Degenerative Diseases

Degenerative Diseases

The progressive deterioration or atrophy of tissue over time is the characteristic of a . Such conditions may be due to poor lifestyle choices, immune responses, genetic dis­eases, or just the wear and tear of time. Degenerative diseases also include those in which tissues change from a higher to a lower form, generally meaning a form that is less functionally active. Degenerative diseases are often contrasted with infectious diseases, diseases caused by pathogenic agents, including bacteria, viruses, and parasites. However, this comparison is not always straightforward, for infectious diseases often have degenerative symp­toms, as in the case of tuberculosis.

General Degenerations

Many types of degenerative diseases are not tissue specific, affecting many different tissue types in the body. One such disease is dystrophic degen­eration, in which the body as a whole degenerates as a result of poor nutrition. This is usually associ­ated with various psychological eating disorders such as anorexia nervosa and bulimia. The malnu­trition associated with these diseases may also lead to other degenerations, such as atrophic pulp , in which the pulpal cells in dental pulp degenerate. A classical systemic degeneration is senile degeneration, in which the age of the patient has caused bodily and mental degenera­tions, and the toll of time causes widespread changes. This includes the atrophy of muscles, declining sight (), dulling senses, a decrease in mental retention and abilities, and fibrous and atheromatous changes. Everyone experiences senile degeneration to some degree as they age and their muscles weaken through time; however, the rate of degeneration depends on many factors, including diet, exercise, familial history, and lifestyle.

The immune system also plays a large role in the degeneration of cells. Cloudy swelling degenera­tion occurs during the local inflammatory response of the immune system. Here, the cells take on water as the macrophages and fluids move to the offended site. This may also be called vacuolar degeneration, as the vacuoles tend to grow as well. If the injury has somehow affected the metabolism of the cell, this cloudy swelling degeneration may persist, but it generally goes away with time. A severe form of cloudy swelling degeneration is hydropic degeneration, in which water droplets can be visualized within the cell. This is also known as . Following the immune response, the body immediately begins the rebuilding process. The plasma protein fibrin migrates to the offended site and begins to aggre­gate to form a clot. This process is known as fibrous degeneration, or fibrosis. This is consid­ered a degenerative process, as a lower form of tissue is replacing a higher one. This fibrous tissue is what forms scars and is a normal part of the healing process. However, when fibrosis becomes excessive, it can lead to many problems within the body. For example, if fibrin is activated within the bloodstream, it may form a blood clot within the vessel, which may travel as an embolus to the heart, causing a myocardial infarction (heart attack), or to the brain, causing a cerebrovascular accident (stroke).

If tissue is not repaired, it can lead to death of the tissue, or necrosis. Necrosis is characterized by several different degenerations, including the afore­mentioned fibrous degeneration. Another type of necrotic degeneration is caseous degeneration, or caseation. The soft, cheesy appearance of the necrotic tissue characterized by this degeneration earned it the name of “cheesy degeneration” as well. This is a common degeneration found in the lungs of tuberculosis patients. Necrosis of striated muscle is known as Zenker’s degeneration, or waxy degeneration, in which the muscle cells die and take on a glassy appearance. This often is the result of a severe infection, such as typhoid fever.

Integumentary and Epithelial Degenerations

The skin, sweat glands, hair, nails, and the exter­nal covering of the body compose the integumen­tary system. The integumentary system is of course prone to senile degeneration like everything else, as the skin tends to become thinner and weaker, especially at the top layer, the epidermis. Epidermal atrophy has also been associated with lupus, hypo­thyroidism, and hyperadrenocorticism. Alopecia is the scientific name given to baldness. In certain types of alopecia, follicular degeneration occurs, in which hair follicles are destroyed and replaced with scar tissue. New hair cannot grow from these hair follicles, and hair growth is no longer observed. Colloid degeneration is when tissue is replaced by a gelatinous form. A common form of colloid degeneration is colloid milium, in which papules, or small hard elevations, are formed on the skin and give the appearance of amber acne. This dis­ease has been linked to prolonged sun exposure. Colloid degeneration is not limited to the integu­mentary system, and benign colloid tumors or growths can occur throughout the body, including the brain.

