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.

Image

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.

Hiccups – the Devil’s plaything

devill

Is that the same devil you had in mind? Twins!!

There’s public radio telethon week, toll roads, vending machines that give you Diet Pepsi when you clearly pushed the “Coke” button, and near the top of the list are hiccups. These are a few of my least favorite things. Oh, you know this guy loves the human body. There are few marvels in this world more elegant, more profoundly complex than the body and it’s nuts and bolts, but son of a [CENSORED], hiccups are the devil! I seriously doubt that a successful pick up line has ever been delivered while battling with the hiccups. Hiccups lie in wait like mean-spirited hecklers waiting to kill the mood of your acceptance speech or interrupt the punch line of your best dirty joke. So in this episode of Forgotten physiology we’ll pose the question; Hiccups, what’s your deal?

Yes, I prefer to think of my hiccups as the old men from the muppet show
http://www.youtube.com/watch?v=PGfx3QAV64M

Synchronous Diaphragmatic Flutter (or Miss Jackson if you’re nasty)

Mechanically speaking, hiccups are nothing more than spasms of the diaphragm; short, involuntary contractions forcing air through the windpipe that is then immediately closed off by the tough, elastic flap of the epiglottis. This closes off the vocal chords like a trap door that says “No more air for you! No!” and produces that signature, sexy frog sound of a classic hiccup.

KF5015

The phrenic nerves begin in the cervical vertebrate (C3-C5) and zip line down between the heart and lungs to connect with the diaphragm.

You have a left and right phrenic nerve that connect to the diaphragm to control its contractions and receive sensory input in return. “Sensory input?” Well sure, you don’t just blindly send out messages. You look for a response. Your nervous system is all touchy feely and needs to be able to sense where everything is…no organ left behind. Those nerves are the only electrical wiring operating the movement of the diaphragm. So any significant disruption or irritation of the phrenic nerves can cause spasms and ultimately hiccups. For example, if you just had a bad breakup and decided to go Tazmanian Devil on 2 large orders of pork fried rice from Wong’s Wok, a full or distended stomach can press on the phrenic nerves and trigger hiccups.

But who is really in control?

We may not think about it but the diaphragm is made of “skeletal” muscle. If you remember our chat from muscle mania, skeletal muscle is under the control of the somatic nervous system. This typically means that it is under our control. We can, for example, contract our diaphragm muscles ourselves and draw in a deep breath. However, we don’t exactly tell our diaphragms to spasm do we? Ahh…here’s where it gets interesting.

A thought experiment..

You and your body are one and the same right? I mean you don’t feel separate from your body do you? If I ask you to pass the mashed potatoes you don’t ask your hand to grab the bowl. Your brain and your hand flow together, without interruption.
Now think about a hiccup. Does that ever feel like something YOU did? No way, the hiccups happen as reflex and your brain gets the feedback. These are controlled by a “reflex arc,” neural pathways (composed networks of neuron cells) that connect to the spinal chord BEFORE reaching the brain. Some neural pathways have a long way to go to reach the brain, your central command center. The spinal chord works like an intermediary traffic control center, managing the local stuff and all the sensory input from the extremities. This allows motor reflexes to occur instantaneously without checking in at the office (brain) first. Your brain isn’t left out of the loop. The motor neurons of the spinal chord are simply the first to respond.

But why me? Why?!!!

Typically when we get the hiccups we were eating too much or eating too fast, drinking too fast, or hitting the sauce a little heavy (either alcohol or carbonated beverages). Episodes can also be brought on by excitement. I’ve always said that too much happiness is dangerous. These hiccups don’t last long and typically resolve on their own without tongue pulling or drinking water upside down.

There are of course persistent hiccups that are linked to an encyclopedia worth of clinical problems ranging from stress to heart issues to neurologic and metabolic disorders. So if 48 hours have gone by and you’ve still got the chirps then it’s probably a good time to see your doctor my friend.

