The Most Life-Threatening Skin Diseases Essay

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Describe several different diseases and disorders of the skin
Describe the effect of injury to the skin and the process of healing
The integumentary system is susceptible to a variety of diseases, disorders, and injuries. These range from annoying but relatively benign bacterial or fungal infections that are categorized as disorders, to skin cancer and severe burns, which can be fatal. In this section, you will learn several of the most common skin conditions.The Most Life-Threatening Skin Diseases Essay

One of the most talked about diseases is skin cancer. Cancer is a broad term that describes diseases caused by abnormal cells in the body dividing uncontrollably. Most cancers are identified by the organ or tissue in which the cancer originates. One common form of cancer is skin cancer. The Skin Cancer Foundation reports that one in five Americans will experience some type of skin cancer in their lifetime. The degradation of the ozone layer in the atmosphere and the resulting increase in exposure to UV radiation has contributed to its rise. Overexposure to UV radiation damages DNA, which can lead to the formation of cancerous lesions. Although melanin offers some protection against DNA damage from the sun, often it is not enough. The fact that cancers can also occur on areas of the body that are normally not exposed to UV radiation suggests that there are additional factors that can lead to cancerous lesions.The Most Life-Threatening Skin Diseases Essay

In general, cancers result from an accumulation of DNA mutations. These mutations can result in cell populations that do not die when they should and uncontrolled cell proliferation that leads to tumors. Although many tumors are benign (harmless), some produce cells that can mobilize and establish tumors in other organs of the body; this process is referred to as metastasis. Cancers are characterized by their ability to metastasize.

Basal cell carcinoma is a form of cancer that affects the mitotically active stem cells in the stratum basale of the epidermis. It is the most common of all cancers that occur in the United States and is frequently found on the head, neck, arms, and back, which are areas that are most susceptible to long-term sun exposure. Although UV rays are the main culprit, exposure to other agents, such as radiation and arsenic, can also lead to this type of cancer. Wounds on the skin due to open sores, tattoos, burns, etc. may be predisposing factors as well. Basal cell carcinomas start in the stratum basale and usually spread along this boundary. At some point, they begin to grow toward the surface and become an uneven patch, bump, growth, or scar on the skin surface (Figure 1). Like most cancers, basal cell carcinomas respond best to treatment when caught early. Treatment options include surgery, freezing (cryosurgery), and topical ointments (Mayo Clinic 2012).The Most Life-Threatening Skin Diseases Essay

This photo shows an enlarged view of a basal cell carcinoma, a large, pink, irregular bump on the skin. The carcinoma is marked with irregular, dark-red stripes that resemble tiny blood vessels. The surrounding skin is the same pink color as the carcinoma, but without the red striping or raised appearance
Figure 1. Basal Cell Carcinoma. Basal cell carcinoma can take several different forms. Similar to other forms of skin cancer, it is readily cured if caught early and treated. (credit: John Hendrix, MD)
Squamous cell carcinoma is a cancer that affects the keratinocytes of the stratum spinosum and presents as lesions commonly found on the scalp, ears, and hands (Figure 2). It is the second most common skin cancer. The American Cancer Society reports that two of 10 skin cancers are squamous cell carcinomas, and it is more aggressive than basal cell carcinoma. If not removed, these carcinomas can metastasize. Surgery and radiation are used to cure squamous cell carcinoma.The Most Life-Threatening Skin Diseases Essay

This photo shows a man’s nose. The squamous cell carcinoma is located just above the tip of the nose and appears as a deep red, irregularly-shaped sore that spans almost the entire bridge of his nose.
Figure 2. Squamous Cell Carcinoma. Squamous cell carcinoma presents here as a lesion on an individual’s nose. (credit: the National Cancer Institute)
A melanoma is a cancer characterized by the uncontrolled growth of melanocytes, the pigment-producing cells in the epidermis. Typically, a melanoma develops from a mole. It is the most fatal of all skin cancers, as it is highly metastatic and can be difficult to detect before it has spread to other organs. Melanomas usually appear as asymmetrical brown and black patches with uneven borders and a raised surface (Figure 3). Treatment typically involves surgical excision and immunotherapy.The Most Life-Threatening Skin Diseases Essay

This photo shows a patch of fair skin containing a large melanoma. The melanoma is black and splotchy in appearance.
Figure 4. Melanoma. Melanomas typically present as large brown or black patches with uneven borders and a raised surface. (credit: the National Cancer Institute)
Doctors often give their patients the following ABCDE mnemonic to help with the diagnosis of early-stage melanoma. If you observe a mole on your body displaying these signs, consult a doctor.

