Understanding Our Skin
- Isle Bee Well
- Sep 16, 2024
- 19 min read
Updated: Oct 25
It should not be a surprise that the first thing we recognize when we look at someone is their skin. Even though we might believe that we have noticed someone's eyes or a friendly smile first, our brain has already developed a rudimentary assessment and assumption of that individual's racial group, health status and hygiene based on skin appearance. The human Skin, however, has yet to be given the spotlight as, say, the brain, despite being the body's largest organ. We will quickly realize that this organ is more than skin deep, more than what meets the eye. Beyond the mere physical barrier skin provides, demarcating internal from external, our skin boasts a host of functional properties necessary for our survival. These functional properties range from Immune Defence, Heat Regulation, Moisture Retention, Sensation detection and Vitamin D Synthesis.
The Integumentary System, What We Know As 'Skin'
The structures encompassed by skin anatomy, including Hair, Nails, Sweat glands, and Oil glands, each have unique functions, complementing overall skin function. This collective of functional subsystems and auxiliary structures is referred to as the Integumentary System. We aim to keep things simple, referring to this diverse system as just 'Skin' for now. The human skin consists of two (2) layers, an outer layer, called the Epidermis, and a layer beneath it, termed the Dermis. Below the Dermis, there is a region that skin anatomists do not consider to be skin-like. This region is referred to as the Hypodermis.
Epidermis
The Epidermis is the visible layer where we apply skincare products. It is what most of us will recognize as skin, but there are more layers beneath. The Epidermis consists of 4-5 layers, stacked like lasagna. Each layer has specific functions to protect and retain water, determine skin colour, and detect sensation. Anatomists have assigned these layers two-part Latin names, each beginning with "Stratum," meaning 'layer'. Here introduction, from outer to inner, are the epidermal layers:
1. Stratum Corneum
2. Stratum Lucidum (only present in palms and soles)
3. Stratum Granulosum
4. Stratum Spinosum
5. Stratum Basale
Advancements in Dermatology called for the need to further ascertain region-specific structures, functions and biochemical processes. Because of this, layers like Stratum Corneum are subdivided into Stratum Compactum and Stratum Disjunctum. More commonly, however, the terms upper and lower are used in place of the Latin names to keep this simple.
Dermis
The Dermis sits just beneath the epidermal layers and is stitched to the overlying Epidermis by protein rivets called Hemidesmosomes, without which the epidermis would completely slough off after a routine shower. The interface between dermis and epidermis is referred to as the Dermal-Epidermal Junction and can be observed under light microscopy as an undulating interdigitations of dermis and epidermis, otherwise known as Dermal Papillae and Rete Ridges, necessary to withstand shear forces. Dermis is further divided into two layers, a Papillary Layer comprising of highly vascularized, thin connective tissue meshwork of loosely packed Type I and Type III collagen; and a Reticular Layer made up of a thick connective tissue layer of densely packed collagen. Notable structures found in the dermis include Blood vessels (which are not present in the Epidermal layers); varying types of Sensory Receptors (Pacinian Corpuscles, Ruffini’s Corpuscles, Meisnner’s Corpuscles, Thermoreceptors, Norciceptors); Sweat Glands (Apocrine, Eccrine); Pilosebaceous Units (Hair follicle and Sebaceous gland); and Lympathics that shuttle out metabolic waste. Also resident in this layer are special structures called Dermal Fibroblasts, which are tiny cell factories that manufacture tissue scaffolding, known as Collagen and Elastin, offering support, strength, and flexibility to the overlying epidermis. Fibroblasts are essential for our skin's plump appearance. As we age, our skin becomes less supple, wrinkled, and prone to everyday external factors like UV Radiation and Pollution. This is due to the progressive decrease in activity of these Dermal Fibroblasts as well as reduced production of youthful compounds such as Elastin, Collagen, Hyaluronic acid and Chondroitin. [1]
The Hypodermis/Subcutaneous Tissue
The Hypodermis, otherwise referred to as Subcutaneous Tissue, is located underneath the outer two skins (2) layers, Epidermis and Dermis, and has noteworthy functions. Composed of fatty tissue and blood vessels, which maintain thermal equilibrium through insulation. The Hypodermis also serves as a shock-absorbing cushion, protecting the inner, visceral organs from blunt trauma. How skin contours over the body is influenced by subcutaneous tissue.
Fun Fact: The surface area of average human Skin is about 20 square feet (sqft), the size of a picnic blanket.