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

Hair Raising

images

electric razors just don’t give you that clean shave

That’s right brothers and sisters Halloween is one of my favorite Hallmark holidays. The candy, ghost stories, bad zombie makeup, and shapely women in revealing witch costumes all put me in the holiday spirit. I have to admit though, something has been bugging me. There I was, watching cheesy, poorly scripted thriller movies at 1am alone in my creepy old apartment. I’m watching one of those scenes where the woman in a low cut top is searching the basement with a flashlight for strange sounds when I feel the hairs raise on the back of my neck. “Why is that?” I think to myself. No, I know why MY hairs stood up. I’m a total wuss when it comes to ghost thrillers, but why does that physiological response happen to all of us when we get spooked?

scared cat

cat demonstrating pilomotor response to confrontation while walking the mean streets

Ancient roots

There is something you and your cat have in common that you may not know. Scientist refer to it as the pilomotor response. You may know it better as “goosebumps” when hundreds of tiny bumps raise on your arms and legs. If you’ve ever gotten out of the shower and stepped into the much cooler air outside of your bathroom that’s typically when you’ll notice them. Well cats display this same behavior when they are confronted by another aggressive cat telling him to “step off my turf” or something scarier like a dog or falling metal trash can. The hairs extend as they rise to their toes to appear as big as possible for competition or predators. Well the cool kids (scientists) believe that this phenomenon in human beings served a similar function. Well I don’t know if you’ve noticed, but humans beings today, version 5.0, aren’t nearly as hairy as our fiercer, planet of the apes ancestors.

goosebumpWell these days goose bumps are a “vestigial” response meaning it has out lived it’s original function. However, this involuntary reaction is still triggered by moments of intense stress and emotion like fear, exhilaration, and you know, moments of intense..um..inspiration (sexual arousal). All of this magic is of course brought to you by our dear friend the sympathetic nervous system, home of the “fight or flight” response.

Let me set the scene… 

Let’s say you just walked out of the shower…No wait better yet, let’s say Michelle Rodriguez just walked out of the shower wearing nothing but a towel when suddenly she hears a loud crash from the kitchen…

About 90% of the heat in Michelle’s super fit body is lost first through the skin, even more so when wet, because water transmits heat away far more efficiently than air.

She slowly walks down the stairs….

Respiration increases along with her heart rate as blood flow is conserved for the brain and other vital organs, temporarily halting digestion. A sudden rush of energy is felt as epinephrine acts on the insulin producing liver cells, allocating glucose so that Michelle’s warrior, Resident Evil reflexes can spring into action if need be.

She approaches the doorway of the kitchen, reaching for her limited edition, zombie killing, 9mm Smith & Wesson…

The adrenaline coursing through her blood stream has taken her mind off the chill in the air but her body is still losing heat through evaporative cooling of the skin and through the rapid breaths (lungs accounting for 10% of total heat loss).

She turns the corner..

Tiny, arrector pili muscles located at the base of the hairs  on her neck, arms, and perfectly toned legs contract forming goose bumps and raising the hairs on Michelle – as both a response to fear and her body’s attempt to conserve heat.

She puts the safety back on her pistol, realizing that it was just her silly cat knocking over a bowl of Captain Crunch. That’s when it dawns on her “I only buy Raisin Bran!”

Happy Halloween my friends and as always…stay curious, stay classy, and never stop learning 🙂

Michelle-Rodriguez-Wallpapers-3

“André tells the best stories”

The Zen of Cardiac Blood Flow

Normal-Heart-Anatomy-and-Blood-Flow-web

So hearts come color coded now? Oh man, surgeons have it easy
source: http://www.pediatricheartspecialists.com

I’ve given up on learning the secrets to winning a woman’s heart and settled for learning
how they tick…or should I say beat. Well, here is what I’ve learned so far…

A Word or Two about Gravity

Yes, gravity is always an issue. It acts on blood moving through the body no differently than
it acts on feathers, wooden balls, Chuck E. Cheese tokens or whatever else that 16th century wild man
Galileo decided to drop from tall buildings in Pisa. The heart performs remarkably well
despite blood’s downstream tendencies, pumping against the stream so that no organ gets
cut out of the action.

