The document discusses thermoregulation, fever, hyperthermia, and hypothermia. It describes the body's mechanisms for heat production and heat loss under normal conditions as well as during fever. Specifically, it outlines the causes of fever including infectious and non-infectious pyrogens and secondary cytokines. It also describes the stages of a fever and metabolic changes that occur during fever. Finally, it discusses the causes and mechanisms of hyperthermia.

1. ThermoregulationThermoregulation
pathologypathology
Fever, hyperthermia,Fever, hyperthermia,
hypothermiahypothermia

2. Human
thermoregulation

3. The sources of heat productionThe sources of heat production
 Body BMR (Basal Metabolic Rate)Body BMR (Basal Metabolic Rate)
 Increased Metabolic Rate:Increased Metabolic Rate:
• muscle activity (shivering);muscle activity (shivering);
• effect of thyroxin on the cells;effect of thyroxin on the cells;
• effects of epinephrine,effects of epinephrine,
norepinephrine and sympatheticnorepinephrine and sympathetic
stimulation on the cells.stimulation on the cells.

4. The ways of heat lossThe ways of heat loss
 Heat conduction to the objectsHeat conduction to the objects
 Heat conduction to the airHeat conduction to the air
(convection).(convection).
 Heat irradiation.Heat irradiation.
 Evaporation.Evaporation.

5. Thermoregulation mechanismsThermoregulation mechanisms

6. The causes of feverThe causes of fever
Primary pyrogensPrimary pyrogens
 Infectious pyrogensInfectious pyrogens (from(from
bacteria, viruses, protozoa,bacteria, viruses, protozoa,
fungi).fungi).
• polysaccharides andpolysaccharides and
lipopolysaccharides of thelipopolysaccharides of the
microbial cell membrane.microbial cell membrane.

7. The causes of feverThe causes of fever
Primary pyrogensPrimary pyrogens
 Non-infectious pyrogensNon-infectious pyrogens
• foreignforeign proteins, lipids or nuclear acids;proteins, lipids or nuclear acids;
• products of tissue decayproducts of tissue decay (burns,(burns,
mechanical traumas, surgicalmechanical traumas, surgical
operations, internal hemorrhages,operations, internal hemorrhages,
infarcts, allergic reactions, autoimmuneinfarcts, allergic reactions, autoimmune
processes, etc.)processes, etc.)

8. The causes of feverThe causes of fever
Secondary pyrogensSecondary pyrogens
 cytokines: IL-1, IL-6, TNF,cytokines: IL-1, IL-6, TNF,
gamma-interpheronegamma-interpherone ((producedproduced
and released by phagocytes)and released by phagocytes)
Pyrogenic cytokines are synthesized inPyrogenic cytokines are synthesized in
every case of primary pyrogensevery case of primary pyrogens
appearance.appearance.

9. Fever stagesFever stages
 Temperature increase stageTemperature increase stage
– stadium incrementi– stadium incrementi
 High temperature standing stageHigh temperature standing stage
– stadium fastigii– stadium fastigii
 Temperature descent stageTemperature descent stage
-stadium decrementi-stadium decrementi

10. Temperature increase stageTemperature increase stage
Secondary
pyrogens
Thermoregulatory
neurons
Activation of phospholipase
Increased AA metabolism
Increased PG E2 synthesis
Accumulation of cAMP
Decrease of
cold neurons
excitation
threshold
Adjusting point
of thermoregulation
becomes higher
Primary
pyrogens

11. Heat loss decreasesHeat loss decreases due to:due to:
• skin periphery vesselsskin periphery vessels
constrictionconstriction
• sweat secretion inhibitionsweat secretion inhibition
• decrease of evaporation.decrease of evaporation.
• pilomotor reflex - “goose-flesh”pilomotor reflex - “goose-flesh”
Temperature increase stageTemperature increase stage

12. Temperature increase stageTemperature increase stage
Peripheral vessels
constriction
shivering,
pilomotor reflex,
feeling of cold
Irritation of skin
cold receptors
thermoregulation
center
excitation
Activation of heat
production
RIGOR

13. Temperature increase stageTemperature increase stage
Heat production increasesHeat production increases due to:due to:
 contractive thermogenesiscontractive thermogenesis
(increased tone of muscles and(increased tone of muscles and
shivering).shivering).
 noncontractive thermogenesisnoncontractive thermogenesis
(increased metabolism of inner(increased metabolism of inner
organs).organs).

