Me Talk Pretty – Syndromes

Hello party people! I know it’s been many moons since I’ve posted an article but hey, let’s not dwell on the past. It’s bad for your complexion. In this episode of Me Talk Pretty I would like to introduce a topic that has wandered the deserts of obscurity for eons in need of clarity, and today we’re gonna make it rain. For many of us, the definition of a syndrome is as elusive as the lyrics to Tiny Dancer (hold me closer Tony Danza..I’m cold). Let’s clear a few things up shall we.

Syndrome versus Disease…FIGHT!

The classifications for diseases and syndromes are so closely related that they could be wearing the same underwear (like 100% cotton with no room to breath). There is a somewhat reliable consensus that a disease is classified as – having recognizable signs and symptoms which have a consistent anatomical or physiological effect on the body and are linked to a KNOWN CAUSE, a.ka etiologic agent. For example, Bacterial Meningitis is the inflammation of the protective layer of the brain in response to some nasty ole bacterial infection in the blood stream.

A) This disease has a known cause – playa hating bacterial infection by the bacteria Neisseria meningitidis (or any number of known pathogens)

B) This disease has a recognizable physiological effect on an organ/organ system – inflammatory response within the meninges of the brain and infiltration of cerebrospinal fluid leading to systemic central nervous system infection.

C) This disease has consistent, recognizable pattern of signs and symptoms – mind numbing headaches, neck stiffness, fever, altered mental state.

Here’s where it gets tricky…

I would like to tell you that a syndrome is distinguishable from a disease by – having recognizable signs and symptoms which have a consistent anatomical or physiological effect on the body but have NO KNOWN CAUSE. However, we know that Acquired Immunodeficiency Syndrome (AIDS) is linked to an infection with HIV (Human immunodeficiency virus) which attacks our CD4 T-cells. AIDS is classified as a syndrome because the condition has such a broad spectrum of symptoms and complications resulting from the breakdown of the immune system that it can not be classified as a single disease process. On the other hand, Carpal Tunnel Syndrome (the chronic pain and impaired functionality of the hand and wrist associated with the constriction of the medial nerve of the wrist) has a consistent pattern of symptoms and physiological effects BUT the causes of carpal tunnel are highly debatable.

So I would like to be so bold as to say that as a general rule of thumb – what makes a syndrome a syndrome is in the complicated nature of identifying a single, consistent cause for a pattern of signs and symptoms that typically appear together.

I know I know…this one is a little messy. So let’s think of it abstractly.

One afternoon I walk outside and notice that everyone is wearing bright green t-shirts, and walking in groups along the sidewalks with four leaf clovers painted on their faces, carrying mugs of bubbly green liquid. As I walk past restaurants I see lunch specials for corned beef and cabbage. Based on these signs and symptoms I immediately check the calendar (March 17th) and quickly diagnose the phenomenon as St. Patrick’s day. It has been well established that these patterns of behavior only occur together on this particular day. So based on what I’ve told you, would you classify this holiday as a disease or a syndrome?

How about this one – One afternoon I walk outside and there’s a parking ticket on my windshield. Later that day I crack the screen to my smart phone and can no longer make calls which causes me to miss a crucial text message about a party that night. Based on these signs and symptoms I immediately look at the calendar (Friday 13th) and I quickly diagnose the phenomenon as Bad luck. The association of these patterns of behavior are both poorly understood and highly debatable. If bad luck were an illness would you classify it as a disease or a syndrome? (yeah I know that’s a lousy example but humor me)

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

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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 :-)

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 🙂

Allergies Oh My!

Hello Internet! No, I missed you more. Let’s chat about allergies shall we

Let me set the scene…

sunny day smile
It’s a beautiful morning in March. No scratch that, it’s a perfect morning. It’s the kind of day that wakes you up before your alarm clock and you are surprisingly ok with it. You’re even singing in the shower (if I don’t sing in the shower I don’t feel quite as clean). So you kick the door open to get outside and get this day started when it hits you, allergies, Mother Nature’s “you don’t belong here” bitch slap to the senses.