Biological versus Chronological Ageing
Biological Ageing represents the functional state of the body, how the cells, tissues and organ systems are impacted by external factors. On the other hand, Chronological Ageing represents the numerical yearly change in human life. Biological Ageing and its causal factors are influenced by external factors such as Ultraviolet Radiation (UVR), Pollutants and Stress. Photoageing from prolonged skin exposure can accelerate telltale signs of ageing like wrinkles and Photopigmentation. Anti-ageing skincare products aim to reduce visible wrinkles, fine lines, and age spots. These products contain active ingredients like Retinoids (Vitamin A derivatives), Antioxidants, and Peptides that promote collagen production, improve skin texture, and enhance hydration, helping to maintain a youthful and radiant complexion.
The Journey of A Mature Skin Cell: The Keratinocyte Life Cycle
We will start by discussing the epidermal sublayers and their functions in the context of a skin cell's journey from the bottom (Stratum Basale) to the top (Stratum Corneum). As a guiding principle, a skin cell called a keratinocyte is programmed to transform into a deactivated, though not entirely dead, flattened skin cell known as a corneocyte.
Let us begin discussing in depth the epidermal sublayers and their functions in the context of a Keratinoctye’s (skin cell) journey up through the sublayers— from bottom, Stratum Basale, to the top layer, Stratum Corneum. As a guiding principle, a skin cell's fate is to relinquish its vital force, Programmed Cell Death, to become a flattened, deactivated skin cell, later termed a Corneocyte. The saga of the Keratinocyte Life Cycle begins with: Proliferation, an expansion in skin cell number as stem cells in the bottom skin layer, Stratum Basale, become numerous by mitotic divisions, self-cloning. The next stage of the skin cycle is referred to as Terminal Differentiation, structural and physiological modifications to the Keratinocyte is underway, necessary for skin cell conversion into a Corneocyte. The last of the stages, is Desquamation, as corneocytes slough off into the surroundings. The duration of the Keratinocyte journey lasts 28 days or about 1 month and is referred to as the Epidermal Turnover Rate. Ensuring skin turnover speed is not hastened, as in conditions like Psoriasis, allows for healthier, fully matured skin. [2]
How skin Product Efficacy is determined relies strongly on prolonged usage of products.
Skin Cell Life Cycle and Its Stages
1. Proliferation
In this stage, keratinocyte stem cells multiply to increase cell numbers.
2. Terminal Differentiation
Structural and physiological changes occur, transforming the keratinocyte into a corneocyte.
3. Desquamation
The final stage is the shedding of corneocytes, commonly called "dead skin.".
The Bottom Layer of the Epidermis: Stratum Basale
Stratum Basale, the base layer, is the lowest and thinnest of the epidermal layers. It is comprosed of a single row of early skin cells fastened to each other by protein rivets called Desmosomes. These molecular rivets confer horizontal tensile strength and structural rigidity to the skin. Providing vertical tensile strength are Hemidesmosomes, smaller protein buttons that fix skin cells to the underlying Basement Membrane. This structure serves as a sturdy platform upon which epidermal layers are stacked, compartmentalising also, Epidermis from Dermis. Stratum Basale, compared to the other epidermal layers, has high cellular activity when observed microscopically. These early skin cells clone themselves by Mitosis, advancing renewed skin cellular layers as old skin cells shed (Cellular Proliferation). For this reason, S. Basale is also termed Stratum Germinativum, reflecting this layer's germinative quality.
