1. D2 Academic Elevator General Pathology: Systemic effects
Kanvar Panesar
10/27/15

2. general effects: fever
fever - IL-1, IL-6, TNF-a
resident M0 and recruited m0 through PAMPs and DAMPs activate NFkB to stimulate cytokines
IL-1 stimulates PGE2 synthesis in hypothalamus increasing basal body temperature
IL-6 and TNF-a directly stimulate hypothalamus

3. general effects: shock
massive trauma/sepsis stimulates TNF-a release
result: generalized vasodilation, hTN, shock

4. 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

5. 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

6. CRP structure similar to IgM - pentameric
binds to - phosphotidyl choline, phosphatidylethanolamine, chromatin, laminin, fibronectin
complement activation via classical pathway
CRP receptors expressed on M0, m0, and PMNs facilitate opsonization

7. CRP and atherosclerosis/MI
Framingham study - INC HDL reduces CVD
Ridker study - RCT, half of group assigned 325mg ASA qd
risk of MI increased 4x higher in highest CRP quartile
1 tab of ASA cut risk more than half
CVD accounts for 1/3rd of all deaths

8. CRP and atherosclerosis/MI

9. CRP and periodontitis
NHANES III - in severe PD ( > 10% of sites with > 4mm pocket) mean CRP was greatest
mean serum IgG 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)