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Authors: Bill Schutt

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Before we get too carried away with just how cool our circulatory systems are, you should know that there are some relatively large organisms that get by just fine without elaborate circulatory systems. Insects, for example have low-pressure systems that are termed
open circulatory systems
because they don't form a completely closed loop between the body and heart. Hemolymph (the arthropod equivalent of blood) is circulated through the body by a series of heartlike dorsal pumps and by movement of the insect's body. The hemolymph moves through vessels that eventually lead to open sinuses called hemocoels. Here, the surrounding internal organs are literally bathed in the nutrient-bearing fluid, which eventually percolates back and reenters the hearts through tiny valves called ostia.

The key here is that unlike animals like vertebrates, insect circulatory systems aren't involved in transporting gases like O
2
and CO
2
or exchanging those gases with body tissues.
*58
A mosquito's oxygen requirements are met through a series of openings (spiracles) along both sides of its thorax and abdomen. Air passes from the environment into the spiracles (which can also be closed to prevent water loss), and then through a complex of tubes called tracheae. The tracheae get smaller and smaller, finally branching into microscopic vessels called tracheoles, through which the air finally arrives to supply the tissues and cells.

This system works just fine for small creatures, but there are limitations. For example, tracheal respiration is probably a key reason why mosquitoes (and other insects like bed bugs) aren't a whole lot bigger in size than they are. Larger animals are composed of too many cells to be efficiently supplied by this type of respiratory system.

Some of you might be saying, “Wait a minute, what about those pictures of ancient dragonflies with three-foot wing spans? How did
they
get enough oxygen?”

The answer is that there is evidence from the Carboniferous period (290–360 million years ago) that widespread forests and lush plant life resulted in a higher percentage of atmospheric O
2
than exists in today's atmosphere. This extra O
2
was apparently enough to support larger species of insects that employed the same tracheal system as their smaller modern-day cousins. Still, during the Carboniferous or even during the age of dinosaurs (when some creatures reached gigantic proportions), there is absolutely no evidence of Mothra-sized insects (or, for that matter, the twin fairies who controlled them).

To help carry out myriad circulatory functions, the average human has between 1.2 and 1.5 gallons (4.5 to 5.7 liters) of blood in their body at any given time. Blood plasma constitutes 55 percent of that volume, while cells (red and white blood cells) and platelets (classified together with cells as “formed elements”) make up the remaining 45 percent. Water makes up about 92 percent of blood plasma, with dissolved stuff making up the remaining 8 percent. The majority of these solutes are proteins produced in the liver.

To be considered a tissue, blood needs to be composed of several cell types—and it is. Blood cells (or corpuscles) come in two flavors: erythrocytes (red blood cells) and leukocytes (white blood cells). Erythrocytes (from
erythrós,
the Greek for “red”) are by far the most numerous, making up over 99 percent of blood cells. Function-wise, they're very much like the old Kentucky Fried Chicken (as opposed to the new KFC). That is “they do one thing and they do it right.” The one thing they do is carry oxygen, and they do it right because each erythrocyte is literally stuffed full of an iron-containing pigment molecule called hemoglobin. Hemoglobin acts like an oxygen magnet, picking it up where it's plentiful (like in the lungs right after you take a breath) and dumping it off in places where it's in short supply (like tissues, whose cells require a constant supply of O
2
> and nutrients). Hemoglobin is so effective at carrying O
2
> (compared to say, water) that without it a person would need to have
seventy-five gallons
of fluid circulating in their body to carry the required O
2
>. And while this would certainly be an exciting development for the fabric industry (bathing-suit sizes would reflect the number of yards of material used to make them), it probably wouldn't be much fun for anyone else.

There is, however, a downside to hemoglobin's efficiency and this is related to the fact that it's even more strongly attracted to carbon monoxide than it is to oxygen. This means that hemoglobin binds to the potentially deadly gas even when there's oxygen present—a property that makes carbon monoxide
extremely
toxic even in small amounts. With the body's hemoglobin tied up with carbon monoxide, the tissues in the brain quickly become starved for oxygen. This leads to a loss of consciousness followed soon after by severe brain damage and death.
*59

All right, back to blood cells.

Erythrocytes are tiny—only about one three-thousandths of an inch in diameter—and each is shaped like an old rubber stickball being squeezed from opposite sides (nonstickball players often refer to this shape as a biconcave disk). Red blood cells are so focused on their single-minded, oxygen-carrying quest that when mature they lack nuclei or any of the organelles many of us once committed to the rote memorization region of our brains. Erythrocytes are formed in red bone marrow and enter into circulation at a rate of two million per second (which means that they're destroyed and recycled at the same rate by the spleen and liver). There are so many erythrocytes that if they were laid side by side in a single layer they would cover about thirty-five hundred square yards. This provides an incredible amount of surface area for oxygen to cross into tissues.

