1. FEVER İstanbul University Cerrahpaşa Medical Faculty Department of Pediatrics Prof. Dr. Ayşe Güler EROĞLU

2. The purpose of the lesson n Learning u The definition of fever u The control mechanisms of body temperature u The circadian rhythm of body temperature u Physiological factors that may increase body temperature u The pathogenesis of fever u Normal and abnormal body temperature u Etiologic classifications of fever u Treatment of the fever (in high–risk patients)

3. Definition of fever n Fever is an elevation of body temperature mediated by an increase of the hypothalamic heat regulatory set-point.

4. Control mechanisms of body temperature n Hypothalamic thermoregulatory center controls body temperature by u Peripheral cold and warm neuronal receptors u Temperature of blood circulating in the hypothalamus

5. Control mechanisms of body temperature n Heat generation u Increased cell metabolism u Muscle activity u Involuntary shivering n Heat conservation u Vasoconstriction n Heat loss u Obligate heat loss (evaporation, radiation, convection, conduction) u Vasodilation u Sweating

6. Human is “homoioterm” (has constant temperature) n Normal core body temperature 37 o C within a narrow range of 1-1.5 o C. n Axillary temperature may be 1 o C lower than core temperature - cutaneous vasoconstriction n Oral temperature may be falsely lowered owing to rapid respirations.

7. Circadian rhythm of body temperature n Early morning temperature is low n Highest level occurs at 4.00-6.00 PM

8. Physiological factors may increase body temperature n Physical activity (maximum 1.1 o C) n Digestion n Changes in environmental temperature n After ovulation in women n First three months of gestation n Exicement

9. Important n The body temperature should be measured u at bed rest or physically inactive for 30 minutes before the temperature is taken u within one hour after a meal u prior intake of cold or hot foods n Before 6 years old - rectal or axillary n After 6 years old - oral temperature measurement

10. Pathogenesis of fever n Various infectious, immunologic or toxin-related agents (exogenous pyrogens) induced the production of endogenous pyrogens by host inflammatory cells. These endogenous pyrogens are cytokines, such as interleukins (IL- 1 , IL-1 , IL-6), tumor necrosis factors (TNF- , TNF-  ), and interferon-  (INF).

11. Pathogenesis of fever n Endogenous pyrogenic cytokines directly stimulate to hypothalamus to produce prostoglandin E2, which then resets the temperature regulatory set point n Endogenous pyrogens induce fever within 10-15 min. Whereas the febril response to exogenous pyrogens has a delayed onset requiring the synthesis and release of pyrogenic cytokines (60- 90 min).

12. NormalLow grade fever High grade fever Rectal36.1-37.8 o C38-38.9 o C  39 o C Axillary35-37.4 o C37.5-38.4 o C  38.5 o C

13. Etiologic classification n Most common cause infections of the upper respiratory tract. n A. Respiratory infections n 1. Common cold n 2. Sinusitis n 3. Pharyngitis: most frequent cause of fever in childhood. n 4. Otitis media, mastoiditis n 5. Pneumonia n 6. Pulmonary tuberculosis

14. Etiologic classification n B. Urinary tract infections n C. Exanthemes n In the prodromal phase of exanthmatous diseases. n D. Enteric infections n 1. Salmonellosis n 2. Campylobacter enteritis n 3. Ascariasis n 4. Amebiazis

15. Etiologic classification n E. Infections of the central neural system n 1. Meningitis n 2. Encephalitis n 3. Poliomyelitis n F. Infections of the liver and biliary tract n 1. Infectious hepatitis n 2. Cholangitis n 3. Liver abscess n 4. Granulamatous hepatitis due to sarcoidosis,tuberculosis,hystoplasmosis, brucellosis.

16. Etiologic classification n G. Infectıons involving the heart n 1. Rheumatic fever n 2. Infective endocarditis n 3. Myocarditis n H. Systemic infections n 1. Bacteremia n 2. Infective endocarditis n 3. Infectiosus mononucleosus n 4. Epidemic influenza

17. Etiologic classification 5. Enterovirus infections 6. Cytomegalovirus infection 7. Psittacosis 8. Epidemic myalgia 9. Malaria 10. Toxoplazmosis 11. Tuberculosis in nonpulmonary form 12. Brucellosis n 13. Others

18. Etiologic classification n I. Abscesses, localized infections n 1. Osteomyelitis n 2. Intracranıal abscess n 3. Lung abscess n 4. Retropharyngeal abscess n 5. Alveolar abscess n 6. Perinephritic abscess n 7. Appendiceal abscess n 8. Pelvic abscess

19. Etiologic classification 9. Mediastinitis 10. Liver abscess 11. Subpherenic abscess 12. Spinal epidural infection 13. Purulant pericarditis 14. Empyema 15. Immunodeficiency diseases 16. Thrombophlebitis

20. Etiologic classification n II. Collagen-vascular or connective tissue disease n A. Rheumatic fever n B. Serum sickness n C. Dermatomyositis n D. Periarteritis nodosa n E. Polyarteritis nodosa n F. Lupus erythematosus n G. Juvenile romatoid artritis n H. Mixed connective tissue disease

21. Etiologic classification n III. Neoplastic diseases n A. Leukemia n B. Hodkin’s disease n C. Ewing tumor n D. Neuroblastoma with bone metastasis n IV. Dehydration n A. Especially in newborn and young infants n B. Hypertonic dehydration n C. Diabetes insipitus

22. Etiologic classification n V. Drugs, immunization n A. Disappears after 72 hours (after the drug is stopped) n B. Immunuzation reactions n VI. Blood diseases n A. Hemolytic anemia, especially during a crisis n B. Transfusion reactions

23. Etiologic classification n VII. Hemorrhage n A. If bleeding occurs into a viscus or other body tissue in hemorhagic disorders n B. Intracranial hemorrhage in the newborn n C. Adrenal hemorrhage in the newborn n D. Hemorrhage into a tumor

24. Etiologic classification n VIII. Miscallenous causes n A. Kawasaki disease n B. Familial mediterranean fever n C. Takayasu’ arteritis n D. Virilizing adrenal hyperplasia n E. Inflammatory bowel disease (Crohn disease) n F. Others

25. Treatment n Other than providing symptomatic relief, antipyretic therapy does not alter the course of common infectious diseases in normal children, and thus its use is controversial in these patients. n Antipyretic therapy is beneficial in high-risk patients u Chronic cardiopulmonary diseases u Metabolic disorders u Neurologic diseases u Febrile seizures

26. Treatment n Acetaminophen n Aspirin n Nonsteroidal anti-inflammatory agents (e.g., ibuprofen) n Aspirin - Reye syndrome n High dose acetaminophen - renal injury and hepatic failure n Ibuprofen - dyspepsi, gatrointestinal bleeding, reduced renal blood flow, and rarely aseptic meningitis, hepatic toxicity, or aplastic anemia n Bathing in warm water (not alcohol)

27. Hyperthermia n High body temperature not caused by hypothalamic thermoregulatory mechanisms n Increased heat production u Vigorous exercise u Malignant hyperthermia u Neuroleptic malignant syndrome u Hyperthyroidism n Decreased heat loss u Wrapping in multiple blanket layers u Atropine intoxication u Prolonged exposure to high environmental temperatures(heat stroke)

28. Malignant hyperthermia n Autosomal dominant disorder u A history of drug exposure u Previously affected family members u Exposure the high environmental temperatue u Absence of the hypothalamic regulated circadian rhythm u It also occurs in patients with various myopathic disorders.

29. Neuroleptic malignant syndrome n Occurs following exposure to phenothiazine-like agents and is indistinguishable from malignant hyperthermia.