Stratum Basale or S. Basale, is comprised of three (3) types of cells: Melanocytes, Keratinocytes and Merkel Cells. Melanocytes, which account for approximately 5% of all epidermal cells, are responsible for producing the skin pigment Melanin. Two forms of melanin are found in specific skin types, Eumelanin, mainly present in darker hues of skin, while Pheomelanin is predominantly found in lighter skin profiles.This pigment is synthesized inside specialized cellular compartments called Melanosomes. Pigment-producing melanocytes have cellular arms that extend, projecting themselves amongst overlying keratinocytes, allowing for uptake of melanin by other cells of the epidermis. Melanin is to the skin as Chlorophyll is to leaves. This pigment gives us many wonderful hues of skin colour we see on the planet, and serves to partially protect us from Ultraviolet Radiation (UVR) by forming a dome-shaped pigmented covering over the skin cell nucleus, the Melanin Barrier/Photoprotection Barrier. The spectrum of skin colour depends on how much pigment is produced rather than the quantity of melanocyte cells present. Keratinocytes, are the default cellular residents of the skin, constituting up to 85% of the Epidermal layer. Skin’s Permeability Barrier, its ability to repel water (waterproofing), is attributed to keratinocytes and their close-neat arrangement. Merkel Cells, after German anatomist Friedrich Merkel, are mechanoreceptors that detect touch sensations, allowing for awareness upon skin contact. They make up 6-10% of total skin cells. [2,3]
Fun Fact: The Fitzpatrick Scale owas established in 1975 by dermatologist Thomas B. Fitzpatrick, serving as a framework to determine or phototype skin tanning from sunlight
Next Skin Layer Up, The Stratum Spinosum
Stratum Spinosum, also known as the Prickle-Cell Layer, is the second layer up from the first layer, Stratum Basale and is also the thickest, 8-10 cell layers. Skin scientists have divided this layer into an upper and lower region based on different physiological and biochemical processes specific to these regions. Overall, the role of Stratum Spinosum is to facilitate the conversion of a Keratinocyte into a Corneocyte, Terminal Differentiation, the second stage of the Keratinocyte Lifecycle. The complex physiological process of Terminal Differentiation need adequate moisture retention, serving as solvent for its biochemical reactions. A fishnet-like mesh made of the structural protein, Keratin, ensures adequate moisture trapping and cell structure for supple skin. Keratin Intermediate Filaments are the skeletal frame of the cell or cytoskeleton, offering a keratinocyte internal strength and rigidity much like our skeletal frame. The body’s first line of Immune Defence takes up post on this Stratum Spinosum epidermal layer as sentinel Langerhans cells (5% of cells in the epidermis). [3] These skin-specific, tissue-resident macrophages continually sample foreign particulates like microbes and allergens, digest them by receptor-mediated endocytosis or present them to other immune players to initiate coordinated responses. In some, this immunological response can become dysregulated resulting in a cascade of inflammatory skin conditions, like Atopic Dermatitis (Eczema) or Rosacea. [2,7,8]
Let us now take a look at the biochemical processes of this layer, particularly in the Upper Stratum Spinosum, keeping in mind that these processes are preparatory events of Terminal Differentiation, the conversion of a Keratinocyte into a Corneocyte. As a conceptual overview, Cornification results in two (2) major structural modifications of the keratinocyte’s plasma membrane: Protein Modification, the development of a Cornified Cell Envelope; and Lipid Modification, the development of a Multilamellar Lipid Structure. These modifications will be addressed in more detail soon. At the Upper Spinosum, cellular machinery such as Free Ribosomes and packaging houses like the Golgi Apparatus, manufacture subcellular structures that 'sound off' the cornification process, these structures are Keratohyalin Granules and Odland Bodies, respectively. Keratohyalin Granules, which have their final resting place at Stratum Granulosum, are cytosol-based, insoluble protein granules that harbour smaller precursor proteins such as Profilaggrin, Tricohyalin, Loricin and Keratin. These precursor players confer Protein Modifications to the Keratinocyte membrane.
Odland Bodies are pouch-like repositories which find their resting place at S. Granulosum (where they are referred to as Lamellar Bodies); and contain Precursor Lipids (Cholesterol Culfate, Glucosyl Ceramides, Sphingolipids and Phospholipids) as well as Lipid-Assembly Enzymes (Acidic Sphingomyelinase, Secretory Phospholipase A2) that confer Lipid Modifications to the keratinocyte membrane. Odland or Lamellar Bodies may also contain other biochemical and immunological players like Kallikrein, Cathepsin, Corneodesmosin, Proteases and Beta 2 Defensins. An intracellular calcium (Ca2+) gradient exists at the Spinosum layer, with Upper S. Spinosum having elevated Ca2+ levels compared to Lower S. Spinosum. This inherent difference in concentration is what initiates early enzymatic mechanisms of Cornified Cell Envelope development, by activating Transglutaminase 1 (TGase 1) and crosslinking major structural proteins, with peak activity at the Stratum Granulosum layer. [2,3]
Getting Granular: The Stratum Granulosum
The Stratum Granulosum is the thinnest of the epidermal layers (3-5 cell layers) and demarcates moisture-rich bottom layers (S. Basale and S. Spinosum), from moisture-poor upper layers (S. Lucidum and S. Corneum). Histologically, this layer appears granular due to the abundance of aggregated keratohyalin granules present in the cytosol of Keratinocytes. The big picture here at this stratum is elevated keratinocyte modification activity (Cornification process), not only to the plasma membrane but to the rest of the skin cell as well. These global cellular changes are mainly made possible by Keratin Filaments. Keratin filamentous proteins start becoming hardened, flattened, and bundled together, a process that reaches its peak at Upper Stratum Granulosum. Intermediate-associated proteins like Trichohyalin and Filaggrin become activated, allowing for water repellence and reduced Trans Epidermal Water Loss (TEWL). This phenomenon, TEWL, can be described as the passive evaporation of moisture from skin due to differences in water vapour pressures between our body and the atmosphere In general, our body water would much rather seep out into the environment than stay in, but if allowed to do so can cause us to literally shrivel up and die. Skin has the important task of ensuring such a disaster does not happen. In some instances, above-threshold water loss does occur, resulting in a host of dry skin conditions collectively referred to as Xerosis.