White blood cells, on the other hand, are a different and altogether more diverse lot than erythrocytes. For starters, they
have
a nucleus and they do not contain hemoglobin (so they don't carry oxygen). Leukocytes have been divided in two major groups (granulocytes and agranulocytes) based on whether or not their cytoplasm (sort of like a matrix inside each cell) looks grainy when stained for viewing under a microscope.
*60

Functionally, some white blood cells (neutrophils and macrophages) are like blood cell versions of amoebas. Highly energetic, macrophages can usually be found scarfing up microscopic material through a process known as phagocytosis. Rather than looking for food, wandering phagocytes (aka free macrophages) circulate through the body, seeking out foreign microorganisms like bacteria and fungi, and gathering in great numbers at sites of infection. Others (fixed macrophages) remain stationary, in places like lymph nodes or tonsils. Like soldiers assigned to guard a fort, fixed macrophages stand by, ready for action if trouble shows up. This concept of forts or outposts is precisely the reason tonsils aren't removed nearly as frequently as they were when I was a kid.

Upon encountering an invader (recognized by foreign proteins embedded in its cell wall, or by the specific chemicals it gives off ), the phagocyte wraps its pseudopods around the microbe, drawing it inward. Inside the phagocyte, ingestion soon gives way to digestion as the foreign microbe is imprisoned within a membranous sac containing a nasty stew of lethal enzymes, bactericides, and strong oxidants. In most cases, the result of this chemical onslaught is a breakdown of the invader's cell wall, followed by a toxic bath and, eventually, death. Any debris that remains is ejected from the phagocyte through a process called exocytosis.

Unfortunately, things aren't always so easy for the phagocyte, and as we all know, the good guys don't always win. Pathogenic (disease-causing) microbes have evolved some tricks of their own and many of these organisms have been at it far longer than our immune system has been around to evolve countermeasures. Pathogens like
staphylococci
bacteria produce their own toxins, which can kill phagocytes. Other invaders, like the AIDS-causing human immunodeficiency virus (HIV), evolve so rapidly that their constantly changing surface proteins are difficult for our immune systems to recognize. Alternately, some invaders, like the tubercle bacillus, are resistant to the phagocyte's usually deadly chemical bath. These pathogens, responsible for the respiratory disease tuberculosis, are taken into the phagocyte. There they multiply within the bag of toxins they've been enclosed in, only to burst forth like Ridley Scott's
Alien,
to kill the phagocyte (and traumatize any phagocytes that might be standing around nearby). Similarly, HIV can hide in these long-lived white blood cells, sometimes emerging after years of dormancy, as if from microscopic Trojan horses.

Some types of white blood cells go about defending the body in a very different way. Leukocytes (like basophils and other connective tissue cells called mast cells) function in the body's inflammatory response. Inflammation is actually a bodily reaction to foreign invaders or tissue damage. During this process, the infecting agent or damaged tissue is partitioned, diluted, and destroyed.

So how does this work?

After getting the call, inflammation-initiating cells release chemicals (like histamine and prostaglandins) that cause blood vessels in the affected area to dilate (increase in diameter) as well as become more permeable. Dilation allows increased blood flow to the site, blood containing oxygen, nutrients, temperature-rising compounds called pyrogens, and an abundance of phagocytic cells. This influx causes the affected area to appear red and even hot to the touch. The increased blood vessel permeability allows plasma (and the phagocyte cavalry) to leak out of the vessels and into the surrounding damaged tissue. The regional swelling that characterizes inflammation is the result.

Macrophages at the site of an inflammatory response to pathogens hunt down and engulf infectious invaders that they encounter. As the battle rages on, millions of them make the ultimate sacrifice and they are posthumously awarded the title of Laudable Pus. Other macrophages get enlisted in the less-popular Cleanup Crew (in which case they get to clean up the laudable pus).
*61
Adding to all this excitement, sensory nerve endings, stimulated by the weird chemicals and the swelling, produce the sensation of pain.

Unfortunately, leukocytes and other protective cells are also responsible for some types of allergic reactions. Most commonly, this “hypersensitivity” results from the body's mistaken (and sometimes life-threatening) attempts to protect itself from non-harmful substances like pollen or dust. Responding to these allergens as if they were a real emergency, basophils and mast cells release their inflammation-promoting chemicals—this time though, in places like the eyes and airways of the lungs (where the allergens have landed).

In far more serious situations, the body's immune system attacks its own joints (rheumatoid arthritis), transplanted organs, or tissue grafts. To prevent extensive tissue damage or transplant rejection, patients sometimes take immune suppressor drugs. One of the most successful has been ciclosporin (or cyclosporine)—a substance originally isolated from a Norwegian soil fungus. It works by decreasing the activity of T cells (discussed below). Although immune suppressor drugs are often taken for extended periods of time, the dangers of attenuating one's own immune system should be readily apparent.

Some leukocytes (killer T cells) recognize foreign surface proteins (antigens) and attack any microscopic organisms that “present” them. Other leukocytes (plasma cells, which develop from leukocytes called B cells) produce zillions of tiny bits of protein known as antibodies. Antibodies fit like highly specific keys into locklike receptors on the antigen's surface. The unfortunate bearer of this gaudy antigen/antibody complex either wobbles off to die or is marked for death in much the same way that a guy with toilet paper stuck to his shoe is marked for ridicule.

Other leukocytes (the oddly named helper T cells) function by helping this immune response to occur, while suppressor T cells throttle down the immune response once the battle is over.

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