Hey don’t fall asleep on me yet. I’m only telling you this painfully obvious fact to point out
that since the heart muscle directs blood flow there really is no reason to go looking uphill to figure out where it all begins. Which direction you choose to describe blood flow starting from is really a matter of perspective, by that I mean the fate of oxygenated versus deoxygenated blood. Since it’s all about me, I’m going to start with the flow of oxygenated blood traveling from the lungs.

Listed in order

Oxygenated Blood

  1. Lungs
  2. pulmonary veins
  3. left atrium
  4. bicuspid valve/atrioventricular valve
  5. left ventricle
  6. aorta – its branching arteries which feed the systemic circulation

Deoxygenated Blood

  1. superior & inferior vena cava
  2. right atrium
  3. tricuspid valve/right atrioventricular valve
  4. right ventricle
  5. pulmonary semilunar valve
  6. pulmonary artery/trunk
  7. lungs

The tune goes like this…

proj_njtpk8a

I was always too busy pumping the brakes and swearing to notice the striking similarities

So the lungs have done their part, allowing red blood cells to exchange their CO2 from the
tissues for oxygen from the aveoli into neighboring capillary beds. Once oxygenated, the
blood returns to the heart from the lungs by a set of pulmonary veins which empty into the
Left atrium like jumper cables to a battery. Medieval architects constructed atriums in
cathedrals to serve as the first giant, open chambers that you would enter. The atriums of
the heart are constructed in much the same way (that’s right, I learned that in public
school). Blood from the atrium enters into the left ventricle after passing through the
bicuspid valve. As the ventricle contracts the oxygen charged blood moves into the aorta
from which it can flow freely into the wild (or the systemic circulation making up the rest of
the body if you want to be boring). The aorta is a major intersection of arteries that branches
off to the body, the Jersey Turnpike of the vascular system.

So now that the blood has had time to mingle with the organs and tissues, toured the
sights, been places…what happens in Vegas stays in Vegas that sort of thing, it is just
about tapped out of oxygen. The blood then returns to the heart from two different
directions. Blood from the upper body will be entering through the superior vena cava and
the blood coming from downtown will be entering through the inferior vena cava. Much like it did on the left, blood will first enter the right atrium. Blood will then flow into the right
ventricle after it has passed through the double doors of the tricuspid valve. Contraction of
the ventricle will move the deoxygenated blood into the pulmonary artery where it will revisit
the lungs for more of that sweet sweet oxgen. I love a happy ending.

A few things to consider..

Valves are a pretty nifty thing to have in a fluid environment under relatively high pressure. The heart has a lot of blood to move and can’t just take a deep breath and let it all out at once
like the big bad wolf. It needs to take a lot of smaller breaths, relax and contract. The valves
stop the blood we started with from being forced backwards under the pressure every time
the heart muscle changes it’s shape.

The left and right sides of the heart are cleverly separated from each other by septa. These are thick, tough walls of cardiac muscle that keep the oxygenated blood from mixing it up with the deoxygenated blood among the atria and ventricles.

The pulmonary veins are kind of special. If you’ve ever studied the difference between arteries and veins, the veins are typically illustrated in textbooks as blue and the arteries are always red. Illustrators do this to emphasize the oxygenated versus deoxygenated nature of the vessels. So then non-conformists like the pulmonary veins come along and throw everything off because they deliver oxygenated blood to the heart. So now what color should we use?

Anyway, I hope this helps you on your way towards academic rock stardom. Stay classy my friends and never stop learning 🙂

https://forgottenphysiology.wordpress.com/2013/02/18/just-breathe/

Oh Those Naughty Diagrams

Do diagrams and biochemical pathways make you shrivel up like cold McDonald’s fries underneath your driver’s seat? Allow me to offer some friendly advice.

