Dark Banquet: Blood and the Curious Lives of Blood-Feeding Creatures

by Bill Schutt

  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 O2> and nutrients). Hemoglobin is so effective at carrying O2> (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 O2>. 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.

  Oh yes, before I forget, some plasma cell precursors called memory T cells stick around the circulatory system once things quiet down. Generally, they’re dormant, but memory T cells are quite capable of jacking up the immune response at a moment’s notice—should the same foolhardy antigen bearer show up again.*62

  And one more thing: inoculations for childhood diseases (like mumps) and regional diseases (like yellow fever) work on this principle as well. In many cases, dead or harmless versions of specific pathogens are injected into the body, which manufactures antibodies to combat the perceived threat. Additionally, memory cells stick around to quickly crank up the immune response should the real pathogen ever show up.

  Unfortunately, much of what we know about blood was determined only within the past hundred years or so. Sometimes, though, it was a lack of technology, and not blind devotion to old views, that constrained early researchers. Although the concept of humors would not be extinguished completely for nearly four hundred years, soon after the 1628 publication of William Harvey’s landmark book on circulation, Anatomical Studies on the Motion of the Heart and Blood, some physicians began to wonder if the benefits of getting someone else’s blood into a patient’s circulatory system might be greater than draining blood from that person—especially in cases where there had already been significant blood loss.

  Dr. Richard Lower performed what is generally considered the first successful blood transfusion in 1666. Using tubing constructed out of goose quills, he connected the carotid artery of one dog (the donor) to the jugular vein of another (the recipient) that he had bled previously to near death. Reportedly, the recipient was resuscitated in a nearly miraculous fashion.

  A year later, encouraged by Lower’s results, a Parisian, Jean-Baptiste Denis, used a similar device to infuse about eight ounces of calf blood into the arm of a mentally disturbed man by the name of Antoine Mauroy. Denis, like other researchers of his day, believed that blood carried in it the essence of its owner’s personality. The rationale for the infusion, therefore, was that the “mildness” of the calf’s blood might mellow out Mssr. Mauroy, who police thought was spending a bit too much time running around naked, setting house fires, and beating his wife.*63

  Tied to a chair, Mauroy was first bled (presumably to eliminate bad blood while freeing up a little space). Then he received about six ounces of calf’s blood, which was introduced through a metal tube. Mauroy complained about some initial burning in his arm but otherwise showed no serious effects. After a short nap, the patient began singing and whistling—which many of the onlookers who had gathered to watch the procedure actually preferred to getting beaten up by Mauroy or having him torch their houses.

  Two days later, encouraged by the results, Dr. Denis injected even more calf blood into Mauroy, but this time the results were quite a bit more dramatic. Reportedly, the patient began sweating, and soon after, he complained of severe pain in his lower back (near his kidneys, claimed Denis). Nearly choking to death, Mauroy vomited his lunch and soon after began urinating gobs of black fluid.

  Today, physicians would have immediately recognized that Mauroy had suffered a serious reaction because of the extreme incompatibility of the nonhuman blood he had received. The unfortunate man’s immune system had in fact mounted a multi-pronged attack against the foreign blood and the results had nearly killed him. This being 1667, however, the interpretation was somewhat different. To Dr. Denis, surely the vomiting and coal-colored liquid Mauroy continued to urinate for days were proof that the man’s madness had been eliminated. After all, the feverish and bedridden patient wasn’t nearly as manic as he’d been previously—in fact, he wasn’t speaking or moving much at all.*64

  Several months later, any enthusiasm over the potential benefits of blood transfusion was shattered when one of Denis’ patients died. The English, who believed that Denis had not only stolen their transfusion techniques but also their limelight, went out of their way to discredit the Frenchman—as did some of his own rival countrymen. Denis tried to defend himself, but the roof fell in when his highest-profile patient, Antoine Mauroy, also died. After a brief respite, the man had reportedly resumed his wild and brutal ways, and this (as it was later discovered) prompted his wife to employ a bit of creative chemistry. Madame Mauroy began adding arsenic to her husband’s diet, but for some reason she failed to mention this fact when she and her husband approached Dr. Denis, asking him to perform a third transfusion. Shaken by his former patient’s appearance, Denis declined, but when Mauroy dropped dead several days later, the physician found himself charged with murder. Denis was eventually exonerated, but the uproar surrounding the case (as well as transfusion-related deaths elsewhere) sounded the death knell for human blood transfusions and any related experiments. Two years later, the procedure was banned in France and soon after in England. Additionally, a pair of transfusion-related fatalities in Italy led to a denouncement of the procedure by the pope. Public outcry, capped with a papal denouncement, resulted in a silence that would last for the next 150 years.*65

