Collagen Vascular Diseases

What are Collagen Vascular Diseases?

What Happens When People Have Collagen Vascular Diseases?

Living with Collagen Vascular Diseases

Resources

Collagen vascular diseases are a diverse group of diseases in which the body reacts against its own tissues, often causing joint pain and inflammation, fever, rash, fatigue, and difficulty swallowing.

KEYWORDS

for searching the Internet and other reference sources

Autoimmunity

Dermatomyositis

Inflammation

Lupus

Polyarteritis nodosa

Polymyositis

Rheumatology

Scleroderma

Sjögren’s syndrome

Collagen vascular diseases have been recognized for a long time. Rheumatoid arthritis is a chronic inflammatory* disease that causes stiffness in the joints (places where bones meet), and can lead to disfigurement. It is an ancient disease; bone changes showing this condition have been identified in skeletons thousands of years old. Systemic lupus erythematosus (er-i-thee-ma-TO-sis), which affects multiple organs and tissues throughout the body, was first described in 1828.

* inflammation

is the body’s reaction to irritation, infection, or injury that often involves swelling, pain, redness, and warmth.

What are Collagen Vascular Diseases?

Collagen vascular diseases, sometimes called connective tissue diseases (CTDs) or autoimmune diseases, cover a wide array of disorders in which the body’s natural immune or self-protection system fails to recognize its own tissues and goes on attack against itself. Some of these diseases limit their damage to a single organ, and others spread problems throughout the body.

Immune responses to foreign bodies

In a healthy immune system, antigens (foreign bodies such as viruses and bacteria) are recognized as different from regular body tissues. When an antigen enters the bloodstream, it triggers the production of antibodies, substances that attack the alien substance. Lymphocytes (LIM-fo-sites) and leukocytes (LOO-ko-sites) are the special white blood cells responsible for creating these antibodies.

Lymphocytes include two subtypes (T cells and B cells), which have the unique ability to recognize the invading alien and alert the immune system to destroy it. The process is highly specialized: different lymphocytes recognize specific antigens and produce antibodies against only that particular antigen.

Autoimmune responses

In collagen vascular diseases, this immune system malfunctions. Rather than responding to foreign antigens, the body produces antibodies (autoantibodies) against its own antigens and normal proteins. Researchers do not understand what gets this autoimmune process started, but they have a fairly good idea of how it proceeds once it begins.

Systemic lupus erythematosus (SLE)

People with lupus develop antibodies to their own nucleic (noo-KLAY-ic) acids* and cell structures,

including those in the heart, kidneys, and joints. As a result of a faulty interaction between lymphocyte B and T cells, the cells fail to identify a protein as normal, mistake it for a foreign antigen, and then move on to produce autoantibodies called antinuclear antibodies. These antinuclear antibodies attack the nucleus and DNA (genetic material) in healthy cells. Immune complexes are the result of this mistaken battle. When they accumulate in the kidney, blood vessels, joints, and other sites, they cause inflammation and tissue damage.

* nucleic acids

are the cell structures that transfer genetic information: DNA (deoxyribonucleic acid) transfers information to RNA (ribonucleic acid), which leads to the production of body proteins.

Rheumatoid arthritis

In rheumatoid arthritis, the autoimmune process begins in connective tissue and the cushiony membranes that surround joints and the ends of bones. Collagen (KOL-a-jen) is the tough glue-like protein that gives joints their support and flexibility, and it represents 30 percent of the body’s protein. Rheumatoid arthritis is thought to begin when T cells mistake the body’s own collagen cells for foreign antigens and alert B cells to produce antibodies to fight the invader. The leukocytes rush in and produce cytokines (SY-to-kines), small proteins that are essential in healing the body but that cause serious damage in large doses. The inflammation and joint damage that result can lead to joint deformities and can spread throughout the body, wherever there is connective tissue.

Causes

Researchers are studying the causes of autoimmune diseases. Some autoimmune diseases have strong genetic components and may be passed down from parents to children. Environmental factors may act to trigger these diseases in some way. Fatigue, stress, and higher levels of certain antibodies also may lead to these diseases. Even ultraviolet rays of sunlight have been suggested as possible contributing causes. Collagen vascular diseases are not contagious; people cannot catch these diseases from one another.

