Hypertrophy

Biology

Anatomy or system affected: All

Definition: The growth of a tissue or organ as the result of an increase in the size of the existing cells within that tissue or organ; the process responsible for the growth of the body as well as for increases in organ size caused by increased workloads on particular organs

Process and Effects

The growth and development of the human body and all its parts require not only an increase in the number of body cells as the body grows but also an increase in the size of the existing cells. It is true that as humans grow, the number of cells in their bodies increases, resulting in a corresponding increase in the size of tissues, organs, systems, and the body. For some tissues, organs, and systems, however, the number of cells is genetically set; therefore, the number of cells will increase minimally, if at all, after birth. Thus, if growth is to occur in those tissues, organs, and systems, it must take place by means of an increase in the size of the existing cells.

This increase in cell size occurs in nearly all tissues in the body but is most common in those tissues in which the number of cells is set at the time of birth. Such tissues include adipose tissue, which is composed of adipose (fat) cells, and nervous tissue, which is found in the brain, the spinal cord, and skeletal muscle tissue. Other tissues, such as cardiac tissue and smooth muscle tissue, also show the ability to increase cell size.

It is generally true that the number of fat cells within the human body is set at birth. Therefore, an increase in body fat is thought to result primarily from an increase in the amount of fat stored within these cells. Increasing the amount of fat consumed in the diet results in more fat being stored inside each fat cell and, thus an increase in the size of each cell.

The number of nerve cells within the brain and spinal cord also is set at birth. The cerebellum of the human brain, however, increases in size about twentyfold from birth to adulthood. This increase is brought about by an increase in the size of the existing nerve cells, and particularly by an increase in the number of extensions protruding from each nerve cell and the length to which the extensions grow. Furthermore, there is an increase in the number of the components within the cell, specifically the number of mitochondria, which provide a usable form of energy so that the cell can grow.

The number of skeletal muscle cells is also, in general, preset at the time of birth. The skeletal muscle mass of the human body increases dramatically from birth to adulthood. This increase is accomplished primarily by means of the growth of individual skeletal muscle cells, brought about by increases in the amounts of the contractile proteins, myosin and actin, as well as the amount of glycogen and the number of mitochondria within individual cells. As each muscle cell increases in size, it causes an increase in the size of the entire muscle of which it is a part.

Each of the above-mentioned examples occurs naturally as part of the growth process of the human body. However, when the increase in cell size is abnormal or excessive, the phenomenon is known as hypertrophy. (The corresponding abnormal or excessive increase in the number of cells is called hyperplasia.) Some tissues are capable of increasing in size as a result of an increased load or demand being placed on them. Such growth in response to greater demand or use is called compensatory hypertrophy. The tissues that most commonly exhibit compensatory hypertrophy are the skeletal, cardiac, and smooth muscles.

Skeletal muscle is particularly responsive to being utilized, although this response is dependent on how the muscle is used. It is well known that an increase in the size of skeletal muscle can be brought about by exercises such as weight lifting. Lifting heavy objects requires strong contractions of the skeletal muscle that is doing the lifting. Repeated weight lifting over a long period of time will eventually result in the growth of the existing muscle fibers, leading to a corresponding increase in the size of the overall muscle. Because the strength of a muscle is a function of its size, this also results in an increase in the muscle's strength. The extent of muscle growth depends on the amount of time spent lifting the objects and the weight of the objects. However, the size that a muscle can achieve is ultimately limited.

Unlike exercises such as weight lifting, endurance-based forms of exercise, such as walking, jogging, and aerobics, do not result in larger skeletal muscles. These types of exercise do not cause the skeletal muscles to contract forcibly enough to produce muscle hypertrophy.

In the same way that an increased load or use will cause compensatory hypertrophy in skeletal muscle, a decreased use of skeletal muscle will result in its shrinking or wasting away. This process is called atrophy. Muscle atrophy commonly occurs when a limb is broken or injured and must be immobilized; after six weeks of immobilization, the limb shows a marked decrease in muscle size. A similar type of atrophy occurs in the limb muscles of astronauts since there is no gravity present in space to provide resistance for the muscles to work against. If the muscles remain unused for more than a few months, about one-half of the unused muscle mass may be lost.

