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Skin Expertise
  About the SKIN - The Physiology of the SKIN  
The skin, the largest organ of the human body, has a surface area between 1.5 and 2.0 square metres. It accounts for 16 % of total body weight. Considered one of the most important organs of the body, the skin protects from harmful substances, insulates and regulates temperatures.

It has following function :
  1. The Hydrolipid Film
  2. The Epidermal Lipids
  3. The Protective Acid Mantle
  4. The Skin's Immune System
  5. Natural Moisturizing Factors (NMF) and Surface Lipids
  6. Regeneration and Repair Mechanisms
  7. Protective Functions at a Glance
  8. Cell Energy
The Hydrolipid Film

The skin surface is covered with what is called a hydrolipid film - an emulsion of water (hydro) and fat (lipos). Its main function is as an external barrier to defend against bacteria and fungi. In addition, it keeps the skin supple. In healthy skin the balance between oil and moisture is intact. The hydrolipid film varies in quantity and composition depending on the body region as well as exogenous and endogenous factors such as the time of day, the season and air humidity or nutrition, stress and illness.

Composition and function of the hydrolipid film
Analysis of the skin structure and the keratinization process shows that the following substances are present on the skin surface:
  • Sweat and sebaceous lipids
  • Substances from the cornification process (protein degradation products)
  • Horny cells still in the shedding process
  • Water from the deepest layers that has reached the surface (transepidermal water, insensible perspiration)
These components form the skin's continuously renewed protective film.

Importance of the hydrolipid film
One function of the hydrolipid film is to repel invaders. At the same time it maintains the suppleness of the skin. Due to the presence of weakly acid components such as lactic acid, pyrrolidine carboxylic acid and amino acids, the hydrophilic portion of the hydrolipid film forms a protective acid mantle.

The Epidermal Lipids

Along with the horny cells, the epidermal lipids are essential to the barrier function of the skin. They form the "mortar", or horny layer cell cement, between the "bricks" – the horny cells. The skin´s own lipids are synthesized in cells of the epidermis from intermediate products of metabolism or from essential, meaning supplied from without, fatty acids. These include apart from mono-, di- and triglycerides also cholesterol, ceramides and phospholipids.

Composition of the epidermal lipids
The composition of the lipids forming the membranes in the horny layer differs from that of the membranes in the living epidermis, which consist mainly of phospholipids. These are degraded during differentiation (cornification) of the keratinocytes. Therefore, ceramides, cholesterol and free fatty acids predominate in the horny layer.

Consequences of damage to the permeability barrier
If the uppermost corneocyte layers are removed, for example with an adhesive plaster, the epidermal lipids are lost with them. Then water, chemicals and pathogenic microorganisms can penetrate into the deeper layers of the skin, and more water is lost from the lower skin layers; transepidermal water loss (TEWL) increases.

Influences on the regeneration mechanism
Activation of the skin's barrier regeneration system is subject to various influences. Thus increased cholesterol, fatty acid and sphingolipid synthesis leads to a restoration of the barrier function. However, it can be shown that after widespread damage to the horny skin layer, for example, from "stripping" or by oil-removing acetone, the natural horny layer barrier can only be restored by acidifying the skin surface. A neutral or alkaline environment noticeably retards the regeneration process.

The Protective Acid Mantle

For over 100 years the function of the protective acid mantle has been under discussion. Initially, the focus was on indirect microbiological defence and direct protection against alkaline noxae. This classical knowledge of the importance of the pH for the skin, however, has since been expanded by more recent biochemical and molecular biological studies.

More recent research findings prove that the acid pH of the horny layer plays an essential role in the formation and structure of the epidermal lipids and with them the permeability barrier. These studies showed that an acidic environment is important for :
  • Activation of the enzymes responsible for the synthesis of important epidermal lipids,
  • Formation of the bilayer lipid membrane and
  • Restoration of the horny layer following mechanical or chemical damage.
An acidic environment is important for synthesis of the epidermal lipids, which consist mainly of ceramides (40%), free fatty acids (25%) and cholesterol (25%). Synthesis of the especially important ceramides is catalysed by an enzyme belonging to the group of acid hydrolases.

The hydrolipid film is made up of several substances :
  • Sweat and sebaceous lipids
  • Substances derived from the cornification process
  • Desquamating but still adhering horny cells
  • Water from the deepest layers that has reached the surface
Due to the presence of weakly acidic components, the aqueous portion of the hydrolipid film forms the protective acid mantle.