14. High temperature standing stageHigh temperature standing stage
 no further temperature increaseno further temperature increase
 heat loss increases (inheat loss increases (in
comparison with 1comparison with 1stst
stage)stage)
 thermoregulation is normalthermoregulation is normal
(heat production and heat loss(heat production and heat loss
are in normal balance)are in normal balance)

15. The types of temperature curvesThe types of temperature curves
Febris continua - temperature fluctuation
within 1 C0
range (abdominal typhus,
croupous pneumonia).
Febris remittens - daily fluctuation
exceeds the 1 C0
range, temperature is high
(exudative pleuritis).
Febris intermittens - daily fluctuation
exceeds the 1 C0
range, temperature may
reverse to normal (malaria, infectious
endocarditis).
Febris hectica - temperature fluctuation
is 3 to 5 degrees (sepsis)

16. The level of temperarure increaseThe level of temperarure increase
SubfebrileSubfebrile temperature up to 38 Ctemperature up to 38 C
FebrileFebrile temperature – 38 - 39 Ctemperature – 38 - 39 C
PyreticPyretic temperature –39 - 41Ctemperature –39 - 41C
HyperpyreticHyperpyretic – temperature is– temperature is
higher than 41Chigher than 41C

17. Temperature descent stageTemperature descent stage
 Decrease of pyrogenic cytokinesDecrease of pyrogenic cytokines
synthesissynthesis
 Adjusting point of heatAdjusting point of heat
regulation center returns to theregulation center returns to the
normal physiological levelnormal physiological level
 Heat loss is prevailingHeat loss is prevailing
 The decrease of fever may beThe decrease of fever may be
lytical (slow) or critical (fast).lytical (slow) or critical (fast).

18. Metabolic changes in feverMetabolic changes in fever
 BMRBMR in the 1in the 1stst
and 2and 2ndnd
fever stage isfever stage is
increased. In the 3increased. In the 3rdrd
stage - decreases.stage - decreases.
 Carbohydrate and lipids metabolismCarbohydrate and lipids metabolism ––
prevalence of catabolic processes in the 1prevalence of catabolic processes in the 1stst
and 2and 2ndnd
fever stage. In the 3fever stage. In the 3rdrd
stage –stage –
normal.normal.
 Protein metabolismProtein metabolism is disturbed in theis disturbed in the
case of long lasting fever – proteolysis willcase of long lasting fever – proteolysis will
increase.increase.

19. Metabolic changes in feverMetabolic changes in fever
Water metabolismWater metabolism
 11stst
stage – increased water loss (duestage – increased water loss (due
to increased diuresis).to increased diuresis).
 22ndnd
stage - accumulation of water instage - accumulation of water in
the organism.the organism.
 33rdrd
stage - increased water lossstage - increased water loss
(increase of diuresis and sweating)(increase of diuresis and sweating)

20. Changes in organs function in feverChanges in organs function in fever
 Nervous systemNervous system – insomnia, high– insomnia, high
irritability, high sensitivity of skin andirritability, high sensitivity of skin and
mucous covers.mucous covers.
 Endocrine systemEndocrine system – increase of ACTH,– increase of ACTH,
catecholamines, TSH, thyroidcatecholamines, TSH, thyroid
hormones.hormones.
 HeartHeart – tachycardia.– tachycardia.
 LungsLungs – increased alveolar ventilation– increased alveolar ventilation
and gas diffusion.and gas diffusion.

