SlideShare ist ein Scribd-Unternehmen logo
1 von 58
Downloaden Sie, um offline zu lesen
Dept. of PathologyDept. of Pathology
Medical CollegeMedical College
Hunan Normal UniversityHunan Normal University
(( 湖南 范大学医学院病理学教研室师湖南 范大学医学院病理学教研室师 )) 1
Chapter 4Chapter 4
FeverFever
( )发热( )发热
22
FeverFever
a.a. IntroductionIntroduction
b.b. Causes and MechanismCauses and Mechanism
c.c. Stages and ManifestationsStages and Manifestations
d.d. Alterations of Metabolism andAlterations of Metabolism and
FunctionFunction
e.e. Pathophysiological Basis ofPathophysiological Basis of
Prevention and TreatmentPrevention and Treatment
Life Stages
0-2 years old 3-10 years old 11-65 years old Over 65
Circadian variation
of body temperature
2am 2pm 2am
37.5
36.5
Q: Why stable temperature?
Normal Temperature range: 36℃ ~ 37.5℃
Oral temperature: 37℃
heat loss
peripheral
thermo-sensors
deep thermo-
sensors
set point
blood vessel
skeletal muscle
heat production
balance
POAH
sweat gland
Regulation of Normal Body Temperature
POAH: preoptic anterior hypothalamus (- body’s thermostat)
Homeostasis (36℃ ~
37℃ )
Activates heat-loss center
in hypothalamus
Skin blood
vessels constrict
Skeletal muscles activated,
shivering begins
Skin blood
vessels dilate
Sweat glands
activated
Imbalance
Imbalance
Body
temperature
decreases
Activates heat-
promoting center in
hypothalamus
Hot stimulus
Blood warmer
than set point
Cold stimulus
Blood cooler
than set point
Body
temperature
increases
Definition of fever
Fever is a complicated pathological process characterized
by regulated elevation of body temperature following the
increased Set Point, which is caused by pyrogenic
substances.
Usually 0.5 higher℃ than normal body temperature.
There is no impairment in the thermoregulatory
mechanism during fever.
Q: Increase of body temperature = Fever?
Pathological elevation
Fever
Hyperthermia
Passive
Set Point: N
Physiological elevation
(Before menstruation, Strenuous exercise,
Stress)
Elevation
of body
temperature
Active
Set Point: ↑
1616
FeverFever
a.a. IntroductionIntroduction
b.b. Causes and MechanismCauses and Mechanism
c.c. Stages and ManifestationsStages and Manifestations
d.d. Alterations of Metabolism andAlterations of Metabolism and
FunctionFunction
e.e. Pathophysiological Basis ofPathophysiological Basis of
Prevention and TreatmentPrevention and Treatment
Pyrogenic
activator
Endogenous
pyrogen (EP)
EP
producing
cell
Producing
Releasing
Process of Fever Development
Causes of Fever
- Pyrogenic Activators
Pyrogenic activators ( 发热激活物 ) are
substances which can activate the EP-producing
cells to produce and release endogenous
pyrogen (EP).
Concept
Pyrogenic Activators
Classification of the
Pyrogenic Activators
Pyrogenic activators
Microbial pyrogens
Bacteria
Viruses
Other microorganisms
Non-microbial
Pyrogenic substances
Antigen-antibody
complexes
Component of
complement cascade
Steroids
Anticancer drugs
Gram-negative Bacteria:
(E. coli)
Pathogenic substance:
LPS (lipopolysaccharide, also named
endotoxin, ET)
Major pyrogenic component is
Lipid A
High m.w. (1,000 kDa)
Heat resistant: inactivated by
160℃ dry heat, 2 h
High pyrogenic activity
1 ng/kg to rabbit → fever
Tolerability (resistance to
repeated injection)
Gram-positive Bacteria:
Staphylococcus aureusStaphylococcus aureus,,
Streptococcus pneumoniaeStreptococcus pneumoniae
Pathogenic substances:Pathogenic substances:
Whole bacteria
ExotoxinExotoxin
PeptidoglycanPeptidoglycan
Viruses
Pathogenic substances:
 Protein coat - lipoprotein
 Haemagglutinin
Influenza virusInfluenza virus
Corona virusCorona virus
Substances that areSubstances that are produced by EP-producingproduced by EP-producing
cellscells under the action of pyrogenic activatorsunder the action of pyrogenic activators andand
cause the increase in the thermoregulatory setcause the increase in the thermoregulatory set
pointpoint in the hypothalamus.in the hypothalamus.
Fever-inducing cytokines (large, hydrophilicFever-inducing cytokines (large, hydrophilic
peptides).peptides).
Endogenous Pyrogens (EPs)
Monocytes/Macrophages
Endothelial cells
Lymphocytes
Tumor cells
Endogenous Pyrogen (EP)-
Producing Cells
Major Endogenous Pyrogens (EPs)
 Interleukin-1 (IL-1)Interleukin-1 (IL-1)
 Tumor necrosis factor (TNF)Tumor necrosis factor (TNF)
 Interferon (IFN)Interferon (IFN)
 Interleukin-6 (IL-6 )Interleukin-6 (IL-6 )
•Interleukin 1 (IL-1)Interleukin 1 (IL-1)
Produced by monocytes/macrophages, epithelialProduced by monocytes/macrophages, epithelial
cells,cells, etc.etc.
IL-1a and IL-1b have the same effect.IL-1a and IL-1b have the same effect.
Pyrogenic activity can be inhibited by cyclooxygenasePyrogenic activity can be inhibited by cyclooxygenase
inhibitorinhibitor (Aspirin).(Aspirin).
Heat sensitive: Inactivated by heating (70 30 min).℃Heat sensitive: Inactivated by heating (70 30 min).℃
No tolerance by repeated injections.No tolerance by repeated injections.
•Tumor necrosis factor (TNF)Tumor necrosis factor (TNF)
Produced byProduced by macrophagesmacrophages,, lymphoid cells, mast cells,lymphoid cells, mast cells,
endothelial cellsendothelial cells,, etc.etc.
Pyrogenic activity can be inhibited by cyclooxygenasePyrogenic activity can be inhibited by cyclooxygenase
inhibitor (Aspirin).inhibitor (Aspirin).
TNF-TNF-αα, TNF-, TNF-ββ are pyrogenic.are pyrogenic.
Heat sensitive: Inactivated by heating (70 30 min).℃Heat sensitive: Inactivated by heating (70 30 min).℃
No tolerance by repeated injections.No tolerance by repeated injections.
Interferon (IFN)Interferon (IFN)
Produced by lymphocytes, NK cells, fibroblasts,Produced by lymphocytes, NK cells, fibroblasts, etc.etc.
IFN-IFN-αα and IFN-and IFN-γγ can cause fever.can cause fever.
Can be tolerated after long period of use.Can be tolerated after long period of use.
Heat sensitive.Heat sensitive.
Interleukin 6 (IL-6)Interleukin 6 (IL-6)
Produced by mononuclear cells, fibroblasts, endothelialProduced by mononuclear cells, fibroblasts, endothelial
cells,cells, etc.etc.
Can be induced by ET, IL-1, TNF.Can be induced by ET, IL-1, TNF.
IL-6 is the downstream mediator of fever from otherIL-6 is the downstream mediator of fever from other
EPs (IL-1 and TNF).EPs (IL-1 and TNF).
Pyrogenic activity can be inhibited by cyclooxygenasePyrogenic activity can be inhibited by cyclooxygenase
inhibitor (Aspirin).inhibitor (Aspirin).
Mechanisms of Fever
POAH
Thermoregulatory Center
Positive regulatory center:Positive regulatory center:
Located at preoptic anteriorLocated at preoptic anterior
hypothalamus (POAH)hypothalamus (POAH)
Warm-sensitive neuronsWarm-sensitive neurons
Cold-sensitive neuronsCold-sensitive neurons
Negative regulatory center:Negative regulatory center:
Medial amydaloid nucleus (MANMedial amydaloid nucleus (MAN [[ 中杏仁核中杏仁核 ])])
Ventral septal area (VSAVentral septal area (VSA [[ 腹中膈腹中膈 ])])
Arcuate nucleus (ARCArcuate nucleus (ARC [[ 弓状核弓状核 ])])
Routes for Endogenous Pyrogens toRoutes for Endogenous Pyrogens to
Enter Thermoregulatory CenterEnter Thermoregulatory Center
a.a. Passive transport via organum vasculosumPassive transport via organum vasculosum
laminate terminal (OVLTlaminate terminal (OVLT [[ 小丘脑终板血管器小丘脑终板血管器 ], also called], also called
supraoptic crestsupraoptic crest))
 Most importantMost important
a.a. Through stimulating vagus nerveThrough stimulating vagus nerve (( 迷走神经迷走神经 ))
b.b. Active transport across the blood brain barrierActive transport across the blood brain barrier
(BBB)(BBB)
 Important in pathological conditionsImportant in pathological conditions
EPs can not directly act on thermoregulatory center
because of BBB.
Positive Regulation of Fever
Central Mediators of FeverCentral Mediators of Fever
- The positive regulatory mediators- The positive regulatory mediators
Prostaglandin E2 (PGE2)Prostaglandin E2 (PGE2)
Corticotrophin-releasing hormone (CRH)Corticotrophin-releasing hormone (CRH)
Cyclic adenosine monophosphate (cAMP)Cyclic adenosine monophosphate (cAMP)
Nitric oxide (NO)Nitric oxide (NO)
NaNa++
/Ca/Ca2+2+
ratioratio
Prostaglandin E2 (PGE2)
PGE2 can induce fever when injected into cerebralPGE2 can induce fever when injected into cerebral
ventricles.ventricles.
Bacterial endotoxin and EP can stimulate theBacterial endotoxin and EP can stimulate the
hypothalamus to produce PGE2.hypothalamus to produce PGE2.
Cyclooxygenase inhibitor can inhibit the production ofCyclooxygenase inhibitor can inhibit the production of