The process of Keratinization continues, as the keratinocyte sequentially forms its most important structure called the Cornified Cell Envelope. This envelope is a result of both Protein and Lipid Modifications. The protein modification happens through the cross linking of several proteins fillaments assemble, forming a scaffold-like supportive structure for lamellar lipids and also serving as a protective physical barrier from injury. Lipid Modification is underway once the lipid triad of Ceramides, Cholesterol and Free Fatty Acids of Odland bodies has been enzymatically assembled. Only then can these lipids be extruded by exocytosis from their pouches and deposited on top of the plasma membrane. Multilamellar Lipids are made up of about 40%-50% Ceramides, 25% Cholesterol, 10-15% Free Fatty Acids, with the remainder being simple lipids (neutral or true lipids). [2]
Ceramides, the most abundant of the lipid triad, are essential for Multilamellar Lipid Structure,
Interestingly, extracellular pH steadily starts dropping from a neutral pH of 7, gradually getting more acidic up through Stratum Corneum, eventually setting up a skin surface pH of 4.5 (Skin Acid Mantle) that renders the surface uninhabitable for most harmful pathogens. There is increased activity at Upper Stratum Granulosum as several events happen concomitantly that ultimately complete the Keratinization Process. This region, straddled between Lower S. Granulosum and Stratum Corneum (S. Disjunctum), is referred to as the Transitional Zone and marks the transition point where a Keratinocyte transforms into a Corneocyte. A major occurrence at this zone is the formation of moisture trapping compounds such as Amino Acids, Pyrrolidone Carboxylic Acid (PCA), Lactate and Uronic acid, these are collectively termed Natural Moisturizing Factors (NMFs), [2,3]
The formation of the Cornified Cell Envelope signifies that the end has been reached for the Stratum Granulosum. This involves the Keratinocyte losing its nucleus and cellular machinery, becoming deactivated, although not lifeless. The Keratinocyte undergoes a named change to Corneocyte.
The Protective Layer of Thick Skin: Stratum Lucidum
The next layer up, Stratum Lucidum, only makes an appearance in Palmoplantar skin, the skin of the palms of hands and soles of feet, where robustness is needed. Anatomists use the term ‘thick skin’ to refer to palmoplantar skin and ‘thin skin’ for the rest of the body's surfaces. This layer is just about the same in thickness as Stratum Granulosum, which is about 3-5 cell layers thick.
It is believed by some skin scientists that Stratum Lucidum can make an appearance in ‘thin skin’ regions in cases of Pruritic Atopic Dermatitis, an itchy eczema-prone variant, inflicting the urge to scratch. In this form of Eczema, it is stipulated that afflicted skin tries to protect itself from high-shear scratching by forming an extra leathery layer that is Stratum Lucidum-like. This explains why the skin of those affected with Atopic Dermatitis struggles with skin roughness, constantly seeking hypoallergenic moisturizers and body lotions with good emollience, which can soften, soothe tame their skin. At this layer also, Keratinocytes are virtually devoid of life and start densely packing together, working along with Stratum Granulosum to enhance the Waterproofing Effect.
The Outermost Epidermal Layer, Stratum Corneum
We have finally reached the last and outermost of the epidermal layers, Stratum Corneum. Like some of the other epidermal layers, this stratum is divided into a Lower and Upper region, called Stratum Compactum and Stratum Disjunctum, respectively. Stratum Compactum captures the final events of Keratinisation in the Transitional Zone, where the Keratinocyte has transitioned into a Corneocyte, as well as the other cell-compacting events. Compaction involves stitching together specialised Corneocytes, otherwise called Squames. To do so, Tonofibrils formed as a result of the Keratiniation process take on the role as specialized protein rivets called Corneodesmosomes, stitching adjacent Corneocytes together in a serrated fashion (Corneocyte Compaction). This process is essential to the integrity of the skin’s barrier defence fronts, particularly its Permeability Barrier. The Permeability Barrier formed due to the stitching of neighbour Corneocytes prevents the free passage of pathogens, allergens and other invaders between cell spaces or interstiches, thereby reducing Trans Epidermal Water Loss (TEWL). Incomplete Corneocyte Compaction can result from a faulty Cornification Process (i.e., poor Cornified Cell Envelope formation), usually due to filaggrin protein deficiency or Filaggrin Mutagenesis.
