Sunburn is the result of over exposure to ultraviolet rays usually orientated from sunlight, characteristically causing overheating, redness, tenderness and peeling of the skin. When the skin is exposed to UV rays, the rays penetrate the skin and start to breakdown DNA in the body; however in the body's homeostatic response to this specialist skin cells called melanocytes which are activated by melanocyte-stimulating hormone (MSH), produce the pigment melanin which helps to protect the DNA of cells. There are receptors for MSH on the surface of the melanocytes cells. UV light increases the quantity of MSH and its receptors, making the melanocytes more active. The melanocytes enclose melanin into organelles called melanosomes. The melanosomes are transported to skin cells where they surround the nucleus, shielding their DNA from the effects of damaging UV rays. The more melanin pigment that is present within the body, characteristically results in a darker skin complexion. Those with a naturally darker complexion are better adapted to longer periods in the sun, as they have a greater level of melanin, so are better protected against cell and DNA damage. (1)
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(http://www.anthelios.com/images/uv_skinLayer.jpg) Sunlight tends to have three sorts of UV rays; UVA rays penetrate deeper into the skin damaging the middle layer (dermis), containing tissues that give skin its elasticity; UVB rays are absorbed by the top layer (epidermis) of the skin. (2) The epidermis then releases chemicals, which cause pain, redness and swelling that are associated with sunburn; and UVC rays, are filtered through the atmosphere, but do not reach the body. Sunburn is essentially a delayed ultraviolet B-induced erythema (redness of the skin) caused by an increase in blood flow to the affected skin. The underlying reason of this vascular response is damage to skin cells from photochemical reactions and the formation of reactive oxygen species. Damage to DNA and the activation of inflammatory pathways, involving prostaglandins are considered to activate reactions, leading to vasodilation and oedema. Erythema implies that enough ultraviolet damage has occurred that inflammatory pathways have been activated. Erythema (sunburn), is thought of as a total failure of sun protection, and is an indicator for severe UV damage. The redness of sunburn is a characteristic of the blood filling up the capillaries within the surface of the skin. This blood helps to bring in additional cells that will fight the damage done to the skin. (3)http://www.skinstore.com/resources/dynamic/store/categories/la_roche_posay/uv_skinLayer.jpg
The preventative measures from sunburn, begin at limiting exposure to the sun, especially fair skinned people who are at greater risk. Wearing loose clothing and hats and wearing a thick layer of sunscreen at SPF15 or above before going out into the sun, protects against the effects of UVA and UVB rays as they block/absorb ultraviolet light. (2)
Treatment of mild sunburn includes, staying out of the sun until the sunburn has healed; cooling the skin through cool compresses and showers; drinking fluids to replace the water lost through sweating; applying moisturising lotion such as 'Aftersun' to help cool the skin and relieve itching and soreness symptoms; paracetamol and anti-inflammatory drugs such as ibuprofen can help relieve the pain and swelling associated with sunburn. Severe sunburn requires specialist attention, and oral steroid therapy and burn cream may be prescribed, as well as stronger pain relief. If blistering is present steroids may be withheld to reduce risk of infection. If extremely dehydrated or suffering from heat stress, IV fluids are given. (2)
Cooling homeostatic mechanisms within the body include; convection, which is the transfer of heat between the body's surface and a gas/fluid with a differing temperature; radiation with the transfer of heat between the body and surroundings; conduction with the transfer of heat between two surfaces with differing temperatures and evaporation where sweat released evaporates and cools the body. (4)
Sunstroke is a form of hyperthermia and is due to acute thermoregulatory failure in warm environments. With this, the individual's core body temperature rises above 40oC, causing biochemical and physiological abnormalities. Sunstroke is further sub-classified into two clinical presentations, classical and exertional heat stroke. Exertional heat stroke is usually seen in younger, active individuals exercising at higher temperatures. Heat is generated beyond the body's ability to cool itself, as the heat and humidity of the environment reduces the efficiency of normal cooling mechanisms. Although thermoregulatory mechanisms are functioning, they struggle by thermal challenges of the environment and in maintaining a stable body temperature. Classic heat stroke however, predominantly affects the elderly or individuals with chronic health conditions in unusually hot weather. (4) The hypothalamus acts like a thermostat, producing more sweat when it detects the body is hotter. In the elderly and those with chronic health problems, the hypothalamus does not work as well, and they are at more risk of heat stroke. Young children are also at more risk, as their cooling mechanisms are less efficient and they sweat less. In general, both exertional and classic heat stroke, the heat-regulating mechanisms eventually become overwhelmed and are unable to deal with the heat, causing body temperatures to climb uncontrollably (hyperthermia). (4)
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Prevention of heatstroke includes keeping out of the sun between peak hours, avoiding extreme physical exertion in high temperatures, wearing loose-fitting cotton clothes and sunscreen. It is important to keep the environment cool, having plenty of fluids and taking cool baths. Those at higher risk of classic sunstroke need to take extra precautions, due to their vulnerability. (2)