PGE2.PGE2.
PGE2PGE2 ↑↑ in cerebrospinal fluid during fever.in cerebrospinal fluid during fever.
Arachidonic Acid Metabolism
Pain
Corticotrophin-releasing hormoneCorticotrophin-releasing hormone
(CRH)(CRH)
IL-1 and IL-6 can stimulate hypothalamus toIL-1 and IL-6 can stimulate hypothalamus to
secret CRH.secret CRH.
Intracerebroventricular injection of CRH causesIntracerebroventricular injection of CRH causes
body and rectum temperature ↑.body and rectum temperature ↑.
CRH receptor antagonist can inhibit theCRH receptor antagonist can inhibit the
fever caused by IL-1fever caused by IL-1ββ ,, IL-6.IL-6.
Cyclic AMP
(cAMP)cAMP levels in cerebrospinal fluid increase during fever induced
by endotoxin
cAMP initiates fever quickly if injected into cerebral ventricles
Adenylate cyclase (AC) inhibitor can decrease the effects
caused by cAMP.
PDE
Phosphodiesterase (PDE) inhibitor can increase the effects
caused by cAMP.
cAMPATP
Breakdown
AC PDE
NaNa++
/Ca/Ca2 +2 +
RatioRatio
NaNa++
/Ca/Ca2+2+
changes in the brain, the body temperaturechanges in the brain, the body temperature
also changes.also changes.
Intracerebroventricular perfusion of NaIntracerebroventricular perfusion of Na++
→ ↑→ ↑
body temperature.body temperature.
 NaNa++
/Ca/Ca2+2+
ratioratio ↑↑ cAMPcAMP ↑↑ Set pointSet point ↑↑
Intracerebroventricular perfusion of CaIntracerebroventricular perfusion of Ca2+2+
→→↓↓body temperature.body temperature.
Nitric Oxide (NO)Nitric Oxide (NO)
Action on OVLT & POAHAction on OVLT & POAH
Stimulating metabolism of brown adipose tissueStimulating metabolism of brown adipose tissue
(in infants)(in infants)
Inhibit the synthesis and secretion of negativeInhibit the synthesis and secretion of negative
regulatory mediators.regulatory mediators.
Negative Regulation of
Fever
Febrile CeilingFebrile Ceiling
(Fever Limit)(Fever Limit)
Upper limit of the febrile response.Upper limit of the febrile response.
Human core body temperature almost neverHuman core body temperature almost never
rises above 41 -42 during fever.℃ ℃rises above 41 -42 during fever.℃ ℃
- This phenomenon is called- This phenomenon is called febrile ceilingfebrile ceiling..
Regulated by negative fever mediators.Regulated by negative fever mediators.
Negative Central Regulatory MediatorsNegative Central Regulatory Mediators
•Arginine vasopressin (AVP)Arginine vasopressin (AVP) - ADH- ADH
•Lipocortin-1 (LC-1)Lipocortin-1 (LC-1)
•αα-Melanocyte stimulating hormone-Melanocyte stimulating hormone
((αα-MSH)-MSH)
↑↑ feverfever
Arginine vasopressin (AVP)Arginine vasopressin (AVP) (ADH)(ADH)
Injection of AVPInjection of AVP
intracerebraventricularlyintracerebraventricularly
↓↓feverfever
AVP receptor antagonistAVP receptor antagonist
αα-melanocyte-stimulating hormone-melanocyte-stimulating hormone
((αα-MSH-MSH ))
Injection ofInjection of αα-MSH-MSH
intracerebraventricularlyintracerebraventricularly
↓↓feverfever
αα-MSH receptor antagonist-MSH receptor antagonist
↑↑ fever causedfever caused
by IL-1by IL-1
EndogenousEndogenous αα-MSH restricts the amplitude and-MSH restricts the amplitude and
duration of fever.duration of fever.
Lipocortin-1 (LC-1)Lipocortin-1 (LC-1)
Biological function of glucocorticoid (relievingBiological function of glucocorticoid (relieving
fever) depends on LC-1fever) depends on LC-1
Central injection of LC-1 inhibits the feverCentral injection of LC-1 inhibits the fever
caused by IL-1, IL-6 and CRHcaused by IL-1, IL-6 and CRH
Pyrogenic
activator
Endogenous
pyrogen (EP)
EP
producing
cell
Producing
Releasing
Pathogenesis of Fever
5757
FeverFever
a.a. IntroductionIntroduction
b.b. Causes and MechanismCauses and Mechanism
c.c. Stages and ManifestationsStages and Manifestations
d.d. Alterations of Metabolism andAlterations of Metabolism and
FunctionFunction
e.e. Pathophysiological Basis ofPathophysiological Basis of
Prevention and TreatmentPrevention and Treatment
Three stages of feverThree stages of fever
I: Fervescence stageI: Fervescence stage
II: Persistent febrile stageII: Persistent febrile stage
III: Defervescence stageIII: Defervescence stage
Stages and Manifestations of Fever
I II III
Clinical manifestations
Shivering
Pale skin
Feeling cold
Goose flesh ( 鸡皮 )
High metabolic rate
Feverescence stage:
Thermal metabolism characteristics
Heat loss↓
Heat production↑
T↑
Persistent Febrile Stage:Persistent Febrile Stage:
Thermal metabolism characteristicsThermal metabolism characteristics
T increases to the new level of set point
Balance of heat production and loss
- in a higher level
Clinical manifestationsClinical manifestations
Feeling hot
Dry skin
Flush (red)
High metabolic rate
Defervescence StageDefervescence Stage
Thermal metabolism characteristicsThermal metabolism characteristics
 Core temperature > set point → heat loss↑Core temperature > set point → heat loss↑
Clinical manifestationsClinical manifestations
SweatingSweating
Skin is warm and flushedSkin is warm and flushed
6262
FeverFever
a.a. IntroductionIntroduction
b.b. Causes and MechanismCauses and Mechanism
c.c. Stages and ManifestationsStages and Manifestations
d.d. Alterations of Metabolism andAlterations of Metabolism and
FunctionFunction
e.e. Pathophysiological Basis ofPathophysiological Basis of
Prevention and TreatmentPrevention and Treatment
Metabolic Changes During FeverMetabolic Changes During Fever
Basal metabolic rate increases by 13% with 1℃Basal metabolic rate increases by 13% with 1℃
elevation in body temperature.elevation in body temperature.
Glycolysis → Lactate ↑Glycolysis → Lactate ↑
Adipose tissue utilization → Ketone ↑, Weight lossAdipose tissue utilization → Ketone ↑, Weight loss
Glycogen degradation → Blood sugar ↑Glycogen degradation → Blood sugar ↑
Vitamin consumption ↑Vitamin consumption ↑
Systematic ChangesSystematic Changes
•Nervous systemNervous system
•Cardiovascular systemCardiovascular system
•Respiratory systemRespiratory system
•Digestive systemDigestive system
•Immune systemImmune system
Nervous systemNervous system
HeadacheHeadache
HallucinationHallucination
TwitchTwitch
Digestive systemDigestive system
Indigestion, anorexiaIndigestion, anorexia (no appetite)(no appetite)
Abdominal distensionAbdominal distension [[ 腹胀腹胀 ]]
ConstipationConstipation
Cardiovascular systemCardiovascular system
Increase of heart rate, 18 bpm/1℃Increase of heart rate, 18 bpm/1℃
Blood pressure changeBlood pressure change
Respiratory systemRespiratory system
Increase of respiratory rateIncrease of respiratory rate
HyperventilationHyperventilation
(may cause acid-base imbalance)(may cause acid-base imbalance)
Beneficial Effects of FeverBeneficial Effects of Fever
- Self defense- Self defense
Fever often increases the anti-infectionFever often increases the anti-infection
capacity of the body.capacity of the body.
The anti-tumor activity is also augmented duringThe anti-tumor activity is also augmented during
fever.fever.
EP can induce the acute phase response.EP can induce the acute phase response.
Biological Significance of FeverBiological Significance of Fever
Friend or Foe?Friend or Foe?
Answer:Answer: BothBoth
6969
FeverFever
a.a. IntroductionIntroduction
b.b. Causes and MechanismCauses and Mechanism
c.c. Stages and ManifestationsStages and Manifestations
d.d. Alterations of Metabolism andAlterations of Metabolism and
FunctionFunction
e.e. Pathophysiological Basis ofPathophysiological Basis of
Prevention and TreatmentPrevention and Treatment
Principles of Fever Treatment
Fever does not necessarily need to be treated.
Basic principles for common fever:
 Care
 Suitable medication when necessary
Need to be Treated Immediately
T > 39℃T > 39℃
Heart disease patientsHeart disease patients
Cachexia patientsCachexia patients
Pregnant womenPregnant women
MedicationMedication
1. Chemical medication1. Chemical medication
SalicylateSalicylate (Aspirin)(Aspirin)
- Inhibit the synthesis of PGE2- Inhibit the synthesis of PGE2
2. Steroid antipyretic drugs2. Steroid antipyretic drugs (Dexamethasone)(Dexamethasone)
Inhibit the synthesis and secretion of the EPsInhibit the synthesis and secretion of the EPs
Inhibit the immune and inflammatory reactionInhibit the immune and inflammatory reaction
Inhibit the synthesis of PGE2Inhibit the synthesis of PGE2
4. Other measures4. Other measures
physical coolingphysical cooling
3.Detoxificating Chinese herbs3.Detoxificating Chinese herbs
Four-Drug Juice [Four-Drug Juice [ 四磨汤四磨汤 ]]