  In 1818 gynecologist James Blundell, in an attempt to reduce the large number of deaths associated with postpartum hemorrhaging, performed what is considered to be the first human-to-human transfusion. He withdrew blood from a donor and injected it into a blood vessel in the arm of the donor’s wife. From his earlier work on animals, Blundell recognized the importance of eliminating air from the syringe before injecting the blood and also the necessity of performing the transfusion quickly, before the blood had a chance to clot. Survival was a hit or miss affair, and Blundell’s first four patients died, not only because they were in a weakened state already but because the well-meaning physician had no knowledge of blood typing or modern anticlotting agents (like heparin). The use of crude, nonsterilized tools only added to the problem.

  In 1901, Dr. Carl Landsteiner, an Austrian pathologist, revolutionized the ground rules for blood transfusion after discovering the ABO blood groups.†66 Simply put, red blood cells (like the foreign microorganisms we saw earlier) have specific surface proteins (antigens) embedded in their cell walls. During transfusions, if the surface proteins on the donor’s red blood cells are different from those of the recipient (e.g., antigen A as opposed to antigen B), then the erythrocytes in the donated blood will be attacked by leukocytes (or antibodies) circulating in the recipient’s blood. This attack by the recipient’s immune system kills the donated erythrocytes through a process called hemolysis—literally, “blood cutting” (a process that resulted in the coal black urine seen in the unfortunate Antoine Mauroy). It also leads to a dangerous form of erythrocyte clumping called agglutination, which can clog small blood vessels, sometimes leading to serious medical problems like strokes.

  Basically, then, any human-to-human transfusions performed before the discovery of ABO typing were really just crapshoots. And animal-to-human transfusions (as well as transfusions of alcoholic beverages like wine and beer)—they were just plain weird.

  On a related note about blood typing, since erythrocytes in people with type O blood have neither A nor B antigens, in theory, their blood isn’t recognized as foreign by any recipient’s immune system (no matter what the recipient’s blood type may be). Because of this, those with type O blood are sometimes referred to as universal donors.

  Likewise, since people with type AB blood (a blood group discovered by Landsteiner’s colleagues several yea
rs later) have both types of antigens, they can theoretically receive blood from any donor. As a result, people with type AB blood are known as universal recipients.

  Unfortunately, the labels universal donor and universal recipient are somewhat misleading since there are other antigens and antibodies in the blood besides those of the ABO system. In modern times, blood is carefully cross-matched and screened for pathogens and toxic substances before any transfusions take place.

  The work of Vesalius, Al-Nafis, and Harvey contributed to the less-than-timely discrediting of Hypocrites’ humoral system, but by the early twentieth century physicians and researchers knew that bacteria and other pathogenic organisms were the cause of most diseases. Drugs like aspirin appeared in the late nineteenth century and the first antibiotics followed some thirty years later. These new treatments rapidly replaced bloodletting as methods to combat many ailments and to reduce the discomfort from wounds, inflammation, and fever.

  Surprisingly, though (or not surprisingly, considering just how long the procedure was employed), therapeutic phlebotomy has shown a positive effect in alleviating some symptoms—especially those tied to elevated blood pressure or increased blood volume.

  For example, aneurysms occur when a weakened portion of an artery bulges outward like a blood-filled water balloon. As the heart beats, the aneurysm pulsates (like rhythmically squeezing a baseball-sized water balloon in your hand). In some instances, there is a warning—as the vessel walls stretch, pain receptors connected to the surface of the vessel are stimulated. Unfortunately, in most instances the aneurysm is painless and goes undetected. The real danger from an aneurysm is fairly obvious, and if this “water balloon” pops, the results can be deadly. Many strokes result from ruptured aneurysms in the brain and a burst aortic aneurysm can lead to massive hemorrhaging and death within a matter of minutes.