Gray and white matter – the cities and highways of the brain

gray and white matter is city and highway

Your brain has around a hundred billion signaling cells called neurons, forming an astronomical number of connections (synapses).  The “wiring” is incredibly complex — an electrician’s nightmare!  Hundreds of functional brain regions and circuits have been identified, but to a large extent the brain is still a “black box”.

One thing that’s plain, though, as you look at a slice of brain, is that it’s divided into two general types of tissue.  Gray matter is where information is processed.  Here you’ll find dendrites, the “input cables” that a neuron uses to take in information.  These are all attached to the cell body, which therefore, in effect represents an “integration zone” for all the signals coming in.   If the neuron decides it has something to say about the matter, it fires off a signal through the axon, the single “output cable” of the cell.

You’ll also find white matter, distinguished by the presence of myelin, a wrapping provided by other cells (here, oligodendrocytes, seen hanging under the “freeway”).   Myelin is a fatty material so the white color is not surprising — think of the pale crust of grease on a refrigerated pot of chicken soup.

Unlike the water that fills and surrounds each cell (remember: keep that hair dryer out of the bathtub!), fat is a poor conductor of electricity, so myelin serves as an insulating covering for axons.  It prevents an axon from being “short-circuited” when two axons lie side by side, and it also greatly speeds up the signal transmission along an axon.  So, a group of myelinated axons (which can be up to several feet long!) is a good way to carry a large body of information from one place to another, quickly and uncorrupted.

What we have, then, is a sprawling “metropolitan area” consisting of “commercial city centers” joined together by high-speed, multi-lane “highways”.  Gray matter tends to have highly branched neurons with many connections, allowing intricate exchange of information.  The flow of “traffic” is complex, and stops are frequent.  White matter is all about rapid, long-distance signaling from one “city center” to another, very much like an expressway.  These axons are insulated against nervous input, but at intervals some will branch off to make a connection.

Proceeding with this fantasy, we see an exit approaching for “Las Vagus” – that’s a reference to the vagus nerve, a major nerve that extends from the brain to many of your internal organs.  You may also have noticed that on white matter, the ride is a bumpy one – That’s because there are gaps in the myelin (nodes of Ranvier).  Paradoxically, though, in real life these gaps actually speed up the signal!

Capillaries do all their work in bed – they’re not lazy, but they’re leaky!

Capillaries do all their work in bed – they’re not lazy, but they’re leaky!

Capillaries leaking in bed

Our tiny capillaries are the most important blood vessels in the body, responsible for supplying virtually all the oxygen and nutrients that our organs depend on.  So how do they behave, under the immense burden of this great responsibility?  They never even climb out of bed!

A capillary bed is the name for a group of capillaries that all receive blood from the same source.  The source vessel is called a metarteriole, and from there, a branching network of capillaries originates.  The large number of branches provides a huge surface area across which diffusion can rapidly deliver the materials demanded by the surrounding tissues.

But there’s something else going on in most capillary beds – they’re leaky.  But don’t worry, it’s perfectly normal!  There are holes in the capillary walls, allowing the fluid component of blood (plasma) to leak out, and this is how the body’s interstitial fluid is produced.  The bulk flow of fluid across the capillary wall, back and forth between the blood and surrounding tissues, permits more rapid exchange than diffusion alone can provide.

Capillary leakiness varies greatly from one organ to the next, depending on the need for exchange.  The liver is the “water purification plant” of the body, and requires tremendous amounts of exchange to do its job – it therefore has among the leakiest capillaries.  At the other extreme, the brain is like a “cleanroom” where contaminants are excluded to prevent “misfires” of the delicate neural machinery – so its capillaries are almost watertight (the blood-brain barrier).

Given that most capillaries are leaky, what happens to all that water?  Does the bedroom flood completely, until a plumber is called to the scene?  Well, not quite.  The answer to this problem is the lymphatic system – it’s the storm drain of the body, which collects all the excess interstitial fluid of the body, and carries it right back to the blood…to be leaked out, all over again, by our hard-working capillaries.

Don’t have a heart attack!