Cardiac muscle, like skeletal muscle, can also be caused to hypertrophy by increasing the resistance against which it works. Although endurance exercise does not cause hypertrophy in skeletal muscle, it does result in hypertrophy of the existing cardiac muscle cells. In fact, the heart mass of marathon runners increases by about 40 percent as a result of endurance training. This increase occurs because the heart must work harder to pump more blood to the rest of the body when the body is endurance exercising. Only endurance-based exercises result in cardiac muscle hypertrophy. Weight lifting has no effect on the cardiac muscle.

Smooth muscle also is capable of compensatory hypertrophy. Increased pressure or loads on the smooth muscle within arteries can result in the hypertrophy of the muscle cells, which in turn causes a thickening of the arterial wall. Smooth muscle, unlike skeletal and cardiac muscle, is capable of hyperplasia as well as hypertrophy.

Complications and Disorders

Hypertrophy also occurs as a result of some pathological and abnormal conditions. The most common pathological hypertrophy is enlargement of the heart as a result of cardiovascular disease. Most cardiovascular diseases put an increased workload on the heart, making it work harder to pump blood throughout the body. In response to the increased workload, the heart undergoes a form of compensatory hypertrophy.

The left ventricle of the heart is capable of hypertrophying to such an extent that its muscle mass may increase four- or fivefold. This increase is the result of improper functioning of the valves of the left heart. Heart valves work to prevent the backflow of blood from one chamber to another or from the arteries back to the heart. If the valves in the left heart are not working properly, the left ventricle contracts and blood that should leave the ventricle to go out to the body instead returns to the left ventricle. The enlargement of the left ventricle increases the force with which it can pump blood out to the body, thus reducing the amount of blood that comes back to the left ventricle despite the damaged heart valves. There is a point at which the enlargement of the left ventricle can no longer help in keeping the needed amount of blood flowing through the body. At that point, the left ventricle finally tires out, and left heart failure occurs.

The same type of hypertrophy can occur in the right side of the heart as well. Again, this is the result of damaged valves that are supposed to prevent the backflow of blood into the heart. Should the valves of both sides of the heart be damaged, hypertrophy can occur on both sides.

High blood pressure, also known as hypertension, may also lead to hypertrophy of the ventricles. In cases of hypertension, the heart must work harder to deliver blood throughout the body because it is pumping blood against increased pressure. As a result of the increased demand on the heart, the cardiac muscle hypertrophies in order to pump more blood.

The hypertrophy of the heart muscle is beneficial in the pumping of blood to the body in individuals who have valvular disease and hypertension; however, extreme hypertrophy sometimes leads to heart failure. One reason this may occur is the inability of the heart's blood supply to keep up with the growth of the cardiac muscle. The cardiac cells outgrow their blood supply, resulting in the loss of blood and, thus a loss of oxygen and nutrients needed for the cardiac cells to survive.

Smooth muscle may also hypertrophy under the condition of high blood pressure. Smooth muscle makes up the bulk of many of the arteries and smaller arterioles found in the body. The increased pressure on the arterial walls as a result of hypertension may cause these smooth muscles to hypertrophy. This increases the thickness of the artery and arteriole walls, which in turn decreases the size of the hollow spaces (lumina) within those vessels. In the kidneys, the narrowing of the lumina of the arterioles may result in a decreased blood supply to these organs. The reduced blood flow to the kidneys may eventually cause the kidneys to shut down, leading to renal failure.

In addition, the smooth muscle of the uterus will undergo dramatic hypertrophy during pregnancy. The uterus is a smooth-muscle organ that is involved in the housing and nurturing of a developing fetus. Immediately prior to the birth of the fetus, there is marked hypertrophy of the smooth muscle within this organ. This hypertrophy is beneficial in providing the strong uterine contractions that are needed for childbirth.