The epithelial system includes the inner lining of all internal organs, most notably the gastrointesti­nal and pulmonary systems. One degeneration common to all epithelial systems is mucinoid degen­eration; this includes mucous, mucinous, colloid, and myelinic degeneration. In mucous and muci­nous degeneration, mucous is abnormally deposited in epithelial tissues. Increased mucous deposits may form in response to irritants and infections. An increase of mucous deposits is also a characteristic of cystic fibrosis, a recessive genetic disorder that affects all endocrine and exocrine glands but affects the epithelial cells most profoundly. This mucous degeneration is also a characteristic of mucinous carcinoma, an aggressive tumor. Research has indi­cated that tumors comprised of 60% mucus or more tend to be more aggressive than other forms of cancer. Mucous tumors are also called colloid tumors. Myelinic degeneration is characterized by a deposition of myelin and lecithin, important sub­stances in the lining of the gastrointestinal tract. If this layer erodes, harmful stomach acids and enzymes may attack the intestinal wall, leading to infections and ulcers.

Muscular and Skeletal Degenerations

As a result of our evolutionary shift to bipeDalíity, our skeletal system, especially our spine, is highly prone to degeneration. Degenerative disc disease of the spinal column is a perfect example of this, in which the spongy disc of connective tissue between the vertebrae is injured. This degeneration is often caused by trauma to the disc, which can occur from something as seemingly harmless as lifting a box. It can also be the sum of many small traumas over time. This disease is also known as spondylo­sis. Because the discs have very limited blood flow, they generally have a difficult time repairing them­selves. Therefore, after the trauma, the discs dry out and lose their shock-absorbing capability. This can compress the nerve fibers radiating from the spinal column, causing a radial pain or numbness. These nerves may swell as part of an immune response, making the compression and pain even more severe. Surgery, most often a spinal fusion, is a frequent choice of treatment; this may be com­bined with physical therapy and anti-inflammatory medications. Experimental treatments are also available that attempt to rehydrate the discs; how­ever, many of these are still in the early stages of development.

Another very common degeneration of the skel­etal system is osteoporosis, in which the bone mineral density of the patient is significantly decreased. This disease is most common in post­menopausal women, but it also may be present in patients with chronic illnesses, especially hormonal disorders. This disease itself has no symptoms but is characterized by an increased risk in fragility fractures, fractures that would not occur in healthy patients. Fractures that reduce mobility, especially hip fractures, can lead to more threatening condi­tions, including deep vein thrombosis, pneumonia, and pulmonary embolism. This disorder can be treated with a combination of medications as well as an increase in vitamin D and calcium in the diet. Lifestyle changes that help to treat and prevent this disease include exercise and a reduction in tobacco smoking and alcohol consumption.

Degeneration in the muscles, or muscular atrophy, is a very common occurrence with age. However, muscular is a group of diseases charac­terized by severe muscular degeneration, regard­less of age. There are nine forms of and more than 100 diseases with simi­lar symptoms. Duchenne muscular dystrophy is the most common of these dystrophies and is inherited by means of the sex-linked X chromo­some. Duchenne muscular dystrophy and Becker’s muscular dystrophy, the two most common forms, occur due to a mutation in the gene that codes for dystrophin, which, as of 2007, has the longest coding segment of any known allele. Dystrophin is a cytoplasmic protein that forms a complex pivotal to muscle form and function. Without this protein in its fully functional form, muscle func­tion declines severely. Muscular dystrophy has no known cure, but physical therapy and orthopedic instruments may be helpful in treating the disease short term.