Ah sweet clarity, good to the last drop…

Classic animal cell model from your youth. Note the intricate jelly bean design

Classic animal cell model from your youth. Note the intricate jelly bean design

Today we’re going to dig deep…haha no no way deep, into the pscyhe, into your most primitive, raw memories of how you first learned about the human cell. Now close your eyes and imagine (only imagine yourself closing your eyes. Please keep reading). There you are, adorable, innocent little you ready to dive in, converse first, into a brand-spankin new science textbook, all shiny and full of promise. Your teacher instructs all of you to turn to the 1st chapter and there it is….the cell. The ribosomes are red and round. The mitochondria are not unlike yellow jelly bellies, and have you ever seen a smoother endoplasmic reticulum? I doubt it. So you’re staring intently at this artist’s rendition of the cell, and it’s huge…like really huge. Now keep in mind that kids are sponges right, you show them a powerful representative image of a cell and explain to them that it’s the most basic unit of all living things and they will remember it. There’s just one thing…cells aren’t huge they’re teeny tiny, and cells don’t just have two or three ribosomes. They have thousands. No, I’m not picking on teachers or textbooks because honestly, biology is intensly complex at times and it’s good to get a firm grasp of the basics. Besides, any decent teacher or text will go on to explain that cells are tiny and that you have a couple trillion in your body. Most kids get that. What I’m suggesting is that when it comes time to add more dimensions to our learning we have a hard time letting go and don’t realize it. A REALLY really hard time. I can’t tell you how many times some one will mention the state of Maine and a giant lobster pops inside my head.

Let’s fast forward to highschool biology class. I’ll never forget it. It was 8am – the caustic waft of chalk dust twirling in the cold, fluorescent light and through the smoke my drowsy, adolescent eyes make out an old, familiar sight traced on the chalk board, the human cell. For a time, all is well. Suddenly, the two dimensional world of my childhood takes a nasty turn down a sketchy alley called “Cellular Metabolism.” The teacher directs our attention to the humble mitochondria “the power house of the cell.” She begins to speak of biochemical pathways, of co-factors, glucose, and enzymes…oh my! It is a complex world indeed, but try as I might to wrap my head around these new concepts all I see are the same two-dimensional jelly beans from my youth.

There are those of us who can compartmentalize, who can simply take that new information and memorize it…learn all the sequences and reactions, and simply spit them back out when test time comes. I call this kind of learning “renting.” That knowledge has no depth or dimensions  It doesn’t really belong to you. Understanding where reactions take place in the cell, how often they occur, and the alternatives to those reactions is an experience that belongs to you. Yes, if you have the ability to just absorb pure facts and recall them my hat goes off to you, but we as students should always always always make an effort to incorporate a sense of scale into our learning or it WILL come back to haunt us. Allow me to demonstrate.

the tune goes like this…

Let’s say I just received new information: “Chickpeas are an excellent source of protein, but they do not provide a complete source of protein.”

I will now trace back through the steps of what I already know. WARNING this may seem tedious and possibly annoying to many of you, but it really does help.

Chickpeas are an excellent source of amino acids, which form chains that make up protein. There are 9 essential amino acids that our body’s need to function. Amino acid chains are produced by ribosomes in our cells from information contained within messenger RNA which is transcribed from a gene which is a specific sequence of DNA, which is tightly bound and coiled around histone proteins. Many tightly packaged bundles of DNA and protein make up chromosomes contained within the nucleus of our cells. The ENd.

No, I don’t do this for every morsel of new information I learn, but it is a great way to ground yourself when you begin to feel overwhelmed.

Now when it comes to biochemical pathways don’t let those intimidate you either. Allow me to quote myself from another lesson;

When approaching any biochemical pathway for the first time you should always ask yourself what factors (enzymes, organic molecules, catalytic elements) are already present within the system. Next, you should ask yourself what factors will be introduced into that system. That is the rhythm of a pathway; what’s already there, what gets introduced, and what gets made when we put them together.”

I just thought that I would take this time to throw out a friendly reminder that when things start to get a little hot and heavy in the classroom (or the boardroom) seek out that sense of scale. That is all for now my friends. As always, stay classy and never stop learning.

Just Breathe

What makes this wiseguy think he could possibly possess the wealth of knowledge to cover a subject as familiar, as fundamentally elemental as breathing? What nerve. What raw, untamed, audacity, arrogance…courage (please ladies, try to focus). Yeah, I’m kind of excited too. Let’s get into it!

