Tag Archives: physiology

That Carpal Tunnel Thing…

Body parts are like politicians. You don’t really think about what they do until something goes wrong. Consider the median nerve. “What’s that?” Well it’s only the peripheral nerve responsible for sensation and motor control of the fingers within the palms of each hand (except for the little finger, but pinkies have problems with authority).

"You say it your way and I shall say it mine."

“You say it your way and I shall say it mine.”

Don’t feel bad if you’re not facebook friends with the median nerve. It never really hits the news until it gets squeezed. Yes, squeezed. Everyone has heard of Carpal Tunnel syndrome, Carpal Tunnel, or “Copper tunnah” if you were raised in the land of sweet tea and magnolias.

The carpal tunnel is a narrow channel of ligaments and bone in the wrist that the median nerve passes through like the DC metro train. In carpal tunnel syndrome this space begins to narrow, compressing the median nerve which leads to numbness and chronic pain in the hand, fingers, and wrist.

What causes the squeeze?

_CARPTUN

I really wanted to give this diagram a high five just now. Weird, I know.

Did I mention that the carpal tunnel is narrow? No space is wasted in the body and the median nerve isn’t just floating happily in first class with all the leg room in the world. It is literally surrounded on all sides by 9 flexor tendons, vessels, small muscles, and of course, the carpal bones of the hand. In such a tight space if any one of those tendons decides to swell (and you know how tendons can get) the median nerve will get squeezed tighter than a dachshund wrestling a Saint Bernard for a bean bag chair.

I’ll just give you a moment to absorb that imagery…

Risk Factors

“Risk” is just a sly statistical term to describe how much wiggle room an individual has in avoiding a disease or condition. In this case, risk factors include any condition that could significantly alter the space within the carpal tunnel.

Injury – wrist fractures, and dislocation of the carpal bones of the wrist

Chronic Illness – Diabetics or anyone with an increased risk of nerve damage, Impaired kidney function, obesity, prolonged fluid retention during pregnancy, or persistent inflammatory conditions

and then there are the Statistically cursed…

fibro-wrist-pain-400x400

“Why did I play World of Warcraft for 7 hours Yesterday?”

Statistically women are 3 times more likely than men to develop CTS, possibly due to their smaller carpal tunnels. Of course, those women who do develop CTS could have any combination of the risk factors that I mentioned above. So I wouldn’t go out making predictions at the bar with your tape measure just yet. A perfectly healthy woman or man with no signs of CTS could have smaller wrists than a woman with CTS.

Work Related? – There are a lot of people (including myself) who associate CTS with mind-numbingly repetitive tasks, such as typing or assembly line work. We can’t start pointing the finger at any one profession (and I know you want to). We can’t just say, for example, that packaging chicken parts for Tyson causes carpal tunnel syndrome. However, it has been established that CTS is three times more common among assembly line workers than individuals who perform data entry.

Any prolonged activity that puts stress on the wrist could easily exacerbate an underlying condition that could lead to CTS. Even if you have wrists the size of tree trunks I wouldn’t compete in any 3 day, speed origami marathons until all the facts are in.

Stay classy, stay curious, and never stop learning my friends 🙂

 

 

Malaria II – Full Circle

dex2Hello party people! So we’re back to finish up our chat about malaria. Last week I took you behind the scenes with the curious parasite (Plasmodium falciparum) that causes malaria, and its obnoxious insect carrier, with the face for radio, the Anopheles mosquito. Today I want to focus on the disease itself. Sure, having a parasite that rapidly divides in the liver and spreads through the blood stream clearly doesn’t sound as fun as dinner and a movie but how exactly does our body respond to these microscopic freeloaders?

Fun fact – Mosquitos do not depend on blood as their primary food
source. Most of the time they eat like vegan, yoga instructors,
feeding on sap and flower nectar for carbohydrate fuel to power their
airborne lifestyle. Blood becomes a necessary source of protein for
developing eggs. So it is actually the female Anopheles that goes buzz
in the night.

Act I – Incubation stage

o-MOVING-INTO-APARTMENT-facebookI don’t know about you, but if I just moved into a new apartment I need a few days to get settled in, unpack some boxes, and tape my Marley posters to the wall before I throw a party. Plasmodium falciparum is no different. At this point the Plasmodium is still hanging out in the liver cells. It can take up to 30 days after the
initial infection before the first symptoms appear, and those range in severity.

