2. 37 ℃ Set point BT normal Pyrogen affected body Fever happened Fever

3. An elevation of body temperature is fever? 36 ℃ 40 ℃ Physiologic elevation of body temperature

4. A pathologic elevation of body temperature is fever? Heatstroke Hyperthyroidism Central nervous system damage hyperthermia

5. Physiologic temperature elevation Physiologic temperature elevation Pathologic temperature elevation Pathologic temperature elevation Temperature elevation Fever Hyperthermia Classification

6. Hyperthermia is an unregulatory temperature rising It is a passive process There is no change of the set point

7. Fever is a regulatory temperature rising It is an active process It is the body’s active reaction to pyrogen

8. How can we prove that there is no temperature regulation dysfunction during the development of fever? Fever Animal model High environment temperature Heat dissipation low environment temperature Heat production

9. Definition Fever is defined as a regulatory body temperature elevation response to the pyrogen, it is induced by an upward shift of the set-point in thermoregulatory center. Fever is defined as a regulatory body temperature elevation response to the pyrogen, it is induced by an upward shift of the set-point in thermoregulatory center.

10. Pathogenesis

11. Pyrogenic Activator Microbial agents: G +, G -, exotoxins etc Microbial agents: G +, G -, exotoxins etc Non-microbial agents: steroid, antigen- antibody complex, urate crystal ect Non-microbial agents: steroid, antigen- antibody complex, urate crystal ect Pyrogenic activator EP-producing cellsEP

12. Endogenous Pyrogens IL-1 IL-1 TNF TNF IFN IFN IL-6 IL-6 IL-8 IL-8 MIP-1 MIP-1

13. Thermoregulatory Center Warm-sensitive neurons Cold-sensitive neurons

14. Pathway of Pyrogenic Signal to The Thermoregulatory Center The blood-brain barrier The blood-brain barrier The blood-brain barrier The blood-brain barrier Organum vasculosum laminae terminalis Organum vasculosum laminae terminalis Vagal afferent nerve fibers Vagal afferent nerve fibers Vagal afferent nerve fibers Vagal afferent nerve fibers

15. Hypertension: high blood pressure opens the BBB Development: the BBB is not fully formed at birth. Radiation: exposure to radiation can open the BBB. Infection: exposure to infectious agents can open the BBB. The BBB can be broken down by:

17. Regulatory Mediators PGE PGE CRH CRH NO NO CAMP CAMP Na + /Ca 2+ Na + /Ca 2+ PGEFever ?

18. PGEFever ? Observation relate to the appearance of number of PGE more or less simultaneously to the development of fever Observation relate to the appearance of number of PGE more or less simultaneously to the development of fever

19. PGEFever ? Observation relate to the appearance of number of PGE more or less simultaneously to the development of fever Observation relate to the appearance of number of PGE more or less simultaneously to the development of fever Injections of PGE evoke fever in various species of experimental animals Injections of PGE evoke fever in various species of experimental animals

20. PGEFever ? Observation relate to the appearance of number of PGE more or less simultaneously to the development of fever Observation relate to the appearance of number of PGE more or less simultaneously to the development of fever Injections of PGE evoke fever in various species of experimental animals Injections of PGE evoke fever in various species of experimental animals Injections of inhibitor suppress fever Injections of inhibitor suppress fever

21. Regulatory Mediators 42 ℃ thermometer

22. Regulatory mediators PGE,CRH,NO,CAMP,Na + /Ca 2+ ect Positive regulatory mediators PGE,CRH,NO,CAMP,Na + /Ca 2+ ect Negative regulatory mediators AVP,α-MSH, lipocortin-I ect

23. ↑Heat production ↑Heat production ↓Heat loss ↓Heat loss Set point 37 ℃ BT Pyrogen affected body

24. ↑Heat production ↑Heat production ↓Heat loss ↓Heat loss ① Chemical reactions of metabolism metabolism ② Sketal muscle tone and contraction contraction ③ Chemical thermogenesis Chills and shivering

26. Mechanism of fever

27. Alteration in Metabolism and Function Carbohydrates Carbohydrates Lipids Lipids proteins proteins

28. Benefits of Fever Simply raising of body temperature kills many microorganisms and adversely affects their growth and replication Simply raising of body temperature kills many microorganisms and adversely affects their growth and replication Higher body temperatures decrease serum levels of iron, zinc, and copper—minerals needed for bacterial replication Higher body temperatures decrease serum levels of iron, zinc, and copper—minerals needed for bacterial replication Increased temperature causes lysosomal breakdown and autodestruction of cells, preventing viral replication in infected cells Increased temperature causes lysosomal breakdown and autodestruction of cells, preventing viral replication in infected cells Heat increases lymphocytic transformation and motility of polymorphonuclear neutrophils, facilitating the immune response. Heat increases lymphocytic transformation and motility of polymorphonuclear neutrophils, facilitating the immune response.

29. Principles of Treatment Treatment of primary affections Treatment of primary affections General treatment to fever General treatment to fever Antifebrile treatment Antifebrile treatment alcohol sponging, aspirin, corticosteroids alcohol sponging, aspirin, corticosteroids