What happens in the skin during urticaria?
Trigger. Many substances can trigger itchiness, whether applied to the skin externally, ingested or inhaled, or produced by the body itself. One common characteristic for most of these substances is that they release histamine, a neurotransmitter believed to play a key role in the triggering of itchiness. This itch-triggering effect of histamine is very clearly evident after an insect bite, for example, or after contact with stinging nettles. Beyond substances that release the body's supply of histamine, the venom of many insects and pruritic (itch-inducing) plants contains histamine that penetrates and stimulates the skin. The impulse is perceived by specialised nerves (the "itch nerves," if you will). A message is sent to the brain, the central switchboard for the nerves: something's itching here! This isn't always a bad thing at all. For insect bites or following contact with pruritic plants, itchiness induces us to scratch the skin, cool it under cold water (and thereby remove the trigger) or rub it (bringing more blood to the spot of the reaction, allowing the itch stimulant or venom to be more quickly transported away through the blood stream). Almost all of the skin's histamine is stored in a specific kind of cell, known as mast cells. If these cells are activated, i.e. if they are "nettled" by a stimulus (and there are a variety of stimuli that can do this), then the mast cells release their histamine into the surrounding tissues, leading to wheal formation and itching.
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Mast cells – the urticaria makers! One process is common to all forms of urticaria: following the activation of the skin's mast cells, histamine is released. The histamine leads to dilation of the skin's blood vessels, followed by swelling and flaring as well as itchiness.
Mast cells more or less serve as the "fire fighters" or "border patrol" for the human body. They are most commonly found in the parts of the body where we have direct contact with our environment: in the skin, in the mucous membranes of the gastrointestinal tract, and in the respiratory tract. They fulfil crucial life functions for the body: dangerous assailants like bacteria or parasites are identified and neutralised – be it because the mast cells block the path of the intruders into the body, because they kill or eat them, or because they alarm the cells of the immune system (our body's defence system) and direct them to the spot of the incident.
The prevalence of mast cells in the skin and in the mucus membranes of the human body explains why urticaria is particularly noticeable in those spots. The activation of the mast cells in the upper (exterior) dermal layers leads to wheals, while the activation of those in the lower (interior) dermal layers leads to deeper swelling. An activation of mast cells in the mucous membranes of the respiratory tract creates shortness of breath and discomfort in swallowing; an activation in the mucous membranes of the gastrointestinal tract leads to stomach aches, nausea and diarrhoea. When human skin or mucous membranes are viewed through a microscope, the mast cells can be easily distinguished through simple colouring methods. They are relatively large compared with other cells, and are filled with highly characteristic little particles called granules. Among other substances, the granules contain histamine to be released into the surrounding tissues following the activation of the mast cells.
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Wheals develop when the blood vessels of the skin become "leaky" in the affected section of the skin. The distance between the cells that form the walls of the blood vessels grows larger, allowing blood plasma and other blood cells to escape from the interior of the blood vessels into the surrounding tissues. Histamine causes the cells of the blood vessels to move apart, as do other mast cell products such as leukotrienes or other messengers (the cytokines) that increase the permeability of blood vessels.
Substances that quiet itchiness related to urticaria in many cases pursue the tact of directly blocking the effect of the histamines. This is why drugs of that kind are called antihistamines. Yet because antihistamines are not effective for all cases of urticaria, one can surmise that histamine is not the only trigger for itchiness and wheals.