Act II – Blood stage

a closer look at the hemoglobin protein. P. falciparum converts the heme subunit to hemozoin.

a closer look at the hemoglobin protein. P. falciparum converts the heme subunit to hemozoin.

The chaos ensues once the Plasmodium disperses from the liver and begins circulating in the blood stream. It’s the hemoglobin protein in our blood that they’re after. I don’t want to wander too deep into biochemistry, but if you recall from my earlier article on blood, each hemoglobin protein contains a vital compartment called a heme group. This contains a tiny molecule of iron at its core. This is what binds

the oxygen in our blood. Heme is also toxic when it is released from the hemoglobin. To get around this toxicity the Plasmodium can store heme molecules in their single-celled body in an insoluble, crystallized form called hemozoin. Inevitably the red cells lyse,
releasing the plasmodium along with all the waste products leftover from their hemoglobin feeding frenzy, to include hemozoin. This becomes bad news for us.

When it comes to our immune system our blood stream is a small town
and our white cells hate strangers with a passion. Eventually,
wandering T-cells with the right receptors will encounter Plasmodium
merozoites in the bloodstream (by detecting dsDNA on their membrane
surface) which triggers the release of pro-inflammatory cytokines. However the hemozoin that is released when the red cell ruptures seems to trigger an immune response on its own.

Unfortunately, our immune response is not always strong enough to
completely clear the infection. This is partly due to the many changes
the plasmodium goes through in its life cycle that allows it to dodge
the immune response. It goes through 7 stages, altering its
biochemistry a little each time.

 

One of the classic presentations of this disease is intermittent
fevers. Typically when your fever stops you start to feel better, but
with a malarial infection fevers often occur in waves every 48-72
hours. This is the result of the rupturing of blood cells as the
parasites continue to multiply and invade new cells.

Signs and Symptoms

 

That's right, I know what you really really want...

That’s right, I know what you really really want…

Think back to the last time you or someone you’re close to had the
flu. When you get hit with the flu you typically look awful, drunk, and exhausted like you haven’t slept since the Spice Girls were last on tour. During classic cases of P. falciparum infections, patients will present with “flu-like” symptoms of high, persistent fever, headaches, chills, sweats, anemia, and vomiting. Remember that during the blood stage of the infection blood cells are being destroyed. So the patient is weak and essentially poorly oxygenated. It is basically a parasite-linked anemia.

Malaria can become deadly if left untreated when infected cells begin to clock capillaries of the brain (cerebral malaria). This can ultimately lead to brain damage, coma, or death.

Testing Methods

We can identify malaria directly from a peripheral blood smear where a
giemsa stain is added to a drop of infected blood on a glass slide and
examined under the microscope. This kind of testing is wonderfully
direct. The problem with poorly developed countries is that proper
testing facilities, microscopic equipment, and trained professionals
who know what to look for are in short supply. So there are RDT’s
(rapid diagnostic tests) available that can identify specific malarial
antigens in patient blood samples. Much like a Strep or flu test, the
patient’s sample is combined with a reagent in a tube or cassette
where a qualitative reaction (positive or negative) can be observed.
However, depending on the concentration of Plasmodium in the blood a
patient may have a false negative. So there is still a need for
confirmatory testing, especially in areas of the world (I’m looking at
you Africa) where drug resistant cases are high.

Treatment

Good Ole Chloroquine…

So we know the plasmodium needs to break down the hemoglobin in order to use those lip-smacking amino-acids while not poisoning themselves with the heme that gets released. So they form hemozoin crystals of the heme to disarm its toxicity.
Welcome to the wonderfully clever world of chloroquine. This drug diffuses into the Plasmodium, halting their ability to form hemozoin crystals. This allows the heme to build up in their nasty little bodies, shutting down their metabolism. Sadly, chloroquine resistant malaria is common place in malarial hot zones. In these cases patients require drug combinations like quinine sulfate and tetracycline. 

You also have to manage the mosquito side of the disease. Spraying for mosquitos to control the population has been effective in many urban settings. We also have to understand the behavior of the mosquito. Anopheles prefers to feed at night until the wee hours of the morning. So distributing sleeping nets in malarial hot zones can literally save lives.