Don’t have a heart attack!

heart with obstructed coronary artery

This week’s image may seem melodramatic, but I’m sure if you were a heart undergoing a heart attack, you’d feel something like this.

Heart attacks teach us that the heart is like any other organ – it consists of cells that require oxygen and nutrients to survive.  The other thing we learn is that, despite the large amount of blood in the heart, almost none of its contents are directly available to the heart’s cells.  That’s because diffusion is only effective across short distances, so the thickness of the heart’s walls prevents all but the inner surface cells (endothelium) from acquiring their vital resources in this way.

The solution is for the heart to have its own network of blood vessels, the coronary arteries, penetrating deep into the heart walls to supply its own tissues with blood.  The suffering heart depicted here is actually anatomically correct (minus the face and heads), allowing us to see all the major blood vessels that deliver blood to and from the body.

Oxygenated blood, from the lungs, reaches the heart through the four pulmonary veins, entering horizontally from the sides.  It enters the left side of the heart, which ejects this oxygen-rich blood (shown in red) into the aorta, the largest artery in the body.  The aorta emerges diagonally from the left side and arches over the top of the heart, branching many times to provide oxygen to the entire body.

From the aorta, the right coronary artery curves around the heart’s right side (on the left side of the page), and the left coronary artery curves toward the heart’s left side, each providing many branches of their own.  If one of these becomes blocked by a blood clot or fatty deposits in the artery walls, then a heart attack results – meaning the heart tissue dies due to the obstructed blood supply, and the resulting lack of oxygen to that region.  This is different from cardiac arrest, in which the heart stops beating – a problem with the electrical conducting system of the heart.  (However, the two problems can be related, if a heart attack damages part of the conducting system.)

Let’s look at the rest of the blood flow, in a healthy heart.  From a coronary artery, tiny branches (capillaries) supply oxygen to the heart’s tissues by diffusion, and drain into cardiac veins (not shown) which drain into the right side of the heart.  This is also where oxygen-depleted blood enters from the rest of the body, through the superior and inferior vena cava (vertical vessels on the left side of the page).  From there, it is pumped through the pulmonary trunk (large vessel crossing in front of the aorta) back to the lungs.

Which tissue do we need the most?

Which tissue do we need the most?

The entire body is composed of only four basic tissue types.  Muscle tissue, of course, allows you to move around.  But it’s also what moves your internal organs – the beating of the heart, the rumbling of the stomach.  Even your blood vessels have muscle tissue, which controls the distribution of blood in the body.  It’s hard to argue we could live without muscle.

But most of our muscles wouldn’t be much good without nervous tissue, which responds to stimuli and coordinates the activity of your organs.  It’s true that many of the slower, internal processes do not depend on nervous input – they may instead involve hormones, for example.  But what good is a body without a brain to give it meaning?

Epithelium, though, really is essential at the most basic level.  This is the tissue that lines all your external surfaces and your internal spaces.  Every substance that enters the body (food, water, oxygen) must cross an epithelium to do so.  These tissues are therefore the “gatekeepers” to the body, in charge of exchange with the environment – although, under the command of nervous tissue.

So the tissues must work together, and there’s no better example of this than the fourth basic type, connective tissue.  As the name suggests, it is the “putty” that holds the body together, filling in all the spaces between epithelium, muscle and nervous tissue.  But it also provides pathways for the movement of materials within the body.  This is the most diverse tissue type, including blood, the essential medium of transport, but many other types such as bone and cartilage.  The key feature of connective tissue is the presence of a large amount of nonliving “stuff” in between the living cells – the extracellular matrix.  Water is often abundant here, and this interstitial fluid forms another major transport medium for substances to move among all the tissues.

So of course, it’s hard to say any one basic tissue is more important than another.  I don’t know about you, but this “exchange” about the “connections” has been a “moving” subject for me that touches a “nerve”.  Pass the box of tissues!