Asymmetry – the two sides are not symmetrical
Borders – the edges are irregular in shape
Color – the color is varied shades of brown or black
Diameter – it is larger than 6 mm (0.24 in)
Evolving – its shape has changed
Some specialists cite the following additional signs for the most serious form, nodular melanoma:

Elevated – it is raised on the skin surface
Firm – it feels hard to the touch
Growing – it is getting larger

Scarring of skin after wound healing is a natural process and does not need to be treated further. Application of mineral oil and lotions may reduce the formation of scar tissue. However, modern cosmetic procedures, such as dermabrasion, laser treatments, and filler injections have been invented as remedies for severe scarring. All of these procedures try to reorganize the structure of the epidermis and underlying collagen tissue to make it look more natural.

Skin and its underlying tissue can be affected by excessive pressure. One example of this is called a bedsore. Bedsores, also called decubitis ulcers, are caused by constant, long-term, unrelieved pressure on certain body parts that are bony, reducing blood flow to the area and leading to necrosis (tissue death). Bedsores are most common in elderly patients who have debilitating conditions that cause them to be immobile. Most hospitals and long-term care facilities have the practice of turning the patients every few hours to prevent the incidence of bedsores. If left untreated by removal of necrotized tissue, bedsores can be fatal if they become infected.The Most Life-Threatening Skin Diseases Essay

The skin can also be affected by pressure associated with rapid growth. A stretch mark results when the dermis is stretched beyond its limits of elasticity, as the skin stretches to accommodate the excess pressure. Stretch marks usually accompany rapid weight gain during puberty and pregnancy. They initially have a reddish hue, but lighten over time. Other than for cosmetic reasons, treatment of stretch marks is not required. They occur most commonly over the hips and abdomen.

When you wear shoes that do not fit well and are a constant source of abrasion on your toes, you tend to form a callus at the point of contact. This occurs because the basal stem cells in the stratum basale are triggered to divide more often to increase the thickness of the skin at the point of abrasion to protect the rest of the body from further damage. This is an example of a minor or local injury, and the skin manages to react and treat the problem independent of the rest of the body. Calluses can also form on your fingers if they are subject to constant mechanical stress, such as long periods of writing, playing string instruments, or video games. A corn is a specialized form of callus. Corns form from abrasions on the skin that result from an elliptical-type motion.The Most Life-Threatening Skin Diseases Essay

Skin cancer is a result of damage to the DNA of skin cells, often due to excessive exposure to UV radiation. Basal cell carcinoma and squamous cell carcinoma are highly curable, and arise from cells in the stratum basale and stratum spinosum, respectively. Melanoma is the most dangerous form of skin cancer, affecting melanocytes, which can spread/metastasize to other organs. Burns are an injury to the skin that occur as a result of exposure to extreme heat, radiation, or chemicals. First-degree and second-degree burns usually heal quickly, but third-degree burns can be fatal because they penetrate the full thickness of the skin. Scars occur when there is repair of skin damage. Fibroblasts generate scar tissue in the form of collagen, which forms a basket-weave pattern that looks different from normal skin.

Bedsores and stretch marks are the result of excessive pressure on the skin and underlying tissue. Bedsores are characterized by necrosis of tissue due to immobility, whereas stretch marks result from rapid growth. Eczema is an allergic reaction that manifests as a rash, and acne results from clogged sebaceous glands. Eczema and acne are usually long-term skin conditions that may be treated successfully in mild cases. Calluses and corns are the result of abrasive pressure on the skin.The Most Life-Threatening Skin Diseases Essay

Review Questions
1. In general, skin cancers ________.

are easily treatable and not a major health concern
occur due to poor hygiene
can be reduced by limiting exposure to the sun
affect only the epidermis
2. Bedsores ________.

can be treated with topical moisturizers
can result from deep massages
are preventable by eliminating pressure points
are caused by dry skin
3. An individual has spent too much time sun bathing. Not only is his skin painful to touch, but small blisters have appeared in the affected area. This indicates that he has damaged which layers of his skin?

epidermis only
hypodermis only
epidermis and hypodermis
epidermis and dermis
4. After a skin injury, the body initiates a wound-healing response. The first step of this response is the formation of a blood clot to stop bleeding. Which of the following would be the next response?

increased production of melanin by melanocytes
increased production of connective tissue
an increase in Pacinian corpuscles around the wound
an increased activity in the stratum lucidum
5. Squamous cell carcinomas are the second most common of the skin cancers and are capable of metastasizing if not treated. This cancer affects which cells?

basal cells of the stratum basale
melanocytes of the stratum basale
keratinocytes of the stratum spinosum
Langerhans cells of the stratum lucidum  The Most Life-Threatening Skin Diseases Essay