First it’s a sneeze, a harmless little sneeze that triggers 3 more sneezes. Then your nose starts to run in that “get me a Kleenex or I’m wiping it on my sleeves and I don’t care who sees me” kind of way. Of course, the last straw…the absolute take me out back and put me out of my misery moment is when the eyes start their itchy, watery awfulness. So you look around to see if this is happening to anyone else…if anyone is hurt…if there is a special report on channel 6 about bio-terrorism attacks in your neighborhood. No one else seems to be effected and it’s not terrorists or a demon possession. Here’s what happens…

I'm fine! It's just allergies ok.

I’m fine! It’s just allergies ok.

The Super Condensed Cliff Notes Version

Allergens in the environment stimulate our B-cells to produce IgE that builds up in our bloodstream eventually attaching to Mast cells and basophils. Upon subsequent exposure, the allergens bind to the membrane bound IgE on the surfaces of the Mast cells and Basophils triggering the release of histamine filled granules, initiating the localized inflammatory response we all love to hate.

Your White cells are angry (localized immune response to allergens)

go joeAlright I’m sorry but I’ve got to review a few things with you people.We learned as kids that our blood is composed of red cells that carry oxygen and white cells that help fight infections. The truth is we have a variety of white cells (leukocytes) that each has its own, nifty G.I. Joe-like skills at combat. Let me draw your attention to 3 cells for now; B-lymphocytes, basophils, and mast cells.
Your B-cells A.K.A B-lymphocytes develop from stem cells in the bone marrow and later hang out in the lymphatic organs (like your lymph nodes) where they are educated in the ways of antigen recognition (sort out the good from the bad) and are armed with the black magic ability to produce antibody for whatever ails you.

If you recall, antigens refer to any substance that can elicit an immune response. Antigens can be composed of carbohydrates, lipids, proteins, or anything that triggers the cascading effects of your immune cells (leukocytes) when they come into contact with it.
Antibodies are highly specialized, fancy-pants proteins produced by B-lymphocytes that have the ability to bind to the antigens of foreign invaders (pathogens) that slip into the bloodstream (Bacteria, viruses, microscopic fungi). The pathogens that invade our bodies display antigenic molecules on their surfaces, which is how they get spotted in the first place. If our B-cells make antibody that fits that antigen molecule (which it pretty much always does) our white cells will begin beating down that pathogen in a large-scale battle royale that involves cell divisions and some serious Pacman-like chomping action.
That’s right, your white cells divide and conquer. That’s why doctors are often expecting your white cell count to be elevated during and infection. They are quite literally forming a clone army.

When they bind to a pathogen it allows white cells like macrophages to engulf them and also facilitates the killing action of another class of bad-ass, ninja protein referred to as complement that are always present in your bloodstream.
Our antibodies come in a variety of shapes, sizes, and classes based on complexity and specificity.
Keep in mind that there is a lot of crap floating around in the air, hanging out on table tops, Bank door knobs, and wherever 4 yr olds are running around, sneezing without covering their mouths.

beach house

Best Summer ever!

These microbes are just looking for their 15 minutes of fame and a chance to raise hell in our blood stream like a Girls Gone Wild, MTV beach house weekend.

So with so much diversity B-cells produce a very generalized, one size fits all, meat and potatoes class of antibody referred to as IgM. The structure of this antibody has a lot of arms that are well suited for grabbing hold of more than one antigen at the same time. Then there is the more specific IgG that gets produced in response to repeat offenders, meaning the body built up immunity to that invader and set aside memory b-cells armed to the teeth with antibody “made to order” for subsequent invasions.

yeah that's real clear. Those star fish looking things are the IgM antibodies and they help that enormous white cell to grab hold of whatever nasty bug they attach to

Uh yeah, that’s real clear. So those star fish looking things are the IgM antibodies and they help that enormous white cell to grab hold of whatever nasty bug they attach to

Let’s get back to Allergies!

basophils

that handsome devil in the center is the basophil. White cells are actually colorless until a stain is added to the slide. Basophils stain in basic (alkaline) pH, thus baso-phil.

When it comes to allergic responses IgE class antibodies are the usual suspects. They have the ability to activate distinct white cells in our body (Basophils in our blood and mast cells in our tissues) Both of these cells contain granules that when freed from their cellular cages unleash a potent substance called histamine which is primarily responsible for the classic symptoms of an allergic response. Your mast cells and basophils like to hang out on the mucous membranes of the nose, ears, throat, and eyes. These are the access points to your body, places of direct exposure to the outside environment. So these groupings of immune cells are just more likely to have a few run ins anyway with bad boys looking for a fight.

