FEVER

Dr K Sathiamoorthy

Consultant Paediatrician

Shree Sakthi Hospital

NORMAL

Axillary temperature 36~37 .0 C

Sublingual temperature 36.7~37.7 C

rectal temperature 36.9~37.9 C

CONCEPT

一、  pyrogen set point of the

thermoregulatory center body temperature

TEMPERATURE

sport physiological T pregnancy luteal phase hyperthermia pathological T （ set point ± ） fever

Hyperthermia : thermogenesis thermolysis dysfunction of thermoregulatory center

二、 Causes and pathogenesis of fever

Pyrogen and activator of fever Activator : the substance can activate the cells

that can produce the pyrogen.

pyrogen: the substance can cause fever

ACTIVATORS OF FEVER

microbe: G- LPS, ET G+ peptidoglycan virus: enveloped virus particle: transfuse response 2. internal production immune complexes etiocholanolone

1. Extragenous

pyrogen

ENDOGENOUS PYROGEN(EP)

interleukin-1(IL-1) :MC,fibroblast IL-6:T,B lymphocyte, tumor cell TNF : TNF Mα φ TNF (lymphotoxin) active T β interferon ( IFN ): T lymphocyte

PRODUCING AND RELEASING OF EP

cell of producing EP

Toll receptor

LPSLPS joint

pro trigger NF-κB

Start transcription ,EP express

LPSLPS joint

pro

sCD14

LPS –sCD14

complexes

T

三、Mechanism : increase of set point1.the pathway: EP entry temperature center

PATHWAYS OF EP SIGNAL TRANSDUCTION TO THE THERMOREGULATION CENTER

a. blood brain barrier

Activator ActivatorActivatorActivatorCell of Producing EP

EP

blood brain barrier

Thermoregulation center

Thermoregulation center

SPSPTT

a.OVLT (organum vasculosum laminace terminalis ）

2.The mechanism: increase of set point

a. Warm sensitive neuron: thermolysis

b. Cold sensitive neuron: thermogenesis

Imbalance:Normal:warm sensitive neuron

cold sensitive neuron

THERMOREGULATION MECHANISM OF FEVER

Thermoregulation center1. The positive regulationpreoptic anterior hypothalamus, POAH

2. The negative regulationmedial amygdaloid nucleus, MANventral septal area, VSA

POSITIVE REGULATION MEDIATORS

1.PGE2: warm sensitive neuron

cold sensitive neuron Effective medicine: Aspirin, ibuprofen

2.CRH(corticotrophin releasing hormone) EP (IL-1 , IL-6 ) CRH media feverβ TNF , IL-1 PGEα α 2 media fever

SP

3. cAMP : SPEP hypothalamus: Na+ /Ca2+ cAMP

SP

4. Na+ /Ca2+ :5. NO:a. Activate metabolism Brown fatb. Inhibit Negative regulation mediatorsc. OVLT POAH T

NEGATIVE REGULATION MEDIATORS

Negative feedback: Febrile ceiling: < 42℃ endogenous cryogens AVP

-MSHα T center T

PERIOD AND METABOLISM OF FEVER

The period of febrile: 1.the fervescence period characteristic: thermogenesis>thermolysis chill brown adipose tissue(scapula

,large vessel of thoracic and

cervical metabolic rate

Thermogenesis

MANIFESTATION:

pale , gooseflesh, chill

warm sensitive neuron (POAH) Chill center

Chill cold sensitive neuron (POAH) cold stimuli Chill center

Chill skin T

Chill

Rubro nucleus

Lateral spinothalamic tract

Rubrospinal tract Reticulospinal tract

anterior motor cells

Up

Down

2.THE PERSISTENT FEBRILE PERIOD

The temperature reaches the new set point ★ Thermogenesis = thermolysis : SP on higher level ★Manifestation: febrile , headache metabolic rate and pulse rate anorexia

3.THE DEFERVESCENCE PERIOD

★ characteristic: Thermogenesis < thermolysis SP is reset to the normal level ★ Manifestation: the skin is warm and flush, sweat

fervescence persistent defervescence set point period period period

39 ℃

38 T℃ 37℃ time

METABOLISM CHANGE OF FEVER

1. Glycometabolism

Glycogenolysis Glycogen storage2. Fat metabolism lipodieresis Fat storage Ketosis3. proteometabolism

