Malaria – The Viscious Cycle

definitely not a mosquito

definitely not a mosquito

Anopheles would make a beautiful name for a daughter wouldn’t it? I mean if my friends set me up on a blind date and they told me that her name was Anopheles I would envision this mind-numbingly gorgeous, Greek goddess of a woman. However, 5 seconds into a google search you would very quickly realize that the name Anopheles has another meaning entirely, a dark, strangely complex story that has shaped human civilization over the eons. (I get so dramatic after I’ve watched “Game of Thrones.”)

This is the story of humans, mosquitoes, and a curiously well adapted parasite responsible for causing a disease known far and wide as “malaria.”
I’ve said it before; we are not alone, and I don’t just mean in the universe. Hell, we aren’t even alone sitting in the bathroom with a Vanity Fair magazine. There are microbes on the sink faucet, and in between the fibers in the carpet. There are viral particles, and fungal spores floating in the air, and no matter how thoroughly you wash your hands with cucumber melon scented soap the bacteria in your gut and the staph bacteria in your mouth could not be happier. Yes my friends, each of us is our own zip code.

So once upon a time our ancient ancestors were dropping like flies from a mysterious disease with no name…well, it had names like “curse from the Gods” and “bad air,” as in Mala = bad + aria = air, but none of those were terribly scientific. Of course, we eventually caught on to the fact that it was mosquitoes that were spreading the disease to humans. Mosquitoes don’t just feed on humans but anything with blood coursing through its veins, also known as “everything.” This makes them the perfect vectors for blood borne diseases. We recognize Anopheles as the genus of mosquitoes that commonly infects humans with malaria, but what exactly is the mosquito carrying?
One of the most ancient and devastating infectious agents to plague humankind is not a bacteria or a virus but a protozoa called Plasmodium falciparum. That’s right a protozoan, one of those curious creatures you read about in biology class and never mentioned again. The chapter on protozoa is like a TV show that only lasted for one season, but they’ve always been here, lurking in the shadows.

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Plasmodium gametocyte shown here dead center. At this stage it can be taken up by a mosquito to begin the cycle again.

Plasmodium falciparum (the deadliest form of malaria) is a single, eukaryotic cell that’s life cycle is completely dependent on two hosts. The life cycle of the Plasmodium is pretty freaky stuff. It reads like the plot of a B-rated, 80’s Sci-fi movie starring Matthew Broderick. Its success as a species is completely dependent on the fact that mosquitoes feed on human blood. At one stage male and female gametes of the plasmodium develop in the gut of a mosquito where they have a little, kinky get together to produce fertilized versions of plasmodium. These will form cysts along the walls of the gut like time bombs that eventually rupture to release a demon horde of sporozoites inside the mosquito. These juveniles move into the salivary glands where they can be passed easily into the bloodstream of an unsuspecting human the next time the mosquito feeds.

Once the Plasmodium sporozoites reach the human blood stream they make a mad dash to the liver. They develop in the hepatocytes, dividing until their massive numbers rupture the liver cells, releasing them back into the blood stream where they now invade red cells. Some of these will differentiate yet again into male and female gametocytes. Yes, this is one of those déjà vu moments. If another mosquito drinks the blood of this infected human the cycle will begin again.

You can literally drive yourself mad thinking about where the original Plasmodium came from. It’s a tragically elegant case of chicken and egg. Sure, the cycle starts with the gametocytes in the gut of the mosquito but the gametocytes can ONLY be produced in the human host cells. Where and how did this all begin?

Stay tuned for a part 2 where we will describe how Malaria affects the human body and how we combat it.

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

map depicting the tropical regions with the highest prevalence of malaria.

map depicting the tropical regions with the highest prevalence of malaria.

Me Talk Pretty – Pyrexia

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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)

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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 :-)

Me Talk Pretty – Nociceptive flexion reflex (NFR)

SU11_GTY_sb10064912a-001_a_hzKnown on the streets as the withdrawal reflex, NFR refers to our body’s involuntary, ninja-quick neuromuscular response to pain. It’s our super sexy physiology term of the week and quite possibly our spiciest one yet. I even like saying it out loud (sometimes in a French accent).

Isn’t it nice to know that our body has our best interests in mind despite our worst judgment? If you’ve ever not been paying attention for a moment and let your hand stray a little too close to a hot stove (like who hasn’t) then it’s highly likely that you’ve witnessed your NFR in action. You probably yanked your hand away at what felt like the same instant you experienced pain. We perceive pain and withdraw from it simultaneously and our body does this seamlessly. If you’re the least bit skeptical just think back to that scolding hot bowl of chili con queso you dropped. YOU didn’t drop it. Your hands let go of it.

What experience could be more direct than pain? In reality, pain may not be as direct a phenomenon as you might think. When it comes to our involuntary withdrawal from pain there are at least 3 stages that occur. Once any part of your body is injured nerves in the vicinity transform that moment into a lightning quick electro-chemical signal. That signal has to take a journey from the site of the injury to the spinal chord. A new signal is sent from the spinal column to the appropriate muscles to flex and manipulate that stray body part away from the pain stimulus. Perhaps one of the reasons this process is so blindingly fast is the fact that the nerve control center in this case is the spinal chord and not the brain.

Let me set the scene…

It’s a perfect July afternoon. The grills are out. The air is saturated in honeysuckle flowers and spicy, charcoal kissed meat. You’re barefoot in the grass, loving life in your favorite shorts and a barbeque stained t-shirt. Oh yeah, you know what I’m talking about. You have a half-eaten bratwurst in one hand. Your other arm is free, innocently reaching out to grab the Frisbee that your friend just tossed to you (you crazy kids). She tossed it high. You take a step back unaware that laying in wait in the grass is a jagged piece of gravel just begging to be stepped on by bare feet. You plant your foot on the rock…

1) Tiny, branching pain receptors suspended within the epidermal layer of your heel, like tree roots, transmit an electrical signal up a long network of neuron fibers that form an intricate junction at the spinal column not unlike a downtown D.C. intersection.

2) Once the message reaches the spinal column an alpha motor neuron sends a signal back down your leg.

3) The signal from the alpha motor neuron reaches a neuromuscular junction in the hamstrings of your leg, initiating their contraction. This flexes the knee, pulling your foot off of the ground to minimize damage to the soft tissue of your foot so you can frolic in the grass another day.

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