Impaired Enzyme Activity Not “Dehydration” By Kai Atkinson

The word “dehydration” is vastly overused within the aesthetics and beauty industry, along with the condition misdiagnosed and at times, treated incorrectly. Why is this? Well, it comes down to understanding the cells and systems involved as to why there is a lack of free water within the epidermis and being able to recognise the link between fast trans-epidermal water loss (TEWL) and an impaired acid mantle.

In order to discuss the lack of free water within the epidermis and how this relates to “impaired enzyme activity,” we first need to understand the role of the circulatory and lymphatic system. These two systems that contribute to immunity are so vitally important when it comes to maintaining balanced hydration and tissue homeostasis, and when compromised, can have serious consequences on the cellular hydration levels of the skin.

Kai Atkinson

The Circulatory & Lymphatic System

The circulatory system is a continuous endothelial tissue network that contains specialised cells called haemoglobin. These red blood cells are attracted to the oxygen-rich molecules that we breathe in through our lungs, and in doing so, will support the transfer of these oxygen molecules throughout the body in order to bring fresh oxygen to all tissues, including the cell producing layers of the skin. The circulatory system contains plasma, and this fluid makes up a very large portion of your blood as it is responsible for transporting oxygen, nutrients, hormones, proteins, enzymes, cytokines and growth factors to where they need to go.

These metabolic substances play a vital role in supporting sufficient water levels within the skin.

In relation to the circulatory system, the hyaluronic acid (HA) component of the glycosaminoglycans (GAG’s) plays a very important role in contributing to balanced hydration levels and tissue homeostasis. The HA brings in the plasma from the circulatory system down into the extracellular matrix of the dermis, where it facilitates the creation of the dermal reserve. The dermal reserve contributes to cellular protection and hydration as it supports the facilitation and recruitment of immune cells, enzymes, proteins, hormones and nutrients.

Part of the dermal reserve (also known as the “extracellular fluid”), will make its way through the perforated connective tissue of the dermal/ epidermal junction (DEJ) in order to nourish the cells and systems of the epidermis, as it contains the oxygen, nutrients, hormones, proteins, enzymes, cytokines and growth factors this tissue requires to function correctly. This water movement is known as trans-epidermal water loss (TEWL), and is a normal metabolic process that is required for sustaining tissue homeostasis.

The lymphatic system is a complex system that works in unison with the circulatory system. It is responsible for transporting fluids, fats and fat soluble vitamins, dendritic cells and infectionfighting white blood cells throughout the body in order to maintain immunity for host defence. The lymphatic system is also responsible for the removal of metabolic waste that accumulates as cells undergo mitosis, proliferation, differentiation and apoptosis.

The lymphatic system is not continuous, unlike the circulatory system, and for a simple analogy, can be thought of as being a fitted glove on the hand. The glove contains specialised compartments for your fingers, but once your fingers are embedded in the glove, there is nowhere else for them to go. In other words, the lymphatic vessels contain dead end capillaries that rely on the circulatory system to help transport the movement of substances through the action of sympathetic movement. This, in turn, supports cellular hydration levels by keeping all fluids in the body constant and in homeostasis.

The lymphatic system together with the circulatory system are invaluable to the health and wellbeing of the body and of course, skin. By supporting these two systems, cellular hydration within the epidermis and dermis will be supported.

Let’s now take a look at the “Epidermal Barrier” and how the keratinocyte in particular, plays a major role in sustaining the water levels within the skin.

The Epidermal Barrier

When we use the terminology “epidermal barrier,” as an industry, we are almost always referring to the stratum corneum and its ability to maintain and regulate TEWL. The keratinocyte plays a leading role in supporting the water retention power of the epidermis, as it creates important lines of skin barrier defence. These defence systems compromise of the following:

Acid mantle/microbiome

Is a complex mixture derived entirely from sebaceous gland secretions, eccrine sweat and the multi-lamellar lipid structure.

Stratum corneum

The end result of the keratinocytes life cycle and is a hydrophobic cell.

Natural moisturising factor (NMF)

Formed by the enzymatic breakdown of profillagrin and is vital for stratum corneum hydration.

Multi-lamellar lipid structure

Composed of ceramides, cholesterol and free fatty acids and is responsible for the permeability barrier function of the epidermis.

Let’s now have an overview the life cycle of the keratinocyte and how its built-in defence mechanisms contribute to the barrier function of the skin, in order to maintain adequate cellular hydration levels.

As keratinocytes of the epidermis migrate from the spinosum layer into the granular layer, a lot of cellular activity takes place. The cornified cell envelope (CCE) via enzymatic activity begins formation along the interior of the keratinocytes plasma membrane. This phospholipid membrane will eventually be enriched by a lipid envelope known as the “multi-lamellar lipid structure” primarily composed of ceramides, cholesterol and free fatty acids, that will covalently attach itself to the exterior of the CCE.