21. Changes in organs function in feverChanges in organs function in fever
 GITGIT - loss of appetite, decrease of- loss of appetite, decrease of
salivation, decreased secretion andsalivation, decreased secretion and
motoric functions.motoric functions.
• Liver and pancreasLiver and pancreas - decreased- decreased
synthesis of digestive enzymes.synthesis of digestive enzymes.
 KidneysKidneys – increased diuresis in– increased diuresis in
the 1 and 3 stage of fever andthe 1 and 3 stage of fever and
accumulation of water in theaccumulation of water in the
second stage.second stage.

22. The role of feverThe role of fever
POSITIVE
•Bacteriostatic and
bactericidal effects on
microbes
• Activation of immune
system (innate and
specific immunity)
•Increased liver function
(detoxication, protein and
vitamins synthesis)
• Active excretion of
toxins (due to increased
sweating and diuresis).
NEGATIVE
•Functional overload of
organs (lungs, heart,
endocrine glands)
•Hypohydration
(cholera) and blood
hemolysis (malaria) may
lead to disturbances of
blood clotting
•Disturbances of GIT
function due to
increased level of toxic
substances

23. The causes of hyperthermiaThe causes of hyperthermia
 ExogenousExogenous – hot climate, hot– hot climate, hot
workshops, heat-isolated cloth, airworkshops, heat-isolated cloth, air
high humidity, insufficienthigh humidity, insufficient
ventilation.ventilation.
 EndogenousEndogenous disturbances of heatdisturbances of heat
regulationregulation, without pyrogens, without pyrogens
formationformation
• heat regulation center violationsheat regulation center violations
(cerebral traumas, encephalitis, cerebral(cerebral traumas, encephalitis, cerebral
edema)edema)
• fever caused by psychical diseases,fever caused by psychical diseases,
nervous excitation, stressesnervous excitation, stresses

24. The causes of hyperthermiaThe causes of hyperthermia
 Endogenous increase of heat productionEndogenous increase of heat production
• intensive muscular loadingintensive muscular loading
• pathologic contractive thermogenesis –pathologic contractive thermogenesis –
tetanus spasms.tetanus spasms.
• disconnection of oxidation anddisconnection of oxidation and
phosphorylation processes which increasesphosphorylation processes which increases
heat production (poisoning by 2,4-heat production (poisoning by 2,4-
dinitrophenolum, hyperthyroidism).dinitrophenolum, hyperthyroidism).
 Endogenous decrease of heat lossEndogenous decrease of heat loss
• sweat secretion decrease under poisoningsweat secretion decrease under poisoning
by cholinolytic medicines (Atropinum);by cholinolytic medicines (Atropinum);
• skin vessels spasms (adrenimimeticskin vessels spasms (adrenimimetic
overdose and adrenali increased rejection).overdose and adrenali increased rejection).

25. Hyperthermia compensation stageHyperthermia compensation stage
Increase of heat lossIncrease of heat loss –dilating–dilating
of skin arterioles, increase ofof skin arterioles, increase of
skin temperature, increasedskin temperature, increased
perspiration.perspiration.
Changes in organism’s functionsChanges in organism’s functions::
• increase of heart rate and BP;increase of heart rate and BP;
• centralization of bloodflow;centralization of bloodflow;
• decrease of alveolar ventilation;decrease of alveolar ventilation;
• decrease of working capacity, weakness,decrease of working capacity, weakness,
drowse, high irritability.drowse, high irritability.

