Why fever is good


The main point of this post is to help me to understand the mechanism and logic behind fever production in response to bacterial infection.  If anyone else happens to gain valuable insight from this, then that will be an added benefit.

The body has a preferred core body temperature that is maintained via homeostatic mechanisms.  As I’m sure most of you know, this body temperature is, on average, 98.6 degrees Fahrenheit, although it does vary minimally from person to person. Temperature sensors in your skin and in the hypothalamus monitor this core temperature and relay any deviations to the anterior hypothalamus.  The anterior hypothalamus then compares this measured temperature to the preferred set-point core temperature.  If the measured temperature is below the preferred set-point core temperature, the anterior hypothalamus communicates this to the posterior hypothalamus.  The posterior hypothalamus is in charge of communicating to the rest of the body that heat needs to be produced, so it sends out signals to ensure that this happens.  For example, the posterior hypothalamus sends a message to skeletal muscle, via alpha motor neurons, telling them to rapidly contract.  This resultant “shivering” generates heat, just as a car engine generates heat when work is being performed. Another mechanism of heat production is prompted by the activation of the sympathetic nervous system (SNS) by cold temperatures;  cold temperatures tell the SNS to activate beta receptors in brown fat, which increases the metabolic rate and heat production in these tissues.  This is one reason, besides having extra insulation, that overweight people in general can stay warmer than thinner people.

So, now that we’ve talked about ways the body generates heat in response to cold, we need to consider ways the body can get rid of excess heat.  For example, if you’ve been out in the heat for an extended period, your core body temperature would also increase to the point of causing tissue damage if not for homeostatic mechanisms to counteract this.  See, heat causes proteins to denature (what we call what happens when heat causes proteins to unravel from their most functional form).  Just think about what happens when you cook hamburger meet.  If not for certain of these homeostatic mechanisms, your heart muscle, for example, would become overheated and denature into a less functional form, which could lead to decreased contractility and death.  The anterior hypothalamus orchestrates the response to excess heat.  One way it does this is by decreasing sympathetic tone to cutaneous blood vessels, which causes them to dilate, allowing more blood to flow through them.  This allows more blood, which is carrying heat, to flow to the skin, enabling the release of excess heat at the body surface.  Furthermore, sweat glands are under sympathetic muscarinic control, so sympathetic stimulation also leads to more evaporation of heat from the body surface.

Now we’ll talk about how bacterial infections cause fever.  Certain bacteria cause an increase in the production of interleukin-1 (IL-1) in macrophages.  IL-1 in turn acts on the anterior hypothalamus, leading to an increase in the production of prostaglandins. Prostaglandins, in turn, lead to an increase in the set-point core temperature.  This will cause the anterior hypothalamus to perceive the core temperature as being too low (since the prostaglandins caused the resetting of the core temperature), prompting it to correct the temperature by implementing heat generating mechanisms, such as shivering.

You see, fever is the body’s natural response to fight off infection. Bacteria are made of proteins, and excess heat causes those bacterial structural proteins to denature the same way our own proteins would denature.  At the same time, certain bacterial enzymes–which are made of protein– that the bacteria require to proliferate are denatured.  So, as you can see, fever is a good thing in moderation and it isn’t necessarily in our best interest to short-circuit it prematurely.  If, for instance, you give aspirin prematurely to reduce a fever, you aren’t giving your body time to kill off the bacteria.  In essence, the bacteria are happy when you take aspirin to reduce the fever because that means that they can proliferate and wreak havoc.  Just for your information, aspirin works by inhibiting an enzyme, called cyclooxygenase.  Cyclooxygenase normally functions in the formation of prostaglandins, which, as you may recall, are required to increase the set point temperature.  So, if you inhibit cyclooxygenase, there are no prostaglandins being produced to increase the set-point temperature.  Therefore, aspirin works by lowering the set-point temperature back to its original pre-infection temperature.  This causes the hypothalamus to read the increased body temperature (caused by the fever) as being higher than the set-point temperature, so the body responds by activating heat loss mechanisms.  So, you may be able to see how giving aspirin to break a fever isn’t always in your best interest.  I personally would rather let my body fight off the infection naturally and would only recommend giving aspirin if the fever stays above a certain temperature for a certain period of time.  I don’t, however, feel comfortable explicitly defining that temperature and time frame, as each situation is different and requires medical expertise to evaluate the specific situation.  That’s why you have doctors!