Weitere ähnliche Inhalte

Was ist angesagt? (20)

Hypothermia
HypothermiaHypothermia
Hypothermia
 
NUTRITIONAL ASSESSMENT.pdf
NUTRITIONAL ASSESSMENT.pdfNUTRITIONAL ASSESSMENT.pdf
NUTRITIONAL ASSESSMENT.pdf
 
Hyperthermia
HyperthermiaHyperthermia
Hyperthermia
 
Typhoid fever
Typhoid feverTyphoid fever
Typhoid fever
 
Fever
FeverFever
Fever
 
Hyperthermia
HyperthermiaHyperthermia
Hyperthermia
 
Bronchitis
BronchitisBronchitis
Bronchitis
 
Hepatitis
HepatitisHepatitis
Hepatitis
 
Cooking preservation, types of cooking and methods of cooking
Cooking preservation, types of cooking and methods of cookingCooking preservation, types of cooking and methods of cooking
Cooking preservation, types of cooking and methods of cooking
 
Pathogenesis of fever
Pathogenesis of feverPathogenesis of fever
Pathogenesis of fever
 
PROTEIN ENERGY MALNUTRITION
PROTEIN ENERGY MALNUTRITIONPROTEIN ENERGY MALNUTRITION
PROTEIN ENERGY MALNUTRITION
 
Heat stroke and its managemnets
Heat stroke and its managemnetsHeat stroke and its managemnets
Heat stroke and its managemnets
 
Food poisoning
Food poisoningFood poisoning
Food poisoning
 
PNEUMONIA
PNEUMONIAPNEUMONIA
PNEUMONIA
 
Fever by prof mohamed ghanem
Fever by prof mohamed ghanemFever by prof mohamed ghanem
Fever by prof mohamed ghanem
 
Iodine deficiency disorder
Iodine deficiency disorderIodine deficiency disorder
Iodine deficiency disorder
 
Dehydration
DehydrationDehydration
Dehydration
 
pathophysiology of burn
pathophysiology of burnpathophysiology of burn
pathophysiology of burn
 
Peptic ulcer and duodenal ulcer ppt2
Peptic ulcer and duodenal ulcer ppt2Peptic ulcer and duodenal ulcer ppt2
Peptic ulcer and duodenal ulcer ppt2
 
Fever
FeverFever
Fever
 

Andere mochten auch

What is body temperature
What is body temperatureWhat is body temperature
What is body temperatureThermal Aid
 
Prolong fever editted
Prolong fever edittedProlong fever editted
Prolong fever edittedsiti hamidah
 
HEMOGLOBIN DERIVATIVES
HEMOGLOBIN DERIVATIVESHEMOGLOBIN DERIVATIVES
HEMOGLOBIN DERIVATIVESYESANNA
 
Temperature regulation
Temperature regulationTemperature regulation
Temperature regulationMegan Lotze
 
Body temperature and its regulation
Body temperature and its regulationBody temperature and its regulation
Body temperature and its regulationphysiology mgmcri
 
Thermoregulation control of body temperature
Thermoregulation control of body temperatureThermoregulation control of body temperature
Thermoregulation control of body temperatureAhmad Fauzan
 
Altered body temperature
Altered body temperatureAltered body temperature
Altered body temperatureNavjeet Chhina
 
Body Temperature Regulation
Body Temperature RegulationBody Temperature Regulation
Body Temperature RegulationRodolfo Rafael
 