The CDC has mapped out malarial zones around the globe. So travelers are encouraged to seek malarial prophylaxis to prevent infections.

Here’s the bad news you already know..

– Children are the most at risk from malaria. In fact it kills more children globally than anything else.

– Diseases thrive in areas where the population is dense and the
availability of adequate healthcare is scarce. This creates a scenario
where the mosquitos are more likely to bite infected individuals. An
infected population left untreated inevitably leads to a more
resistant disease.

Luckily we don’t live in a vacuum and we can contribute. There are a number of organizations out there committed to finding solutions for this global problem. Here’s one organization I happen to like (no, I’m not affiliated with them)

http://www.malarianomore.org/pages/the-challenge

Hopefully I cleared a few things up about this topic. If you have questions please leave me a comment.

As always, stay curious, stay classy, and never stop learning my friends 🙂

Me Talk Pretty – Pyrexia

Image

Maybe you should lie down…

That’s right, it’s time for another super sexy physiology term. Pyrexia (known on the streets as a fever) is one of the most well known signs that “something ain’t right.” Here’s an obnoxiously obvious statement to start your day; the human body is all about balance. For example, our body is only really happy if it’s core temperature is maintained within roughly 36.5-37.5 C or 97.7-99.5 F. That’s a pretty tight range for a lot of metabolic processes to take place. You’ll find more leg room flying coach. We have a temperature set point that our body is practically calibrated to. When we are experiencing hypothermia or hyperthermia the temperature of the environment we are in has affected our core temperature and pushed us beyond our cozy little set point. HOWEVER, a fever occurs when something triggers the body to temporarily raise it’s set point. That “something” is typically an infection (bacterial, viral, etc.). When this happens our immune system is making a declaration of war on the offending pathogen, turning up the heat.

Fevers happen when a pyrogen (thing that triggers a fever) causes the release of potent chemical messengers (produced by our cells) called prostaglandins that work on our hypothalamus. If you recall, our hypothalamus is our brain’s team captain of homeostasis with such popular hits as hunger, thirst, hormonal control, and temperature regulation. We love the guy but probably wouldn’t invite him to hang out very often because he would want to control EVERY little thing.
On the one hand, a fever creates a less cozy temperature range for the pathogen to thrive and reproduce. It has also been shown that the activity of immune cells like neutrophils (your marines on the ground) and T-cells (CIA operatives providing intelligence on the enemy) is greatly enhanced. This is basically the fight they’ve been training for their entire, short little lives. On the other hand, raising the body’s set point takes a lot of energy. When our temperature rises the small vessels at the surface of our skin constrict to conserve heat for the sake of our core. We start to shiver, which generates heat by our muscles while demanding more energy from our already weakened body. As we begin to adjust to our new set point we get warm and sweat to cool back down, losing water and salts. It’s no suprise that you feel so wiped out after you’ve recovered from a fever. So is a fever worth all that trouble or is it simply an evolutionary relic, a souvenir of our adaptive immunity’s epic saga of trial and error? It’s interesting that such a metabolically demanding process that can often spiral out of control (reaching temps of 105 F in cases of severe infection or autoimmune response) would stay with us. Despite it’s cost or contribution to our body’s war on bio-terror, we are not the only chosen ones on this planet to get the shakes and the sweats. Many other vertebrates and invertebrates from Rottweilers to Iguanas have been shown to exhibit fever-like responses to infection. Oh yeah, pyrexia gets around and it looks like she’s here to stay.

Stay curious, stay classy, and never stop learning my friends.

 

Mosquito Profiling?

mosquito_sick

Observe, the enemy!

So I feel a little awkward asking you this but…do you often have this feeling you just can’t shake that someone, somewhere is out to get you? Does it seem like trouble follows you wherever you go? I know your friends and family think you’re paranoid (I’ve heard them talking) but listen, I believe you. There is an ancient evil lurking in the shadows that is out to get all of us and it is a fraction of a centimeter in size. That’s right, I am talking about mosquitoes, the phantom buzz in your ear that wakes you on summer nights, those bite-sized bio-terrorists that have spread disease over the millennia. I know what you’re saying, “what does this have to do with physiology? Have you been drinking?” No, but thank you for asking. The truth is some of us DO get singled out by these tiny demons more than others. What is it about us that draws them to us like…little old ladies to a yard sale…no wait, like a wrestling team to half-priced burger night? Let’s talk some physiology!