Gastrointestinal Degenerations

Many of the degenerative diseases of the gastroin­testinal system were included in the epithelial degenerations, including mucous and myelinic degeneration. However, some of the most debili­tating degenerative diseases of the gastrointestinal system are from abnormalities in the liver. The liver is responsible for the breakdown of fats into triglycerides, less complex substances that can be stored in the body. When this process is disrupted, it can lead to fatty degeneration of the liver, also known as steatosis. This condition is character­ized by fat droplets (mainly triglycerides accumu­lating within the cells) as they cannot be broken down and stored by the normal processes. This is also known as adipose degeneration. This disease is most commonly caused by chronic alcoholism, but it also may be caused by pregnancy, malnutri­tion, or poisoning. Fatty degeneration usually has no outward symptoms; internally the patient’s liver may grow to be up to three times the normal size, which may cause pain from crowding in the abdominal cavity. In more severe forms, the patient may appear jaundiced. This condition is generally reversible as long as the underlying problem, such as alcoholism, is corrected.

Hepatolenticular degeneration, or Wilson’s dis­ease, is characterized by a systemic accumulation of copper within the tissues. Patients with this autosomal recessive disease often initially present with liver problems at a young age (10-14 years) but may also have neurological symptoms as well. The mutant allele in Wilson’s disease prevents the normal excretion of copper in the bile, resulting in excessive buildup in the liver cells. This leads to chronic hepatitis and eventual cirrhosis and may even lead to complete liver failure. Once the liver cells are significantly damaged they release the copper into the bloodstream, which then affects the entire body, especially the heart and nervous system. Treatment of this disorder includes medi­cations such as trientine hydrochloride that remove copper from the tissues in combination with a diet low in copper and high in zinc and vitamin B6.

Genitourinary Degeneration

The deposits of uric acid throughout the body characterize uractic degeneration. This disorder is caused by the inability of the kidneys to regulate the amount of uric acid expelled in the urine. The uric acid is instead transported in the bloodstream and eventually forms crystals that deposit through­out the body, most commonly in the large toe. The condition is known as gout and is character­ized by intense joint pain and inflammation. High levels of uric acid can also result in one form of kidney stone as well. Treatments generally focus on treating the inflammatory response in the joints as well as pain management, but an increase of vitamin C in the patient’s diet as well as a reduced intake of purines help to lower the uric acid level in the bloodstream.

Degenerations in the uterus are very common in premenopausal women. One such degeneration is leiomyoma, which may be found in nearly 20% of all women. This degeneration is characterized by the formation of benign uterine growths or cysts in the smooth muscle of the uterus. Because estrogen and progesterone usually stimulate growth, leio­myomas tend to grow in size during pregnancy. Symptoms of this disorder include uterine bleed­ing, and if left untreated anemia and even infertil­ity may result. Oftentimes leiomyomas undergo further degenerations themselves. The most com­mon form of degeneration of leiomyomas is hya­line degeneration, in which the cyst takes on a glassy appearance. Other degenerations include mucous, fatty, cystic, and carneous or red degen­eration, in which the tissue loses blood flow and becomes necrotic. Laser removal of these cysts is becoming a safe and common treatment of this degeneration. These cysts can also grow in the intestine, small bowel, and esophagus.

Cardiovascular Degeneration

Fatty degeneration also has a large impact on the cardiovascular system as well. Deposits of fat and cholesterol along artery walls are known as ath­erosclerosis, which is a potentially lethal condi­tion. This condition is found in all patients to some degree, but large and numerous deposits become a major problem. If these deposits become too large, they may clog the vessel, preventing blood and nourishments from reaching all of the tissue the artery feeds. When this occurs it is known as an infarction, and if it occurs in the coronary arteries of the heart, it is known as a myocardial infarction, or heart attack. This deposit can also break off from the artery wall and travel, and an embolus may form, eventually blocking a new area of the vessel it reaches. Sometimes, the vessel may grow outward to allow blood flow past the deposit. However, this can result in an aneurysm or local dilation of the vessel wall, which may eventually rupture. Atherosclerosis is the most common underlying cause of heart dis­ease and stroke. Treatment may include widening the affected vessel by inserting a stent or bypass­ing it using the patient’s own vessels harvested from elsewhere in the body.