I felt the same way when I lost my tiny car in the Disneyland parking lot.

I felt the same way when I lost my tiny car in the Disneyland parking lot.

Sorry, you won’t find some dusty ole “from the top” general biology review about the way in which terrestrial organisms evolved to tolerate and then utilize oxygen in their metabolism on here. Who has time for that? (that’s another article) No sir, we’re focusing this talk on human physiology. It’s all about us baby, the tool users, opposable thumbs waved high…USA! USA! USA! Sorry. Ok, so my grasp of comparative anatomy is severely limited but the nuts and bolts of the human respiratory system will just as easily huff, puff, and blow your mind.

The complexity of breathing is really a matter of what perspective you are looking at it from. It has an anatomical side, a fluid dynamics aspect, and a biochemical aspect. Well hell, let’s just chat about them all…just a little, so they (my science critics) can say that we tried 😛

A Word or Two about Biomechanics…

We move air in and out of our lungs by changing the shape of our diaphragm muscles which get their orders directly from the medulla oblongata of the brain (which is always fun to say). The muscles contract, pull air in like a dirt devil vacuum, and we inhale. When the muscles relax, or flatten and push air out like really ugly bag pipes, we exhale. That is breathing from a basic mechanical point of view, but I know that won’t satisfy you will it? Hellz to the no! Let’s talk about gas exchange.

Respect the Lungs

I know it's a creepy diagram but boy howdy do I love that sweater!

I know it’s a creepy diagram but boy howdy do I love that sweater!

What you should appreciate about the lungs as organs is the way in which they interact with the external environment. They are not only exposed to the air but are able to manipulate it in such a way as to allow the oxygen component of the air to diffuse into the bloodstream by way of the capillaries. To understand the diffusion of oxygen into the bloodstream you must visualize the way in which the airways leading to the lungs branch and articulate into smaller and smaller vessels. Our respiratory anatomy really reminds me of the root system of a cedar tree. From our mouths the air flows down our trachea (wind pipe), which splits at a fork in the road at our left and right lungs into two primary bronchi. The bronchi of each side (feeding each lung) spread out and branch until they can’t branch any further.

What Rhymes with Alveoli?

you'll find these handsome devils at the very ends of our bronchioles.

you’ll find these handsome devils at the very ends of our bronchioles.

If we took our hypothetical magnifying glass and looked at the inside of the lungs…got up close and personal at about 400 – 500x magnification, then we would be able to see the point where the bronchioles branch no further, the alveoli. These are tiny, no seriously, TINY sacs of tissue covered on all sides by blood rich capillaries. This is the site of gas exchange, where the vessels have branched down so thin that there is a single layer of red blood cells ready to accept molecular oxygen as it diffuses from the air space of each alveolar sac. Those red cells exchange CO2, bound to hemoglobin molecules, for that sweet sweet oxygen

Woody seen here taking questions after his lecture on respiratory pathophysiology

Woody seen here taking questions after his lecture on respiratory pathophysiology

The capillaries that transport deoxygenated blood to the alveoli are fed by the pulmonary arteries and the capillaries siphoning oxygenated blood away from the alveoli to the heart are fed by the pulmonary veins. The heart feeds the blood supply to the lungs and receives freshly oxygenated blood from the lungs to pump to the rest of the body. So it is certainly no coincidence that your heart and lungs are anatomical bunk mates with the left and right lung literally draped around the heart like a magician’s cape. Also, remember that we are not just bringing oxygen into our body but letting carbon dioxide (which can be thought of as spent air) out of our bodies. So you should have some appreciation at this point for how well our bodies do this “simple” task 24/7 without mixing the good air with the bad or as Woody from Toy Story would say “poisoning the water hole.”(honk if you like obscure Pixar references)

I could probably go on and on about the respiratory system and shifting oxygen dissociation curves but your eyes are probably glazing over about now and I’m missing a Burn Notice marathon. So stay classy my friends and never stop learning.

https://forgottenphysiology.wordpress.com/2013/02/24/the-zen-of-cardiac-blood-flow/