Once in the stratum corneum, the CCE contains anchoring protein structures called corneodesmosomes that anchor into the corneocyte. This, in turn, supports cell barrier alignment to ensure a densely compacted and well structured stratum corneum. By having a compacted and well formed stratum corneum,

it will provide physical defence against foreign materials from getting into the skin, but also slow down the evaporation of TEWL that arises from the dermis(extracellular fluid).

Together, the CCE and the multi-lamellar lipids provide effective physical and water barrier functions within the skin.

Alongside the creation of the cornified cell envelope in the granular layer, is the hydrophilic and free radical scavenging Natural Moisturising Factor (NMF). NMF is a combination of amino acids, sugars and salts that are crucial elements for epidermal barrier function. The NMF is released into the keratinocytes cytosol and is stored within the corneocytes upon completion of the keratinization process. The cytosol is an aqueous fluid internal to the plasma membranes and together with NMF, contributes to cellular hydration of a cell.

So, what do all of these built-in defence systems have in common to facilitate their successful formation? Enzymes!

Enzymes are biological protein catalysts that increase the rate in which a chemical reaction occurs, and any shortage or absence of an enzyme can have a detrimental effect. There are many different types of enzymes found within the skin, but the main ones that are responsible for supporting and regulating epidermal barrier formation are transglutaminases, kinases, caspases, proteases amongst other hydrolytic enzymes.

Enzymes that help such reactions require water to function, and any reduction in water will compromise cell formation, viability and repair.

If cellular hydration levels were low due to an impaired lymphatic system or poor fluid intake and/or medications with diuretic side effects, these enzymes would be unable to perform efficiently and this would impair the integrity of the skin. Without proper functioning enzymatic activity, the CCE, NMF, cytosol and the multilamellar lipid structure would be compromised, because it is enzymes that are responsible for the formation of a well structured stratum corneum and permeability barrier function in order to slow down the evaporation of TEWL. Did you know a human cell can contain around 1300 enzymes? Yes! This, in turn, makes these microscopic biological catalysts so fundamentally important for the operation of the body and skin barrier defence systems.

Let’s take a look at the leading causes of impaired enzyme activity:

1. Essential fatty acid deficiency (EFAD) 2. Lipid-dry skin 3. Hormone imbalances (menopause) 4. Impaired lymphatic system 5. Fluid intake 6. Ambient humidity 7. Medications with a diuretic side effect 8. Alcohol and coffee

It will be during the consultation process that you will determine any negative connotations that your client may be exposed to that will cause fast or slow TEWL, and in turn, result in impaired enzyme activity of the skin.

As we have discussed, water regulates many enzymatic and chemical reactions to sustain balanced hydration and tissue homeostasis, and because of this, gives a very different perspective to the overused word “dehydration.”

There are four main factors that determine balanced hydration and they are as follows:

1. The relative humidity 2. The retention power of the epidermis 3. The quantity and quality of water transmitted from the inner to the outer layers of the entire ecosystem of the skin 4. The time span the water takes to move from the inner to outer layers

If the relative humidity is low, the water movement from the skin will be faster because there is less water in the atmosphere to slow it down. Drier air also contributes to faster evaporation, so artificial atmospheres such as air conditioning will have a negative impact on TEWL. Understanding the relevance of enzyme activity and balanced hydration as well as supporting defence systems is what needs to be understood when there is a lack of free water within the viable epidermis. So, working topically, where does one start to improve impaired enzyme activity?

When the first three lines of skin barrier defence are compromised, skin has the ability to reflect changes in other cells and systems of the body. Understanding and appreciating this synergy between cells and supporting systems of the epidermis, dermis and body is imperative if one is to improve the water levels within the skin.

Many skincare products will aggravate skin conditions that have lost the first three lines of skin barrier defence and require topical formulations that do not contain conventional emulsifiers or other foreign ingredients. Instead, physiological lipids such as phosphatidylcholine (PC) which makes up a large proportion of all biological plasma membranes, should be used, as well as ceramides, cholesterol, triglycerides and free fatty acids which make up the acid mantle and multi-lamellar lipid structure of the stratum corneum.

The simple law of physics says that oil sits on top of water, and when this statement is applied to the skin it translates into: epidermic lipids slow down the evaporation of water and this results in better hydration levels of the skin, this is thinking like a chemist.

Before throwing a water-based substance such as hyaluronic acid to someone’s skin that does not have a functioning lipid metabolism, it’s important to take a step back and link product composition to the cells and systems affected, so you can move forward with a treatment program that will repair supporting defence systems and enzymes in order to encourage and maintain balanced hydration levels within the skin.

To summarise, skin analysis and consultation is key when it comes to establish the leading causes and/or triggers as to why someone is experiencing impaired enzyme activity, because understanding the relevance of enzymes, cellular hydration and supporting defence systems that are required to maintain the water levels within the skin, gives a very different perspective to the overused word “dehydration.”