Know the Enemy

Once upon a time called 170 million years ago a family of tiny flies (Culicidae) made a bold, annoying, adaptive leap in their evolution. It discovered an inexhaustible, readily accessible food source, human blood, and they’ve been tailgating our cookouts for as long as we’ve been drawing doodles on cave walls. That’s right, they are flies, meaning that they have an additional set of modified wings along their metathorax (oh, you care). Of course, there are more species of mosquito than YouTube Harlem shake videos but one characteristic they all seem to share is that the females are the blood drinkers. They have hungry mouths to feed after all, hundreds of tiny eggs that they can lay on the surface of still, stagnant water. Their versatility is our problem. Mosquito larva are aquatic and don’t require large ponds to spawn. In fact, their breeding sites can range from ponds to plastic kiddie pools, to a neglected paint bucket left out in the rain. The point is mosquitos are opportunists who will go after the easiest meal they can get and let’s face it..we’re pretty easy.

But why me?!

Oh if you want theories I’ve got theories, but how about we stick to statistics for now. They seem to prefer pregnant women, obese individuals, and adults over children. Mosquitoes are tiny beings flying around in an enormous space. They use their sense of smell, sensitivity to movement, and Jedi mind powers (aka unknown factors) to detect our body heat, movement, and CO2 production. Adults produce more CO2 and conserve more heat than children. Of course, some people naturally have higher body temperatures and children are constantly in motion so it really depends on who is hiking with you. Pregnant women also produce more CO2, their body heat spikes, and they have an increase in the amount of circulating blood. Mosquitoes also love us after a good workout. They have a demonic sense of smell and many compounds such as lactic acid are excreted in our sweat that draw them in like a terriyaki
marinade. Our body heat also spikes when we workout but I didn’t have to tell you that.

Picky Eaters?

They also seem to have a preference for blood type. People like myself with type O blood are far more likely to get bitten (mama told me I was special). If you’ll recall, type O blood cells lack the surface antigens A or B. The absence of those antigens or “O” is how it get’s it’s name. Why don’t you meditate on that for a while.
Studies have also shown that blood cholesterol levels are a factor which is just another reason to skip that drive-thru on the way home and stick to your New Year’s resolutions…that’s right, we all heard you.

Stay curious, stay classy, and never stop learning my friends 🙂

 

Fun Facts – Last Call

beer glassesHappy Late Patty’s Day everybody! If you’re town was anything like mine, you’ve probably seen your fair share of blissfully intoxicated co-eds in electric green t-shirts, shiny green beads, and glazed over smiles, glittering the local bar patios like grass clippings. Speaking of blissfully intoxicated…

What do yeast, fruit flies, and human beings all have in common? We can all hold our alcohol. More accurately, we each come equipped with our very own alcohol dehydrogenase enzymes that allow us to convert that toxic, nasty ole alcohol into more user-friendly byproducts that our cells can use.

In case you didn’t know, alcohol is toxic to the body. [That’s right, I’m looking at you, Ethanol…I haven’t forgotten about New Year’s!] Not only do our bodies have no real nutritional use for it (which is why you won’t find it in your Flintstone vitamins) but when set loose in the body it can sabotage our organ systems one by one.

speed-bomb-diffusion

this is how I feel trouble-shooting my high-speed internet

Luckily, we have a generous helping of miracle-working, alcohol converting enzymes in our liver and stomach to soften the blow. We actually have 3 different enzymes in our anti-alcohol arsenal but the vast majority of the damage control is carried out by that smooth talker, alcohol dehydrogenase. These 80 kilodalton molecules step in like a bomb squad to disarm the alcohol molecules by stripping away their hydrogen atoms (that’s why we call them de-hydrogenases). This converts them into acetaldehyde, but we aren’t out of the danger zone yet. The acetaldehyde (close cousin to formaldehyde) is even more toxic than the alcohol we started with. Not unlike disarming a bomb (like I’d know) just because you snipped the red wire doesn’t turn the C4 into pound cake. What is left still packs a
punch. The acetaldehyde gets converted further into acetic acid radicals (acetic acid gives us vinegar). Alcohol dehydrogenase joins those nasty radicals with Coenzyme-A molecule to form happy little Acetyl-CoA molecules that our cells can now use in their metabolism.

