A 6 year old boy is brought to the
pediatric clinic by his mother
with complaints of fever, malaise
and cough for the the past 2 days.
The mother mentions that initially the fever
was low-grade and intermittent in nature
but later became high-grade and continuous.
The patient is also anorexic.
Physicial examination reveals a pulse of 130, temperature
of 38.3 celsius and a respiratory rate of 32.
Oropharyngeal examination reveals
that the patient's palatine tonsils
are covered with pus and erythema
of the surrounding mucosa.
Which of the following mediator is responsible
for this patient’s abnormal temperature?
Answer choice (A) - leukotriene D4
Answer choice (B) - thromboxane A2
Answer choice (C) - Prostaglandin E2
Answer choice (D) - prostaglandin I2
ans answer choice (E) - prostaglandin F2
Now take a moment to come to an answer by
yourself before we go through it together.
Okay, let's jump right in to this question.
The first thing we need to do is
determine the subject we're discussing
and this falls under general
pathology as they're asking us,
'which of the following mediators
is responsible for fever?
Now this is a 2-step question because
we have to first diagnose - one,
the cause of the abnormal temperature and
then second, the mediator responsible.
And the stem is absolutely required to
understand the clinical history, the diagnosis.
and then 2nd step, we have to then figure
out on our own the mediator cause.
So let's walk through this question.
Step 1 - we have todetermine the type of
abnormal temperature we're appreciating with.
Now we know a normal body temperature is
between 36.5 and 37.5 degrees celsius,
and the differential diagnosis for abnormal temperature
can be hypothermia, which is less than 36.5
or hyperthermia which is also called
the fever, which is greater than 37.5.
This patient's fever is 38.3 and thus the
patient has a fever or hyperthermia.
Now the cause of this patient's hyperthermia is
likely infectious in nature given the infection
or the tonsillitis that appears
to be present in this case.
Now we have to determine the actual
chemical mediator of the fever.
Now this patient has alteration in the
hypothalamic thermoregulatory center of the brain.
Now the hypothalamus actually sets a "set
point" as to what temperature the body wants
and fever is caused when you have an alteration
in this hypothalamic thermoregulatory center.
Now substances that actually induce fever are called
pyrogens which can be exogenous or endogenous.
Now the important endogenous pyrogens are interleukin-1,
TNF-alpha, interleukin-6 and prostaglandin E2,
and prostaglandin E2 is also
involved in inflammation.
Now looking at the answer choices, the answer choice
in this case is answer choice (C) - prostaglandin E2
as the mediator for fever.
Now if we refer to our image, we can see here the
arachidonic acid pathway - very important prostaglandins.
Now starting with the cell membrane phospholipids,
we have the enzyme phospholipase A2
which breaks it down into arachidonic acid.
And here we have a bifurcation, we have
5-lipooxygenase which give us our leukotrienes
and we also have cyclooxygenase
which gives us our prostaglandins.
And that's where we will find prostaglandin E2, thus it is a
derivative of arachidonic acid where prostaglandin E2 arises.
Now let's review some high-yield
facts regarding fever.
Now fever is induced by substances that can
be endogenous or exogenous called pyrogens
which actually change the hypothalamic regulatory
setpoint in the brain which is in the hypothalamus.
Now major mechanisms that increase the body's temperature
are vasoconstriction, and this is done to reduce heat loss
that is, we have redirection of blood from
the peripheral to central vascular system.
And also shivering is a mechanism that the
body uses to increase heat production.
Now the underlying causes are manifold and generally
related to both infection and inflammation.