Skeletal muscle also may be caused to hypertrophy in some diseases in which there is an increase in the secretion of male sex hormones, particularly testosterone. Men’s higher levels of testosterone, a potent stimulator of muscle growth, are responsible for the fact that males have greater muscle mass than do females. Furthermore, synthetic testosterone-like hormones, called anabolic steroids, have been used by some athletes to increase muscle size. While the use of anabolic steroids does result in the hypertrophy of skeletal muscle, it has also been shown to have harmful side effects.

Obesity is a condition that results largely from the hypertrophy of existing fat cells. However, childhood obesity is thought to result not only from an increase in the size of fat cells but also from an increase in their number. When an adult loses weight, it is due to a decrease in the size of the existing fat cells; the number of fat cells remains constant. Thus, it is important to prevent further weight increases in overweight children to prevent the creation of fat cells that will never be lost.

In the onset of diseases that result in muscle degeneration, such as muscular dystrophy, there is hypertrophy of the affected muscles. This hypertrophy differs from other forms of muscle hypertrophy in that the muscle cells grow not because of an increase in their contractile protein, mitochondria, or glycogen but because the contractile protein in them is being replaced with fat. As a result, the affected muscles are no longer useful.

Perspective and Prospects

The exact mechanisms that bring about and control the hypertrophy of cells and tissues are not well understood. During the growth and developmental periods, cell growth in many tissues is thought to be controlled by blood-borne chemicals known as hormones. Among these hormones is one that promotes growth and is thus called growth hormone (or, in humans, human growth hormone). Growth hormone (GH) brings about an increase in the number and size of cells and also causes existing cells to grow by increasing their protein-making capability.

GH also causes the release of chemicals known as growth factors. There are several different growth factors, but one of particular importance is nerve growth factor, which is involved in increasing the number of cell processes of single nerve cells. Such chemicals have been shown to enhance the growth of damaged nerve cells in the brains of animals. As a result, it is possible that nerve growth factor could be used to treat nerve damage in humans by causing the nerves to grow new cell processes and form new connections to replace those that were damaged. This may be of great importance for the treatment of those suffering from brain or spinal cord damage.

Other hormones may have similar effects on tissues other than nervous tissue. For example, the hypertrophy of the smooth muscle in the uterus is thought to be brought about hormonally. Immediately prior to birth, when the hypertrophy of the uterus is occurring, there is an increased amount of estrogen, the primary female hormone, in the blood. It is this increase in estrogen that is thought to lead to the great enlargement of the uterus during this time. Some hormones have the effect of preventing or inhibiting the hypertrophy of body tissues. The enlargement of the uterus prior to birth is brought about not only by an increase in estrogen but also by a decrease in another hormone known as progesterone. Progesterone levels are high in the blood throughout pregnancy. Immediately prior to birth, however, there is a dramatic decrease in the level of progesterone in the blood. Thus, it is believed that the high level of progesterone prevents or inhibits the hypertrophy of the smooth muscle cells in the uterus since the hypertrophy of this organ will not occur until estrogen levels are high and progesterone levels are low.

It has been suggested that compensatory hypertrophy occurs as a result of the stretching of muscle. Some studies have shown that the stretching of skeletal, cardiac, and smooth muscle does lead to hypertrophy. However, American astronauts and Russian cosmonauts showed a loss in muscle mass after returning from space flights even though they exercised and stretched their muscles as much as three hours per day, seven days per week. This suggests that mechanisms other than the stretching of muscles may be involved in compensatory muscle hypertrophy.

Through an understanding of the mechanisms involved in muscle hypertrophy, it may one day be possible to prevent the atrophy that occurs during space flights, prolonged bed rest, and immobilization due to injury. Furthermore, the understanding of the mechanisms that control hypertrophy may help alleviate the effects of disabling diseases such as muscular dystrophy by reversing the effects of muscle atrophy.

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