Fever
Fever
?Normal body temperature,
37oC,Circadian variation <1o C
?Definition of fever,
An elevation of core body temperature above the
normal range
rectal T 0.5oC > oral T 0,5oC > axillary T（ 腋温 ）
Fever
?Hyperthermia (体温过高）
fever due to a disturbance of thermal regulatory
control
excessive heat production
decreased dissipation
loss of regulation
Fever
?Shifting of the Thermoregulatory set-point
?Maintaining an abnormally elevated Temperature
?Accelerating energy production
T increase 0.6oC = BMR increase 10%
Pathophysiology
?Body temperature is determined by two opposing
processes
heat production heat loss
? They are regulated by the central nervous system
? Energy in the form of heat is generated by living
tissues (thermogenesis)
? Energy may be passively absorbed from the
environment and transfer the energy to the
surrounding medium
Pathophysiology
?The body temperature is under control of the
preoptic area of the anterior hypothalamus（下丘脑）
Thermostat （恒温器）
?It receives input from both central receptors and
peripheral receptors
Heat production and heat loss
?Basal metabolic rate is controlled by hypothalamus,
by varying the level of circulating thyroxine （肾上
腺素）
?Increased muscle sensitivity (shivering)
?By varying the volume of blood flowing to skin?s
surface (>100 fold)
?By vaporization (exocrine sweating)
Set point
370C
390C
Heat Production Heat Loss
Heat
Production
Heat
Loss
Pathophysiology
?Elevation of body Temperature
shivering thermogenesis and dermal vasoconstriction
sympathetic outflow
?Cooling mechanism
sweating and dermal vasodilation
mixture of sympathetic and parasympathetic pathways
Pathophysiology
?Hypothalamic thermostat
Set point,37oC
lowest,4 a.m; peak,6~10 p.m
?Fever follow this pattern
?Factors affect body Temperature
exercise
menstrual cycle
environmental temperature
Pyrogens
?Neuroimmunoendocrine
?Substances that can cause fever
?Either exogenous or endogenous
Exogenous Pyrogens
?From outside the host
(some may be the endogenous products)
?Majority are microorganism,their products or
toxins
G-,endotoxin(内毒素）
(lipopolysaccaride,LPS) （脂多糖）
G+,lipoteichoic acid （脂磷壁酸）
peptidoglycan（肽聚糖）
varies superantigens and enterotoxins
Exogenous Pyrogens
?Others (endogenous products)
complement products
steroid hormone metablites
antigen-antibody complex with complement
?Most of them are with high molecule weight
?Could not penetrate blood-brain barrier
Endogenous Pyrogen
?In response to invasive stimuli,
exogenous pyrogen
chemical agents (amphotericin and other drug)
?Produced by the host,cells of immune system
?Designated ?monokines? and ?lymphokins?
cytokines （ 细胞因子 ）
Endogenous Pyrogen
?Cytokines
IL-1? IL-1? TNF?
TNF? IFN? IL-6
?Phagocytes and lymphocytes,major source of
pyrogenic cytokines
?It may also released through autonomous
production and secretion
Pathogenesis of fever
?Pyrogenic cytokines bind receptors present on
vascular endothelial cells that lie within the
hypothalamus
?Resetting the hypothalamic thermoregulatory
center by increased prostaglandin and cAMP
Pathogenesis of fever
?Bacteria provoke release of IL-1
Viral proteins stimulate IFN
?Combined production of several cytokines
cause fever
Production of endogenous pyrogens
Etiology and classification
?Infective fever
?Non-infective fever
Infective fever
?Metabolites from organism cause fever
?Most common causes of fever (50%~60%)
?Bacteria pyrogens,
common cause of infective fever (43%)
?Viral pyrogens,(6%)
Non-infective fever
?Absorption of necrotic substances,
injury ischemic necrosis cell necrosis
?Allergy Antibiotics
?Endocrine and metabolic disturbances,
hyperthyroidism dehydration
?Decreased elimination of heat from skin,
heat failure
Non-infective fever
?Dysfunction of central heat regulation
physical,heat stroke
chemical,barbiturate poisoning
mechanical,cerebral hemorrhage
?Dysfunction of vegetative nervous system
sympathetic overactivity
Clinical manifestation
?The grade of fever
Low grade fever,37.3~38oC
Moderate fever,38~39oC
High fever,39.1~41oC
Hyperthermia fever,>41oC
Clinical manifestation
?Clinical course of fever
Onset,Sudden onset within few hours
pneumonia
Gradual onset gradually for few days
typhoid
Persistence,varies pattern
Subsidence,by crisis or lysis
Character of fever
?Continued
T,kept at 39oC~40oC constantly
Circadian variation,< 1oC
pneumonia typhoid fever
?Remittent
T,>39oC circadian variation >2oC
rheumatic fever tuberculosis
septicaemia septic inflammation
Character of fever
?Intermittent
T,sudden rising (few hours) and sudden decreasing
malaria acute pyelonephritis
?Recurrent
T,abruptly rising to the peak,lasting for several
day,sudden decrease to the normal repeatedly