Posted in What I learned today | 4 Comments

JLMM


JLMM=Just Like My Mother

During the process of becoming a physician, I have learned about all types of terrifying disease scenarios.  Well, Micah Paul, this can’t bode well for you.  I hate to inform you of this, but you have a father who is just like his mother.  To make a long story shorter, while you were here staying with me over the past 3 weeks–in between my 4th and 5th semesters–you developed a cough.  During the day you were your usual, wonderful self, but at night, when you were recumbent in bed, you had a bad cough.  I got very little sleep–maybe 2 hours a night–because every time I would pass out from exhaustion, I would wake up alarmed, being as quiet as possible while I got close to your beautiful sleeping face in order to listen to your breathing.  You see, I knew that respiratory syncytial virus and parainfluenza virus cause croup, otherwise known as laryngotracheobronchitis.  I also knew that with croup, the causative virus invades the tissues surrounding the airway, and that when lymphocytes invade those tissues to go and battle the virus, the battleground (the tissues surrounding the airway) may become damaged.  One of the ways our bodies try to repair tissue damage is by swelling with fluids, which better allows the damaged tissues to wash away anything that doesn’t belong, such as viral particles.  This is good for the most part, but when the tissues surrounding your airway begin to swell, your airway becomes constricted.  The scary thing about croup is that it becomes very difficult to breathe, which can evolve in to a life-threatening emergency.  So, Micah Paul, even though you didn’t have croup, I still lost a lot of sleep fearing that you did.  I’m afraid I’ll always be overprotective when it comes to you, and I hope you can except it for what it is.  As annoying as you will think it is at times–and trust me, you will–please know that I am overprotective because you are the center of my universe.  I love you with all of my heart, and the last 3 weeks have been an indescribable joy for me.  Now, I must return to the island for one final semester, and I won’t be able to see you for another 3.5 months.  I’m sure the next time I see you, your feet will be able to reach the pedals of the Thomas the Tank big wheel I bought you for Christmas, and you will have learned so many new words.  The pain and regret of not being able to watch you grow intertwined with the pride and accomplishment of becoming a doctor is bittersweet (more bitter than sweet).  Please, Micah Paul, don’t ever forget that you are ultimately the reason I am doing this.  This is a small sacrifice in time that will, in the end, open up so many doors for you.  Me doing this now will pay dividends in the future.  I love you.

Posted in What I learned today | 2 Comments

Preeclampsia/Eclampsia


Preeclampsia is a syndrome that is defined by the presence of hypertension, proteinuria (protein in the urine), peripheral edema (swelling in the extremities), coagulation abnormalities, and DIC (disseminated intravascular coagulation).  Add hyperreflexia and convulsions to the mix and you have eclampsia. The etiology of preeclampsia/eclampsia is a medical mystery, but the following may be involved:
•Inadequate maternal bloodflow to the spiral arteries feeding the placenta leads to hypoperfusion w/ an increased propensity for infarction
•Hypertension is the result of inadequate production by the trophoblast of prostacyclin, PGE2, and NO, which in normal pregnancies oppose the effects of renin-angiotensin
•Production by the ischemic placenta of thromboplastic substances such as tissue factor and thromboxane probably account for the genesis of DIC (endothelial damage exposes tissue factor (thromboplastin), which is involved in thrombin formation; thrombin cleaves fibrin clots formed by ischemia generated necrotic thrombosis))
•Preeclampsia generally presents in the 24th or 25th week of gestation
So, it seems that the primary underlying cause of preeclampsia/eclampsia is inadequate circulation in the mother to perfuse the placenta.  Obviously, mothers with poorer overall health will have a harder time adapting to the added burden of supplying the placenta with adequate blood flow.  For example, smoking deprives the body of oxygen and adds carbon dioxide, which ultimately makes the heart work harder to supply the body with the requisite oxygen (more blood is also required to wash away the added carbon dioxide).  Since smoking makes the heart work harder, the heart of the smoker is already at a disadvantage to begin with.  With the added burden of supplying the placenta, you can see how the spiral arteries supplying the placenta may not get enough perfusion by a suboptimal pump (the heart).  Therefore, any woman considering bearing a child should strongly consider smoking cessation.
Author: Me
Posted in What I learned today | Leave a comment

Why poop is usually brown


Red blood cells are around for approximately 120 days before becoming senescent.  When it is their time to go, the RBCs are broken down and the heme (what binds oxygen) is metabolized to bilirubin.  This occurs in, for example, splenic macrophages.  The bilirubin is then transported to the liver, where it is conjugated to glucuronic acid; we do this to make bilirubin more soluble, so that it is made more excreteable by the kidneys.  Some of this newly conjugated bilirubin is transported to the duodenum (the first portion of the small intestine), where bacteria metabolize the conjugated bilirubin into urobilinogen.  Some of this urobilinogen is reabsorbed at the ileum of the small intestine and is subsequently transported to the kidneys, where it is converted to the yellow colored metabolite urobilin.  The urobilinogen that remains in the gut is oxidized into stercobolin, the brown colored pigment found in feces.  So, basically, the breakdown of red blood cells (aka erythrocytes) leads to fecal and urinary coloration.  This knowledge can be applied medically, for example, in determining differential diagnoses involving liver diseases(e.g. hepatitis) and hemolytic anemias.