This fulfils three important functions : Support of the formation and maturation of the epidermal lipids and hence maintenance of the barrier function, Indirect protection against invasion by microbial pathogens, Direct protection against alkaline noxae (base neutralizing capacity).

From hydrolipid film to protective acid mantle
Closer examination of the components of the hydrolipid film reveals why this protective film was first named by Schade and Marchionini in 1928 the protective acid mantle :
  • Sweat contains lactic acid and various amino acids.
  • Sebum contains free fatty acids.
  • Amino acids and pyrrolidine carboxylic acid are produced by the cornification process.
The physiological pH of healthy skin has an average value lying between 5.4 and 5.9. In this pH range the skin is populated by a normal skin-typical flora. Pathogenic microorganisms are hindered from spreading. In the armpits, anal folds and the genitals, however, the pH is approximately 6.5 (physiological gaps).

An important mechanism : base neutralizing capacity
A rise in the pH into the alkaline range - for example due to excessive use of soap - disturbs the physiological balance of the skin. If the pH is higher than that of the normal physiological range for an extended period, the function of the bacteriological defence mechanism of the skin is compromised, favouring infections.

To counteract the influence of alkaline substances the protective acid mantle uses what are called buffer substances. They neutralize alkaline substances and ensure the acidic milieu is restored and stabilized. This capability is referred to as the base neutralizing capacity. Alkaline noxae (harmful substances) include substances that act as bases ("alkali-like", pH>7) in aqueous solution. Examples are soap or sodium carbonate solutions, which can have a pH of up to 11.

The Skin's Immune System

The skin is the largest organ in area. With the Langerhans cells in the lowest epidermal layers, it is equipped with specialized immunologically competent cells. The Langerhans cells play a central role in the skin's immune system and are an integral part of the body's total defence system.

The body's own defence against microorganisms begins directly at the skin surface. Special fatty acids from the sebaceous glands and the secretions of certain bacteria belonging to the physiological skin flora inhibit the growth of fungi and bacteria. Certain enzymes present in sweat (lysozymes) can destroy the cell walls of invading bacteria. If a foreign body passes this first line of defence - for example, due to skin damage - the skin's immune system responds. Many cells help fend off foreign bodies. Among these are cells - like the Langerhans cells - that are specific to the skin's immune system.

Functions of the Langerhans cells
The Langerhans cells specifically activate dormant T-helper cells and thus initiate a primary T-cell dependent immune response. Therefore they play an important role in contact allergies, the rejection of skin grafts and other immunological processes in the skin. After contact with the corresponding antigens (viruses, contact allergens, skin grafts) the Langerhans cell leaves the epidermis and reaches a lymph node via the lymphatic system. On its journey the Langerhans cell undergoes a maturation process leading to the presentation of the antigen on its surface. The migrating cells are replaced by a corresponding number of new Langerhans cells from the bone marrow.

In the lymph nodes the mature Langerhans cells activate the T-helper cells that have the matching antigen-specific receptors on their surface. In this way they initiate the systemic immune response.

External influences on the skin's immune system
Factors influencing the activity of the Langerhans cells in the epidermis include the following :
  • Cellular messengers (cytokines) such as interleukin-10
  • UV radiation
  • Photochemotherapy
  • Immunosuppressive drugs (for example, corticoids)
After intensive UV exposure it was observed that the Langerhans cells retract their dendritic cell protuberances and leave the epidermis. In addition, interleukin-10 (IL-10), which is released by the skin cells when exposed to UV radiation, impairs the function of the entire immune system, even in the non-irradiated areas. This creates immunosuppressed areas in the skin that give UV-damaged skin cells a chance to repair themselves and not be eliminated by a premature immune response.

Skin

Natural Moisturizing Factors (NMF) and Surface Lipids

The most important substance for the suppleness of the skin is water. The water content of the upper horny layer is between 10 and 20% in young skin. Without natural moisturizing factors, this water would soon evaporate and the skin would become dry & cracked.

The skin's moisture comes from water from deeper layers (transepidermal water) and from normal perspiration. Various factors such as a lack of moisture-binding substances or extremely low humidity can lead to an increased loss of moisture to the environment. Especially prone to this are more exposed regions such as the face and hands. A distinction is made between active, glandular and passive extraglandular or transepidermal water loss.

NMF - substances with a special relationship to water
Some of the body´s own substances, the natural moisturizing factors (NMF), are capable of retaining water in the horny layer. These substances with a special water binding capacity are derived from sweat and the sebaceous oils (e.g. urea) as well as the cornification process (e.g. pyrrolidine carboxylic acid).