What Happens When People Have Collagen Vascular Diseases?

Symptoms Symptoms differ depending on the illness, but they often include joint pain, fever, rash, recurrent infections, fatigue, mouth ulcers, dry mouth and dry eyes, hair loss, difficulty swallowing, swollen glands, or fingers and toes that get overly cold when exposed to cooler temperatures. In addition to systemic lupus erythematosus and rheumatoid arthritis, collagen vascular diseases include:

• Scleroderma: This progressive and systemic sclerosis (skle-RO-sis) causes skin to thicken and tough fibrous tissue to form in the internal organs of the digestive tract, kidneys, heart, and lungs.
• Sjögren’s syndrome: This causes dry mouth, dry eyes, and other symptoms.
• Polymyositis and dermatomyositis: These are inflammatory muscle disorders that may also affect the skin, the heart, and the lungs.
• Mixed connective tissue diseases: These combine features of lupus, scleroderma, and polymyositis.

• Polyarteritis nodosa: This disorder can damage small and medium-sized arteries of almost any organ, including the kidneys, heart, and intestines.

Diagnosis A complete medical history and a physical examination are the basis for the diagnosis of autoimmune disease. A number of laboratory tests can be used to help diagnose collagen vascular diseases. Blood tests can check levels of autoantibodies. Other tests include rheumatoid factor tests, urinalysis, blood counts, liver and kidney tests, and a sedimentation rate, which will give a nonspecific indicator of inflammation. A chest x-ray and other tests of specific lung function also may be done, since collagen vascular disorders occasionally produce breathing difficulties.

Treatment At present, there are no cures for autoimmune diseases, although some may go into remission as symptoms disappear for periods of time. Treatment depends on the extent of the disease. Doctors may prescribe steroid creams or anti-inflammatory medications to ease discomfort. In advanced cases, immunosuppressant drugs may help lessen the immune system’s over-reaction.

Living with Collagen Vascular Diseases

These serious diseases often require adjustments in activities of daily living. People with rheumatoid arthritis often have early morning stiffness that lasts for about an hour, after which they can go on about their day. Avoiding certain foods, and reducing physical and emotional stresses, also seem to reduce symptoms for some people.

See also

Arthritis

Fever

Hair Loss

Infection

Lupus

Resources

American Autoimmune Related Diseases Association, 15475 Gratiot Avenue, Detroit, MI 48205

Telephone 313-371-8600
http://www.aarda.org

Lupus Foundation of America, 1300 Piccard Drive, Suite 200,
Rockville, MD 20850-4303
Telephone 301-670-9292
http://www.lupus.org

Sjögren’s Syndrome Foundation, 333 North Broadway,
Jericho, NY 11753
Telephone 800-4-SJOGRENS
http://sjogrens.com

Scleroderma Foundation, 89 Newbury Street, Suite 201,
Danvers, MA 01923
Telephone 800-722-HOPE
http://www.scleroderma.org

Collagen Periurethral Injection

Definition
Purpose
Description
Aftercare
Risks
Normal results
Alternatives

Definition

Collagen periurethral injection is a procedure in which collagen is injected around the urethra and bladder neck as a treatment for stress incontinence in women.

Purpose

The bladder and urethra are supported by muscles, ligaments, and connective tissues around the base of the bladder. This support prevents the leakage of urine, along with the watertight seal provided by the urethra.

KEY TERMS

Anesthetic— A drug that causes unconsciousness or a loss of general sensation.

Bladder— A membranous sac that serves as a reservoir for urine. Contraction of the bladder results in urination.

Catheterization— The placement of a catheter in a specific anatomic area most commonly for the purpose of treatment or diagnosis.

Collagen— The protein substance of the white fibers (collagenous fibers) of skin, tendon, bone, cartilage, and all other connective tissue.

Cystoscope— An instrument that allows the doctor to see inside the bladder and remove tissue samples.