Author: Me

Posted in What I learned today | 2 Comments

A Little About Cerebrospinal Fluid


Cerebrospinal fluid (CSF) is basically water that surrounds your brain and spinal cord.  One of the main functions of CSF is that it serves to protect you brain from injury.  For instance, if you’re rear-ended, your head flies back and hits the seat.  This basically causes your brain to bounce around off of the inside of your skull inside your head.  Obviously, this is bad news, but at least you have the CSF to cushion the impact; without it, you would definitely suffer brain damage just by being rear-ended!

Carbonic Anhydrase plays an important part in CSF secretion, but before we talk about that, let’s cover the basics.  Blood is pumped out of the heart and into the ascending aorta.  When blood reaches the arch of the aorta, some of it (the blood we’re interested in) courses into the common carotid artery, which runs up the neck towards the head.  On its way up, the common carotid artery bifurcates (splits) into the external and internal carotid arteries.  The blood we’re interested in courses into the internal carotid artery, which has many branches.  One of these branches is the anterior choroidal artery, which delivers blood to capillaries that, along with modified ependymal cells, form the choroid plexus.  The choroid plexus if what produces and secretes CSF.

So, once blood reaches the capillaries in the choroid plexus, it is filtered through fenestrae (tiny pores in the capillary walls), which are only large enough to allow the fluid portion of the blood through.  This newly formed fluid moves from the outside of the capillary, through interstitial tissue, toward the basolateral side of the choroid epithelium (the modified ependyma)–keep in mind that at this point, we are in the subarachnoid space.  Here is where we reach a critical point, because the fluid can’t just enter the epithelial cells (which it must do so that it can be secreted out of the cell on the apical side, into the ventricular system which surrounds the brain, where the CSF likes to hang out (the ventricular space is the area inside the brain that distributes nutrients to the surrounding brain tissue)).  You see, all cells have membranes that surround them, allowing some things in while keeping others out.  Cells have to have membranes to protect themselves from substances that may enter and harm them.

One way that the choroidal epithelial cells can bring this newly formed fluid inside is through osmosis, which in essence is water moving from an area of high concentration to an area of lower concentration.  We’ll use the actions of carbonic anhydrase as an example.  Carbonic anhydrase is an enzyme that takes carbon dioxide and water and combines them to form hydronium and bicarbonate.  The hydronium can then be used in exchange for sodium at the basolateral membrane of the choroidal epithelial cell, bringing in sodium, while expelling hydronium from the cell.  In addition, the bicarbonate is exchanged for chloride, with chloride moving into the cell and bicarbonate moving out.  So, I will get to the point.  All of these particles (sodium and chloride) that we are bringing into the cell are taking up space that could otherwise be filled with water.  Which means there is a lower concentration of water inside the cell than outside, so via osmosis, water flows down its concentration gradient from outside to inside the choroid epithelial cell.  Once we have water inside the cell, we need to move it out into the ventricles, through the apical membrane of the choroid epithelial cell.  I won’t bore you with the details but will keep it brief by telling you that it is the same basic concept we used to get water into the cell.  Once the fluid enters the ventricles (passively through aquaporins in the apical membrane) from inside the choroid epithelial cell, we call it cerebrospinal fluid.

Author: Me

Posted in What I learned today | Leave a comment

Contralateral Neglect Syndrome


If someone suffers a stroke and the right parietal lobe is injured (especially at the Angular Gyrus), Contralateral Neglect Syndrome (AKA Spatial Neglect) can manifest.  This is a really interesting disorder that renders the sufferer of the stroke unable to acknowledge his/her left side.  Not only does the victim neglect the left side of his/her own body, but they don’t acknowledge the left side of anything.  If you see someone walking around half dressed, with their left arm and leg unclothed, it may be because they couldn’t acknowledge that they had a left side when getting dressed that morning.  Also, if you asked them to draw a house or anything else, they would only draw you the right half of it, as if the left half of the house didn’t exist.  Also, these people get lost in their own houses, always opening doors on the right, being unable to acknowledge doors on the left.  Another example is that even if one of these people was starving, they would starve to death with food on the left side of their plate!  Of course, I’m sure a lot of you have already figured out that all of this has to do with how the right side of the brain controls the left side of the body and perception.  I’m not exactly clear on the details regarding this phenomenon, so I’ll ask my professor tomorrow and update this segment.

Posted in What I learned today | 3 Comments

If you get a stye


A stye may arise if a microbe gets into and infects the gland at the root of an eyelash, which will lead to an inflammatory response.  Two of the main culprits are Staphylococcus aureus and Propionibacterium acnes.  The best thing to do to get rid of a stye is to apply a warm compress to it for about 15 minutes, 4 times a day.  What this does is it loosens up the connective tissue surrounding the swollen gland, allowing the stye to get even larger.  You might be saying, “Wait a minute, this doesn’t make any sense.  Why would you want to make the damn thing larger?”  Well, once it gets to a certain size, the stye will rupture.  This does not mean you should just try to burst it like a pimple, which could worsen the situation.  It is ok, however, to lightly massage the stye (speeds up the drainage) if it is already draining.

Author:  Me

Posted in What I learned today | Leave a comment