Temperature measurement ppt
Temperature measurement pptTemperature measurement ppt
Temperature measurement pptAVISHEK KUMAR
 

Andere mochten auch (15)

What is body temperature
What is body temperatureWhat is body temperature
What is body temperature
 
Prolong fever editted
Prolong fever edittedProlong fever editted
Prolong fever editted
 
Fever
FeverFever
Fever
 
Body Temperature
Body TemperatureBody Temperature
Body Temperature
 
HEMOGLOBIN DERIVATIVES
HEMOGLOBIN DERIVATIVESHEMOGLOBIN DERIVATIVES
HEMOGLOBIN DERIVATIVES
 
Temperature regulation
Temperature regulationTemperature regulation
Temperature regulation
 
Post Op
Post OpPost Op
Post Op
 
Body temperature and its regulation
Body temperature and its regulationBody temperature and its regulation
Body temperature and its regulation
 
Thermoregulation control of body temperature
Thermoregulation control of body temperatureThermoregulation control of body temperature
Thermoregulation control of body temperature
 
Temperature regulation
Temperature regulationTemperature regulation
Temperature regulation
 
Altered body temperature
Altered body temperatureAltered body temperature
Altered body temperature
 
Temperature Lesson PowerPoint
Temperature Lesson PowerPointTemperature Lesson PowerPoint
Temperature Lesson PowerPoint
 
Body Temperature Regulation
Body Temperature RegulationBody Temperature Regulation
Body Temperature Regulation
 
Temperature
TemperatureTemperature
Temperature
 
Temperature measurement ppt
Temperature measurement pptTemperature measurement ppt
Temperature measurement ppt
 

Ähnlich wie 04 fever

Ähnlich wie 04 fever (20)

Fever
FeverFever
Fever
 
Fever
FeverFever
Fever
 
Fever
FeverFever
Fever
 
Fever
FeverFever
Fever
 
Fever.pptx
Fever.pptxFever.pptx
Fever.pptx
 
Fever of Unknown Origin.pptx. unknown febrile , fever with no cause
Fever of Unknown Origin.pptx. unknown febrile , fever with no causeFever of Unknown Origin.pptx. unknown febrile , fever with no cause
Fever of Unknown Origin.pptx. unknown febrile , fever with no cause
 
Pyrogen 112070804004
Pyrogen  112070804004Pyrogen  112070804004
Pyrogen 112070804004
 
Approach to history taking in a patient with fever
Approach  to  history  taking  in  a  patient  with  feverApproach  to  history  taking  in  a  patient  with  fever
Approach to history taking in a patient with fever
 
Clinical guidelines Fever in the Picu
Clinical guidelines Fever in the PicuClinical guidelines Fever in the Picu
Clinical guidelines Fever in the Picu
 
Fever patho.drjma
Fever patho.drjmaFever patho.drjma
Fever patho.drjma
 
Petient caretaker fever (pyrexia)....pdf
Petient caretaker fever (pyrexia)....pdfPetient caretaker fever (pyrexia)....pdf
Petient caretaker fever (pyrexia)....pdf
 
Thermoregulation
ThermoregulationThermoregulation
Thermoregulation
 
Anaphylaxis ( IgE Mediated Hypersensitivity )
Anaphylaxis ( IgE Mediated Hypersensitivity )Anaphylaxis ( IgE Mediated Hypersensitivity )
Anaphylaxis ( IgE Mediated Hypersensitivity )
 
Body Temperature Regulation.pptx
Body Temperature Regulation.pptxBody Temperature Regulation.pptx
Body Temperature Regulation.pptx
 
Mechanism of body temperature
Mechanism of body temperatureMechanism of body temperature
Mechanism of body temperature
 
termoreglarea.ppt
termoreglarea.ppttermoreglarea.ppt
termoreglarea.ppt
 
PHYSIOLOGY OF TEMPERATURE REGULATION
PHYSIOLOGY OF TEMPERATURE REGULATION PHYSIOLOGY OF TEMPERATURE REGULATION
PHYSIOLOGY OF TEMPERATURE REGULATION
 
Short febril illness2016 new
Short febril illness2016 new  Short febril illness2016 new
Short febril illness2016 new
 
Neuropeptides
NeuropeptidesNeuropeptides
Neuropeptides
 
RECENT ADVANCES IN MANAGEMENT OF HIE
RECENT ADVANCES IN MANAGEMENT OF HIERECENT ADVANCES IN MANAGEMENT OF HIE
RECENT ADVANCES IN MANAGEMENT OF HIE
 

Mehr von Prabesh Raj Jamkatel

18 mycoplasm,chlmydia,rickettsia
18 mycoplasm,chlmydia,rickettsia18 mycoplasm,chlmydia,rickettsia
18 mycoplasm,chlmydia,rickettsiaPrabesh Raj Jamkatel
 
16 zoonoses [zoʊ'ɒnəsɪs] pathogens
16 zoonoses [zoʊ'ɒnəsɪs] pathogens16 zoonoses [zoʊ'ɒnəsɪs] pathogens
16 zoonoses [zoʊ'ɒnəsɪs] pathogensPrabesh Raj Jamkatel
 
7 prevetion of pathogenic microbial infection
7 prevetion of  pathogenic microbial infection7 prevetion of  pathogenic microbial infection
7 prevetion of pathogenic microbial infectionPrabesh Raj Jamkatel
 
6 laboratory diagnosis of bacterial infection
6 laboratory diagnosis  of bacterial infection6 laboratory diagnosis  of bacterial infection
6 laboratory diagnosis of bacterial infectionPrabesh Raj Jamkatel
 
5 immune defense against bacterial pathogens
5 immune defense against bacterial  pathogens5 immune defense against bacterial  pathogens
5 immune defense against bacterial pathogensPrabesh Raj Jamkatel
 
4 bacterial infection and pathogenesis
4  bacterial infection and pathogenesis4  bacterial infection and pathogenesis
4 bacterial infection and pathogenesisPrabesh Raj Jamkatel
 
3 heredity and variation of bacteria
3 heredity and variation of bacteria3 heredity and variation of bacteria
3 heredity and variation of bacteriaPrabesh Raj Jamkatel
 
0 introdution to Medical Microbiology
0  introdution to Medical Microbiology0  introdution to Medical Microbiology
0 introdution to Medical MicrobiologyPrabesh Raj Jamkatel
 

Mehr von Prabesh Raj Jamkatel (20)

18 mycoplasm,chlmydia,rickettsia
18 mycoplasm,chlmydia,rickettsia18 mycoplasm,chlmydia,rickettsia
18 mycoplasm,chlmydia,rickettsia
 
17 spirochetes
17  spirochetes17  spirochetes
17 spirochetes
 
16 zoonoses pathogens
16 zoonoses pathogens16 zoonoses pathogens
16 zoonoses pathogens
 
16 zoonoses [zoʊ'ɒnəsɪs] pathogens
16 zoonoses [zoʊ'ɒnəsɪs] pathogens16 zoonoses [zoʊ'ɒnəsɪs] pathogens
16 zoonoses [zoʊ'ɒnəsɪs] pathogens
 
15 corynebacterium diphtheriae
15 corynebacterium diphtheriae15 corynebacterium diphtheriae
15 corynebacterium diphtheriae
 
14 mycobacteria
14 mycobacteria14 mycobacteria
14 mycobacteria
 
13 anaerobic bacteria
13 anaerobic bacteria13 anaerobic bacteria
13 anaerobic bacteria
 
12 campylobacter helicobacter
12 campylobacter helicobacter12 campylobacter helicobacter
12 campylobacter helicobacter
 
11 vibrios
11 vibrios11 vibrios
11 vibrios
 
10 enterobacteriaceae
10 enterobacteriaceae10 enterobacteriaceae
10 enterobacteriaceae
 