Hodgkin disease
Character of fever
?Undulant
T,rising gradually to the peak (>39oC)
decreasing gradually to the normal
repeatedly for several times
Brucellosis
?Irregular
tuberculosis rheumatic fever brochopneumonia
Fever pattern as diagnostic clues
Fever Pattern Cause
Alternate-day fever Plasmodium vivax,P,Ovale
Fever every third day P,Malariae
Relapsing fever
daily for 3~6 days Borrelia sp,rat bite fever
fever-free interval (Streptobacillus moniliformis;
for about 1 week Spirillum minus)
supervenes
Continuous,undulating” Brucellosis,typhoid
Periodic pyrexia Hodgkin?s disease
(Pel-Ebstein Phenomenon)
with variable cycles
Associated symptoms
?Chills or rigor,septicemia acute infections
?Congestion of conjunctiva,hemorrhage fever
?Herpes simplex,herpes virus (lobar pneumonia)
?Bleeding tendency,in severe infection (hepatitis)
blood dyscrasia (leukemia)
Associated symptoms
?Lymphadenopathy,lymphoma cancer metastasis
?Enlargement of liver and spleen,hepatitis
?Rash,drug rash measles
?Arthralgia,gout rheumtic disease
?Coma,barbiturate posioning hemorrhage
Diagnostic points
?Other symptoms besides fever
?Duration and magnitude of fever
?Close contacts with similar illness
?Occupational,travel,recreational exposure
?History of diseases associated with other organ
(diabetes chronic renal failure)
?Current medication (antibiotics and antipyretics)
?Allergy
Fever of unknown origin (FUO)
?FUO defined by Petersdorf and Beeson (1961)
Fevers higher than 38.3oC on several occasions
A duration of more than 3 weeks
Failure to reach a diagnosis after 1 week of inpatient
investigation
70%~90% of the cases can be diagnosed
?Modification
Three outpatient visits or three days in the hospital
Two weeks of fever
Summary
? Fever,elevation of set point
? Heat production/conservation
shivering dermal vasoconstriction
? Heat loss sweating dermal vasodilation
? Pyrogen,exogenous or endogenous
endotoxin (LPS) pyrogenic cytokines
PGEs cAMP Set-point
? Etiology,infective or noninfective
? Fever types
Fever
?Normal body temperature,
37oC,Circadian variation <1o C
?Definition of fever,
An elevation of core body temperature above the
normal range
rectal T 0.5oC > oral T 0,5oC > axillary T（ 腋温 ）
Fever
?Hyperthermia (体温过高）
fever due to a disturbance of thermal regulatory
control
excessive heat production
decreased dissipation
loss of regulation
Fever
?Shifting of the Thermoregulatory set-point
?Maintaining an abnormally elevated Temperature
?Accelerating energy production
T increase 0.6oC = BMR increase 10%
Pathophysiology
?Body temperature is determined by two opposing
processes
heat production heat loss
? They are regulated by the central nervous system
? Energy in the form of heat is generated by living
tissues (thermogenesis)
? Energy may be passively absorbed from the
environment and transfer the energy to the
surrounding medium
Pathophysiology
?The body temperature is under control of the
preoptic area of the anterior hypothalamus（下丘脑）
Thermostat （恒温器）
?It receives input from both central receptors and
peripheral receptors
Heat production and heat loss
?Basal metabolic rate is controlled by hypothalamus,
by varying the level of circulating thyroxine （肾上
腺素）
?Increased muscle sensitivity (shivering)
?By varying the volume of blood flowing to skin?s
surface (>100 fold)
?By vaporization (exocrine sweating)
Set point
370C
390C
Heat Production Heat Loss
Heat
Production
Heat
Loss
Pathophysiology
?Elevation of body Temperature
shivering thermogenesis and dermal vasoconstriction
sympathetic outflow
?Cooling mechanism
sweating and dermal vasodilation
mixture of sympathetic and parasympathetic pathways
Pathophysiology
?Hypothalamic thermostat
Set point,37oC
lowest,4 a.m; peak,6~10 p.m
?Fever follow this pattern
?Factors affect body Temperature
exercise
menstrual cycle
environmental temperature
Pyrogens
?Neuroimmunoendocrine
?Substances that can cause fever
?Either exogenous or endogenous
Exogenous Pyrogens
?From outside the host
(some may be the endogenous products)
?Majority are microorganism,their products or
toxins
G-,endotoxin(内毒素）
(lipopolysaccaride,LPS) （脂多糖）
G+,lipoteichoic acid （脂磷壁酸）
peptidoglycan（肽聚糖）
varies superantigens and enterotoxins
Exogenous Pyrogens
?Others (endogenous products)
complement products
steroid hormone metablites
antigen-antibody complex with complement
?Most of them are with high molecule weight
?Could not penetrate blood-brain barrier
Endogenous Pyrogen
?In response to invasive stimuli,
exogenous pyrogen
chemical agents (amphotericin and other drug)
?Produced by the host,cells of immune system
?Designated ?monokines? and ?lymphokins?
cytokines （ 细胞因子 ）
Endogenous Pyrogen
?Cytokines
IL-1? IL-1? TNF?