Calcium deposits may also contribute to arte­riosclerosis and have strong implications in valvu­lar diseases. Calcareous degeneration is any disease that is characterized by deposits of calcium in the tissues, the underlying cause of which may include problems with the parathyroid gland, which con­trols calcium concentration in the blood. Calcium is often deposited on plaque deposits in atheroscle­rosis, which helps to stabilize them within the ves­sel. This is known as Mönckeberg’s degeneration or a form of angiolithic degeneration, in which mineral deposits coat vessel walls. When calcium is deposited on any of the four valves in the heart, it may narrow the opening, resulting in a condition known as valvular stenosis. The symptoms of this vary according to the valve the calcium is depos­ited on. For example, in aortic stenosis, narrowing of the aortic valve, the left ventricle must work harder to pump blood through the narrow opening and is thus larger in size, or hypertrophied. As the muscle thickens it needs more and more blood flow, most of which it is already not receiving. If this is not corrected, the hypertrophied muscle may become ischemic, resulting in chest pain. Syncope, or fainting, is also a common symptom, as less blood is being distributed throughout the body due to a decrease in cardiac output. One of the most serious implications of aortic stenosis is the possibility of congestive heart failure, in which the backflow of blood can cause shortness of breath, dizziness, widespread swelling or edema, and eventual heart failure. Pulmonary valve steno­sis is characterized by a decrease in blood flow to the lungs. Patients have symptoms that are much less severe and may include hypertrophy of the right ventricle and cyanosis due to a decrease in oxygenated blood. Mitral stenosis by calcification is characterized by a decrease in blood flow between the left atrium and left ventricle. This results in a reduction in cardiac output and back­flow of blood that can result in congestive heart failure and pulmonary hypertension. To compen­sate for the decreased cardiac output, the patient’s heart rate may increase, a condition known as tachycardia, and may enter dangerous rhythms such as atrial fibrillation. Tricuspid stenosis usu­ally is caused by rheumatic fever and rarely caused by calcareous degeneration. The treatment of all valvular diseases includes medical management, balloon valvuloplasty (which expands the valve), or valve replacement. Valve replacements may include mechanical, homograft valves from cadav­ers or heterograft valves from animals such as pigs. Mechanical valves last the longest; however, the patient must be on blood thinners for the rest of his or her life to avoid clotting.

Nervous System

Degenerations of the nervous system, or neurode- generative diseases, are among the most wide­spread and the most debilitating. One of the best-known and most common degenerations of the nervous system is found in amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, which develops in 1 to 2 people per 100,000 every year. ALS is characterized by the degeneration of motor neurons, which facilitate voluntary muscle move­ment. The net result of this degeneration is general muscle weakness, difficulty with movement (ataxia), muscle twitches (fasciculations), and an ultimate loss of voluntary movement (except for the eyes). Most patients ultimately die of respira­tory failure due to an inability to breathe without the assistance of a ventilator. The majority of ALS patients (90%-95%) develop the disease sporadi­cally or idiopathically, with no known cause. The remainder of the ALS patients show a genetic basis to the development of this disease. There is no known cure for ALS, although a new drug, Riluzole, was recently approved to slow the degeneration of motor neurons.

Another common and well-known neurodegen- erative disease is Parkinson’s disease, which is characterized by the degeneration of dopamine- secreting cells in the brain. This greatly affects motor control and results in tremors, rigidity, slowness in movement (bradykinesia), and pos­tural instability or a difficulty with balance, among many other symptoms. Cognition is affected as well and may ultimately lead to dementia as the disease progresses. The majority of all individuals with Parkinson’s disease develop the disorder idio- pathically with no known cause. A very small number have shown a genetic basis to this disease. Most treatments focus on drugs that replace the lost dopamine in the patients. However, generally only 1% to 5% of the drug given produces the desired effect on the target area of the brain, with the rest being metabolized throughout the body, creating adverse side effects. Also, due to feedback loops, these treatments actually further the degen­eration of dopamine-secreting cells, which are no longer needed due to the replacement therapy. Other treatments include dopamine agonist drugs and monoamine oxidase B inhibitors, which inhibit the breakdown of dopamine. Many treatments focus on treating the symptoms; these treatments include speech therapy, physical therapy, and deep brain stimulation, which acts as a “brain pace­maker,” reducing tremors. Currently there is no known cure for Parkinson’s disease.