Protein catatabolism, negative nitrogen4. water\electrolyte metabolism\vitamin

metabolism T 1 metabolism rate 13%℃ acute phase response WBC

PHYSIOLOGICAL CHANGES:

1.CNS: headache , dizzy,drowsiness, febrile convulsion: 24h inheritance hypoxia discharge

2.immunity system IL-1: activator of lymphocyte IL-6 ： differentiation factor IFN: humoral factor TNF: anti-tumor

3.Digestion system Sympathetic digestive juice EP hypothalamus nauseated,vomit abdominal distention constipation

4. circulation system HR 1 HR 18℃ /min CO induce heart failure

5. Respiratory system Tachypnoea

PRINCIPAL OF TREATMENT

1.medicine Inhibit production of pyrogen: glucocorticoid:

inhibit IL-6 and TNFInhibit production of PGs: salicylic

2. physics: brain 1g water 2.5KJ(lose)

50%1~2%

ADVANTAGE AND DISADVANTAGE

1. Disadvantage Side effects

2. Advantage Signal: malariaSerious underlying infectionInflammation

NICE GUIDELINES:

ASSESSMENT AND INITIAL MANAGEMENT OF FEVERISH ILLNESS IN CHILDREN YOUNGER THAN 5 YEARS

WHY GUIDELINES NEEDED Fever = commonest reason for child to be take to a

doctor Fever = second commonest reason for a child being

admitted to hospital Infection = leading cause of death in children under five

years Fever without apparent source (FWS) particular

diagnostic difficulty Current variable management Difference in mortality and morbidity secondary to

health inequality

EVIDENCE BASE

Best available evidence Consensus technique: Delphi consensus Traffic light system to assess the risk of serious

illness as LOWLOW INTERMEDIATEINTERMEDIATE HIGHHIGH Direct management accordingly

CLINICAL ASSESSMENT

Identify life threatening features ABCD Assess the risk of serious illness using the traffic light

system Measure and record temperature, heart rate,

respiratory rate, and capillary refill time Attempt to identify a focus of infection or features of

specific serious conditions: Meningococcal disease, Meningitis, Herpes simplex

encephalitis, Pneumonia, UTI, Septic arthritis/ osteomyelitis, Kawasaki disease

Guidance on further ix if FWS

Copyright ©2007 BMJ Publishing Group Ltd.

Assessing the risk of serious illness in feverish children under age 5 years

MANAGEMENT OF CHILDREN < 3MTHS Febrile infants under 3 mths of age should have the

following ix: FBC, Blood cultures, CRP, Urine testing, CXR (if resp signs

present), Stool culture (if diarrhoea) LP (without delay and if poss < abx) if:

< 1 month 1-3 months who appear unwell 1-3 mths with WBC < 5 or >15

RX: 3rd generation cephalosporin + abx active against listeria

DETECTION OF FEVER

< 4 weeks: electronic thermometer, axilla chemical dot

thermometer 4wks-5yrs: electronic thermometer, axilla

chemical dot thermometer,

infra-red tympanic thermometer

Reported parental perception of fever should be taken seriously

Do not routinely use oral and rectal routes in children aged < 5 yrs

ANTIPYRETIC INTERVENTIONS Tepid sponging not recommended Do not under dress OR over wrap Antipyretic agents should not be routinely used

with sole aim to reduce fever in a child who is otherwise well

Paracetamol/Ibuprofen should not be administered at the same time

Paracetamol/Ibuprofen should not be given alternately to children with fever

Antipyretic agents do not prevent febrile convulsions and should not be given specifically for this purpose

OTHER RECOMMENDATIONS Healthcare professionals should not rely on a decrease or

lack of decrease in temp following anti-pyretic administration to differentiate between serious and non-serious illness

Children with symptoms and signs suggesting pneumonia who are not admitted should not routinely have an CXR

Oral antibiotics should not be prescribed to children with fever without apparent source

QUESTIONS