9 cocci
9 cocci9 cocci
9 cocci
 
8 drug resistance
8 drug resistance8 drug resistance
8 drug resistance
 
7 prevetion of pathogenic microbial infection
7 prevetion of  pathogenic microbial infection7 prevetion of  pathogenic microbial infection
7 prevetion of pathogenic microbial infection
 
6 laboratory diagnosis of bacterial infection
6 laboratory diagnosis  of bacterial infection6 laboratory diagnosis  of bacterial infection
6 laboratory diagnosis of bacterial infection
 
5 immune defense against bacterial pathogens
5 immune defense against bacterial  pathogens5 immune defense against bacterial  pathogens
5 immune defense against bacterial pathogens
 
4 bacterial infection and pathogenesis
4  bacterial infection and pathogenesis4  bacterial infection and pathogenesis
4 bacterial infection and pathogenesis
 
3 heredity and variation of bacteria
3 heredity and variation of bacteria3 heredity and variation of bacteria
3 heredity and variation of bacteria
 
2 biosafety
2 biosafety2 biosafety
2 biosafety
 
0 introdution to Medical Microbiology
0  introdution to Medical Microbiology0  introdution to Medical Microbiology
0 introdution to Medical Microbiology
 
1 basic characters of bacteria
1 basic characters of bacteria1 basic characters of bacteria
1 basic characters of bacteria
 

Kürzlich hochgeladen

Philosophy of Education and Educational Philosophy
Philosophy of Education  and Educational PhilosophyPhilosophy of Education  and Educational Philosophy
Philosophy of Education and Educational PhilosophyShuvankar Madhu
 
Practical Research 1 Lesson 9 Scope and delimitation.pptx
Practical Research 1 Lesson 9 Scope and delimitation.pptxPractical Research 1 Lesson 9 Scope and delimitation.pptx
Practical Research 1 Lesson 9 Scope and delimitation.pptxKatherine Villaluna
 
Quality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICEQuality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICESayali Powar
 
In - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptxIn - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptxAditiChauhan701637
 
General views of Histopathology and step
General views of Histopathology and stepGeneral views of Histopathology and step
General views of Histopathology and stepobaje godwin sunday
 
Ultra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxUltra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxDr. Asif Anas
 
M-2- General Reactions of amino acids.pptx
M-2- General Reactions of amino acids.pptxM-2- General Reactions of amino acids.pptx
M-2- General Reactions of amino acids.pptxDr. Santhosh Kumar. N
 
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptxClinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptxraviapr7
 
HED Office Sohayok Exam Question Solution 2023.pdf
HED Office Sohayok Exam Question Solution 2023.pdfHED Office Sohayok Exam Question Solution 2023.pdf
HED Office Sohayok Exam Question Solution 2023.pdfMohonDas
 
The Stolen Bacillus by Herbert George Wells
The Stolen Bacillus by Herbert George WellsThe Stolen Bacillus by Herbert George Wells
The Stolen Bacillus by Herbert George WellsEugene Lysak
 
Presentation on the Basics of Writing. Writing a Paragraph
Presentation on the Basics of Writing. Writing a ParagraphPresentation on the Basics of Writing. Writing a Paragraph
Presentation on the Basics of Writing. Writing a ParagraphNetziValdelomar1
 
How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17Celine George
 
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptx
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptxPISA-VET launch_El Iza Mohamedou_19 March 2024.pptx
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptxEduSkills OECD
 
3.21.24 The Origins of Black Power.pptx
3.21.24  The Origins of Black Power.pptx3.21.24  The Origins of Black Power.pptx
3.21.24 The Origins of Black Power.pptxmary850239
 
How to Add a many2many Relational Field in Odoo 17
How to Add a many2many Relational Field in Odoo 17How to Add a many2many Relational Field in Odoo 17
How to Add a many2many Relational Field in Odoo 17Celine George
 
The Singapore Teaching Practice document
The Singapore Teaching Practice documentThe Singapore Teaching Practice document
The Singapore Teaching Practice documentXsasf Sfdfasd
 
What is the Future of QuickBooks DeskTop?
What is the Future of QuickBooks DeskTop?What is the Future of QuickBooks DeskTop?
What is the Future of QuickBooks DeskTop?TechSoup
 
5 charts on South Africa as a source country for international student recrui...
5 charts on South Africa as a source country for international student recrui...5 charts on South Africa as a source country for international student recrui...
5 charts on South Africa as a source country for international student recrui...CaraSkikne1
 

Kürzlich hochgeladen (20)

Philosophy of Education and Educational Philosophy
Philosophy of Education  and Educational PhilosophyPhilosophy of Education  and Educational Philosophy
Philosophy of Education and Educational Philosophy
 
Practical Research 1 Lesson 9 Scope and delimitation.pptx
Practical Research 1 Lesson 9 Scope and delimitation.pptxPractical Research 1 Lesson 9 Scope and delimitation.pptx
Practical Research 1 Lesson 9 Scope and delimitation.pptx
 
Quality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICEQuality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICE
 
In - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptxIn - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptx
 
Personal Resilience in Project Management 2 - TV Edit 1a.pdf
Personal Resilience in Project Management 2 - TV Edit 1a.pdfPersonal Resilience in Project Management 2 - TV Edit 1a.pdf
Personal Resilience in Project Management 2 - TV Edit 1a.pdf
 
General views of Histopathology and step
General views of Histopathology and stepGeneral views of Histopathology and step
General views of Histopathology and step
 
Ultra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxUltra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptx
 
M-2- General Reactions of amino acids.pptx
M-2- General Reactions of amino acids.pptxM-2- General Reactions of amino acids.pptx
M-2- General Reactions of amino acids.pptx
 
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptxClinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptx
 
HED Office Sohayok Exam Question Solution 2023.pdf
HED Office Sohayok Exam Question Solution 2023.pdfHED Office Sohayok Exam Question Solution 2023.pdf
HED Office Sohayok Exam Question Solution 2023.pdf
 
The Stolen Bacillus by Herbert George Wells
The Stolen Bacillus by Herbert George WellsThe Stolen Bacillus by Herbert George Wells
The Stolen Bacillus by Herbert George Wells
 
Presentation on the Basics of Writing. Writing a Paragraph
Presentation on the Basics of Writing. Writing a ParagraphPresentation on the Basics of Writing. Writing a Paragraph
Presentation on the Basics of Writing. Writing a Paragraph
 
How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17
 
Finals of Kant get Marx 2.0 : a general politics quiz
Finals of Kant get Marx 2.0 : a general politics quizFinals of Kant get Marx 2.0 : a general politics quiz
Finals of Kant get Marx 2.0 : a general politics quiz
 
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptx
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptxPISA-VET launch_El Iza Mohamedou_19 March 2024.pptx
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptx
 
3.21.24 The Origins of Black Power.pptx
3.21.24  The Origins of Black Power.pptx3.21.24  The Origins of Black Power.pptx
3.21.24 The Origins of Black Power.pptx
 
How to Add a many2many Relational Field in Odoo 17
How to Add a many2many Relational Field in Odoo 17How to Add a many2many Relational Field in Odoo 17
How to Add a many2many Relational Field in Odoo 17
 
The Singapore Teaching Practice document
The Singapore Teaching Practice documentThe Singapore Teaching Practice document
The Singapore Teaching Practice document
 
What is the Future of QuickBooks DeskTop?
What is the Future of QuickBooks DeskTop?What is the Future of QuickBooks DeskTop?
What is the Future of QuickBooks DeskTop?
 
