6-year-old (male) with fever and cough

00:02 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.

00:10 The mother mentions that initially the fever was low-grade and intermittent in nature but later became high-grade and continuous.

00:18 The patient is also anorexic.

00:20 Physicial examination reveals a pulse of 130, temperature of 38.3 celsius and a respiratory rate of 32.

00:29 Oropharyngeal examination reveals that the patient's palatine tonsils are covered with pus and erythema of the surrounding mucosa.

00:37 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.

01:08 Okay, let's jump right in to this question.

01:10 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.

01:30 And the stem is absolutely required to understand the clinical history, the diagnosis.

01:34 and then 2nd step, we have to then figure out on our own the mediator cause.

01:39 So let's walk through this question.

01:40 Step 1 - we have todetermine the type of abnormal temperature we're appreciating with.

01:44 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.

02:03 This patient's fever is 38.3 and thus the patient has a fever or hyperthermia.

02:09 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.

02:19 Now we have to determine the actual chemical mediator of the fever.

02:23 Now this patient has alteration in the hypothalamic thermoregulatory center of the brain.

02:32 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.

02:43 Now substances that actually induce fever are called pyrogens which can be exogenous or endogenous.

02:50 Now the important endogenous pyrogens are interleukin-1, TNF-alpha, interleukin-6 and prostaglandin E2, and prostaglandin E2 is also involved in inflammation.

03:03 Now looking at the answer choices, the answer choice in this case is answer choice (C) - prostaglandin E2 as the mediator for fever.

03:12 Now if we refer to our image, we can see here the arachidonic acid pathway - very important prostaglandins.

03:18 Now starting with the cell membrane phospholipids, we have the enzyme phospholipase A2 which breaks it down into arachidonic acid.

03:26 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.

03:35 And that's where we will find prostaglandin E2, thus it is a derivative of arachidonic acid where prostaglandin E2 arises.

03:44 Now let's review some high-yield facts regarding fever.

03:47 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.

03:59 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.

04:11 And also shivering is a mechanism that the body uses to increase heat production.

04:16 Now the underlying causes are manifold and generally related to both infection and inflammation.