Fever Normal Axillary temperature 3637 0 C Sublingual

Fever

Normal Axillary temperature 36~37. 0 C Sublingual temperature 36. 7~37. 7 C rectal temperature 36. 9~37. 9 C

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

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)

Etiology and Mechanism of Fever

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

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

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.

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

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

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

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 Endogenous pyrogenic cells other cells： lymphocytes 、 fibroblast 、 endothelial cells

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

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

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

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

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

Mediators of negative regulation 1. Arginine vasopressin, 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. A 1(annexin A 1) the working together of positive and negative regulation to produce heat rise in the course of fever

Ventral Septal Area Action mode of EP EP Positive regulation center POAH CRH↑ c. AMP↑ PGE 2↑ Ca 2+↓ Medical Amygdaloid Neuleus Negative regulation center VSA, MAN ↑AVP ↑α-MSH Elevated set point ↑Ca 2+

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

1. Metabolic features and clinical manifestations Clinical manifestations phase characteristics 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 normal set point Subsidence of Set point Dissipation > production fever Heavy perspiration

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

3. Changes in immune systems q 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 q Cancer cells to some extent, EP could inhibit cancer cells growth. q 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

Prevention and treatment 1. Primary affection 2. Basic treatment of fever Cases need emergency treatment 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

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

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℃, Ｐ 100/min, R 20/min, Bp 100/70 mm. Hg, congestion of throat, swelling of tonsil, respitatory rudeness, no bubbling sound

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 Ｔ 41. 3℃, Ｐ 120/min, R 24/min, Dexamethasone intravenous injection

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?