to distant sites of inflammation via circulation ✤ PAVE study - periodontal therapy did NOT decrease incidence of subsequent MI (study design questioned)