The lipids of the skin surface
The skin surface lipids are made up of the epidermal lipids and lipids from sebum - important for the hydrolipid film. Various fatty acids, especially those originating from sebum and only found on the skin surface, give the lipophilic portion of the hydrolipid film an antibacterial and fungicidal effect.

Regeneration and Repair Mechanisms

The skin has several regeneration and repair mechanisms to eliminate any damage caused by external influences and restore lost function.

Regeneration following UV-induced damage
Intense UV-exposure causes primary damage to the genetic material. Secondary damage is inflicted on the cell proteins and membranes by UV-induced free radicals. The skin is known to have many mechanisms for the repair of damaged DNA. In humans the most important are the excision repair and post-replication repair mechanisms: The excision repair mechanism is based on recognition, removal and replacement of the damaged DNA segment.

In this way mutations are prevented as long as the repair mechanism is not overburdened or defective. The post-replication repair mechanism, on the other hand, initially works around the damaged DNA segment, meaning the damage is ignored when the genetic code is read. Only later is the damage repaired. This mechanism is so faulty, however, that often more mutations are caused by the repair than by the original radiation damage.

Regeneration following skin injury
The layer of epidermal mother cells - the basal layer - ensures a steady renewal of the epidermis through continual cell division (proliferation). If an injury is confined to the uppermost skin layer, this damage, which is known as erosion, can heal without scarring. If the damage reaches the dermis (e.g. an ulcer) and thus involves the basal membrane, then healing is usually accompanied by scar formation. In this case destroyed skin cells are replaced by connective tissue. Wound healing takes place in several consecutive stages: in the first stage coagulating blood forms a membrane with a hard surface that adheres to the wound (crust). In the following skin cleansing stage, autolysis and phagocytosis of damaged and dying cells take place. At the same time connective tissue fibres are dissolved by enzymes. This activates mobile immune cells, and phagocytes and lymphatic fluids flow into the wound.

In the tissue building or proliferation phase, epithelisation of the wound base occurs, including the formation of capillary buds, new connective tissue and collagen fibres. Cell division during the proliferation phase can be stimulated and supported by the application of topicals such as dexpanthenol. This is conducive to better and faster healing.

Protective Functions

The skin protects the organism from mechanical, microbial, chemical and physical influences.

Damaging influence Protective mechanism
Mechanical influences Thickening of the horny layer (callus formation) , elasticity of the dermis and subcutaneous fatty tissue
Alkaline noxae Buffer capacity of the hydrolipid film and protective acid mantle
Penetration of skin bacteria and Harmful substances Protective acid mantle, 
permeability barrier of the horny layer
Dehydration Epidermal lipids, hydrolipid film, natural moisturizing factors (NMF)
UV radiation Increased melanin formation, thickening of the horny layer
Heat Perspiration, widening of the vessels in the skin
Cold Narrowing of the vessels in the skin

Skin

Several systems present in the skin contribute to the protective function of the skin. The corneocytes combine with the epidermal lipids (brick and mortar model) to form what is known as the permeability barrier. The skin surface lipids have an antibacterial and fungicidal effect. With its physiological pH of approximately 5.5 the protective acid mantle protects the skin from microbial invasion and alkaline noxae.

Cell Energy

As in other body tissues, the cells in the skin need energy to maintain their vital functions and their ability to regenerate and repair themselves as well as to grow. This energy is generated during intracellular metabolic processes.

Dermal blood flow supplies the basal cells with nutrients like fats, carbohydrates, proteins and oxygen. Free fatty acids, if in sufficient supply, play the largest role in energy production in skin cells. Cells like those in the stratum granulosum - into which little glucose diffuses – seem to use even the fatty acids set free during degradation of the cell membrane to produce energy.

Skin aging and a special electron carrier
More recent findings show that a deficiency of a certain enzyme, coenzyme Q10 (CoQ10), in the respiratory chain plays an important role in the reduced cell regeneration capacity resulting from aging or oxidative stress. Patients with cardiovascular disease often take Co Q10 orally to make up for this deficiency.

A biophysical study has now shown for the first time that topical application of CoQ10 can also reduce signs of skin ageing. The third stage of metabolism, the respiratory chain, plays an important role in energy production. It could be shown in a biophysical study that coenzyme Q10, which acts as an electron carrier and collecting point for reduction equivalents, reduces the signs of skin aging when applied topically.