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Pathophysiology of
FEVER
Presented by:
Dr. Faisal Abdullah
MBBS
Measured from:
• Mouth Cavity
• Rectum
• Esophagus
Body
Temperature
Core
Temperature
Skin/Shell
Temperature
Measured from:
• Axilla
• Groin
• Popliteal Fossa
Temperature of deep tissues of
the body – the core of the body.
Temperature of the skin- shell of
the body.
Normal Body Temperature 96-100° F
Guyton & Hall:
• Oral: 98° – 98.6° F
• Rectal: 99° – 99.6° F
Harrisons Medicine:
• 97.7° – 99.5° F
• Rectal temperature is 0.7° F or 0.4° C
more than oral temperature.
• Mean core temperature in healthy
adults 36.8° ± 4° C Or 98.2° ± 0.7° F
Circadian Rhythm/Diurnal variation of temperature is 0.5° C or 0.9° F.
More in the evening ( 4.00 pm )
Less in the morning ( 6.00 am )
Normal Body Temperature is maintained by Thermoregulatory center of
Hypothalamus by controlling the balance between Heat Production & Heat
Loss.
Heat Loss
Heat
Production
Body
Temperature
Maintained by Thermoregulatory
center of hypothalamus ( Pre-optic
anterior hypothalamic & Posterior
hypothalamic nucleus )
• Radiation
• Conduction to air
• Conduction to
Object
• Evaporation
• Basal Metabolic Rate
• Extra metabolism Rate
• Muscle contraction by
shivering
• Effect of hormones. EG:
Thyroxine, Growth
hormone, testosterone
• Effect of epinephjrine,
noirepinephrine,
sympathetic
stimulation
• Increased chemical
activity inside cells
• Thermogenic effect of
food
How does Hypothalamus control
Body Temperature ?
Hypothalamus maintains the body temperature by controlling the balance between heat loss and heat
production.
Whenever body temperature goes beyond a critical core temperature of 37.1° C or 98.8° F , drastic
changes occur in the rate of heat loss and heat production.
When temperature falls below 98.8° F, Heat Production > Heat Loss
When temperature rises above 98.8° F, Heat Production < Heat Loss
When temperature falls below 98.8° F
Body takes measures to rise the temperature to the set point:
Skin Vasoconstriction
throughgout the body,
first in the limbs, causing
shunting of blood from
periphery to limb which
conserves more heat.
Increased Heat
Production by increasing
thermogenesis
Piloerection occurs due
to contraction of
arrector pili muscles
attatched to hair follicles
as a result of
sympathetic stimulation.
Temperature increased to 98.8° F (set point)
Behavioural adjustments eg: putting on more clothes facilitates heat conservation, thereby increasing
body temperature.
When temperature rises above 98.8° F
Body takes measures to lower the temperature back to the set point:
Skin Vasodilation
throughgout the body,
causing pulling of blood
to periphery which
increasess heat loss upto
eightfold.
Reduced Heat Production by
decreasing thermogenesis.
Sweating occurs due to
sympathetic stimulation
in response to
stimulation of the
anterior preoptic
hypothalamic nucleus.
Temperature reduced to 98.8° F (set point)
Behavioural adjustments eg: remove clothings, facilitates heat loss and thereby reducing the body
temperature.
What happens if the Hypothalamic Set
Point is elevated ?
• Fever ?
• Hyperthermia ?
• Hyperpyrexia ?
• Fever is an elevation
of body temperature
that exceeds the
normal daily variation
and occurs in
conjunction with an
increase in the
hypothalamic set
point.
• Occurs in response to
Pyrogens.
• Hypothalamic
thermoregulatory set
point is raised.
• Antipyretics reduce
body temperature.
• Hyperpyrexia is a fever
of > 41.5° C or 106.7° F
• Occurs in response to
pyrogens.
• Hypothalamic
thermoregulatory set
point is raised
• Antipyretics reduce
body temperature.
• Hyperthermia is an
uncontrolled increase in
body temperature that
exceeds body’s ability to
lose heat.
• Occurs due to excessive
heat production or excess
exogenous heat. No role
of pyrogens.
• Hypothalamic
thermoregulatory set
point is unchanged.
• Antipyretics doesn’t work.
FEVER HYPERPYREXIA HYPERTHERMIA
Reference: Harrison’s Principles of Internal Medicine
PYROGENS
Substances that cause fever
when they are present in
blood in appropriate
concentrations.
Derived from outside the
patients body.
Eg: Microbial products,
microbial toxins, micro-
organisms.
Classic example is: Endotoxin
(LPL) derived from gram (-)ve
bacteria.
Cytokines that cause fever.
Cytokines are small proteins that regulate
immune, inflammatory, hematopoietic
process.
Endogenous pyrogens are conventionally
called Pyrogenic Cytokines.
