1. Fever

3. Normal rectal temperature 36.9~37.9 C
Axillary temperature 36~37 .0 C
Sublingual temperature 36.7~37.7 C
rectal temperature 36.9~37.9 C

4. Elevation of body temperature
physiological elevation
Pathophysiological elevation
fever
hyperthermia

5. Fever and hyperthermia
An elevation of body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamic set point----fever
Fever due to a disturbance of thermal regulatory control----hyperthermia
For example:
● excessive heat production (vigorous exercise, reaction to some anesthetics)
● decreased dissipation (dehydration)
● loss of regulation (hypothalmic injury)

6. Etiology and Mechanism of Fever

7. Development of fever fever Pyrogenic activator
Macrophage, monocyte, lymphocyte, etc.
Endogenous pyrogen
Thermoregulatory Centre
Mediators in regulation of body temperature
Rise in set point
fever

8. Pyrogenic activator
A substance that can manufacture and release endogeneous pyrogen which produces a fever.
1．Exogenous pyrogen
bacteria
virus
other microorganism
2. internal metabolic product
antigen-antibody complex
steroid
inflammatory substance

9. Exogenous pyrogen 1. Gram-negative bacterium Lipoplysaccharide,LPS
Endotoxin,ET
structure of ET
pyrogenic and toxic substance----lipid A
LPS---strong heat resistance which allows bacteria to endure 160 ℃ dry heat for about 2 hours.

10. Exogenous pyrogen 2. gram-positive bacterium engulfed by macrophages；
exogenous toxin （enterotoxin 、erythogenic toxin, diphthera toxin）
peptide polysaccharide
3. Virus and other microorganism
1. pyrogen of virus related with lipoprotein, hemagglutinin within the envelope；
2. pyrogens of fungus、Spirochaeta 、Chlamydia 、plasmodium may be considered to be LPS

11. Producing and releasing of EP
LPS joint pro
LPS
cell of producing EP
Toll receptor
Start transcription ,EP express
trigger NF-κB

12. Pyrogenic activator—internal metabolic product
1. Ag-Ab complex
activation of pyrogenic cells。
2. Steroid and inflammatory
Testosterone’s metabolic intermediate （etiocholanolone ）
Uric Acid Crystals

13. Endogenous pyrogenic cells
A fever-inducing substance (protein) produced by cells of the host body, such as leukocytes and macrophages
Source of EP
monocytes and macrophages ：blood mononuclear cell 、hepatic stellate cells 、pulmonary alveolar macrophage 、peritoneal macrophage
Cancer cell：hodgkin cancer cell、leukemia cell 、renal carcinoma cell
other cells：lymphocytes 、fibroblast 、endothelial cells
Endogenous pyrogenic cells

14. Types of EP （1）IL-1 (Interleukin-1) （2）IL-6 (Interleukin-6)
mainly from monocytes and macrophages
（2）IL-6 (Interleukin-6)
mainly from monocytes fibroblasts and TB lymphocytes
（3）TNF (Tumor necrosis factor)
TNF- 、TNF-
rTNF used for treatment during the stage I of tumor, however with side effect “ fever ” to the patients
（4）IFN (Interferon)
IFN- with strong pathogenicity
（5）Macrophage inflammatory protein -1（MIP-1）

15. Advanced thermoregulator centre- Lower thermoregulator centre-
Site affected by EP：
Pyrogenic activator
Advanced thermoregulator centre-
Macrophage, monocyte, lymphocyte, etc.
Preoptic anterior hypothalamus（POAH）
Endogenous pyrogen
Thermoregulatory Centre
Lower thermoregulator centre-
Mediators in regulation of body temperature
Medulla oblongata、pons、mesencephalon、spinal cord
Rise in set point
fever

16. EP’s ways of affecting nervous system
（1）blood-brain barrier
IL-1, IL-6, TNF through saturable transport system
infilterating to the brain from choroid plexus
（2）organum vasculosum laminae terminalis (OVLT)
OVLT: the blood-brain barrier’s weakest site comprising
fenestrated capillary with high permeability
（3）indirect regulation through vagus nerve
EP conduct impulse to the brain by stimulating vagus nerve.