Behind the Scenes

jack-russell-terrier-100309

D-awww adorable!

Let’s say you’re frolicking through the fields one day like a happy Jack Russell terrier, kick up some ragweed pollen and think nothing of it. For whatever reason ragweed pollen just rubs your white cells the wrong way (meaning white cells possess a membrane receptor that matches the antigenic determinant of the pollen granule and become sensitized on contact). Over the next few weeks your body will produce a line of B-cell clones that will only produce IgE for that pollen strain which will circulate in your blood stream attaching itself to the membranes of Basophils and Mast cells.

funnel-cake1

I mean if it’s a choice between land mines and funnel cake I choose cake not war.

These cells literally get coated in IgE like powdered sugar on funnel cake (man that sounds really good right now). So the next time that you’re exposed to ragweed pollen the IgE on those cell membranes grabs a hold of the antigen and triggers the basophils and mast cells to release their histamine granules like land mines.

When Histamine Attacks

The histamine released by your white cells acts on the cells of capillaries. It increases their permeability, opening up the blood vessels allowing white cells and plasma proteins access to the site of infection. This is what we call inflammation. So allergic responses to allergens are an inflammatory process. In the case of a runny nose it is the histamine released by mast cells in your nasal cavity acting on the vessels in your nose. The histamine molecule only has about 17 atoms so it passes quite easily through cellular membranes. A good portion of cold, sinus, and seasonal allergy medications available in the pharmacy section of your grocery store are “antihistamines” counteracting the effects of histamine to relieve your symptoms.

Anaphylaxis

So unfortunately the occasional runny nose isn’t all that allergic responses are capable of and in a select percentage of the population the triggering of inflammation can be a critical and often fatal, systemic reaction. I’m referring to anaphylaxis. This process reflects the most extreme form of immediate immune response whereby widespread inflammation can lead to severe swelling of the eyes, constriction of airways and even shock where the blood pressure drops. Yes, well you know how I like to end things on a light note so….take a look at this beagle puppy playing with a stuffed animal.

beagle

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

The Liver Files

Ok, so I thought she had pretty eyes. Don't judge.

Ok, so I thought she had pretty eyes. Don’t judge.

I mean frankly, the liver performs so many necessary functions that it’s almost boring. The liver is like that movie in the Oscars that wins every award…best screen play, best performance, best soundtrack…and you’re like “come on, give someone else a little credit.” Well when it comes to the body the liver deserves all the credit. For starters the people who write textbooks can’t even decide what organ system to put the liver in. It produces enzymes that are necessary for the emulsion of fat, and the metabolism of proteins and carbohydrates so obviously it’s part of the digestive system…well kinda. It has a hefty blood supply, produces lymph, and harbors antibodies for the destruction and removal of old and ineffective red cells so maybe it’s part of the immune system…well kinda. It produces an [EXPLETIVE] load of useful proteins that aid in everything from helping your blood to clot to detoxifying drugs, and toxins that enter the blood stream so….don’t look at me, your guess is as good as mine. If you want a meeting with the Liver you’ve got to ride the elevator to the top floor, follow the arrows to the door labelled “The Man” and wait in line. Well ok, this stays between me and you, but I can tell you what I know. Keep your voice down and close the door behind you…

Is it just me or does the invisible man have great biceps?

Is it just me or does the invisible man have great biceps?

The Liver is the original Renaissance man. I mean forget the Dos Equis commercials. Just take a look at this organ’s resume..

Metabolism

glycogen synthesis and degradation, gluconeogenesis from protein, amino acid, and lipid / non-carbohydrate sources

Toxicology

drug metabolism and detoxification

Digestion

synthesis of bile salts…nasty but necessary

Synthesis

plasma proteins, cholesterol and its carrier lipoproteins

And I wouldn’t be suprised if it knows magic tricks

Digestion and Metabolism

The liver produces bile which looks a lot like it sounds, nasty, but it gets stored in the gallbladder to aid in the breakdown of lipids (fats basically) in the small intestine.

