thermoregulation and Fever physiology .ppt

thermoregulation

1. Pathogenesis of Fever
Aug 29, 2024 Fever 1

2. Introduction
Thermoregulation
Definition of fever
Pathogenesis of fever
Adaptive function of fever
Heat stress & hypothermia
Aug 29, 2024 Fever 2

3. Thermoregulation
Normal Body Temperature
Regulatory Mechanisms
Aug 29, 2024 Fever 3

4. Aug 29, 2024 Fever 4
42.2
0
C Irreversible brain Damage
41.1
0
C Convulsion – Children
37.5
0
C
37.0
0
C Normal Body Temperature
36.5
0
C
32.8
0
C Loss of consciousness
30.0
0
C
28.5
0
C Atrial & Ventricular Fibrillation
BODY TEMPERATUREBODY TEMPERATURE

5. Regulation of Body Temperature
•Thermal homoestasis depends on
•Integrated neuroendocrine system
•Heat gain & heat loss are maintained
•To prevent development of
•Hyperthermia
•Hypothermia
Aug 29, 2024 Fever 5

6. Regulation of Body Temperature
•Mechanism of heat transfer to the environment
•depend on
•Temperature gradient between
•Body & environment
•Involve
•Radiation, conduction, convection, evaporation
Aug 29, 2024 Fever 6

7. Regulation Of Body Temperature
•Organisms employ a simple mechanism for temperature regulation
1.Blood flow to the skin and subcutaneous tissues
•Vasoconstriction increases accumulation of heat
•Vasodilatation secures its quick loss
2.Chemical and mechanical thermo-genesis
Aug 29, 2024 Fever 7

8. Regulation Of Body Temperature
•Regulated by nervous feedback mechanisms
•Hypothalamic temperature control centre
•Receive information from
•Peripheral & central thermo-receptors
•Anterior hypothalamic pre optic area contains
•Heat and cold sensitive neurons
•Heat sensitive neurons increase rate of firing as temperature increase
•Cold sensitive neurons increase rate of firing as temperature
decreases
Aug 29, 2024 Fever 8

9. Aug 29, 2024 Fever 9

10. Aug 29, 2024 Fever 10
Peripheral cold
receptors
Peripheral
warm
receptors
Internal
warm
receptors
Anterior
hypothalamus
Posterior
Hypothalamus
Internal cold
receptors
Heat
production
Heat loss
+
Hypothalamic Temperature Control System
+
-
+
-
+
+

11. Aug 29, 2024 Fever 11
Set
Point
37
0
C
Heat gain
Body temp
37
0
C
Heat loss
Ext. disturbances
Body heat
content
Temp
Control
Centre
receptors
THERMOREGULATORY SYSTEM

12. Fever
• Elevation of body temperature above the normal daily variations
•Not related to
•Work
•Exposure to hyperthermic conditions
•Drugs
•Breakdown of temperature control system
Aug 29, 2024 Fever 12

13. Pathogenesis
•Fever is a “disorder” of the thermoregulatory system
•Appears as if there is an upward displacement of the set point
•Body actively seeks to raise the temperature
Aug 29, 2024 Fever 13

14. Aug 29, 2024 Fever 14
New Set
Point
39
0
C
Heat gain
Body temp
37
0
C
Heat loss
Ext. disturbances
Body
heat
content
Temp
Control
Centre
receptors
THERMOREGULATORY SYSTEM
Leading to fever
Vasoconstrictio
n, Piloerection
Thermo genesis New body
temp 39
o
C

15. Fever Inducing Agents
•Pyrogens
•Substances that are capable of inducing fever
•Cause the hypothalamic set point to rise
•Leading to the development of fever
Aug 29, 2024 Fever 15

16. Fever Inducing Agents
•They are
•Breakdown products of proteins
•Lipopolysaccharides
•Microbial agents: virus, bacteria, fungi
•Toxins secreted by bacteria
•Certain steroids
•Antigen antibody complexes
Aug 29, 2024 Fever 16

17. Fever Inducing Agents
•Exogenous pyrogens evoke an apparent common mediator
•Endogenous pyrogens
•Endotoxins
•Cytokines IL-1, alpha, beta, IL-6
•TNF
•Interferons
Aug 29, 2024 Fever 17

18. Thermostat Resetting
•Chemical substances
originally called
•Endogenous pyrogens
•Released from
•Macrophages, monocytes
•In presence of infection
Aug 29, 2024 Fever 18
Infections,
bacterial
breakdown
products
Monocytes,
tissue
macrophage,
endothelial
cells, killer
lymphocytes
Endogenous
pyrogens: IL1,
TNF
Thermoregulation
center
New set
point
Fever

19. Thermostat Resetting
•These substances act on
thermoreceptors
•Hypothalamus
•? Other areas
•Alter rate of firing
•To integrating centers
•Action mediated
•Local release of prostaglandin
•Alter the central
thermoreceptor function
Aug 29, 2024 Fever 19
Infections,
bacterial
breakdown
products
Monocytes,
tissue
macrophage,
endothelial
cells, killer
lymphocytes
Endogenous
pyrogens: IL1,
TNF
Thermoregulation
center
New set
point
Fever