Epidural— Located within the spinal canal, on or outside the dura mater, the tough membrane surrounding the spinal cord.

Incontinence— The inability to control excretory functions, as defecation (fecal incontinence) or urination (urinary incontinence).

Periurethral— Surrounding the urethra.

Stress incontinence— Involuntary loss of urine that occurs during physical activity such as coughing, sneezing, laughing, or exercise.

Urethra— The tube that passes urine from the bladder to the outside.

As a result of pregnancy, childbirth, and aging, or damage by scarring from surgery or radiotherapy, these structures may become damaged or weakened, thus causing stress incontinence, meaning an involuntary loss of urine that occurs during physical activity such as coughing, sneezing, laughing, or exercise.

The injection of bulking agents, such as collagen, around the urethra aims to improve the lost support of the bladder and urethra. The substance most commonly used for injection is collagen; other bulking agents are being developed; for example, a silicon base suspended in a viscous gel called Macroplastique. Teflon paste, introduced in the 1970s, initially gave good results, but was discontinued after reported problems with excessive scarring and with the migration of Teflon particles to other tissues in the body. The collagen used in the procedure comes from the cartilage of cattle and has been extensively sterilized to produce a viscous paste for injection. There is no risk

WHO PERFORMS THE PROCEDURE AND WHERE IS IT PERFORMED?

Collagen periurethral injection is a procedure that is performed in a hospital or clinic on an outpatient basis by a surgeon.

of bovine spongiform encephalopathy (BSE) transmission because the processing of the paste destroys any bacterial or viral particles.

Description

The collagen periurethral injection procedure is quick, and usually over within 15-20 minutes. No incisions are made, meaning that it can be carried out using a local anesthetic or a regional anesthetic such as an epidural. The surgeon uses a fine fiber-optic cystoscope to examine the inside of the urethra and bladder, and then inserts a fine needle to inject the collagen. Usually three injections are made around the urethra. The exact amount of collagen used depends on how much closure the urethra requires.

Aftercare

Since the procedure is very short and there is little discomfort afterwards, it is performed on an outpatient basis, and women can go home the same day. Recovery from the operation is very quick.

Risks

Periurethral injection is not associated with major complications. Urinary tract infection is common in up to a fifth of the women having undergone the procedure, but is usually quickly and easily treated with antibiotics. Some women experience difficulty urinating immediately after the procedure, but this is not unexpected following an operation involving the bladder and urethra that may easily lead to swelling and bruising of the tissues. It is an uncommon problem after periurethral injection. The condition usually settles quickly, but may require catheterization. Long-term problems are very rare.

Normal results

Since periurethral injection is so quick and easy with very few complications, it would appear to be an ideal treatment for stress incontinence; however, there is a problem with the longer-term results. Within three

QUESTIONS TO ASK THE DOCTOR

• How is a collagen periurethral injection performed?
• Why is the collagen injection required?
• What are the risks of the procedure?
• Is the injection procedure painful?
• Are there alternatives?
• How long will it take for me to recover?
• What are the after-effects of the injection?
• How many collagen periurethral injections do you perform each year?

months after injection, good results are reported with at least 80% of women cured or improved. After two years, less than half of these women will still be cured. Longer-term studies are still being performed, but it is likely that positive results will continue to diminish. This is due to the injected collagen dispersing away from the urethra over time. Injections can be repeated and some women do require more than one injection before they are cured. Ongoing research into new injection substances may improve these results. The results in younger, physically active women are also less successful, usually lasting for a shorter time. Repeated injections are not a simple solution because collagen is very expensive and the long-term effects of repeated injections are unknown. Physicians prefer one of the alternative operations if long-term cure of stress incontinence is the aim.

Alternatives

Other treatments are available to treat incontinence. They include:

• Physiotherapy—this treatment aims to increase the strength and support provided by the pelvic floor muscles.
• Surgical procedures—operations such as colposuspension, sling procedures, needle-suspensions, and vaginal repair operations are all based on lifting and re-supporting the bladder and urethra.