5 charts on South Africa as a source country for international student recrui...
5 charts on South Africa as a source country for international student recrui...5 charts on South Africa as a source country for international student recrui...
5 charts on South Africa as a source country for international student recrui...
 

04 fever

  • 1. Dept. of PathologyDept. of Pathology Medical CollegeMedical College Hunan Normal UniversityHunan Normal University (( 湖南 范大学医学院病理学教研室师湖南 范大学医学院病理学教研室师 )) 1 Chapter 4Chapter 4 FeverFever ( )发热( )发热
  • 2. 22 FeverFever a.a. IntroductionIntroduction b.b. Causes and MechanismCauses and Mechanism c.c. Stages and ManifestationsStages and Manifestations d.d. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction e.e. Pathophysiological Basis ofPathophysiological Basis of Prevention and TreatmentPrevention and Treatment
  • 3. Life Stages 0-2 years old 3-10 years old 11-65 years old Over 65 Circadian variation of body temperature 2am 2pm 2am 37.5 36.5 Q: Why stable temperature? Normal Temperature range: 36℃ ~ 37.5℃ Oral temperature: 37℃
  • 4. heat loss peripheral thermo-sensors deep thermo- sensors set point blood vessel skeletal muscle heat production balance POAH sweat gland Regulation of Normal Body Temperature POAH: preoptic anterior hypothalamus (- body’s thermostat)
  • 5. Homeostasis (36℃ ~ 37℃ ) Activates heat-loss center in hypothalamus Skin blood vessels constrict Skeletal muscles activated, shivering begins Skin blood vessels dilate Sweat glands activated Imbalance Imbalance Body temperature decreases Activates heat- promoting center in hypothalamus Hot stimulus Blood warmer than set point Cold stimulus Blood cooler than set point Body temperature increases
  • 6. Definition of fever Fever is a complicated pathological process characterized by regulated elevation of body temperature following the increased Set Point, which is caused by pyrogenic substances. Usually 0.5 higher℃ than normal body temperature. There is no impairment in the thermoregulatory mechanism during fever. Q: Increase of body temperature = Fever?
  • 7. Pathological elevation Fever Hyperthermia Passive Set Point: N Physiological elevation (Before menstruation, Strenuous exercise, Stress) Elevation of body temperature Active Set Point: ↑
  • 8. 1616 FeverFever a.a. IntroductionIntroduction b.b. Causes and MechanismCauses and Mechanism c.c. Stages and ManifestationsStages and Manifestations d.d. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction e.e. Pathophysiological Basis ofPathophysiological Basis of Prevention and TreatmentPrevention and Treatment
  • 10. Causes of Fever - Pyrogenic Activators
  • 11. Pyrogenic activators ( 发热激活物 ) are substances which can activate the EP-producing cells to produce and release endogenous pyrogen (EP). Concept Pyrogenic Activators
  • 13. Pyrogenic activators Microbial pyrogens Bacteria Viruses Other microorganisms Non-microbial Pyrogenic substances Antigen-antibody complexes Component of complement cascade Steroids Anticancer drugs
  • 14. Gram-negative Bacteria: (E. coli) Pathogenic substance: LPS (lipopolysaccharide, also named endotoxin, ET) Major pyrogenic component is Lipid A High m.w. (1,000 kDa) Heat resistant: inactivated by 160℃ dry heat, 2 h High pyrogenic activity 1 ng/kg to rabbit → fever Tolerability (resistance to repeated injection)
  • 15. Gram-positive Bacteria: Staphylococcus aureusStaphylococcus aureus,, Streptococcus pneumoniaeStreptococcus pneumoniae Pathogenic substances:Pathogenic substances: Whole bacteria ExotoxinExotoxin PeptidoglycanPeptidoglycan
  • 16. Viruses Pathogenic substances:  Protein coat - lipoprotein  Haemagglutinin Influenza virusInfluenza virus Corona virusCorona virus
  • 17. Substances that areSubstances that are produced by EP-producingproduced by EP-producing cellscells under the action of pyrogenic activatorsunder the action of pyrogenic activators andand cause the increase in the thermoregulatory setcause the increase in the thermoregulatory set pointpoint in the hypothalamus.in the hypothalamus. Fever-inducing cytokines (large, hydrophilicFever-inducing cytokines (large, hydrophilic peptides).peptides). Endogenous Pyrogens (EPs)
  • 19. Major Endogenous Pyrogens (EPs)  Interleukin-1 (IL-1)Interleukin-1 (IL-1)  Tumor necrosis factor (TNF)Tumor necrosis factor (TNF)  Interferon (IFN)Interferon (IFN)  Interleukin-6 (IL-6 )Interleukin-6 (IL-6 )
  • 20. •Interleukin 1 (IL-1)Interleukin 1 (IL-1) Produced by monocytes/macrophages, epithelialProduced by monocytes/macrophages, epithelial cells,cells, etc.etc. IL-1a and IL-1b have the same effect.IL-1a and IL-1b have the same effect. Pyrogenic activity can be inhibited by cyclooxygenasePyrogenic activity can be inhibited by cyclooxygenase inhibitorinhibitor (Aspirin).(Aspirin). Heat sensitive: Inactivated by heating (70 30 min).℃Heat sensitive: Inactivated by heating (70 30 min).℃ No tolerance by repeated injections.No tolerance by repeated injections.
  • 21. •Tumor necrosis factor (TNF)Tumor necrosis factor (TNF) Produced byProduced by macrophagesmacrophages,, lymphoid cells, mast cells,lymphoid cells, mast cells, endothelial cellsendothelial cells,, etc.etc. Pyrogenic activity can be inhibited by cyclooxygenasePyrogenic activity can be inhibited by cyclooxygenase inhibitor (Aspirin).inhibitor (Aspirin). TNF-TNF-αα, TNF-, TNF-ββ are pyrogenic.are pyrogenic. Heat sensitive: Inactivated by heating (70 30 min).℃Heat sensitive: Inactivated by heating (70 30 min).℃ No tolerance by repeated injections.No tolerance by repeated injections.
  • 22. Interferon (IFN)Interferon (IFN) Produced by lymphocytes, NK cells, fibroblasts,Produced by lymphocytes, NK cells, fibroblasts, etc.etc. IFN-IFN-αα and IFN-and IFN-γγ can cause fever.can cause fever. Can be tolerated after long period of use.Can be tolerated after long period of use. Heat sensitive.Heat sensitive.
  • 23. Interleukin 6 (IL-6)Interleukin 6 (IL-6) Produced by mononuclear cells, fibroblasts, endothelialProduced by mononuclear cells, fibroblasts, endothelial cells,cells, etc.etc. Can be induced by ET, IL-1, TNF.Can be induced by ET, IL-1, TNF. IL-6 is the downstream mediator of fever from otherIL-6 is the downstream mediator of fever from other EPs (IL-1 and TNF).EPs (IL-1 and TNF). Pyrogenic activity can be inhibited by cyclooxygenasePyrogenic activity can be inhibited by cyclooxygenase inhibitor (Aspirin).inhibitor (Aspirin).
  • 25. POAH Thermoregulatory Center Positive regulatory center:Positive regulatory center: Located at preoptic anteriorLocated at preoptic anterior hypothalamus (POAH)hypothalamus (POAH) Warm-sensitive neuronsWarm-sensitive neurons Cold-sensitive neuronsCold-sensitive neurons Negative regulatory center:Negative regulatory center: Medial amydaloid nucleus (MANMedial amydaloid nucleus (MAN [[ 中杏仁核中杏仁核 ])]) Ventral septal area (VSAVentral septal area (VSA [[ 腹中膈腹中膈 ])]) Arcuate nucleus (ARCArcuate nucleus (ARC [[ 弓状核弓状核 ])])
  • 26. Routes for Endogenous Pyrogens toRoutes for Endogenous Pyrogens to Enter Thermoregulatory CenterEnter Thermoregulatory Center a.a. Passive transport via organum vasculosumPassive transport via organum vasculosum laminate terminal (OVLTlaminate terminal (OVLT [[ 小丘脑终板血管器小丘脑终板血管器 ], also called], also called supraoptic crestsupraoptic crest))  Most importantMost important a.a. Through stimulating vagus nerveThrough stimulating vagus nerve (( 迷走神经迷走神经 )) b.b. Active transport across the blood brain barrierActive transport across the blood brain barrier (BBB)(BBB)  Important in pathological conditionsImportant in pathological conditions EPs can not directly act on thermoregulatory center because of BBB.
  • 28. Central Mediators of FeverCentral Mediators of Fever - The positive regulatory mediators- The positive regulatory mediators Prostaglandin E2 (PGE2)Prostaglandin E2 (PGE2) Corticotrophin-releasing hormone (CRH)Corticotrophin-releasing hormone (CRH) Cyclic adenosine monophosphate (cAMP)Cyclic adenosine monophosphate (cAMP) Nitric oxide (NO)Nitric oxide (NO) NaNa++ /Ca/Ca2+2+ ratioratio
  • 29. Prostaglandin E2 (PGE2) PGE2 can induce fever when injected into cerebralPGE2 can induce fever when injected into cerebral ventricles.ventricles. Bacterial endotoxin and EP can stimulate theBacterial endotoxin and EP can stimulate the hypothalamus to produce PGE2.hypothalamus to produce PGE2. Cyclooxygenase inhibitor can inhibit the production ofCyclooxygenase inhibitor can inhibit the production of PGE2.PGE2. PGE2PGE2 ↑↑ in cerebrospinal fluid during fever.in cerebrospinal fluid during fever.