TNF? IFN? IL-6
?Phagocytes and lymphocytes,major source of
pyrogenic cytokines
?It may also released through autonomous
production and secretion
Pathogenesis of fever
?Pyrogenic cytokines bind receptors present on
vascular endothelial cells that lie within the
hypothalamus
?Resetting the hypothalamic thermoregulatory
center by increased prostaglandin and cAMP
Pathogenesis of fever
?Bacteria provoke release of IL-1
Viral proteins stimulate IFN
?Combined production of several cytokines
cause fever
Production of endogenous pyrogens
Etiology and classification
?Infective fever
?Non-infective fever
Infective fever
?Metabolites from organism cause fever
?Most common causes of fever (50%~60%)
?Bacteria pyrogens,
common cause of infective fever (43%)
?Viral pyrogens,(6%)
Non-infective fever
?Absorption of necrotic substances,
injury ischemic necrosis cell necrosis
?Allergy Antibiotics
?Endocrine and metabolic disturbances,
hyperthyroidism dehydration
?Decreased elimination of heat from skin,
heat failure
Non-infective fever
?Dysfunction of central heat regulation
physical,heat stroke
chemical,barbiturate poisoning
mechanical,cerebral hemorrhage
?Dysfunction of vegetative nervous system
sympathetic overactivity
Clinical manifestation
?The grade of fever
Low grade fever,37.3~38oC
Moderate fever,38~39oC
High fever,39.1~41oC
Hyperthermia fever,>41oC
Clinical manifestation
?Clinical course of fever
Onset,Sudden onset within few hours
pneumonia
Gradual onset gradually for few days
typhoid
Persistence,varies pattern
Subsidence,by crisis or lysis
Character of fever
?Continued
T,kept at 39oC~40oC constantly
Circadian variation,< 1oC
pneumonia typhoid fever
?Remittent
T,>39oC circadian variation >2oC
rheumatic fever tuberculosis
septicaemia septic inflammation
Character of fever
?Intermittent
T,sudden rising (few hours) and sudden decreasing
malaria acute pyelonephritis
?Recurrent
T,abruptly rising to the peak,lasting for several
day,sudden decrease to the normal repeatedly
Hodgkin disease
Character of fever
?Undulant
T,rising gradually to the peak (>39oC)
decreasing gradually to the normal
repeatedly for several times
Brucellosis
?Irregular
tuberculosis rheumatic fever brochopneumonia
Fever pattern as diagnostic clues
Fever Pattern Cause
Alternate-day fever Plasmodium vivax,P,Ovale
Fever every third day P,Malariae
Relapsing fever
daily for 3~6 days Borrelia sp,rat bite fever
fever-free interval (Streptobacillus moniliformis;
for about 1 week Spirillum minus)
supervenes
Continuous,undulating” Brucellosis,typhoid
Periodic pyrexia Hodgkin?s disease
(Pel-Ebstein Phenomenon)
with variable cycles
Associated symptoms
?Chills or rigor,septicemia acute infections
?Congestion of conjunctiva,hemorrhage fever
?Herpes simplex,herpes virus (lobar pneumonia)
?Bleeding tendency,in severe infection (hepatitis)
blood dyscrasia (leukemia)
Associated symptoms
?Lymphadenopathy,lymphoma cancer metastasis
?Enlargement of liver and spleen,hepatitis
?Rash,drug rash measles
?Arthralgia,gout rheumtic disease
?Coma,barbiturate posioning hemorrhage
Diagnostic points
?Other symptoms besides fever
?Duration and magnitude of fever
?Close contacts with similar illness
?Occupational,travel,recreational exposure
?History of diseases associated with other organ
(diabetes chronic renal failure)
?Current medication (antibiotics and antipyretics)
?Allergy
Fever of unknown origin (FUO)
?FUO defined by Petersdorf and Beeson (1961)
Fevers higher than 38.3oC on several occasions
A duration of more than 3 weeks
Failure to reach a diagnosis after 1 week of inpatient
investigation
70%~90% of the cases can be diagnosed
?Modification
Three outpatient visits or three days in the hospital
Two weeks of fever
Summary
? Fever,elevation of set point
? Heat production/conservation
shivering dermal vasoconstriction
? Heat loss sweating dermal vasodilation
? Pyrogen,exogenous or endogenous
endotoxin (LPS) pyrogenic cytokines
PGEs cAMP Set-point
? Etiology,infective or noninfective
? Fever types