Resources

BOOKS

American Medical Association. American Medical Association Family Medical Guide, 4th ed. Hoboken, NJ: Wiley & Sons, 2004.

Burgio, K. L., L. Pearce, A. J. Lucco, and K. F. Jeter. Staying Dry: A Practical Guide to Bladder Control. Baltimore: Johns Hopkins University Press, 1990.

Kaschak Newman, D. Managing and Treating Urinary Incontinence. Baltimore: Health Professions Press, 2002.

PERIODICALS

Block, C. A., C. S. Cooper, and C. E. Hawtrey. “Long-term Efficacy of Periurethral Collagen Injection for the Treatment of Urinary Incontinence Secondary to Myelomeningocele.” Journal of Urology 169 (January 2003): 327–329.

Culligan, P. J., et al. “The Safety of Reusing Injectable Collagen: A Multicenter Microbiological Study.” International Urogynecological Journal of Pelvic Floor Dysfunction 13 (2002): 232–234.

Dmochowski, R. R., and R. A. Appell. “Injectable Agents in the Treatment of Stress Urinary Incontinence in Women: Where Are We Now?” Urology 56 (December 2000): 32–40.

Kassouf, W., G. Capolicchio, G. Berardinucci, and J. Cor-cos. “Collagen Injection for Treatment of Urinary Incontinence in Children.” Journal of Urology 165 (May 2001): 1666–1668.

OTHER

National Women’s Health Information Center.http://www.womenshealth.gov/.

Rackley, Raymond. “Periurethral Injection Therapy for Incontinence.” eMedicine. June 29, 2006. www.emedicine.com/med/topic3049.htm.

“Stress Incontinence.” Medline Encyclopedia. May 15, 2006. www.nlm.nih.gov/medlineplus/ency/article/000891.htm.

ORGANIZATIONS

Office of Women’s Health, U.S. Food and Drug Administration, 5600 Fishers Lane, Rockville, MD, 20857, (301) 827-0350, http://www.fda.gov/womens/default.htm.

Monique Laberge, Ph.D.

Laura Jean Cataldo, R.N., Ed.D.

Colon anastomosis seeIleoanal anastomosis

Collagen periurethral injection

Definition

Collagen periurethral injection is a procedure in which collagen is injected around the urethra and bladder neck as a treatment for stress incontinence in women.

Purpose

The bladder and urethra are supported by muscles, ligaments, and connective tissues around the base of the bladder. This support prevents the leakage of urine, along with the watertight seal provided by the urethra. As a result of pregnancy, childbirth, and aging, or damage by scarring from surgery or radiotherapy, these structures may become damaged or weakened, thus causing stress incontinence, meaning an involuntary loss of urine that occurs during physical activity such as coughing, sneezing, laughing, or exercise .

The injection of bulking agents such as collagen around the urethra aims to improve the lost support of the bladder and urethra. The substance most commonly used for injection is collagen; other bulking agents are being developed, for example, a silicon base suspended in a viscous gel called Macroplastique. Teflon paste, introduced in the 1970s, initially gave good results, but was discontinued after reported problems with excessive scarring and with the migration of Teflon particles to other tissues in the body. The collagen used in the procedure comes from the cartilage of cattle and has been extensively sterilized to produce a viscous paste for injection. There is no risk of bovine spongiform encephalopathy (BSE) transmission because the processing of the paste destroys any bacterial or viral particles.

Description

The collagen periurethral injection procedure is quick, and usually over within 15–20 minutes. No incisions are made, meaning that it can be carried out using a local anesthetic or a regional anesthetic such as an epidural. The surgeon uses a fine fiber-optic cystoscope to examine the inside of the urethra and bladder, and then inserts a fine needle to inject the collagen. Usually three injections are made around the urethra. The exact amount of collagen used depends on how much closure the urethra requires.

Aftercare

Since the procedure is very short and there is little discomfort afterwards, it is performed on an outpatient basis, and women can go home the same day. Recovery from the operation is very quick.