  • 31. Corticotrophin-releasing hormoneCorticotrophin-releasing hormone (CRH)(CRH) IL-1 and IL-6 can stimulate hypothalamus toIL-1 and IL-6 can stimulate hypothalamus to secret CRH.secret CRH. Intracerebroventricular injection of CRH causesIntracerebroventricular injection of CRH causes body and rectum temperature ↑.body and rectum temperature ↑. CRH receptor antagonist can inhibit theCRH receptor antagonist can inhibit the fever caused by IL-1fever caused by IL-1ββ ,, IL-6.IL-6.
  • 32. Cyclic AMP (cAMP)cAMP levels in cerebrospinal fluid increase during fever induced by endotoxin cAMP initiates fever quickly if injected into cerebral ventricles Adenylate cyclase (AC) inhibitor can decrease the effects caused by cAMP. PDE Phosphodiesterase (PDE) inhibitor can increase the effects caused by cAMP. cAMPATP Breakdown AC PDE
  • 33. NaNa++ /Ca/Ca2 +2 + RatioRatio NaNa++ /Ca/Ca2+2+ changes in the brain, the body temperaturechanges in the brain, the body temperature also changes.also changes. Intracerebroventricular perfusion of NaIntracerebroventricular perfusion of Na++ → ↑→ ↑ body temperature.body temperature.  NaNa++ /Ca/Ca2+2+ ratioratio ↑↑ cAMPcAMP ↑↑ Set pointSet point ↑↑ Intracerebroventricular perfusion of CaIntracerebroventricular perfusion of Ca2+2+ →→↓↓body temperature.body temperature.
  • 34. Nitric Oxide (NO)Nitric Oxide (NO) Action on OVLT & POAHAction on OVLT & POAH Stimulating metabolism of brown adipose tissueStimulating metabolism of brown adipose tissue (in infants)(in infants) Inhibit the synthesis and secretion of negativeInhibit the synthesis and secretion of negative regulatory mediators.regulatory mediators.
  • 36. Febrile CeilingFebrile Ceiling (Fever Limit)(Fever Limit) Upper limit of the febrile response.Upper limit of the febrile response. Human core body temperature almost neverHuman core body temperature almost never rises above 41 -42 during fever.℃ ℃rises above 41 -42 during fever.℃ ℃ - This phenomenon is called- This phenomenon is called febrile ceilingfebrile ceiling.. Regulated by negative fever mediators.Regulated by negative fever mediators.
  • 37. Negative Central Regulatory MediatorsNegative Central Regulatory Mediators •Arginine vasopressin (AVP)Arginine vasopressin (AVP) - ADH- ADH •Lipocortin-1 (LC-1)Lipocortin-1 (LC-1) •αα-Melanocyte stimulating hormone-Melanocyte stimulating hormone ((αα-MSH)-MSH)
  • 38. ↑↑ feverfever Arginine vasopressin (AVP)Arginine vasopressin (AVP) (ADH)(ADH) Injection of AVPInjection of AVP intracerebraventricularlyintracerebraventricularly ↓↓feverfever AVP receptor antagonistAVP receptor antagonist
  • 39. αα-melanocyte-stimulating hormone-melanocyte-stimulating hormone ((αα-MSH-MSH )) Injection ofInjection of αα-MSH-MSH intracerebraventricularlyintracerebraventricularly ↓↓feverfever αα-MSH receptor antagonist-MSH receptor antagonist ↑↑ fever causedfever caused by IL-1by IL-1 EndogenousEndogenous αα-MSH restricts the amplitude and-MSH restricts the amplitude and duration of fever.duration of fever.
  • 40. Lipocortin-1 (LC-1)Lipocortin-1 (LC-1) Biological function of glucocorticoid (relievingBiological function of glucocorticoid (relieving fever) depends on LC-1fever) depends on LC-1 Central injection of LC-1 inhibits the feverCentral injection of LC-1 inhibits the fever caused by IL-1, IL-6 and CRHcaused by IL-1, IL-6 and CRH
  • 42. 5757 FeverFever a.a. IntroductionIntroduction b.b. Causes and MechanismCauses and Mechanism c.c. Stages and ManifestationsStages and Manifestations d.d. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction e.e. Pathophysiological Basis ofPathophysiological Basis of Prevention and TreatmentPrevention and Treatment
  • 43. Three stages of feverThree stages of fever I: Fervescence stageI: Fervescence stage II: Persistent febrile stageII: Persistent febrile stage III: Defervescence stageIII: Defervescence stage Stages and Manifestations of Fever I II III
  • 44. Clinical manifestations Shivering Pale skin Feeling cold Goose flesh ( 鸡皮 ) High metabolic rate Feverescence stage: Thermal metabolism characteristics Heat loss↓ Heat production↑ T↑
  • 45. Persistent Febrile Stage:Persistent Febrile Stage: Thermal metabolism characteristicsThermal metabolism characteristics T increases to the new level of set point Balance of heat production and loss - in a higher level Clinical manifestationsClinical manifestations Feeling hot Dry skin Flush (red) High metabolic rate
  • 46. Defervescence StageDefervescence Stage Thermal metabolism characteristicsThermal metabolism characteristics  Core temperature > set point → heat loss↑Core temperature > set point → heat loss↑ Clinical manifestationsClinical manifestations SweatingSweating Skin is warm and flushedSkin is warm and flushed
  • 47. 6262 FeverFever a.a. IntroductionIntroduction b.b. Causes and MechanismCauses and Mechanism c.c. Stages and ManifestationsStages and Manifestations d.d. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction e.e. Pathophysiological Basis ofPathophysiological Basis of Prevention and TreatmentPrevention and Treatment
  • 48. Metabolic Changes During FeverMetabolic Changes During Fever Basal metabolic rate increases by 13% with 1℃Basal metabolic rate increases by 13% with 1℃ elevation in body temperature.elevation in body temperature. Glycolysis → Lactate ↑Glycolysis → Lactate ↑ Adipose tissue utilization → Ketone ↑, Weight lossAdipose tissue utilization → Ketone ↑, Weight loss Glycogen degradation → Blood sugar ↑Glycogen degradation → Blood sugar ↑ Vitamin consumption ↑Vitamin consumption ↑
  • 49. Systematic ChangesSystematic Changes •Nervous systemNervous system •Cardiovascular systemCardiovascular system •Respiratory systemRespiratory system •Digestive systemDigestive system •Immune systemImmune system
  • 50. Nervous systemNervous system HeadacheHeadache HallucinationHallucination TwitchTwitch Digestive systemDigestive system Indigestion, anorexiaIndigestion, anorexia (no appetite)(no appetite) Abdominal distensionAbdominal distension [[ 腹胀腹胀 ]] ConstipationConstipation
  • 51. Cardiovascular systemCardiovascular system Increase of heart rate, 18 bpm/1℃Increase of heart rate, 18 bpm/1℃ Blood pressure changeBlood pressure change Respiratory systemRespiratory system Increase of respiratory rateIncrease of respiratory rate HyperventilationHyperventilation (may cause acid-base imbalance)(may cause acid-base imbalance)
  • 52. Beneficial Effects of FeverBeneficial Effects of Fever - Self defense- Self defense Fever often increases the anti-infectionFever often increases the anti-infection capacity of the body.capacity of the body. The anti-tumor activity is also augmented duringThe anti-tumor activity is also augmented during fever.fever. EP can induce the acute phase response.EP can induce the acute phase response.
  • 53. Biological Significance of FeverBiological Significance of Fever Friend or Foe?Friend or Foe? Answer:Answer: BothBoth
  • 54. 6969 FeverFever a.a. IntroductionIntroduction b.b. Causes and MechanismCauses and Mechanism c.c. Stages and ManifestationsStages and Manifestations d.d. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction e.e. Pathophysiological Basis ofPathophysiological Basis of Prevention and TreatmentPrevention and Treatment
  • 55. Principles of Fever Treatment Fever does not necessarily need to be treated. Basic principles for common fever:  Care  Suitable medication when necessary
  • 56. Need to be Treated Immediately T > 39℃T > 39℃ Heart disease patientsHeart disease patients Cachexia patientsCachexia patients Pregnant womenPregnant women
  • 57. MedicationMedication 1. Chemical medication1. Chemical medication SalicylateSalicylate (Aspirin)(Aspirin) - Inhibit the synthesis of PGE2- Inhibit the synthesis of PGE2 2. Steroid antipyretic drugs2. Steroid antipyretic drugs (Dexamethasone)(Dexamethasone) Inhibit the synthesis and secretion of the EPsInhibit the synthesis and secretion of the EPs Inhibit the immune and inflammatory reactionInhibit the immune and inflammatory reaction Inhibit the synthesis of PGE2Inhibit the synthesis of PGE2
  • 58. 4. Other measures4. Other measures physical coolingphysical cooling 3.Detoxificating Chinese herbs3.Detoxificating Chinese herbs Four-Drug Juice [Four-Drug Juice [ 四磨汤四磨汤 ]]

