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  • 1. FEVER ENRIQUE DE LA MORA GLASKER M.D. www.freelivedoctor.com
  • 2. BODY TEMPERATURE
    • Controlled by the hypothalamus
      • (preoptic hypothalamus)
      • (post hypothalamus)
      • Monitoring body temperature
      • 1.- peripheral warmth / cold receptors-peripheral nerve
      • 2.-blood temperature of the regions
    www.freelivedoctor.com
  • 3. BODY TEMPERATURE
    • The metabolic rate of humans consistently produces more heat than is necessary to maintain the core body temp. of 37 oC
    • Body temperature is controled by heat dissipation from skin and lungs.
    www.freelivedoctor.com
  • 4. “ NORMAL” MEAN TEMPERATURE
    • Oral: 36.8 + - 0.4 oC (98.2 + - 0.7 o F
      • Low at 6 a.m.
      • High at 4 to 6 pm
      • Daily variation: 0.5 oC
      • Rectal temp. 0.4 oC (0.7oF) higher than oral
    www.freelivedoctor.com
  • 5. FEVER
    • A.M. TEMP. >37.2oC (98.8oF)
    • P.M. TEMP >37.7 oC (99.9oF)
    www.freelivedoctor.com
  • 6. TYMPANIC MEMBRANE THERMOMETER
    • Measuring radiant heat energy from the tympanic mebrane
    • Absolute value (unadjusted mode)
    • Adjusted value: calculated from data (absolute reading + radiant temp from clinical study results)
    • The masurements may be more variable than those obtained directly from oral or rectal means.
    www.freelivedoctor.com
  • 7. BODY TEMPERATURE
    • - 0.4 oC + 0.4 oC
    • TM oral rectal
    • -------I-----------I-------------I--------
    www.freelivedoctor.com
  • 8. FEVER
    • Elevation of body temp that exceeds the normal daily variation
    • Occurs in conjunction with an increase in the hypothalamic set point
    • For every increase of 1oC over 37 oC, 13% increase in oxygen consumption
    www.freelivedoctor.com
  • 9. FEVER
    • Once hypothalamic setpoint is raised, neurons in the vasomotor center are activated (vasoconstriction)
    • Vasoconstriction first noted in hands and feet (“cold hands and feet”)
    • Shivering is not required if heat conservation mechanisms sufficently raise blood temp
    www.freelivedoctor.com
  • 10. FEVER
    • When the hypothalamic setpoint is reset downward (due to (1) reduction in pyrogen concentration or (2) use of antipyretics), the process of heat loss initiates ( vasodilation, sweating)
    www.freelivedoctor.com
  • 11. HYPERPYREXIA
    • Fever > 41.5 oC (106.7o F)
    • Occurs with CNS hemorrhages (most common), sever infection
    www.freelivedoctor.com
  • 12. HYPERTHERMIA
    • Uncontrolled increase in body temp without changing setting of the thermoregulatory center.
    • Example: over-insulating clothes “heat stroke”
      • Work or exercise in hot environment
    www.freelivedoctor.com
  • 13. HYPERTHERMIA
    • Drug-induced hyperthermia
      • Monoamine oxidase (MAO) inhibitors
      • Tricyclic antidepressants amphetamines
      • Phencyclidine(PCP)
      • Lysergic acid diethylamide (LSD)
      • Cocaine
    www.freelivedoctor.com
  • 14. PYOGENIC CYTOKINES
    • IL-1, IL-6, TNF, ciliary neurotropic factor (CNTF), interferon (INF) alfa
    • The synthesis and release of endogenous pyogenic cytokines are induced by a wide spectrum of exogenous pyrogens.
    • Most of exogenous pyrogens are microbial products, microbial toxins or whole microorganisms.