Risks

Periurethral injection is not associated with major complications. Urinary tract infection is common in up to a fifth of the women having undergone the procedure, but is usually quickly and easily treated with antibiotics . Some women experience difficulty urinating immediately after the procedure, but this is not unexpected following an operation involving the bladder and urethra that may easily lead to swelling and bruising of the tissues. It is a relatively uncommon problem after periurethral injection, but may occur. The condition usually settles quickly, but may require catheterization. Long-term problems are very rare.

Normal results

Since periurethral injection is so quick and easy with very few complications, it would appear to be an ideal treatment for stress incontinence. However, there is a problem with the longer-term results. Within three months after injection, good results are reported with at least 80% of women cured or improved. However, after two years, less than half of these women will still be cured. Longer-term studies are still being performed, but it is likely that the results will keep becoming poorer as time goes by. This is due to the injected collagen dispersing away from the urethra over time. Injections can be repeated and some women do require more than one injection before they are cured. Ongoing research into newer injection substances may improve these results. The results in younger, physically active women are also less successful, usually lasting for a shorter time. Repeated injections are not the simple solution they may seem, because collagen is very expensive and the long-term effects of repeated injections are unknown. Physicians thus tend to prefer one of the alternative operations if long-term cure of stress incontinence is the aim.

Alternatives

Other treatments are available to treat incontinence. They include:

• Physiotherapy. This treatment aims to increase the strength and support provided by the pelvic floor muscles.
• Surgical procedures. Operations such as colposuspension, sling procedures, needle-suspensions, and vaginal repair operations are all based on lifting and re-supporting the bladder and urethra.

Resources

books

Burgio, K. L., L. Pearce, A. J. Lucco, and K. F. Jeter. Staying Dry: A Practical Guide to Bladder Control. Baltimore: Johns Hopkins University Press, 1990.

Kaschak Newman, D. Managing and Treating Urinary Incontinence. Baltimore: Health Professions Press, 2002.

periodicals

Block, C. A., C. S. Cooper, and C. E. Hawtrey. "Long-term Efficacy of Periurethral Collagen Injection for the Treatment of Urinary Incontinence Secondary to Myelomeningocele." Journal of Urology 169 (January 2003): 327–329.

Culligan, P. J., et al. "The Safety of Reusing Injectable Collagen: A Multicenter Microbiological Study." International Urogynecological Journal of Pelvic Floor Dysfunction 13 (2002): 232–234.

Dmochowski, R. R., and R. A. Appell. "Injectable Agents in the Treatment of Stress Urinary Incontinence in Women: Where Are We Now?" Urology 56 (December 2000): 32–40.

Kassouf. W., G. Capolicchio, G. Berardinucci, and J. Corcos. "Collagen Injection for Treatment of Urinary Incontinence in Children." Journal of Urology 165 (May 2001): 1666–1668.

organizations

National Association for Women's Health. 300 W. Adams Street, Suite 328, Chicago, IL 60606-5101. (312) 786-1468. <http://www.nawh.org/>.

other

National Women's Health Information Center. <www.4woman,org/>.

"Periurethral Injection Therapy for Incontinence." eMedicine. <www.emedicine.com/med/topic3049.htm>.

"Stress Incontinence." MEDLINE Encyclopedia. <www.nlm.nih.gov/medlineplus/ency/article/000891.htm>.

Monique Laberge, Ph.D.

WHO PERFORMS THE PROCEDURE AND WHERE IS IT PERFORMED?

Collagen periurethral injection is a procedure that is performed in a hospital or clinic on an outpatient basis by a surgeon.

QUESTIONS TO ASK THE DOCTOR

• How is a collagen periurethral injection performed?
• Why is the collagen injection required?
• What are the risks of the procedure?
• Is the injection procedure painful?
• Are there alternatives?
• How long will it take to recover?
• What are the after-effects of the injection?
• How many collagen periurethral injection do you perform each year?