Hinweis der Redaktion

  1. http://v.qihuang99.com/player/1777.html?1777-0-2
  2. Even moderate elevations of body temperature cause cell malfunction and irreversible protein denaturation.
  3. Deep thermosensors are in the blood. POAH: preoptic anterior hypothalamus (视前区-下丘脑前部)
  4. Typhoid (伤寒)
  5. Undulant: 56556 resembling waves in form or outline or motion
  6. Strenuous: vigorous Hyperthermia: Non-regulatory/Passive elevation of Temp Hyperthermia differs from fever in that the body's temperature set point remains unchanged.
  7. (Ichthyosis [鱼鳞癣]: fish skin disease.) There are many types of Ichthyosis and an exact diagnosis may be difficult. Types of Ichthyosis are classified by their appearance and their genetic cause. Ichthyosis caused by the same gene can vary considerably in severity and symptoms. Some Ichthyoses don't appear to fit exactly into any one type. Also different genes can produce Ichthyoses with similar symptoms. ses) is a heterogeneous family of at least 28,1 generalized, mostly genetic skin disorders. All types of ichthyosis have dry, thickened, scaly or flaky skin.
  8. Pyrogenic activator (called exogenous pyrogen initially) Endogenous pyrogen (EP)
  9. Other microorganisms include fungus, Spirochetes, parasites. Pyretic (similar to pyrogenic)
  10. Be very careful about aseptic operation. LPS m.w.: 5 – 9000 kDa, can’t pass through BBB. 1 ng/kg (rabbit) is 1/10,000 of toxic dose.
  11. 葡萄球菌
  12. Originally called granulocytic/leukocytic pyrogens.
  13. Initially people thought neutrophils are EP-producing cells (actually they are, but they are much weaker than monocytes.) These are almost all immune cells.
  14. Essence: small molecule proteins.
  15. There are many sub-types of ILs, the receptor of ILs were located throughout the brain, with the highest density located in the outer hypothalamas near the thermoregulatory center.
  16. TNF shares many biological activity with IL-1, while the amino sequence of them shares no discernable region of significant homology. TNF-alpha is able to induce IL-1beta in vitro and in vivo, while the vise versa is allright as well.
  17. IFN: Anti-viral ,anti-tumor function
  18. The weakest among the major Eps. The critical role played by IL-6 in the induction of fever was recently demonstrated in IL-6 gene knockout mice, which were un-responsive to the pyrogenic effectors of LPS and TNF.
  19. Active transport by cytokine-specific carriers across the blood brain barrier (BBB) The organum vasculosum of the lamina terminalis (OVLT) (or supraoptic crest) is one of the circumventricular organs of the brain. OVLT as a circumventricular organ has special atypical blood-brain barrier. Cerebellum 英 [ˌserə'beləm]     美 [ˌserə'beləm]     n.【医】小脑
  20. Capillary in OVLT serving as atypical BBB, allowing transport of some molecules. #3 is through local neurons. Supraoptic recess (视上隐窝)
  21. Arachidonic acid other than PGE2 may be involved as central mediators.
  22. Generation of arachidonic acid metabolites and their roles in inflammation Robbins and Cotran Pathologic Basis of Disease 7th edition
  23. CRH: 促皮质激素释放素
  24. CA inhibitor: cholera toxin PDE inhibitor: thyroid hormone, Viagra
  25. LC-1 (脂皮质蛋白-1) is also called annexin A1, it is a phospholipid-binding protein found in 1980s. LC-1 functions by inhibiting phospholipase A2 (PLA2). Glucocorticoids (GCs) are a class of steroid hormones that bind to the glucocorticoid receptor (GR),[1] which is present in almost every vertebrate animal cell. The name glucocorticoid (glucose + cortex + steroid) derives from its role in the regulation of the metabolism of glucose, its synthesis in the adrenal cortex, and its steroidal structure (see structure to the right). Cortisol (or hydrocortisone) is the most important human glucocorticoid. Others include: Prednisone, Dexamethasone, etc.
  26. Pyrogenic activator (called exogenous pyrogen initially) Endogenous pyrogen (EP)
  27. Dynamic curve of set point Curve of normal body temperature
  28. Breakdown of brown fat tissue (infants).
  29. Protein degradation, negative nitrogen balance.
  30. Hallucination (a false sense, 幻觉), Twitch (quick, short movement, 抽搐)
  31. respiratory alkalosis
  32. acute phase response: seen in acute inflammation.
  33. 四磨汤:乌药、人参、沉香、槟榔