Diabetes mellitus is a condition in which the body is unable to control blood glucose levels adequately, resulting in high blood glucose levels (hyperglycaemia). Symptoms include frequent urination due to the osmotic effect of excess glucose in the urine, thirst due to loss of fluids and weight loss. Possible long-term complications of diabetes if blood glucose has been poorly controlled include cardiovascular disease (such as atherosclerosis and stroke) and damage to nerves, the kidney and eyes, which can potentially lead to blindness. Diabetes is a major health problem with an estimated 425 million people affected worldwide, and these numbers are predicted to rise. The rise in numbers is associated with an increase in obesity in the population and treating the complications is a major healthcare cost. In the U.K., some estimates predict the cost could reach 17% of the NHS budget.The Most Life-Threatening Skin Diseases Essay

Most people will be familiar with the classification of diabetes into the two main forms, Type 1 and Type 2; however, it is increasingly clear that there are in fact several different types of diabetes, some of which overlap to some extent. Recent research analysing nearly 15000 diabetics showed they could be clustered into five distinct groups based on specific biomarkers1 of the condition, which is significant because this better classification system may lead to improved treatment strategies in the future. Type 1 diabetes is an autoimmune disease in which cells of the body’s immune system cause destruction of insulin secreting β-cells in the pancreas, leading to a deficiency of insulin production. There are typically antibodies against key pancreatic proteins involved in insulin storage and secretion. It is a relatively rare form of the disease affecting 5–10% of diabetics, which is usually diagnosed in childhood and is not associated with excess body weight. Type 2 diabetes is the more common form of the disease, affecting 90–95% of diabetics, and is characterised by a loss of ability to respond to insulin (i.e. there is insulin resistance, also termed as insulin insensitivity). At diagnosis, individuals are typically over 30 years old, overweight, have high blood pressure and an unhealthy lipid profile (referred to as the metabolic syndrome). Established disease is associated with hypersecretion of insulin, but this is still inadequate to restore normal blood glucose levels, and the condition may progress towards insulin deficiency. The causes of diabetes are thought to be a combination of genetic and environmental factors, and it is recognised that being overweight is a strong risk factor for developing Type 2 diabetes.The Most Life-Threatening Skin Diseases Essay

Insulin action
In healthy individuals, blood glucose levels range between 3.5 and 5.5 mmol/l before meals. This range is maintained by the actions of hormones (primarily insulin and glucagon, but also adrenaline, cortisol and growth hormone) which control the production and uptake of glucose, levels of glycogen (the stored form of glucose), and fat and protein metabolism, as required following meals, during fasting and exercise. Both insulin and glucagon are polypeptides produced by the pancreas (β-cells – insulin; α-cells – glucagon).

Insulin is secreted in response to an increase in blood glucose levels and its overall effect is to store chemical energy by enhancing the uptake and storage of glucose, amino acids and fats; consequently reducing blood glucose levels, via actions on liver, muscle and adipose tissue (specifically adipocytes – fat cells). Glucagon, on the other hand, via a complex interplay with other hormones and the nervous system increases blood glucose by stimulating the breakdown of glycogen, fat and protein. When blood glucose is high, after a meal for example, insulin acts on the liver to decrease glucose synthesis (gluconeogenesis), increase glucose utilisation (glycolysis) and increases glycogen synthesis (glycogenesis). When the storage capacity for glycogen is reached, insulin increases synthesis of fatty acids (lipogenesis), via acetyl CoA as an intermediate, which is then exported for triglyceride synthesis in adipocytes. In muscle, insulin stimulates uptake of glucose, by recruiting the glucose uptake transporter type 4 (GLUT-4), and enhances glycogen synthesis and glycolysis. In adipose tissue, there is facilitated uptake of glucose which is metabolised to glycerol and subsequently used together with fatty acids to synthesise triglycerides. Insulin also inhibits pathways involved in lipolysis. In addition, insulin increases amino acid uptake and protein synthesis in muscle and is considered an anabolic hormone (i.e. one that builds up organs and tissues).The Most Life-Threatening Skin Diseases Essay

At the biochemical level, insulin produces its effects by binding to the insulin receptor – a cell surface glycoprotein composed of two extracellular α subunits and two β subunits that span the membrane (Figure 1). The receptor has tyrosine kinase activity (i.e. enzyme activity that catalyses the transfer of a phosphate group from ATP to a tyrosine amino acid within a protein, also known as tyrosine phosphorylation). Binding of insulin to the receptor initially causes tyrosine phosphorylation of the receptor itself, and then phosphorylation of intracellular proteins termed as insulin receptor substrate (IRS)-1 and IRS-2, followed by a complex series of intracellular signalling events involving many other kinases that lead to the physiological changes in carbohydrate, fat and protein metabolism discussed above via changes in gene expression and the activity of metabolic enzymes. The effects of insulin on glucose uptake are mediated via the glucose transporter GLUT-4, which is stored in intracellular vesicles in an inactive state, and insulin stimulates the movement of these vesicles to the plasma membrane where GLUT-4 becomes inserted into the membrane forming a pore that allows glucose uptake into the cell The Most Life-Threatening Skin Diseases Essay

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