Collagen

KEY TERMS

Resources

Collagen is a protein found abundantly throughout the bodies of animals including humans. In humans, collagen makes up about one-third of the total body weight. Collagen is an important component of the body’s connective tissues, which perform a variety of functions in the body. These tissues provide the framework, or internal scaffolding, for various organs such as the kidneys and lymph nodes. Connective tissues also impart great support and strength to structures such as the bones and tendons. Blood, an important type of connective tissue, transports oxygen and nutrients throughout the body.

Connective tissue is composed of a nonliving, gellike material called a matrix, in which living cells are embedded. The matrix is composed of different kinds of protein fibers, the most common of which is collagen.

Collagen is a fibrous protein; that is, it is composed of many fibers. Each fiber consists of three microscopic ropes of protein wrapped around each other. The fibers in collagen are arranged parallel to each other, and are often grouped together in bundles. The bundling of collagen fibers gives the fibers greater strength than if they occurred individually. Collagen fibers are extremely tough and can resist a pulling force, but because they are not taut, they allow some flexibility.

Collagen is a primary component of the connective tissue located in the dermis, the tough inner layer of the skin. This kind of connective tissue is also found in mucous membranes, nerves, blood vessels, and organs. Collagen in these structures imparts strength, support, and a certain amount of elasticity. As the skin ages, it loses some of its elasticity, resulting in wrinkles. Recently, injections of animal collagen given under the surface of the skin have been used to “plump up” the skin and remove wrinkles. However, this treatment is controversial. Many people develop allergic reactions to the collagen, and the procedure must be performed by a qualified physician.

Collagen is also a component of a kind of connective tissue that surrounds organs. This connective tissue encases and protects delicate organs like the kidneys and spleen.

Other locations where collagen fibers are prominent are in the tendons and ligaments. Tendons are straps of tough tissue that attach muscles to bones, allowing for movement. Ligaments are structures that hold the many bones of a joint, such as the knee joint,

KEY TERMS

Cartilage— A connective tissue found in the knees, tip of the nose, and outside of the ears; it provides flexibility and resilience to these structures.

Ligaments— Structures that hold the bones of joints in the proper position.

Matrix— The nonliving, gellike component of connective tissue.

Tendon— A strap of tissue that connects muscle to bone, providing for movement.

in proper position. Tendons and ligaments differ slightly in structure. In ligaments, the collagen fibers are less tightly packed than in tendons; in some ligaments, the fibers are not parallel.

Collagen adds strength to tendons and ligaments, and it imparts some stretch to these structures by allowing for some flexibility. However, collagen is not extremely elastic. If tendons and ligaments are stretched too far, these structures will tear, which may lead to problems in movement and bone position. Many athletes tear tendons and ligaments. When tearing occurs, the joint or bone in which the structures occur must be immobilized to allow for proper healing.

Cartilage is a connective tissue found in various places throughout the body, including the tip of the nose, the outside of the ears, the knees, and parts of the larynx and trachea. Cartilage consists of collagen fibers and cartilage cells. At these locations, collagen provides flexibility, support, and movement. Cartilage soaks up water like a sponge and is therefore somewhat springy and flexible. For example, if the tip of the nose is pushed in and let go, it springs immediately back into place.

In vertebrates, which include all animals with a backbone, connective tissues are highly organized and developed. In invertebrates, which include the animals without backbones, connective tissues are not as well organized. However, in nematodes, also known as roundworms (an invertebrate animal), collagen plays a role in movement. The outer covering of the nematode, called the cuticle, consists primarily of collagen. The collagen helps the nematode move and also imparts some longitudinal elasticity. Because the collagen fibers crisscross each other and are not parallel in the nematode cuticle, nematodes are limited in side-to-side movement.

See also Muscular system.

Resources

BOOKS

Brandt, Frederic. AgeLess: The Definitive Guide to Botox, Collagen, Lasers, Peels, and Other Solutions for Flawless Skin. New York: Willima Morrow, 2002.

Brinckmann, Jurgen, Holger Notbohm, and P.K. Muller, eds. Collagen: Primer in Structure, Processing and Assembly. New York: Springer, 2005.

Kane, Michael A.C. The Botox Book. London: Piatkus Books, 2002.