26. Changes in the organism due toChanges in the organism due to
body’s temperaturebody’s temperature
 38°C38°C - Sweating.- Sweating.
 39°C39°C - Severe sweating, redness of the skin,- Severe sweating, redness of the skin,
fast heart rate and breathlessness.fast heart rate and breathlessness.
 40°C40°C - + Fainting, dehydration, weakness,- + Fainting, dehydration, weakness,
vomiting, headache and dizziness, profusevomiting, headache and dizziness, profuse
sweating.sweating.
 41°C41°C - + hallucinations, delirium, drowsiness.- + hallucinations, delirium, drowsiness.
 42°C42°C - + severe delirium and vomiting, coma,- + severe delirium and vomiting, coma,
convulsions.convulsions.
 43°C43°C - + serious brain damage, continuous- + serious brain damage, continuous
convulsions and shock, cardio-respiratoryconvulsions and shock, cardio-respiratory
collapse will occur.collapse will occur.
 44°C44°C or moreor more - almost certainly death will- almost certainly death will
occur.occur.
Com
pensation
Decom
pensation

27. Hyperthermia decompensationHyperthermia decompensation
stagestage
 cardiovascular disturbancescardiovascular disturbances ––
progressive tachycardia, decrease ofprogressive tachycardia, decrease of
heart stroke volume, microcirculationheart stroke volume, microcirculation
disorders, increased blood clotting.disorders, increased blood clotting.
 acidosisacidosis due to hypoxia.due to hypoxia.
 hypohydrationhypohydration (du to profound(du to profound
sweating)sweating) leads to increased bloodleads to increased blood
viscosityviscosity
 metabolic violationsmetabolic violations

28. The biochemical effectsThe biochemical effects of longof long
exposure to high temperatureexposure to high temperature
 Denaturation of proteinsDenaturation of proteins – blocking of– blocking of
all enzyme pathwaysall enzyme pathways
 Liquefaction of lipid membraneLiquefaction of lipid membrane ––
destroying cell wallsdestroying cell walls
 Damage of mitochondrial membranesDamage of mitochondrial membranes
- paralysis of energy production- paralysis of energy production
 Increase of Na+ leakIncrease of Na+ leak

29. The biochemical effectsThe biochemical effects of longof long
exposure to high temperatureexposure to high temperature
 Increase of peroxidative oxidation ofIncrease of peroxidative oxidation of
lipidslipids – accumulation of high toxic– accumulation of high toxic
suboxidized lipid metabolismsuboxidized lipid metabolism
productsproducts
 Carbohydrate metabolismCarbohydrate metabolism and otherand other
energy pathways are disrupted.energy pathways are disrupted.
The loss of energy in the cell reducesThe loss of energy in the cell reduces
normal cellular functions andnormal cellular functions and
thermoregulation fails.thermoregulation fails.

30. Heat stroke manifestationHeat stroke manifestation
 Body temperature >40 CBody temperature >40 C
 CNS depressionCNS depression (the most important sign(the most important sign
of heat stroke).of heat stroke).
• bizarre behaviorbizarre behavior
• amnesiaamnesia
• collapse, delirium, stupor, and coma.collapse, delirium, stupor, and coma.
 The skin color may be ashen, implyingThe skin color may be ashen, implying
circulatory collapse, or pink.circulatory collapse, or pink.
 Symptoms of autonomic nervous systemSymptoms of autonomic nervous system
dysfunction, miosis, decreased paindysfunction, miosis, decreased pain
response, and dehydration symptomsresponse, and dehydration symptoms

31. Thermotherapy (pyrotherapy)Thermotherapy (pyrotherapy)
General thermotherapyGeneral thermotherapy - injection- injection
of bacterial lipopolysaccride (primaryof bacterial lipopolysaccride (primary
pyrogens).pyrogens).
 Aims:Aims:
• to increase adaptive and innateto increase adaptive and innate
immunity in chronic infectious diseasesimmunity in chronic infectious diseases
(arthritis, syphilis)(arthritis, syphilis)
• to intensify reparative processes into intensify reparative processes in
bones and other tissues after theirbones and other tissues after their
damage, trauma, surgical operations.damage, trauma, surgical operations.