About that whole bile thing…

bile facilitates the action of pancreatic amylase which actually degrades triglycerides. The bile’s salts have two sides, molecularly speaking, hydrophobic and hydrophyllic. The main reason why fats don’t dissolve in water is because their molecular surface repells water. So bile salts can surround fats with their water loving (hydrophillic) sides out which gives enzymes like pancreatic amylase the back stage pass.

Synthesis

So not only does the Liver make cholesterol but it produces the carrier molecules, lipoproteins like HDL and LDL that transport the stuff. Cholesterols are insoluble in water so the lipoproteins facilitate their deep sea journey through the bloodstream.

Some light anatomy

so the main cellular component of the liver is the hepatocyte. They make up roughly 70-80% of the total mass so naturally, because I do choose favorites, that’s what I’m focusing on in this article. They are the working parts of the organ that together make the magic happen. An organ is the sum of it’s parts…microscopic processes equating to bigtime changes. Ah yes, and it get’s it’s hefty blood supply from the hepatic arteries and portal vein. Now you know in case Jay Leno asks you in the street. You’re welcome.

Da Sugar

When I say metabolism I want you to think “what happens to the glucose?” Let’s say it’s half priced Tuesday at The Gringo Burger Bodega (I made that name up. Can you tell?) and you’ve treated yourself to the #6 diablo fries with a dulce shake made extra dulce. While being transported to takeout heaven you wonder “What is my body doing with that access glucose?” You’re always thinking. I love that!

Here’s what happens…

Blood from your portal vein supplies your hepatocytes with fresh glucose. Those cells will form long chains of the glucose molecules linked by a-1,4 glycosidic bonds to form this nice biggie sized storage form of energy called glycogen which happens when your blood glucose levels are high hence there is a raise in blood sugar so having all those hepatocytes uptake glucose lowers blood sugar. So in classic, clever physiology fashion when blood sugar is low the glycogen can be broken down/degraded into glucose which is then available to adjust for blood glucose level.

Gluconeogenesis

Another neat trick…

another innocent victim clearly possessed by 10k demons

another innocent victim clearly possessed by 10k demons

The other thing you have to know about the liver is that it doesn’t like to let anything go to waste. If it’s an organic molecule and your body can make use of it, chances are your liver is breaking it down and recycling it as we speak…no seriously, like just now. oh you missed it.

Sometimes carbohydrates just aren’t enough. Sorry blue box mac n cheese, I know we go way back but it’s true. The body needs a way to derive glucose, that oh so sexy cellular currency, from non-carbohydrate sources. The process by which the liver pulls this off is of course referred to by the cool kids (scientists) as gluconeogenesis. Your kidneys can also pull this off, but don’t get too excited about this clever trick. It’s just another way the body compensates for potentially “bad news” drops in blood glucose apart from the breakdown of glycogen. It’s the kinda thing that is supposed to kick in when you’ve been fasting, starving, or exercising like you’ve been possessed by demons.

Detox Rocks! (see what I did there)

So one more thing…

hell yeah

hell yeah

The liver is probably the best defense our body has to protect us from ourselves. If it’s toxic or in a form the body can’t use…the liver will convert, breakdown, and package it like there’s no tomorrow..because if it didn’t there really would be no tomorrow. This is typically referred to as xenobiotic metabolism and it’s made possible by the bountiful community of enzymes and their biochemical pathways that call the liver home. The liver typically accomplishes this by modifying the fat loving (lipophilic) nature of many pharmaceuticals into a more user friendly and excretion friendly, water loving (hydrophilic) form. However, it’s not always about solubility. Some nasty little substances require a little versatility (I’m looking at you Alcohol..you know what you did last weekend). Thankfully our livers come equipped with a nifty alcohol dehydrogenase that allows for the reduction reactions that keep this party animal in its cage reasonably well.

I should mention however that the liver’s gift can also be its curse. The liver has such mad skillz for the bio-conversion of compounds that every now and then it can convert foreign compounds into substances that are actually more toxic than what you started with. We call these metabolites and they are no fun.

Well my friends it’s time for me to go make a difference (eat dinner). Stay curious, stay classy, and as always never stop learning 🙂