Who supports your support system? An unsung hero — connective tissue

Connective tissue, the inner part of the wall that conveys the body's infrastructure

If you’ve been reading this blog, by now you’ll know that the oxygen and nutrients your cells depend upon first enter the cell’s neighborhood by means of your crowded capillaries.  Molecules then diffuse outward across the interstitial fluid to reach most cells in your body.  The cardiovascular system is the most obvious “support system” in the body because it circulates the blood that keeps your cells alive.  It also works with the kidneys to remove wastes.  I’d also add the lymphatic system (see lymph nodes) which drains excess interstitial fluid and filter pathogens from it.  And, I’d include the nervous system which carries a crucial pipeline of information that many cells depend on to do their job.

But who supports the “support system”?  Do your blood vessels, lymph vessels and nerves simply meander through the body, or is there a structure – a scaffolding — that holds them in place?  Yes, there is – our unsung hero, the connective tissues of the body.

In a typical organ like your stomach, lungs, or skin, you’ll have one or more layers of epithelium at the surface (shown in yellow) to interact with your food, air, or the external environment.  Always behind that epithelium you’ll have connective tissue (shown in brown) which carries the blood vessels, lymph vessels, and nerves that serve that region of the body.  Even a muscle layer (for example in the stomach), as seen at far right, actually contains, between the muscle cells, a great deal of intervening connective tissue, which is where the vessels and nerves travel.  (This is the endomysium, the “first class seat” that supplies all the muscle cell’s needs.)

As you go about your business indoors, at work or home, think of the wall surfaces as an epithelium.  They provide electrical outlets, faucets, heating vents and other necessities for life.  But all of these things come to you through an infrastructure of electrical wires, water and sewage pipes, ventilation ducts, and internet cables that travel, unseen, through the walls.  Inside your body, that role of the “internal wall space”, which supports and conceals the “support system” of the body, is served by connective tissue.

Your crowded capillaries

Red blood cells in capillary

Your blood is crowded with red blood cells, or erythrocytes — they occupy around 45% of blood volume in most people (that number is the hematocrit).  This becomes more evident when you look at the capillaries, the tiniest blood vessels.  These vessels are literally what keeps you alive from one moment to the next — providing virtually all the oxygen and nutrients, and removal of wastes, that allows your organs to survive — brain, muscles, skin, bones, and so on… even the heart itself.

Red blood cells travel in single file down your capillaries.  This is no accident, because exchange here depends on the rate of diffusion, the passive drift of molecules from regions of high to low concentration.  Diffusion is a cheap, but slow, way for a cell to get its “groceries”, so the only way this can work is to minimize the diffusion distance those molecules have to travel.

Capillaries accomplish this in two ways.  The narrow vessel means that an oxygen molecule, for example, is never more than half a cell’s diameter away from the wall of the vessel.  But also, the wall itself is extremely thin (endothelium — a type of simple squamous epithelium), further minimizing the diffusion distance.

On top of this, your capillaries branch many times to permeate the tissues.  It’s been estimated that if all your capillaries were laid end-to-end, they would total 50,000 miles — enough to wrap twice around the Earth.  Packed into your tissues, this provides an enormous contact surface, across which exchange can occur.

Not only does this branching increase contact, it also decreases the velocity of blood flow — in the same way that a wide hose ejects water more slowly than one with a thumb placed partway over the end.  The speed of blood flow in the aorta (the largest artery) is about 1 ft./sec. but goes down to around 1/1000 that speed in the capillaries — about 3/10 of a millimeter (equivalent to around 30 cells) each second.

So, picture a long, but crowded buffet line that moves briskly along — each cell has a chance to exchange everything it needs to (albeit without much elbow room) before it shoots out the other end of the capillary, to head back toward the lungs.

Lymph nodes: Police stations of the body

Lymph node as a police stationA lymph node is a bit like a jungle gym for our microscopic police force.  A filter or dragnet, evolved to catch unsavory characters like bacteria and viruses — drifters who are up to no good.  Our hundreds of lymph nodes function like district police headquarters, situated around the body with concentrations in the armpits, neck and other areas.

Tissue fluids throughout the body make their way into the lymphatic vessels, carrying any infectious microbes along.  Lymph nodes like the one shown above are stationed along those vessels, and here is where the “crooks” meet a concentration of leukocytes, or white “blood” cells.  (I add quotes around “blood” because they spend most of their time patrolling through other body tissues.  It’s a bit like calling someone a “streetwalker” just because you caught them crossing the street now and then.)

