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