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

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

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

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

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

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

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

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.

Pathogenesis

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

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

Thermoregulatory Center Warm-sensitive neurons Cold-sensitive neurons

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

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:

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

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

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

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

Regulatory Mediators 42 ℃ thermometer

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

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

↑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

Mechanism of fever

Alteration in Metabolism and Function Carbohydrates Carbohydrates Lipids Lipids proteins proteins

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.

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