Fever

Shanghai Institute of Digestive Disease

Department of Gastroenterology , Renji Hospital

Shanghai Jiaotong University, School of Medicine

 Fever
Normal body temperature:
37oC (set point)
Circadian variation <1o C 36.3 - 37.2oC

Definition of fever:
An elevation of core body temperature above the
normal range

rectal T 0.5oC > oral T 0. 5oC > axillary T

 Fever
Pyrogens

Elevated set-point

Maintaining an abnormally elevated Temperature

BMR(basal metabolic rate) increases

BMR 10%
= T 0.6oC
T = Elevated set-point
 Hyperthermia (
fever due to a disturbance of thermal regulatory
control
excessive heat production
(e.g. vigorous exercise, a reaction to some anesthetics)
decreased dissipation
(e.g. dehydration)
loss of regulation
(injury to the hypothalamic() regulatory center)
 Hyperthermia
Excessive heat Decreased Loss of
production dissipation regulation

T > unchanged set-point

 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
 Heat production
Increased BMR, by varying the level of circulating
thyroxine )
( controlled by hypothalamus )

Increased muscle sensitivity (shivering)

 Heat loss
By varying the volume of blood flowing
to skins surface (>100 fold)

By vaporization (exocrine sweating)

 Pathophysiology

The body temperature is under control of the

preoptic area of the anterior hypothalamus

Thermostat

It receives input from both central receptors and

peripheral receptors
 Pathophysiology
Elevation of body Temperature
shivering thermogenesis and dermal vasoconstriction
sympathetic (outflow

Cooling mechanism
sweating and dermal vasodilation
mixture of sympathetic and parasympathetic pathways
 Set -point

Heat Heat Loss

390C
Production Sweating
Vasodilation

elevating
cooling
Shivering vasoconstriction
Metabolic activity
Heat
Heat Production 370C Loss
 Pathophysiology
Hypothalamic thermostat
Inherent 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
 Pathogenesis of fever

Pyrogens (
Substances that can cause fever
Either exogenous or endogenous

 Exogenous Pyrogens
From outside the host
(some may be the endogenous products)
Most of them are with high molecule weight
Could not penetrate blood-brain barrier

Stimulating monocytes and macrophages to

induce the formation of endogenous pyrogen
 Exogenous Pyrogens
Majority are microorganism, their products or
toxins
Gram-: endotoxin
(lipopolysaccaride , LPS)
Gram+: lipoteichoic acid
peptidoglycan
exotoxins()and enterotoxins(
 Exogenous Pyrogens
Others
complement products
steroid hormone metabolites
antigen-antibody complex with complement
 Endogenous Pyrogen
In response to invasive stimuli:
exogenous pyrogen
chemical agents (amphotericin and other drug)
B
Produced by cells of immune system of the host
(macrophages, lymphocytes)
Proteins designated monokines and lymphokines
cytokines
 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
Bacteria provoke release of IL-1
Viral proteins stimulate IFN

Combined production of several cytokines

cause fever
 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 (PGE, )
and cAMP
Production of endogenous pyrogens

 Macrophage
ExP lymphocyte EnP hypothalamus

Heat loss
Fever Set point
Heat production
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 (penicillin-based)
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 (),
fever-free interval rat bite fever
for about 1 week
Continuous undulating Brucellosis, typhoid
Periodic pyrexia Hodgkins 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 rheumatic disease

Coma: barbiturate posioning cerebral 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
2 weeks of fever
 Summary
Fever: elevation of set point hypothalamus
Heat production
shivering dermal vasoconstriction
Heat loss sweating dermal vasodilation

Pyrogen: exogenous or endogenous

endotoxin (LPS) pyrogenic cytokines
PGEs cAMP Set-point
 Summary
Etiology: infective or noninfective

Fever types

Associated symptoms

Diagnostic points