Alzheimer’s disease is also a very common neu- rodegenerative disorder and is the leading cause of dementia worldwide. This disease is characterized by a progressive loss of cognitive ability, including mood and behavioral changes, loss of language organization, and ultimately dementia. Plaques of amyloid beta, a misfolded peptide form within the brain, along with Alzheimer’s neurofibrillary degeneration, in which protein aggregates form in neurons of the brain. This disease is also idiopathic in origin; however, early-onset Alzheimer’s disease (before 65 years of age) has shown a genetic link. There is no known cure for Alzheimer’s disease, and most patients die within 7 to 10 years after the onset of the first symptoms. As of 2004, Alzheimer’s disease was the seventh leading cause of death in the United States. Treatments generally focus on treating the symptoms socially and include occu­pational and lifestyle therapies as well as psycho­social interventions. Other treatments, such as acetylcholinesterase inhibitors and ginkgo biloba supplements have shown to slow the progression of the disease, but they do not reverse its effects and do not slow it completely.

Special Senses

The loss of the special senses—taste, smell, hearing, and sight—is a normal part of aging. The number and sensitivity of taste buds on the tongue decrease over time from normal wear and tear. Thousands of tiny hairs within the cochlea of the ear are damaged over time, decreasing hearing sensitivity. However, these special senses also may degenerate prema­turely, secondary to other disorders, especially those that affect nerve function, including the aforemen­tioned Parkinson’s disease and Alzheimer’s disease, both of which affect smell, taste, and hearing.

Macular degeneration is characterized by the degeneration of the macula area of the retina and is the leading cause of blindness in the United States in patients over 50 years of age. In macular degen­eration, yellow deposits called drusen form between the retinal pigment epithelium and choroid. This leads to atrophy of the retinal pigment epithelium resulting in a loss of photoreceptors in the offended area, generally the center of the eye. This is known as the “dry” form of macular degeneration. The “wet” form is caused by the formation of a small blood vessel within Bruch’s membrane, the inner­most layer of the choroid. This leads to blood leak­age and scarring near the macula, destroying the photoreceptors, resulting in vision loss. Macular degeneration that forms at a young age (juvenile macular degeneration) is usually genetically linked and is found in many forms, including Best’s disease (congenital macular degeneration), Doyne’s honey­comb retinal dystrophy (Doyne’s honeycomb degen­eration), Sorsby’s disease, and Stargardt’s disease (Stargardt’s macular degeneration). Treatments focus on slowing the progression of vision loss and incidence in high-risk patients and include dietary changes, drugs that reduce cholesterol, and, in indi­viduals with wet macular degeneration, drugs that reduce the formation of new blood vessels.

The sheer number of degenerative diseases is con­siderable; volumes could be filled classifying and discussing the various degenerative diseases, as only the most common were briefly discussed in this entry. As modern progresses, it is hoped that treatments will be discovered for many of these conditions. However, short of discovering the Fountain of Youth, with the passage of time all of us remain subject to the effects of aging.

Christopher D. Czaplicki

See also DNA; Dying and Death; Gerontology; Longevity

Further Readings

Huether, S. E., & McCance, K. L. (2000). Understanding pathophysiology (2nd ed.). St. Louis, MO: Mosby.

Lewis, M. A., & Tamparo, C. D. (2000). Diseases of the human body (3rd ed.). Philadelphia: Davis.

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