Primary therapy of sunstroke and hyperthermia includes cooling and decreasing thermogenesis, by moving the individual to a shaded, cooler area, removing clothes and constantly wetting the skin, and giving plenty of fluids to rehydrate them (not caffeine or alcohol as they are dehydrating agents); in more severe cases, gently massaging the skin to encourage circulation. (4) Hospital treatment involves immersing their body in an ice-bath, or spraying the individual with a mist of cool water while warm air is fanned over the body - the combination of cool water and warm air encourages rapid heat loss through evaporation. (2)
To make validated therapeutic decisions, the fundamental concepts linking drug doses to clinical responses must be understood. The relationship between the dose of a drug and the response observed can depend on a number of factors, including metabolism, elimination of the drug, absorption, the position of action of the drug in the body; and the presence of other drugs or disease. (5)The relationship between the concentration of the drug and the observed effect (dose-response relationship) can thus be graphically represented by a hyperbolic curve. The dose-response relationships for drugs can be presented as either quantal response curves or graded response curves. (6)
Image illustrating a 'graded' response curve
(http://www.pharmacology2000.com/General/Pharmacodynamics/dc_de%20(Copy%202).gif) A graded-dose response curve is constructed for responses that are measured on a continuous scale, and represents the relationship between both dose and drug. (5)These curves relate the magnitude of response to the drug against the size of the dose given, and are therefore useful for characterizing the actions and effectiveness of drugs. (6)An example of the use of this is in diabetic patients, whereby the magnitude of the glucose disposal rate is plotted against the size of the dose of insulin concentration given. This would consequently portray the effectiveness of a varied dose of insulin, and the response of the glucose disposal rate in conjunction with this. http://www.pharmacology2000.com/General/Pharmacodynamics/dc_de%20(Copy%202).gif
Image illustrating a 'quantal' response curve
(http://www.osha.gov/Preamble/Images/ac6_f2.gif) A quantal dose-response curve is the relationship between three: percentage of population, response and dosage. This means it illustrates how many patients have exhibited the predefined response at a specified dose. The curve can be composed for drugs that display an all-or-nothing response. In these curves, the concentration of the drug is plotted against the percentage of a specific population in whether the drug produces the predefined effect or not. For most drugs, the doses that are required to create a specified quantal response in a population are log normally spread, so that the frequency distribution of responses plotted against log dose is presented as a normal distribution curve. The median response dose and the median lethal dose can therefore be estimated from the normal distribution curve. With these curves the overall efficiency of various drugs for producing a desired or undesired response as well as relative safety between drugs can be established. The percentage of the population requiring a particular dose to exhibit the effect can also be determined from the curve. When data is plotted as a cumulative frequency distribution, a sigmoidal dose-response curve is produced. (5) An example of the use of a quantal dose-response curve is the percentage of individuals who have responded by having a drop in blood pressure (not how much it has fallen by, but simply has it fallen or not), against the log dose of the β-blocker atenolol (normally distributed). http://www.osha.gov/Preamble/Images/ac6_f2.gif
For analytical purposes and to aid effective prescribing, curves are used as a means to display the efficiency and dosage effects of drugs. A quantal response curve only explains the dose of drugs related to a specific response (discontinuous); however, with graded response curves, the effectiveness of dosage is compared to the extent of response (continuous). Converting a quantal response curve to a graded one can help aid therapeutic decisions in efficiency and ideal doses of drugs that can be distributed.
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To convert a quantal response curve into a graded one, the y-axis needs to display a continuous variable response instead of an all-or-nothing discontinuous response. This can be done, by using the percentage of population from the quantal curve results, and seeing whether the all-or-nothing (discontinuous) response, can be further classified into the extent of it (continuous). For example, if the predefined response for the quantal curve was whether or not there was a drop in blood pressure, then to convert it to a graded response curve, it would evaluate the extent the blood pressure dropped by, in comparison to the dosage of the drug (atenolol). The x axis on the quantal curve can remain the same, but it shouldn't be log normally distributed, as it is now representing the relationship between both the concentration of dose and effect of response, whereas with a quantal curve there were three, the population percentage, whether or not the predefined response was exhibited and the concentration of the dose. With the quantal curve the overall population response of the drug can be established, whether or not the drug works and its viability; whereas the graded response curve evaluates the efficiency of doses by looking at the extent of the response of the drug and aiding future therapeutic changes.