What is hypertrophy?

Process and Effects

The growth and development of the human body and all its parts requires not only an increase in the number of body cells as the body grows, a process known as hyperplasia, but also an increase in the size of the existing cells, a process known as hypertrophy. It is true that as humans grow, they increase the number of cells in their bodies, resulting in an 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.

The process of hypertrophy 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. Among such tissues are adipose tissue, which is composed of fat cells, and nervous tissue, which is found in the brain, in the spinal cord, and in skeletal muscle tissue. Other tissues, such as cardiac tissue and smooth muscle tissue, also show the ability to undergo hypertrophy.

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 the fat cells. An increase in the amount of fat consumed in the diet increases the amount of fat that is placed inside a fat cell, resulting in an increase in the fat cell’s size.

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, there is an increase in the number of mitochondria within the cell, 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 individual skeletal muscle cell hypertrophy. This increase in the diameter of the individual muscle cells is brought about by increases in the amounts of the contractile proteins, myosin and actin, as well as increases in 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. Some tissues, however, are capable of increasing in size as the result of an increased load or demand being placed upon them. This increased load or demand is usually brought about by an increased use of the muscle. This increase in the size of cells in response to an increased demand or use is called compensatory hypertrophy. The most common tissues that show the phenomenon of compensatory hypertrophy are the skeletal, cardiac, and smooth muscles.

Skeletal muscle is particularly responsive to being utilized. This response, however, is dependent upon the way in which the skeletal muscle is used. It is well known that an increase in the size of skeletal muscle can be brought about by such exercises as weight lifting. Lifting heavy weights or objects requires strong contractions of the skeletal muscle that is doing the lifting. If this lifting continues over a long period of time, it eventually results in an increase in the size of the existing muscle fibers, leading to an increase in the size of the exercised muscle. Because the strength of a muscle is dependent upon its size, the increase in the muscle’s size results in an increase in its strength. The extent to which the size of the muscle increases is dependent upon the amount of time spent lifting the objects and the weight of the objects. The size that a muscle can reach is, however, limited.

Unlike exercises such as weight lifting, endurance types of exercise, such as walking, jogging, and aerobics, do not result in larger skeletal muscles. These types of exercise do not force 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 referred to as muscle atrophy. This type of atrophy commonly occurs when limbs are broken or injured and must be immobilized. After six weeks of the limb being immobilized, there is 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 against which the muscles must work. If the muscles remain unused for more than a few months, there can be a loss of about one-half of the muscle mass of the unused muscle.

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 an increased size of the heart because of the hypertrophy of the existing cardiac muscle cells in this organ. In fact, the heart mass of marathon runners enlarges by about 40 percent as a result of the increase in 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 forms of exercise result in the hypertrophy of the cardiac muscle. Weight lifting, which causes hypertrophy of skeletal muscle, 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. This in turn causes a thickening of the arterial wall. Smooth muscle, however, 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 the blood throughout the body. In response to the increased workload, the heart increases its size, 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. The valves of the heart 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 the 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, however, 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 and does 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 of the heart.

High blood pressure, also known as hypertension, may also lead to hypertrophy of the ventricles of the heart. With high blood pressure, the heart must work harder to deliver blood throughout the body because it must pump blood against an increased pressure. As a result of the increased demand upon the heart, the heart 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, an extreme hypertrophy sometimes leads to heart failure. One of the reasons this may occur is the inability of the blood supply of the heart to keep up with the growth of the cardiac muscle. As a result, 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, like cardiac 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 high blood pressure may cause the hypertrophy of the smooth muscles within the walls of the arteries and arterioles. This increases the thickness of the walls of the arteries and arterioles but also decreases the size of the hollow spaces within those vessels, which are known as the lumina. 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.

Smooth muscle may also hypertrophy under some unique conditions. During pregnancy, the uterus will undergo a dramatic hypertrophy. The uterus is a smooth muscle organ that is involved in the housing and nurturing of the developing fetus during pregnancy. Immediately prior to the birth of the fetus, there is marked hypertrophy of the smooth muscle within this organ. This increase in the size of the uterus is beneficial in providing the strong contractions of this organ 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 a larger muscle mass than do females. Furthermore, synthetic testosterone-like hormones have been used by some athletes to increase muscle size. These synthetic hormones are called
anabolic steroids. The use of these steroids does result in the hypertrophy of skeletal muscle, but these steroids have been shown to have harmful side effects.

Obesity is another condition that results largely from the hypertrophy of existing fat cells. In children, however, obesity is thought to result not only from an increase in the size of fat cells but also from an increase in their number. In adults, when weight is lost, it is the result of 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 a hypertrophy of the affected muscles. This hypertrophy differs from other forms of muscle hypertrophy in that the muscle cells do not increase in size because of an increase in the contractile protein, mitochondria, or glycogen, but because the muscle cells are being filled with fat. As a result of the contractile protein being replaced with fat, 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, however, the hypertrophy of many tissues is thought to be under the control of blood-borne chemicals known as hormones. Among these hormones is one that promotes growth and is thus called
growth hormone. Growth hormone brings about an increase in the number and size of cells. Growth hormone causes the hypertrophy of existing cells by increasing the protein-making capability of these cells. Thus, there is an increase in the number of organelles, such as mitochondria, within the cell, which leads to an increase in cell size.

Growth hormone 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. Nerve growth factor is involved with the increase in 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 in the treatment of 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 as a result of 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, such as that which occurs in skeletal, smooth, and cardiac muscle, 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. American astronauts and Russian cosmonauts, however, showed a loss in muscle mass 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 necessitated by the injury of limbs. Furthermore, the understanding of the mechanisms that control hypertrophy may help to alleviate the effects of disabling diseases such as muscular dystrophy by reversing the effects of muscle atrophy.

Bibliography

Alan, Rick. "Muscular Dystrophy." MedlinePlus, September 20, 2011.

Guyton, Arthur C., and John E. Hall. Guyton and Hall Textbook of Medical Physiology. 12th ed. Philadelphia: Saunders/Elsevier, 2011.

"Is Cardiac Hypertrophy Compensatory or Harmful?" Medical Roundtable: Cardiovascular Edition 2, no. 3 (2011): 149–156.

Kronenberg, Henry M., et al., eds. Williams Textbook of Endocrinology. 11th ed. Philadelphia: Saunders/Elsevier, 2008.

Marieb, Elaine N., and Katja Hoehn. Human Anatomy and Physiology. 9th ed. San Francisco: Pearson/Benjamin Cummings, 2010.

"Muscle Atrophy." Health Library, February 5, 2012.

Shier, David N., Jackie L. Butler, and Ricki Lewis. Hole’s Essentials of Human Anatomy and Physiology. 10th ed. Boston: McGraw-Hill, 2009.

Shostak, Stanley. Embryology: An Introduction to Developmental Biology. New York: HarperCollins, 1991.

Tortora, Gerard J., and Bryan Derrickson. Principles of Anatomy and Physiology. 12th ed. Hoboken, N.J.: John Wiley & Sons, 2009.