PATHOPHYSIOLOGY OF FEVER

Fever is the elevation of an individual's core body temperature above a 'set-point' that is
normally regulated by the body's thermoregulatory center in the hypothalamus.
This increase in the body's 'set point' temperature is often secondary to a pathological process
that involves the release of immunological mediators to trigger the thermoregulatory center of
the hypothalamus to elevate the body's core temperature.
The normal temperature of the human body is considered to be 37 degrees C and varies by
about 0.5 degrees C through the course of the day. This minor variation of the core
temperature is the result of many normal physiological processes of the human body, including
sleep/wake cycles, metabolic changes, hormone variability, and activity levels. In fever,
however, the increase in the core body temperature is often greater than 0.5 degrees C and
attributed to a fever-inducing substance (pyrogen).
It is important to distinguish that the definition of fever is not synonymous with the definition
of hyperthermia. In fever, there is an increase in the 'set-point' temperature brought about by
the hypothalamus, which enables the body to maintain a controlled 'increase' of the core
temperature and general functionality of all organ systems. In hyperthermia, however, the
increase of the body's core temperature is beyond the confines of the set-point temperature
and regulation of the hypothalamus.
DEVELOPMENT
Numerous proteins and their breakdown products, and certain substances, particularly
lipopolysaccharide toxins liberated from bacterial cell layers, can raise the set-point of the
hypothalamic thermostat. Substances that cause this impact are called pyrogens. Pyrogens
discharged from toxic microscopic organisms or those discharged from disintegrating body
tissues cause fever during infectious conditions.
At the point when the set-point of the hypothalamic thermostat gets higher than typical, all the
processes for raising the internal heat level come into play, including heat preservation and
heat production increases. Within a couple of hours, after the set-point has elevated, the body
temperature as well moves toward this level.
In older adults, the ability to develop fever becomes impaired, and most of the times, have low
baseline body temperatures compared to younger adults. Due to this impaired ability, only
modest fever is observed in older adults even when they are severely infected.
The most crucial component initiating fever in the human body is the presence of a pyrogen.
A pyrogen is a substance that physiologically induces fever in the body. Pyrogens can be
classified as endogenous or exogenous depending on whether they originate from inside the
body or a fever triggering component from outside the body (e.g., toxins).
Many infectious pathogens normally trigger exogenous pyrogens as a part of their virulence.
For example, the cause of a febrile response in a Neisseria Meningitides infection is commonly
triggered by the lipopolysaccharide (LPS) component of this bacteria's cell wall, which
subsequently induces the production of the cytokine prostaglandin-E2. Cytokines, natural
mediators of the body's immunological response, operate as endogenous pyrogens to trigger
the activation of the fever response. Common cytokines known to induce the febrile response
include but are not exclusive to IL-1, IL-6, and TNF.
After the release of cytokine or exogenous pyrogens into the circulatory system, they bind to
specific receptors on the epithelial, vascular system. This process subsequently causes the
production and release of prostaglandin-E2 (PGE2), which is the ultimate inflammatory
mediator associated with many of the effects and symptoms related to the febrile response. In
the brain, the presence of the PGE2 stimulates the increase in the set-point temperature of the
hypothalamus and enables the increase in the core body temperature.

MECHANISM
The quick change in the set point in the hypothalamic thermostat causes an elevation in core
body temperature by triggering several physiological reactions. Temperature-increasing
mechanisms incorporate the following:
1. Posterior hypothalamic sympathetic center stimulation causes skin vasoconstriction all
through the body.
2. Piloerection, which is hairs "raising on end." The excitement of the sympathetic system
causes the contraction of the arrector pili muscles, which results in a standing position
of the hairs. This process is significant in lower creatures, which permits them to capture
a layer of non-conducting air close to the skin, which significantly depresses the heat
transfer to surroundings.
3. Heat production or thermogenesis increases through shivering, sympathetic stimulation,
and thyroxin discharge.
THE EFFECTS OF FEVER:
 METABOLIC EFFECTS:
o Increased need for oxygen
 Increases heart rate
 Increases respiration
 o Increased use of body proteins as an energy source
o During fever body switches from using glucose (an excellent medium for
bacterial growth) to metabolism based on protein and fat breakdown
 ENHANCES IMMUNE FUNCTION
o Increases motility and activity of WBC
o Stimulates interferon production and activation of T cells

 INHIBITS GROWTH OF CERTAIN MICROBIAL AGENTS

o Many microbial agents that cause infection to grow at normal body
temperatures

ADVERSE EFFECTS OF HIGH TEMPERATURE:

The pathological effects observed in a person who died of hyperpyrexia are local hemorrhages
and parenchymatous degeneration of cells all through the whole body, however particularly in
the brain. Damaged neuronal cells can never be replaced. Likewise, harm to the liver, kidneys,
and different organs can regularly be serious enough that damage of at least one of these
organs, in the long run, causes demise, which usually occurs after several days of the
occurrence of heatstroke.

SIGNIFICANCE
 Fever occurs when there is an elevation in the body's thermoregulatory set-point either
by endogenous or by exogenous pyrogen. In hyperthermia, the set-point is unaltered,
and the body temperature becomes elevated in an uncontrolled fashion due to
exogenous heat exposure or endogenous heat production.

 Hyperpyrexia is the term for an exceptionally high fever (>41.5 degrees C), which can
occur in patients with serious infections; however, most ordinarily happen in patients
with CNS hemorrhages.

 Inhibitors of cyclooxygenases, for example, aspirin and acetaminophen help reduce

fever

 Observation of a pattern of fever can be helpful in certain conditions; for example, a

fever that occurs every 48 to 72 hrs. in certain types of malaria, evening rise of
temperature occurs in tuberculosis.

 For instance, the everyday highs and lows of typical temperatures are emphasized in
many fevers. However, these variations might be turned around in typhoid fever and
 disseminated tuberculosis. Temperature-pulse dissociation occurs in typhoid fever,
brucellosis, leptospirosis, some medication prompted fevers, and factitious fever. In
healthy people, the temperature-pulse relationship is directly proportional with an
expansion in the pulse of 4.4 beats/minute for each 1 degree C (2.44 beats/minute for
each 1 degree F) an increase in core temperature.

 During infections, fever may not be observed in babies, older adults, patients with CKD,
and in patients taking corticosteroids; on the contrary, hypothermia may be present.