Chapter 5 Fever

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Chapter 5 Fever
Pain of China in 2003, difficulty to forget
forever
Zhao Mingyao zzu
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Child's temperature depends on where it is
measured
Method Temperature equal or higher than
Armpit 37.3 C
Oral 37.5 C
Ear (tympanic) 38.0 C
Rectal 38.0 C
.
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• fever means enhance of body temperature?

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Enhance of body temperature
Physiological
3 types
Body T?
Hyperthermia
Pathological
Fever
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Hyperthermia

• due to a disturbance of thermal regulatory
  control
• excessive heat production
• decreased dissipation
• loss of regulation

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Fever Definition

• a regulatory body temperature elevation
  response to the pyrogen, it is induced by an
  upward shift of the set-point in thermoregulatory
  center

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Fever
37?
normal
Set point
37?
Pyrogen affected body
BT
37?
Fever happened
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The Comparison between Hyperthermia and
Fever

• Hyperthermia
  Fever
• 1. Cause body or environment changes
  pyrogens
• 2. Set-point unchanged or damaged,
  up regulating
• or effector or
  gains fails
• 3. Body T very high level
  higher level
• 4. Treatment water-alcohol bathing
  antipyretics and
• 
  eliminate the cause
•  

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Section 1 Regulation of normal body temperature
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hypothalamus
Set point 37 ?
CSN
cold
WSN
Heat


effectors
Heat production
Heat loss
Body T 37 ?
Regulation of body T
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Section 2 Etiology

• Infectious factors
• Noninfectious factors

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Infective fever

• Metabolites( pyrogens) from microorganism
• Most common causes (5060)
• Bacteria (43)
• Viral pyrogens (6)

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Non-infective fever

• Absorption of necrotic substances cell necrosis
• AllergyAntibiotics
• (Ag Ab C)

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Section 3 Pathogenesis of fever

• Pyrogens Substances that can cause fever
• Either exogenous or endogenous (EP)

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1. Exogenous Pyrogens

• (1)From outside the host
• Majority are microorganism
• G- endotoxin (LPS)
• G lipoteichoic acid
• peptidoglycan

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Exogenous Pyrogens

• (2)Others (endogenous products)
• complement products
• steroid hormone metablites (mesostate) ------
  etiocholanolone
• Ag Ab C

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(3) Features of Exogenous Pyrogens

• Most with high molecule weight
• Could not penetrate blood-brain barrier

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2. Endogenous Pyrogen

• Features of EP
• In response to invasive stimuli
• Produced by the host, cells of immune system
• Designated cytokines

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Features of EP

• MW small, less than 20 000
• peptide
• sensitive to heat, 56 70 ?, 30 min,
  deactivation
• sensitive to enzyme
• acting site in brain

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(2) EP producing cells

• monocyte
• macrophage
• lymphocyte
• endothelium
• starlike cell
• neutrophil
• tumor cell
• glial
• mesenchymal cells

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Production of EP
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(3)Kinds of EP

• Determined
• IL-1
• TNF
• IFN
• IL-6
• MIP-1 ( macrophage inflammatory protein-1 )
• Related
• ciliary neurotrophic factor,
• endothelin,
• IL-8,
• IL-2(?)

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Total tendency

• Bacteria provoke release of IL-1
• Viral proteins stimulate IFN

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• (4) LPS trigger EP-releasing from cell

• Activator receptor(/Toll-like receptor,TLR)
• ?signal transduction system
• ?nuclear transcription(NF-?B)
• ?expression of cytokine gene
• ? EP ?

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Section 4 Thermoregulation of fever

• 1. Thermoregulation center
• Positive preoptic anterior hypothalamus
• (POAH)
• organum vasculosum laminae
• terminalis ( OVLT)
• Negative ventral septal area (VSA)
• medial amydaloid nucleus(MAN)

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2.Routes of peripheral signals into
thermoregulation center
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(1)
Indirective action of EP
OVLT area
Supraoptic recess third ventricle of brain
OVLT neuron
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Directive action of EP
(2)
OVLT area
Supraoptic recess third ventricle of brain
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(3) EP stimulating Hepatic Vagal Nerve
brain
If cut off
Vagal nerve
Liver
Kuffer cell
IL-R rich
fever
ipIL-1
ivLPS
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3. Central mediators of fever

• (1) the positive
• (2) the negative

hyperthermic ceiling
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Regulatory mediators

• Positive
• PGE, CRH, NO, cAMP, Na/Ca2 ect
• Negative
• AVP,a-MSH, lipocortin-I ect

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Febrile centric regulatory mediators

CRH ? EP? ? PGE ? ?Hypothalamus
Na/Ca2?? cAMP? NO ?
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Infection
noninfection
EP (Pyrogenic cytokines)
Exogenous pyrogens
Circumventricular organs (OVLT)
EP-produced Cells (MO/MF etc.. )
POAH VSA(MAN)
Central Chemical Febrile Mediators ? ??
Elevated set-point
Heat Conservation?
Fever
Heat loss?
Steps in pathogenesis of fever
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Section 5 Effect of fever on body

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• 1. Pathogenesis of sign and symptom during fever
• Base on
• Directive heat stimulation
• Sympathetic nerve system
• Metabolism synthesize?
• decompose?,but katolysis
• Cytokines

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Heat metabolism in fever

• Heat production/conservation
• shivering
• dermal vasoconstriction
• goose skin
• Heat loss
• sweating
• dermal vasodilation

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• Goose Skin

Goose skin
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• 2. Periods of fever
• (1)fervescence
• (2)persistent febrile
• (3)defervescence

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Clinical manifestation

• The grade of fever
• Low grade fever 37.338oC
• Moderate fever 3839oC
• High fever 39.141oC
• Hyperthermia fever gt41oC

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• (3)The biological roles of fever
• beneficial
• harmful

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Benefits of Fever

• kills and limits microorganisms
• decrease iron, zinc, and coppers
• lysosomal breakdown and autodestruction of cells
• increases lymphocytic transformation and motility
  of phagocytes

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Harmfulness of Fever

• Metabolism
• Function
• Structure

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Section 6 Prevention and treatment
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• How to treat fever
• 1. Remove causes
• 2. Under the status of heart disease, gt40C ,
• CNS symptom
• 3. Antipyretics aspirin---PGE
• GC----NF-?B, stabilize
  
• phagocyte
  membrane
• 4. Physical method ice water or alcohol
• sponging

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Thanks!