Eg: IL-1, IL-6, TNF, Ciliary neurotropic factor
etc derived from myeloid and endothelial
cells.
Exogenous Endogenous
Fever can occur due to
presence of exgenous
pyrogens via microbial
infections.
Inflammatory process such as Pericarditis;
Trauma, Stroke, Routine immunization may
induce the production of Pyrogenic Cytokines
and therefore induce fever.
Either of these two can trigger the hypothalamus to raise the set
point of hypothalamic thermoregulation to a febrile level.
FEVER
Infection, Microbial
toxins, Inflammatory
mediators, Immune
reactions
Pyrogenic Cytokines ( IL-1,
IL-6, TNF, IFN ) released
from macrophages/
monocytes, endothelial
cells & other cells
Microbial toxins
(Exogenous Pyrogens )
Hypothalamic Endothelium Arachidonic Acid
PGE2
Cyclooxygenase
cAMP
Activation of neuronal
endings from hypothalamic
thermoreghulatory centre.
Elevated Set Point
Body will take
measures to raise
the temperature to
setpoint.
Elevated Set Point
Setpoint is elevated
Body temperature
is still below the
setpoint.
Patient will feel cold
Chills Increased tone of skeletal
muscles throughout the body by
facilitating the activity of the
anterior motor neurons.
Shivering occurs when the tone
rises above a certain critical
level.
Activation of primary motor centre for
shivering which is located in the
dorsomedial portion of the posterior
hypothalamus near the wall of the third
ventricle.
Nonrhythmical signals via lateral
columns of spinal cord to the
anterior motor neurons
Rigor
Sympathetic stimulation
Contraction of
arrector pili
muscles attatched
to the hair follicles
to contract.
Upright projection of Hair
follicles
Piloerection
Entrapment of thick layer of
insulator air next to the skin,
allowing greater degree of heat
conservation.
• All these processes continue until the body reaches this temperature,
meaning Blood bathing the Hypothalamic region matches the new
set point temperature.
• When the hypothalamic thermoregulatory set point temperature is
achieved throughout the body, Congratulations ! Now you have
Fever.
• Now all these processes are going to stop. Chills, Rigor, Shivering,
Piloerection – everything. The body will now work to maintain this
elevated set point temperature.
How does FEVER subside?
To be continued..
• Guyton & Hall Textbook of Medical Physiology
• Harrison’s Principle of Internal Medicine
• Long Cases in Clinical Medicine by Prof. ABM Abdullah Sir
• Short Cases in Clinical Medicine by Prof. ABM Abdullah Sir
• Practical Manual in Clinical Medicine by Prof. ABM Abdullah Sir
• Lecture on Fever, by Prof. Ridwanur Rahman Sir, on Axis Medical School.
Suggested Reading :

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Pathophysiology of FEVER: Hypothalamic Regulation and Mechanisms

  • 2. Measured from: • Mouth Cavity • Rectum • Esophagus Body Temperature Core Temperature Skin/Shell Temperature Measured from: • Axilla • Groin • Popliteal Fossa Temperature of deep tissues of the body – the core of the body. Temperature of the skin- shell of the body.
  • 3. Normal Body Temperature 96-100° F Guyton & Hall: • Oral: 98° – 98.6° F • Rectal: 99° – 99.6° F Harrisons Medicine: • 97.7° – 99.5° F • Rectal temperature is 0.7° F or 0.4° C more than oral temperature. • Mean core temperature in healthy adults 36.8° ± 4° C Or 98.2° ± 0.7° F Circadian Rhythm/Diurnal variation of temperature is 0.5° C or 0.9° F. More in the evening ( 4.00 pm ) Less in the morning ( 6.00 am )
  • 4. Normal Body Temperature is maintained by Thermoregulatory center of Hypothalamus by controlling the balance between Heat Production & Heat Loss. Heat Loss Heat Production Body Temperature Maintained by Thermoregulatory center of hypothalamus ( Pre-optic anterior hypothalamic & Posterior hypothalamic nucleus ) • Radiation • Conduction to air • Conduction to Object • Evaporation • Basal Metabolic Rate • Extra metabolism Rate • Muscle contraction by shivering • Effect of hormones. EG: Thyroxine, Growth hormone, testosterone • Effect of epinephjrine, noirepinephrine, sympathetic stimulation • Increased chemical activity inside cells • Thermogenic effect of food
  • 5. How does Hypothalamus control Body Temperature ? Hypothalamus maintains the body temperature by controlling the balance between heat loss and heat production. Whenever body temperature goes beyond a critical core temperature of 37.1° C or 98.8° F , drastic changes occur in the rate of heat loss and heat production. When temperature falls below 98.8° F, Heat Production > Heat Loss When temperature rises above 98.8° F, Heat Production < Heat Loss
  • 6. When temperature falls below 98.8° F Body takes measures to rise the temperature to the set point: Skin Vasoconstriction throughgout the body, first in the limbs, causing shunting of blood from periphery to limb which conserves more heat. Increased Heat Production by increasing thermogenesis Piloerection occurs due to contraction of arrector pili muscles attatched to hair follicles as a result of sympathetic stimulation. Temperature increased to 98.8° F (set point) Behavioural adjustments eg: putting on more clothes facilitates heat conservation, thereby increasing body temperature.