20. Thermostat Resetting
•Cytokines like IL1
•Act on cells of OVLT
•Prostlandin E
•Released
•Crosses the BBB to
hypothalamus
•Exert its pyrogenic effect
•On the pre-optic area
Aug 29, 2024 Fever 20
Cytokines
IL1,
(OVLT) Organum (OVLT) Organum
Vasculosum Vasculosum
Laminae Laminae
TerminalisTerminalis
Prostaglandin E
Pre-Optic
area
Fever

21. Aug 29, 2024 Fever 21
From: Cecil Textbook of Medicine

22. Adaptive function of fever
Aug 29, 2024 Fever 22

23. Adaptive Function of Fever
•The benefit of fever to the organism is uncertain
•Presumably beneficial
•Has persisted through evolution
•As a response to infections and other diseases
Aug 29, 2024 Fever 23

24. Adaptive Function of Fever
•Probably to enhance
•Host defense response to infections
•Many microorganisms
•Grow best within a relatively narrow temperature
range
•A rise in temperature inhibits their growth
Aug 29, 2024 Fever 24

25. Adaptive Function Of Fever
•Some heat sensitive micro-organism that produce disease
•Syphilis, gonorrhoea can be killed in vivo by artificially induced fever
•Hyperthermia benefit individuals with some diseases like
•Anthrax; pneumococcal pneumonia; rickesttial and viral infections
•Hyperthermia also slows the growth of some tumours
Aug 29, 2024 Fever 25

26. Adaptive Function Of Fever
•However, very high temperatures are harmful
•When the rectal temperature is over 41
o
c for a long time
•Brain damage occurs
Aug 29, 2024 Fever 26

27. Adaptive Function of Fever
•Small elevation of body temperature
•Like those observed during fever
•Enhance immune response
•Increase chemotactic, phagocytic and bactericidal activity of
Polymorphonuclear leucocytes
•Stimulates the process of antibody production
•Putative effect of IL-1 and IL-6
•Reduction of plasma concentration of iron, zinc and copper
•Slow the proliferation of micro organisms
Aug 29, 2024 Fever 27

28. Endogenous Cryogen
•Endogenously produced antipyretic factors
•That counteract the effect of pyrogen
•It is critical to the host that body temperatures do not get close to
lethal limits
•There are many peptide that can act as antipyretics
•Arginine Vasopressin
•-melanocyte simulating hormone
•Uromodulin
Aug 29, 2024 Fever 28

29. Disorders Due To Heat Stress
•Hyperthermia is present
•When body core temperature
•Is >37.5
o
C
•Heat injury syndrome
•May result when body temp  above 40
o
C
Aug 29, 2024 Fever 29

30. Disorders Due To Heat Stress
•When temperature  > 41
o
C
•Multi-system failure occurs
•Enzymes are denatured
•Mitochondrial function is disturbed
•Cell membranes are destabilized
•O
2 dependent metabolic pathways
•Disrupted
Aug 29, 2024 Fever 30

31. Disorders Due To Heat Stress
•Include
•Heat cramps
•Heat exhaustion
•Heat stroke
•Heat hyperpyrexia
•Sunstroke
•Malignant hyperthermia
Aug 29, 2024 Fever 31

32. Heat Cramps
•Painful spasms of voluntary muscles
•Usually follows strenuous exercise with excessive sweating
•In an unacclimatized
•Related to absolute or relative deficiency
•Sodium chloride
•Water
Aug 29, 2024 Fever 32

33. Heat Cramps
•Individual complains of
•Nausea, vomiting, fatigue
•Muscle cramps
•Symptoms occur
•Several hrs after cessation of strenuous activity
Aug 29, 2024 Fever 33

34. Heat Exhaustion
•Most common heat injury syndrome
•May be preceded by heat cramps
•Is due to severe
•Dehydration
•Electrolyte loss
Aug 29, 2024 Fever 34

35. Heat Exhaustion
•In young individuals
•Usually occurs after strenuous activity
•Hot & humid environment
•Un-acclimatized
•In the old and elderly occurs due to
•Inadequate CVS response to heat
•Disruption of normal compensatory mechanisms
Aug 29, 2024 Fever 35

36. Heat Exhaustion
•Patient complains of
•Muscle cramps
•Headaches
•Fatigue
•Nausea
•Vomiting
•They appear
•Listless with pallor of skin
•Have profuse sweating
Aug 29, 2024 Fever 36

37. Heat Exhaustion
•Other findings include
•Orthostatic hypotension
•Core temp 37.5 to 39
o
C
•Altered mental state
•In-coordination
•Weakness
•Syncope may also occur
Aug 29, 2024 Fever 37