Kathleen Scogna

collagen The word collagen means ‘glue-producing’. Collagen in the body does indeed help to hold it all together, but the notion of glue is not very apt. It strengthens and connects things with a network of tough fibres, rather than sticking them to each other — more like a cat's cradle than an adhesive. Collagen is the protein which forms the ubiquitous white fibres in all the connective tissues of the body, including bone, teeth, cartilage, and tendons; the skin; and all the sheaths, partitions, and supporting frameworks which abound in all organs and tissues. The exception is the central nervous system, which has its own different variety of internal supporting tissue — the glia — though there is collagen in the membranes which cover the brain and spinal cord.

Collagen is one of the ‘structural proteins’ (the other widespread one is elastin), which provide support to the tissues. By crude analogy with string, the principal mechanical property of collagen is its ability to resist distending force (tensile strength), which is vastly greater than its ability to resist compression or twisting (compression and torsion strengths). The tensile strength of collagen is so high as to be comparable, weight for weight, with that of steel. Elastin, by contrast, has a low tensile strength but the important mechanical properties of distensibility and resilience: the capability for relatively long range stretching under load and for returning to the original dimensions when the distending force is removed. Collagen can stretch only by about 2% without damage.

Collagen and elastin fibres often co-exist, notably in tissues which regularly undergo considerable changes in shape, such as skin, lungs, and blood vessels. The essentially inextensible, high tensile strength collagen is able to exist and function alongside the elastic fibres simply by having considerable slack. This can easily be illustrated if you pinch up the skin on the back of the hand: it returns to its original shape on release by virtue of the elastic fibres (a property progressively impaired in old age due to degeneration of the elastic fibres, with consequent increase in skin wrinkling). Now with the fingertips push the same skin on the back of the hand sideways and note that it slides quite freely until displacement comes to a distinct halt (when the collagen has used its slack and the tough fibres are pulled into alignment, resisting the distending force).

Collagen is synthesized by fibroblasts, the living cells present in all connective tissue, so named because they generate fibres — of collagen. There are in fact several types, with minor variations of molecular structure. Like all proteins, collagens are constructed from amino acid units; they are all glycoproteins, meaning that glucose and other simple sugars are attached to the amino acid chains. Each long, thin molecule consists of three chains of over 1000 units; each chain is helical, and the three in turn form a triple helix. A molecule is about 300 nm long — over 3000 end-to-end would measure 1 mm — but in fully-formed collagen they overlap lengthwise, and are also linked side to side, providing longer, wider, and very tough fibres. Again like all proteins in the body, collagen has a finite life span after which it is degraded to the constituent amino acids and replaced by new fibres. The synthesis within the fibroblasts is a complex process; the three chains are separately assembled, and then wound into the triple helix, which is extruded. Once outside the cell, the molecules aggregate and forge links as described.

The complexity of collagen synthesis involves multiple enzymes, so that a congenital deficiency of any of these can lead to some disorder of its formation. This accounts for there being a wide variety of clinical syndromes associated with such disorders: there can be fragile bones, with fractures from minimal trauma; fragile blood vessels with widespread bruising; dental defects; readily dislocating joints; a bent or twisted spine; thin, hyperelastic skin; and poor wound healing. Apart from these inborn defects, deprivation of ascorbic acid (vitamin C) at any time of life interferes with a step in collagen synthesis; the resulting bleeding, bruising, and poor healing are part of the picture of scurvy.

With ageing, habitually exposed areas of skin in white-skinned people show broken and disordered collagen fibres, related to the effects of UV light. Deficient replacement of collagen also contributes to thinning and wrinkling of the skin, and, together with mineral loss, to osteoporosis — decreasing bone mass.

These changes suggest that the continuous production of new fibroblasts, and by them of new collagen, progressively declines. Fibroblasts in culture outside the body divide again and again, but do not continue to replicate indefinitely. When such cultures from different animal species are compared, it is found that the number of cell divisions is related to the lifespan of each species, and is also related inversely to the age of the donor from any one species: a finding of considerable interest in the study of the ageing process.

Hugh Elder, and Sheila Jennett