17. Mediators of positive regulation
1. PGE
2. cAMP（Cyclin adenosine monophosphate）
cAMP, second messager cells，regultion of cellular function and synaptic transmission in POAH neurons，positive regulation of body temperature。
3. CRH（Corticotrophin releasing hormone）

18. Mediators of positive regulation
4. Na+/Ca2+ ratio
＊ Na+/Ca2+ratio↑ elevated thermoregulation
＊ ventricle[Ca2+] ↑ limit EP and cAMP in cerebrospinal fluid ↑
EP PGE2↑ Na+/Ca2+ratio↑ cAMP↑ elevated thermoregulation ↑
5. NO
＊ new type of neurotransmitter
＊ mechanism ①act on POAH、OVLT
②stimulate metabolism of brown fat to produce heat
③inhibit negative regulation

19. Mediators of negative regulation
1. Arginine vasopressin, AVP
AVP ↑ VSA、MAN
EP↓ PO/AH temperature↓
OVLT cap permeability ↓
2. α-melanocyte stimulating hormone,α-MSH
decomposition product of adrenocorticotropic hormone，highly effective in reducing temperature
3. A1(annexin A1)
the working together of positive and negative regulation to produce heat rise in the course of fever

20. Positive regulation center POAH Negative regulation center VSA,MAN
Ventral Septal Area
Medical Amygdaloid Neuleus
Action mode of EP EP
Positive regulation center POAH
Negative regulation center VSA,MAN
CRH↑
cAMP↑
PGE2↑
Ca2+↓
↑AVP
↑α-MSH
↑Ca2+
Elevated set point

21. The phase of fever Ⅰ Ⅱ Ⅲ .feverscence period .fastigium
.defeverscene period Ⅰ Ⅱ Ⅲ

22. Clinical manifestations
1.Metabolic features and clinical manifestations
phase
characteristics
Clinical manifestations
Onset of fever
Set point core temperature lower than the set point
Dissipation < production
Pale skin，chilly，shiver
Persistent of fever
Core temeprature meets set point
Dissipation = production
rubefaction ，dry skin，hot
Subsidence of fever
Set point normal set point
Dissipation > production
Heavy perspiration

23. 2.Changes in physiological functions
■ cardiovascular：heartbeat, blood pressure
■ respiratory: fever, blood temperature,
metabolism, acid production,
respiration frequency
■ digestive：appetite，digestion
■CNS: headache, illusion, febrile convulsion

24. 3.Changes in immune systems
Anti-infection
　　 inactivation of some heat-sensitive pathogenic microorganism like streptococcus , enhancement of the ability of some immune cells like human lymphocytes, while reduced function of some immune cells like NK cells
Cancer cells
to some extent, EP could inhibit cancer cells growth.
Acute phase response
definition：a series of reactions against injury caused
by bacteria infection and tissue damages, including
increased acute phase proteins and changes in microelements
of blood plasma and white cells

25. Prevention and treatment
Cases need emergency treatment
1. Primary affection
2. Basic treatment of fever
3. Cases in need of treatment in time
1. high fever (> 40℃)
2. patients with heart disease
3. pregnant women
4. headache, disturbance of consciousness, infantile convulsion

26. Treament drugs Physical measures Chemicals like salicylic acid
Steroids like
glucocorticoids
Herbal drugs

27. Case study
A 36-year-old man, One day prior to admission he was made worse by headach ,dizzy,aching pain and fever.
Check:
T 39℃,Ｐ100/min,R 20/min,Bp 100/70mmHg,congestion of throat,swelling of tonsil,respitatory rudeness,no bubbling sound

28. Lab findings: WBC：13.3×109/L,lymphocyte 16%, neutrophil 83%。
Treatment:
He was given antibiotic.
During transfusion, the patient suffer from chilly, shake, dysphoria and tempreture rose to Ｔ41.3℃,
Ｐ120/min, R 24/min,
Dexamethasone intravenous injection

29. Questions
1.What pathogenic mechanism account for this patient`s fever?
2.Why the patient shown chilly , shake, dysphoria and tempreture rose more?
3.How to treat and give medical order of nursing?