32. Thermotherapy (pyrotherapy)Thermotherapy (pyrotherapy)
 Local thermotherapyLocal thermotherapy may be used inmay be used in
cancer treatment:cancer treatment:
• tumor cells have difficulty dissipating heat.tumor cells have difficulty dissipating heat.
• local increase of temperature brake mitoses inlocal increase of temperature brake mitoses in
cancer cells, cause denaturation of cancer cellcancer cells, cause denaturation of cancer cell
membrane proteins.membrane proteins.
• Even if the cancerous cells do not die, theyEven if the cancerous cells do not die, they
become more susceptible to ionizing radiationbecome more susceptible to ionizing radiation
treatments or to certain chemotherapies.treatments or to certain chemotherapies.

33. Differences between fever andDifferences between fever and
hyperthermiahyperthermia
FeverFever HyperthermiaHyperthermia
CauseCause Bacterial pyrogens,Bacterial pyrogens,
tissues decay productstissues decay products
with secondarywith secondary
pyrogens synthesispyrogens synthesis
External andExternal and
internal factors,internal factors,
which don’t causewhich don’t cause
secondarysecondary
pyrogens synthesispyrogens synthesis
OntogeneticOntogenetic
aspectsaspects
Is formed in the end ofIs formed in the end of
the first year of lifethe first year of life
Is formed in anyIs formed in any
period of lifeperiod of life

34. Differences between fever andDifferences between fever and
hyperthermiahyperthermia
FeverFever HyperthermiaHyperthermia
TemperatureTemperature
adjusting pointadjusting point
Higher thanHigher than
normalnormal
NormalNormal
ThermoregulationThermoregulation NormalNormal ImpairedImpaired
SymptomsSymptoms Depends on theDepends on the
stagestage
Don’t depend on theDon’t depend on the
stage but severitystage but severity
increases with timeincreases with time
The role for theThe role for the
organismorganism
Both positive andBoth positive and
negativenegative
Only negativeOnly negative
TreatmentTreatment AntipyreticAntipyretic
medicinesmedicines
Physical coolingPhysical cooling

35. When fever treatment is neededWhen fever treatment is needed
 when fever is accompanied with highwhen fever is accompanied with high
pyretic temperature (pyretic temperature (more than 38,5more than 38,5
CC););
 when fever is observed in the patientwhen fever is observed in the patient
withwith cardio-vascular failure, diabetescardio-vascular failure, diabetes
mellitus or other endocrine diseasesmellitus or other endocrine diseases;;
 in newborns (0-2 months), infants (2in newborns (0-2 months), infants (2
months till 1 year) and aged peoplemonths till 1 year) and aged people..

36. The causes of hypothermiaThe causes of hypothermia
 not effective thermoregulation (infants,not effective thermoregulation (infants,
babies and aged people);babies and aged people);
 too long exposure to the coldtoo long exposure to the cold
surroundings;surroundings;
 disturbances of nervous system functiondisturbances of nervous system function
(drugs, alcohol, toxic substances,(drugs, alcohol, toxic substances,
parkinson disease);parkinson disease);
 disturbances of endocrine system functiondisturbances of endocrine system function
(hypothyroidism, hypopituitarism, adrenal(hypothyroidism, hypopituitarism, adrenal
insufficiency) that lead to decreased heatinsufficiency) that lead to decreased heat
production.production.

37. Hypothermia compensation stageHypothermia compensation stage
 Behavioral thermoregulationBehavioral thermoregulation
 Reduction of heat lossReduction of heat loss - peripheral blood- peripheral blood
vessels constriction.vessels constriction.
 Increase of heat productionIncrease of heat production - activation of- activation of
bloodflow in inner organs, induction ofbloodflow in inner organs, induction of
contractive thermogenesis (shivering).contractive thermogenesis (shivering).
 Heart and lungsHeart and lungs: tachycardia, increase of: tachycardia, increase of
BP and heart stroke volume, increasedBP and heart stroke volume, increased
ventilation of lungs.ventilation of lungs.