  • 7. When temperature rises above 98.8° F Body takes measures to lower the temperature back to the set point: Skin Vasodilation throughgout the body, causing pulling of blood to periphery which increasess heat loss upto eightfold. Reduced Heat Production by decreasing thermogenesis. Sweating occurs due to sympathetic stimulation in response to stimulation of the anterior preoptic hypothalamic nucleus. Temperature reduced to 98.8° F (set point) Behavioural adjustments eg: remove clothings, facilitates heat loss and thereby reducing the body temperature.
  • 8. What happens if the Hypothalamic Set Point is elevated ? • Fever ? • Hyperthermia ? • Hyperpyrexia ?
  • 9. • Fever is an elevation of body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamic set point. • Occurs in response to Pyrogens. • Hypothalamic thermoregulatory set point is raised. • Antipyretics reduce body temperature. • Hyperpyrexia is a fever of > 41.5° C or 106.7° F • Occurs in response to pyrogens. • Hypothalamic thermoregulatory set point is raised • Antipyretics reduce body temperature. • Hyperthermia is an uncontrolled increase in body temperature that exceeds body’s ability to lose heat. • Occurs due to excessive heat production or excess exogenous heat. No role of pyrogens. • Hypothalamic thermoregulatory set point is unchanged. • Antipyretics doesn’t work. FEVER HYPERPYREXIA HYPERTHERMIA Reference: Harrison’s Principles of Internal Medicine
  • 10. PYROGENS Substances that cause fever when they are present in blood in appropriate concentrations. Derived from outside the patients body. Eg: Microbial products, microbial toxins, micro- organisms. Classic example is: Endotoxin (LPL) derived from gram (-)ve bacteria. Cytokines that cause fever. Cytokines are small proteins that regulate immune, inflammatory, hematopoietic process. Endogenous pyrogens are conventionally called Pyrogenic Cytokines. Eg: IL-1, IL-6, TNF, Ciliary neurotropic factor etc derived from myeloid and endothelial cells. Exogenous Endogenous
  • 11. Fever can occur due to presence of exgenous pyrogens via microbial infections. Inflammatory process such as Pericarditis; Trauma, Stroke, Routine immunization may induce the production of Pyrogenic Cytokines and therefore induce fever. Either of these two can trigger the hypothalamus to raise the set point of hypothalamic thermoregulation to a febrile level. FEVER
  • 12. Infection, Microbial toxins, Inflammatory mediators, Immune reactions Pyrogenic Cytokines ( IL-1, IL-6, TNF, IFN ) released from macrophages/ monocytes, endothelial cells & other cells Microbial toxins (Exogenous Pyrogens ) Hypothalamic Endothelium Arachidonic Acid PGE2 Cyclooxygenase cAMP Activation of neuronal endings from hypothalamic thermoreghulatory centre. Elevated Set Point Body will take measures to raise the temperature to setpoint.
  • 13.
  • 14. Elevated Set Point Setpoint is elevated Body temperature is still below the setpoint. Patient will feel cold Chills Increased tone of skeletal muscles throughout the body by facilitating the activity of the anterior motor neurons. Shivering occurs when the tone rises above a certain critical level. Activation of primary motor centre for shivering which is located in the dorsomedial portion of the posterior hypothalamus near the wall of the third ventricle. Nonrhythmical signals via lateral columns of spinal cord to the anterior motor neurons Rigor Sympathetic stimulation Contraction of arrector pili muscles attatched to the hair follicles to contract. Upright projection of Hair follicles Piloerection Entrapment of thick layer of insulator air next to the skin, allowing greater degree of heat conservation.
  • 15. • All these processes continue until the body reaches this temperature, meaning Blood bathing the Hypothalamic region matches the new set point temperature. • When the hypothalamic thermoregulatory set point temperature is achieved throughout the body, Congratulations ! Now you have Fever. • Now all these processes are going to stop. Chills, Rigor, Shivering, Piloerection – everything. The body will now work to maintain this elevated set point temperature.
  • 16. How does FEVER subside? To be continued..
  • 17. • Guyton & Hall Textbook of Medical Physiology • Harrison’s Principle of Internal Medicine • Long Cases in Clinical Medicine by Prof. ABM Abdullah Sir • Short Cases in Clinical Medicine by Prof. ABM Abdullah Sir • Practical Manual in Clinical Medicine by Prof. ABM Abdullah Sir • Lecture on Fever, by Prof. Ridwanur Rahman Sir, on Axis Medical School. Suggested Reading :