NO WONDER the ancients called it the liver—so many of our life processes are involved in its activities. You could live only a few hours if it were removed. Its three pounds of intricate cellular mechanisms serve as the primary depot, processing plant, and distribution center for almost everything that enters the body through the digestive tract. Products of digestion along with other sub stances are absorbed into the blood and carried into the liver, where they are slowly filtered among the liver cells. Here nutrients and other materials are removed, transformed by chemical reactions, sometimes stored, and then re leased into the general blood circulation. Glucose, for example, is converted into glycogen and stored, to be converted back into glucose as the body requires; amino acids are made into proteins and other nitrogen-containing compounds. And drugs and other toxic substances are detoxified.
Although its cells are merely microscopic dots in size, they do so many things at the same time that one can only gaze in awe. You might want to describe their abilities as incredible. Perhaps miraculous would be a better word.
Because of its diverse activities, a single cell could be described as (1) ware house—it stores many valuable nutrients, such as glycogen (animal starch), iron, and certain vitamins; (2) factory— it manufactures many chemical com pounds used by the body in resisting dis ease, coagulating the blood, and trans porting fat; (3) power plant—it produces considerable heat as it converts and breaks down chemical compounds; (4) waste disposal plant—it excretes bile pigments, urea, and various detoxification products. It is this last function, that of altering the chemical make-up of toxic materials so that they are rendered harmless to body tissues, that we wish particularly to look at in this article.
The way a given drug affects your body depends on its effectiveness in producing a response and the length of time it is present in sufficient concentration to be effective. This is determined to a great degree by the rate at which it is metabolized or broken down by the body tissues. If nothing happened to a drug after it entered the body and reached the tissue or organ for which it was given (called the target organ of the drug) it might continue to act on the body indefinitely. This could easily be harmful. Fortunately, something does happen: most drugs are transformed into inert (inactive) substances and excreted through the kidneys. Some drugs are changed chemically in the intestine, some in the skin, kidney, or lung. But by far the greatest amount of these chemical changes (biotransformations) occur in the liver, which not only inactivates drugs but also most of the foreign chemicals to which the body is exposed.
Thus the liver is important not only in determining the effectiveness of a drug taken to assist the body in recovering from illness but also in defending the body against an array of potentially toxic chemicals in our environment— insect, rodent, and weed poisons; food preservatives, dyes, and assorted additives; a number of materials that are suspected of causing the development of cancer.
The liver accomplishes its task of chemically altering drugs and other foreign substances by several remark able enzyme systems (enzymes are organic molecules that accelerate chemical reactions). These organized enzyme groups can metabolize a wide variety of structurally unrelated chemicals. Drugs, toxic agents, and environmental pollutants gain entrance into the body primarily through the intestine, but also through the skin and lungs.
The enzyme systems are attached to membranes that fill the interior of the liver cells. This interconnected network of tube or bladderlike structures (collectively called the endoplasmic reticulum) are found in the fluid portion of most animal cells. There are two kinds of endoplasmic reticulum, smooth and rough, and they differ in function as well as in appearance. The rough membranes are covered with small granulelike attachments called ribosomes, which are the sites at which amino acids are joined together in unique sequences to form the particular proteins required by the human (or animal) for normal function. The smooth membranes lack these ribosomes. In the liver a major function of both kinds of membranes is to assemble the groups of enzymes required to chemically change drugs and other foreign substances, and then to provide the site where such reactions are carried out.
There are relatively few kinds of chemical reactions carried out by the liver cells on drugs and foreign com pounds. However, the effect of each is essentially the same: substances that are soluble only in fat (lypophilic) are changed into water soluble (hydrophilic) compounds. Water soluble sub stances are more readily removed from the blood by the kidneys and excreted in the urine.
The basic function of these liver cell enzyme systems is to chemically change substances normally produced in the body that might build up to concentrations potentially harmful if unchecked. Such substances include cholesterol, various hormones, blood pigments, and fatty acids. However, in our Creator's foresight these same protective systems are capable of coping with drugs and toxic pollutants.
It is commonly known that a new born infant is far more sensitive than an adult to many drugs. This is why physicians must exert caution in administering drugs to an expectant mother. Morphine (a narcotic) or barbiturates (seconal, nembutal, phenobarbital, et cetera) given to a woman during child birth can be stored in the baby's tissues and result, after birth, in slowed breathing or even death. Thus it appears that the ability of the body to withstand the harmful effects of drugs requires a period of time to develop after birth. For example, young mice treated with small doses of a hypnotic drug, hexobarbital, will sleep more than six times as long as an adult mouse given ten times the dose of the same drug.
Let's trace the path of a drug through the body, assuming it is one taken orally with a glass of water. It is absorbed through the intestinal wall and travels to the liver via blood. Some of the drug may be rendered inactive by the liver cells. The portion of the drug that re mains active enters the general circulation and has an effect on the target organ. It eventually returns via the blood stream to the liver, where more of the drug will be converted into an inert material. This cycle may be repeated many times until the effective drug has been completely eliminated by the action of liver cell enzymes. The inactive material may be carried by the bile into the intestines for excretion or removed from the blood stream and excreted by the kidneys into the urine.
Humans vary markedly in their response to various drugs and combinations of drugs. Then, too, there is the problem that in certain combinations of drugs unpredictable and often undesirable effects occur. One drug may inhibit or stimulate the action of liver enzymes on another drug. Or it may compete with it so that excessive concentrations of one of the drugs remain in the body.
Research studies, using animals, have shown that a class of insecticides that includes DDT stimulates the liver cell enzyme destruction of drugs and natural sex hormones. At the level of DDT equivalent to that commonly found in humans the effect of the sleep-inducing drug pentobarbital was decreased.
And what about the numerous other chemicals to which we are daily exposed? Many of these have been identified as chemical carcinogens; that is, they cause cancerous growths when administered to laboratory animals. It seems safe to assume that any factor that might inhibit or enhance the action of the liver cells on such substances may affect the development of cancers in humans. Among the most widespread carcinogens are the polycyclic aromatic hydrocarbons, which include benzopyrene. They are present in tobacco smoke, in char coal-broiled and smoked foods, and in polluted city air. The particular liver cell enzyme system that acts on these compounds sometimes does a strange thing. Rather than render them harm less it appears to make some of them more toxic. It will be interesting to see what role this reaction may play in the development of human cancer. Even without experimental confirmation, it is reasonable to assume that by avoiding exposure to such environmental hazards we may decrease our risk of serious illness.
Excuse the pun, but "long livers have healthy livers," and as we provide our livers the best possible environment in which to carry out their work, they will serve us faithfully.