Yes I do love a happy ending, but just because a few fancy-pants liver enzymes allow us to convert ETOH (alcohol) into useful cellular byproducts doesn’t mean we can go out chugging margaritas like protein shakes. Be safe. Hey, look at me….I care.

Stay curious, stay classy, and never stop learning my friends 🙂

Medical Marvels – the Bayer facts (see what I did there)

Image

First a little history…

The story of Aspirin is an old one. I know you’re probably tired of

giving credit to the ancient Greeks for every little thing just

because they wrote everything down, but as early as 5th century B.C.

good folks like Hippocrates, in their flowing togas were describing

miracle pain relieving powders made from ground willow bark. Now let’s

fast-forward to the 18th century where scientist representing three

corners of the globe were playing around with salicin, as if it were

an Olympic sport. First a German named Johann Andreas Buchner

identified the compound salicin as the active ingredient to that wacky

Willow powder I mentioned earlier. Back in France, Henri Leroux was

figuring out ways to produce larger, biggie-sized quantities of the

compound. The cool kids (scientists) figured out along the way that

salicin gets it’s medicinal potency from being converted into

salicylic acid (its metabolite) by the body. Though this form can also

be found in plants a crafty Italian by the name of Raffaele Piria

would later figure out a way to convert salicin to salicylic acid in

his lab.

Turning down the volume….

I won’t bore you in this article with feedback mechanisms (I’ll bore

you in another article). Let’s just say that for many of the chemical

signals that our cells produce there is usually a mechanism to

interfere, inhibit, or amplify that signal. In the case of pain our

body really wants to get that message across loud and clear. There is

a family of cellular messengers called prostaglandins that, among other

things, switches our neurons on to pain. The enzyme cyclooxygenase

(COX-2) increases the production of these pain happy molecules during

inflammation. Salicylic acid blocks the expression of COX-2 (as in

it’s gene expression into protein). It’s kind of like throwing water

over the logs so the fire never gets a chance to start.

The trouble with Sally is…

Despite its magical pain relieving and anti-inflammatory properties,

salicylic acid could be pretty harsh on the stomach lining. In fact, a

lot of people suffered from intestinal bleeding after taking the

powder (Now that’s harsh). Along comes this hot-shot chemist out of

Germany, Felix Hoffman who decides that it’s the “acid” portion of

salicylic acid that’s the problem. After performing a little

biochemical black magic (Adding an acetyl group like acetyl chloride

to the compound to take the edge off a little) Felix produces a more

user friendly compound that his employer Friederick Bayer & Co would

later market as “the wonder drug.” When the biochemical nerd dust

settled we were left with Acetylsalicylic acid (ASA), or Aspirin.

Stay curious, stay classy, and never stop learning my friends 🙂

Me Talk Pretty – Cross extensor reflex

That’s right party people we’re not done. You get two zesty physiology terms relating to the body’s response to pain for the price of one. Now that’s a value! Ok maybe I was just too lazy to include this one in our last brief chat about pain. I’m only human. Don’t make it awkward (I can feel you judging me and it’s so cold).

Well in addition to our lighting quick withdrawal from pain (NFR) orchestrated by sensory neurons, interneuron connections, and the spinal column, our body takes counter measures to maintain balance and stability. That’s right while one foot dodges sharp objects the other foot plants firmly on the ground to keep balance. Like the withdrawal reflex, this occurs within a fraction of a second as well. It is an opposing process. While flexor muscles on one side contract (for example hamstring muscles on the side of injury) the extensor muscles on the opposite side relax (quadriceps of the supporting leg relaxes to fully extend and support the weight). Once the pain receptors on the effected side are triggered by a pain stimulus (broken glass, sharp nail, etc) that signal flows down the sensory neuron like telephone wire to the spinal chord. From there the signal crosses over to the opposite side of the spinal chord to an excitatory interneuron. An alpha neuron takes it from there to its final destination, the neuromuscular junction controlling the extensor muscles in the opposite leg. This allows the weight to be evenly distributed to the support leg thereby taking pressure off of the injured side, minimizing further injury. I love a happy ending.

Stay curious, stay classy, and never stop learning my friends :-)