38. Changes in the organism due toChanges in the organism due to
body’s temperaturebody’s temperature
35°C35°C - Intense shivering, numbness and bluish /- Intense shivering, numbness and bluish /
greyness of the skin.greyness of the skin.
34°C34°C - Severe shivering, loss of movement of- Severe shivering, loss of movement of
fingers, blueness and confusion.fingers, blueness and confusion.
33°C33°C + sleepiness, depressed reflexes,+ sleepiness, depressed reflexes,
progressive loss of shivering, slow heart beat,progressive loss of shivering, slow heart beat,
shallow breathing.shallow breathing.
32°C32°C + Hallucinations, delirium, comatose.+ Hallucinations, delirium, comatose.
Shivering and nervous reflexes are absent.Shivering and nervous reflexes are absent.
31°C31°C + shallow breathing and slow heart rate.+ shallow breathing and slow heart rate.
Possibility of serious heart rhythm problems.Possibility of serious heart rhythm problems.
28°C28°C + Severe heart rhythm disturbances,+ Severe heart rhythm disturbances,
problems with breathing.problems with breathing.
24-26°C or less24-26°C or less - Death due to irregular heart- Death due to irregular heart
beat or respiratory arrest.beat or respiratory arrest.
Com
pensation
Decom
pensation

39. Hypothermia decompensationHypothermia decompensation
stagestage
 slowing of biochemical reactions (inhibitionslowing of biochemical reactions (inhibition
of metabolism);of metabolism);
 increase of blood viscosity, slowing ofincrease of blood viscosity, slowing of
blood flow, increase of blood coagulation;blood flow, increase of blood coagulation;
 development of tissue’s hypoxia.development of tissue’s hypoxia.
Cold core temperature (below 25Cold core temperature (below 2500
C) causesC) causes
the depression of brain respiratory,the depression of brain respiratory,
vascular and thermoregulation centers,vascular and thermoregulation centers,
the violation of heart contraction.the violation of heart contraction.

40. Vicious circles during hypothermiaVicious circles during hypothermia
Low
body temperature
Metabolic circle
Metabolism
inhibition
Low
heat production

41. Vicious circles during hypothermiaVicious circles during hypothermia
Low
body temperature
Vascular circle
Dilation of
peripheral
vessels
Increased
heat loss

42. Vicious circles during hypothermiaVicious circles during hypothermia
Low
body temperature
Neuro-muscular circle
Decreased excitability
of nervous centres
Absence of contractive
thermogenesis

43. Controlled hypothermiaControlled hypothermia
Systemic controlled hypothermiaSystemic controlled hypothermia is usedis used
in surgical operations on the organs within surgical operations on the organs with
stopped bloodflow – heart, brain, largestopped bloodflow – heart, brain, large
vessels.vessels.
• Cells and tissues in the controlled hypothermiaCells and tissues in the controlled hypothermia
decrease their functional activity.decrease their functional activity.
• It prevents disturbances of ABB, water and ionIt prevents disturbances of ABB, water and ion
metabolism, increase tissue’s resistance tometabolism, increase tissue’s resistance to
hypoxia and other pathogenic stimuli.hypoxia and other pathogenic stimuli.
Local induced hypothermiaLocal induced hypothermia (brain,(brain,
kidneys, liver, prostate etc.) is providedkidneys, liver, prostate etc.) is provided
complex surgical operations.complex surgical operations.

44. The prospects of using medicalThe prospects of using medical
hibernationhibernation
 Organ preservationOrgan preservation (for(for
transplantation)transplantation)..
 Strokes treatmentStrokes treatment (prevention of(prevention of
brain death).brain death).
 TraumaTrauma (decrease of body's(decrease of body's
oxygen demand to surviveoxygen demand to survive
bleedings)bleedings)..