38. Heat Stroke
•Heat hyperpyrexia, sunstroke
•Exertional
•Non exertional
•Syndrome due
•To acute disruption of thermoregulatory mechanisms
•Manifested by
•Depression of CNS & regulatory centre
•Depressed sweating
•Body temp   41
o
C
•Several physiologic & biochemical abnormalities
Aug 29, 2024 Fever 38

39. Heat Stroke
•Exertional heat stroke
•Occurs in people
•Working or exercising in hot environment
•The regulatory system is
•Unimpaired
•Overwhelmed
•Excessive exposure to high external temperature
•Body’s ability to loose heat is overridden
•Body temp rises to dangerous level
Aug 29, 2024 Fever 39

40. Heat Stroke
•Non-exertional occurs in
•Elderly, debilitated, intoxicated or paralyzed
•Have impaired regulatory mechanisms
•Physiologic or drug induced
•Autonomic impairment
Aug 29, 2024 Fever 40

41. Heat Stroke
•Have impaired awareness or ability
•To leave a hot environment
•Poor acclimatization
•Inadequate ability to
• CO in response to heat
Aug 29, 2024 Fever 41

42. Malignant Hyperthermia
•Occur in certain individual with inherited disorder
•Body temperature
•Following administration of inhalation anaesthesia
•Halothane, methoxyflurane, ethyl ether, cyclopropane
Aug 29, 2024 Fever 42

43. Malignant hyperthermia
•Anaethetic agent causes
•Release of ca
++
from sarcoplasmic reticulum
•Activation of ATPase
•Hydrolysis of ATP yielding heat
Aug 29, 2024 Fever 43

44. Heat Injury Syndrome
•Consequences of heat induced cell damage
•Rhabdomyolysis
•Heart failure, arrhythmias, vasodilatation, hypotension
•Cytotoxic cerebral damage
•Acute renal failure
•Acute respiratory distress syndrome
•GIT bleeding
•Acute hepatic failure
Aug 29, 2024 Fever 44

45. Heat Injury Syndrome
•Laboratory abnormalities include
•Hyperkalemia, hypocalcaemia
•Hypo- or hyper-phosphatemia
• Creatinine
•Haemoconcentration, stress leukocytosis, thrombocytopenia
•Consumptive coagulopathy
•Lactic acidosis
•Hypoglycaemia
•Proteinuria
Aug 29, 2024 Fever 45

46. Hypothermia
•Defined as
•Core body temperature < 35
o
C
•Classified as
•Accidental
•Primary
•Secondary
Aug 29, 2024 Fever 46

47. Accidental Hypothermia
•Accidental form
•Spontaneous decrease of core temperature to < 35
o
C
• After accidental exposure to cold environment
•May be associated with acute medical problems
•Occurs without
•Disturbance of temp regulatory center
Aug 29, 2024 Fever 47

48. Secondary Hypothermia
•Characterized by
•Dysfunction of hypothalamic thermoregulatory center
•An underlying illness or drugs
•In patients with myxoedema, pituitary insufficiency, Addison
disease, cirrhosis of the liver, pancreatitis, cerebrovascular
diseases, and myocardial infarction
•Malnutrition
•Kwashiorkor
•After ingestion of drugs or alcohol
Aug 29, 2024 Fever 48

49. Effects of Hypothermia
•Hypothermia affects several systems
•The following are some of the effects
•Generalized slowing of metabolic activity
•Slowing of enzymatic activity
•Uncoupling of oxygen dependent metabolism
•Peripheral vasoconstriction
Aug 29, 2024 Fever 49

50. Effects of Hypothermia
•Alteration in CVS
•Early stages
•HR, CO, MAP
•Mediated by catecholamine
•Later stages
•Negative inotropic & chronotropic effects
•Due to hypothermia
• effective BV cause
•CO & tissue perfusion
Aug 29, 2024 Fever 50

51. Effects of Hypothermia
•ECG changes include
•Sinus bradycardia
•Slowing of conduction
•A-V block
•Prolonged QT interval
•Widening of QRS complex
•T wave inversion
•Cold heart is highly irritable
•Ventricular fibrillation
Aug 29, 2024 Fever 51

52. Effects of Hypothermia
•Pronounced hypothermia
•Depress respiratory center
•Alveolar ventilation
• PaO
2
• Pa
CO2
• pH
•Renal conc ability is lost
•Passage of very dilute urine
•Perfusion may lead to
•Acute tubular necrosis
Aug 29, 2024 Fever 52

53. Effects of Hypothermia
•Laboratory findings include
•Metabolic acidosis
•Hyperkalemia, hyponatremia
•Hyperglycaemia, hyperphosphatemia
Aug 29, 2024 Fever 53

54. Effects of Hypothermia
•Complications include
•Rhabdomyolysis
•Gastric dilatation
•Ileus
•Upper GIT bleed
•Acute pancreatitis
•Severe hepatic dysfunction
Aug 29, 2024 Fever 54

55. Effects of Hypothermia
•Haematological alterations include
•Haem-oconcentration
•Blood viscosity
•Thrombocytopenia
•Granulocytopenia
•Consumptive coagulopathy
Aug 29, 2024 Fever 55