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Fever

Fever. Preoptic anterior hypothalamus, POAH. Set-point ， 37℃. Thermal receptor. Regulation mode of normal body temperature . Heat dissipation. Heat production . Elevation of body temperature. physiological elevation Pathophysiological elevation fever hyperthermia.

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Fever

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  1. Fever

  2. Preoptic anterior hypothalamus, POAH Set-point，37℃ Thermal receptor Regulation mode of normal body temperature Heat dissipation Heat production

  3. Elevation of body temperature • physiological elevation • Pathophysiological elevation • fever • hyperthermia

  4. 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)

  5. Etiology and Mechanism of Fever

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

  7. 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

  8. 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 。

  9. 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

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

  11. Development of fever Pyrogenic activator endogenous pyrogenic cells Endogenous pyrogen Nerve center Mediators in regulation of body temperature Rise in set point fever

  12. Endogenous pyrogenic cells Endogenous Pyrogen 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

  13. Types of EP （1）IL-1 (Interleukin-1) mainly from monocytes and macrophages （2）IL-6 (Interleukin-6) mainly from monocytes fibroblasts and TB lymphocytes （3）TNF (Tumor necrosis factor) TNF-、TNF- rTNFused 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）

  14. Site affected by EP： Pyrogenic activator Macrophage, monocyte, lymphocyte, etc. Advanced thermoregulator centre- 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

  15. 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.

  16. 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）

  17. 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↑ Mediators of positive regulation 5. NO ＊new type of neurotransmitter ＊mechanism ①act on POAH、OVLT ②stimulate metabolism of brown fat to produce heat ③inhibit negative regulation

  18. 1. Arginine vasopressin, AVP AVP ↑ VSA、MAN EP↓ PO/AH temperature↓ OVLT cappermeability ↓ Mediators of negative regulation 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

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

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

  21. 1.Metabolic features and clinical manifestations

  22. 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

  23. 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

  24. Prevention and 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 Cases need emergency treatment

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

  26. Thank You

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