    • Inflammation, trauma, tissue necrosis, or Ag-Ab complexes can induce the production of IL-1, TNF and / or IL-6
    www.freelivedoctor.com
  • 15. Neuroinmunoendocrine link
    • Exogenous pyrogen, chemicals
      • Proteins (“pyogenic cytokines”)
      • (behave as “endogenous pyrogens”)
        • Monokine (TNF-alfa)
        • Lymphokine (TNF-beta)
    www.freelivedoctor.com
  • 16. CYTOKINES
    • FEVER
    • HEMATOPOIESIS
    • INFLAMMATION
    • CELLULAR METABOLISM REGULATION
    • PRODUCTION OF ACUTE PHASE REACTANTS
    www.freelivedoctor.com
  • 17. CYTOKINES
    • Bind receptors on vascular endothelial cells in hypothalamus—reset hypothalamus thermoregulatory center
    www.freelivedoctor.com
  • 18. FEVER
    • ENDOTHELIAL CELLS-----cytokines----prostaglandin (PGE2,PGF2 a) production
    www.freelivedoctor.com
  • 19. THERMOGENESIS
    • Cytokines(IL-1 beta, etc) also directly interact with neural tissue—release of corticotropin---releasing factors---trigger thermogenesis
    www.freelivedoctor.com
  • 20. FEVER
    • In response to pyogenic stimuli, macrophages/monocytes, endothelial cells, and other cells produce pyrogenic cytokines (IL-1,IL-6, TNF, IFNO that enter the systemic circulation.
    • Circulating pyogenic cytokines cause increase in PGE2 in the periphery, causing nonspecific myalgias and arthralgias.
    • Also PGE2 in the brain is increased that starts the process of raising the hypothalamic setpoint for temperature
    www.freelivedoctor.com
  • 21.
    • Through one (EP-3) of four PGE2 receptors, PGE2 triggers glial cells resulting in the rapid release of cyclic adenosine 5`-monophosphate (cyclic AMP) that is a neurotransmitter
    • The release of cyclic AMP induces the release of monoamine neurotransmitters, and the hypothalamic set point is reset
    • (PGE2 appears to play no role in normal thermoregulation)
    www.freelivedoctor.com
  • 22. CLINICAL MANIFESTATION OF FEVER
    • “ Intermittent fever”
      • Can be seen in many conditions and diagnostically offering little help
      • “ drug fever”
        • Occurs with nearly any medication
        • No characteristic pattern
        • Many (20 to 60%) accompany with rash, nephritis, neutropenia.
    www.freelivedoctor.com
  • 23. CLINICAL MANIFESTATION OF FEVER
    • Dissociation between temp and pulse
      • Seen in:
      • Typhoid fever
      • Legionnaire`s disease
      • Psittacosis
      • Brucellosis
    www.freelivedoctor.com
  • 24. CLINICAL MANIFESTATION OF FEVER
    • Extreme pyrexia (Temp >106oF)
      • Failure of distal thermoregulation mechanism
      • (example)
      • Heat stroke
      • Neuroleptic malignat syndrome
      • Succinylcholine-associated malignant hyperthermia
    www.freelivedoctor.com
  • 25. MECHANISMS OF ANTIPYRETIC AGENTS
    • The rate of PGE2 synthesis from arachidonic acid depends on the activity of cyclooxygenase, and inhibitors of cyclooxygenase are potent antypiretics.
    • As effective antypiretics, glucocorticoids reduce PGE2 synthesis by inhibiting the activity of phospholipase A2 that is needed to release arachidonic acid from the cell membrane.
    • Glucocorticoids also block the transcription of the MRNA for the pyrogenic cytokines.
    www.freelivedoctor.com
  • 26. TREATMENT OF FEVER
    • Objectives:
    • 1.-To reduce the elevated hypothalamic set-point.
    • 2.-Facilitate heat loss.
    www.freelivedoctor.com
  • 27. ASPIRIN AND NSAIDS
    • Oral aspirin and NSAIDS effectively reduces fever.
    • Also reduce systemic symptoms of headache, myalgias, arthralgias due to reduction of PGE2 production.
    www.freelivedoctor.com
  • 28.
    • TREATMENT OF HYPERTHERMIA
    • The attempt to lower the already normal hypothalamic set-point is of little use
    • Inmediate physical cooling, I.V. Fluids and appropiate pharmacologic agents (dantrolen sodium, procainamide) are needed.
    www.freelivedoctor.com

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