The “jungle gym” in a lymph node is built of reticular connective tissue, specially evolved to provide “networking” opportunities (“reticular” means “net-like”).  This facilitates interaction among the cops while also giving them a good chance of nabbing a microbe.  Some leukocytes may respond immediately (cop reaching for gun), and will later serve as an antigen-presenting cell to communicate their findings to the others (the “wanted” slide shown at top).  After the initial encounter, certain leukocytes with a receptor for the specific microbe (“I was born for this assignment, boss!”) divide into many identical clones that are specifically on the lookout for said crook.  The production of clones is what produces the swollen lymph nodes during an illness.  Memory cells (the cop with the desk job) remain on high alert (perhaps with the help of coffee and a donut) even after the crooks have been executed, in case they show up again, when the body will be prepared for a more rapid response (adaptive immunity).  Some memory cells can live for decades – very old “cops” indeed — and they never forget.  Leukocytes communicate with a variety of signals (cops joking around at right), some of which encourage them to “bulk up” for the encounter, like the cop doing pull-ups.

We run into the larger lymph nodes (around 1-2 cm) with every dissection in the cadaver lab.  They’re nondescript, and firm, but with a dense, spongy texture that, with a touch of imagination, is suggestive of their “cop station” function.

Interstitial fluid: Our internal life aquatic

I would love to shrink down to microscopic size and greet the cells in my own body face-to-face, like something out of the movie Fantastic Voyage.  Of course, I won’t “hold my breath” waiting for such an opportunity to come along.  But even if there were some way to do this, I would quickly drown without SCUBA equipment!  This underscores the fact that our internal environment is an aquatic one.  Our living cells depend on the special properties of water, both to exchange gases, nutrients and wastes, and to facilitate the chemical reactions necessary for life.  Evolution has not yet found a way to allow life to thrive without internal water (a few creatures are capable of surviving complete desiccation, but they do so in suspended animation).

Indeed, a cell out of water is like a fish out of water.  This means that the dry skin surface of the human body is all dead tissue.  It also means that all our internal tissues are moist.  Even bone tissue, despite being largely composed of calcium phosphate, is permeated with water and houses living bone cells that live comfortably within tiny water-filled “lagoons” known as lacunae.

Some tissues contain more water than others.  Blood is the tissue with the greatest water content, but all other tissues have, between their cells, a fluid known as tissue fluid, or interstitial fluid.  The tissue depicted above might represent areolar connective tissue, a ubiquitous tissue found in many parts of the body, which contains a large amount of interstitial fluid. Because it’s found adjacent to all blood vessels, it plays an important “middleman” role allowing molecules to make their way between the blood and nearby tissues.  The two typical cells shown here would be fibroblasts, which produce the protein fibers giving structure to the tissue (collagen fibers are shown in gray, and reticular fibers in magenta); these in turn provide attachment points for the cells, as they go about living their aquatic lives. Unfortunately, the interstitial fluid is also a benign environment for bacteria (shown in pink) — but that’s a story for another day.

Endomysium: A first-class seat for your muscle cells

Endomysium is like a first-class airplane seat for your muscle cells

Strapped into an economy seat as we fly across the country for the holidays, it’s hard not to appreciate life’s basic necessities — a cup of soda, a bag of pretzels, the relief of seeing “vacant” on the lavatory door. It’s also a good time to remember that the real protagonists in this story are your trillions of cells, each of whom has the same basic needs you have. Each muscle cell, for example, needs an oxygen supply, nutrients, a way to eliminate wastes, a command system telling it whether to contract (or just relax), and a physical attachment allowing it to work with the rest of the muscle. All of these things are provided by a thin sheath of connective tissue called the endomysium which surrounds each muscle cell. The endomysium, in effect, acts as a scaffolding to support the infrastructure of blood vessels and nerve cells that allow the muscle cell to function. What kind of airplane seat does a muscle cell occupy? Considering that the bloodstream keeps the cell supplied with a constant stream of goodies, I imagine it’s got to be a first-class seat.