At the Upper Stratum Corneum layer, known as Stratum Disjunctum, skin cells arrive at their fate after serving their purpose of Skin Barrier Defence and must now be shed from the body to allow for new replacements. This replacement of old with new happens by a dynamic process of enzymatic dissolution at the level of the Corneodesmosomes. Desquamation is the term used to describe this event, as Corneocytes slough off into the environment— a process initiated by an acidic pH environment and proteolytic enzymes like Cathepsin and Kallikrein Serine Proteases (KLK5, KLK7, KLK14). This process of shedding must be carefully regulated to prevent excess, partial or incomplete shedding of Corneocytes. This is accomplished by the delicate regulation of those proteolytic enzymes mentioned prior, in an acidic environment like the Acid Mantle by protease inhibitors such as Lymphoepithelial Kazal-Type Inhibitor (LEKTI) and Cholesterol Sulfate. [2,3,6]
Homeostatic balance of the Desquamation process ensures a good Stratum Corneum thickness and viable Skin Barrier Defence. The rate of Corneocyte shedding increases moving up from lower epidermal layers through the Stratum Corneum layers. The fine balance of Desquamation between pro- and inhibitory enzymes is a marvel of Stratum Corneum. Adequate hydration throughout S. Corneum facilitates this intricate process. Disorderly or incomplete desquamation, sometimes seen in extremely dry, Xerotic skin can result in the clumping or build-up of unseparated Corneocytes, appearing scaly in nature, compromising barrier integrity and increasing the likelihood of exogenous factors like pollutants to infiltrate deep into the body
Evidence of a well-ordered Desquamation process appears under light microscopy as a Honeycomb, representing the structural remains of Cornification.
The Pursuit of Knowledge in Skin Science
It has been the ongoing and passionate pursuit of scientific work by Corneobiologists, Dermatologists, and a diverse array of other Skin Scientists to shed light on the remarkable complexities and wonders of the Epidermis and its functional layers. This multidisciplinary approach not only enhances our understanding of the skin but also paves the way for groundbreaking advancements in modern, high-performance Skin Care Formulations that cater to a wide variety of skin types and concerns.
Histological Processing: A Window into Skin Structure
One of the key methodologies that has significantly advanced our understanding of skin structure is Histological Processing. This technique allows scientists to prepare and visualize stained slices of skin under a light microscope, providing a detailed view of the various skin layers and their respective cellular compositions. By employing specific staining techniques, researchers can highlight different components of the skin, such as Keratinocytes, Melanocytes, and Fibroblasts, enabling them to study their arrangement, health, and interactions in great detail.
Through histological analysis, scientists can observe how the skin responds to various stimuli, including environmental factors, ageing, and skincare treatments. This visual representation not only enriches our knowledge of the skin's architecture but also aids in identifying potential areas for therapeutic intervention. For instance, understanding the changes in skin structure that occur with ageing can lead to the development of targeted anti-ageing products that effectively address these specific concerns.
Advancements in Skin Care Formulations
The insights gained from these scientific explorations have been instrumental in the formulation of advanced skincare products. By integrating findings from Corneobiology and Dermatology, formulators can create products that are not only effective but also safe for a diverse range of skin types. Innovations such as the incorporation of bioactive compounds, Peptides, and Advanced Delivery Systems like Liposomal Enclosures, have emerged as a result of this rigorous scientific inquiry. Additionally, the rise of personalized skincare—tailored to individual skin needs and conditions—has been made possible through a better understanding of skin biology. This approach allows for the creation of bespoke formulations that address specific issues such as acne, hyperpigmentation, and dryness, ultimately leading to improved outcomes for consumers.
The Future of Skin Science
As Corneobiologists, Dermatologists, and Skin Scientists continue to collaborate and share their findings, the future of skin science looks promising. Ongoing research into the Skin Microbiota, genetic factors influencing skin health, and the impact of lifestyle choices on skin conditions will undoubtedly lead to further innovations in skincare. The integration of technology, such as artificial intelligence and machine learning, may also play a pivotal role in advancing our understanding and treatment of skin-related issues. In conclusion, the relentless pursuit of knowledge by these dedicated scientists is not only illuminating the intricate workings of the Epidermis but also driving the evolution of skincare formulations that are more effective and tailored to meet the needs of the modern consumer. The intersection of science and skincare continues to open new avenues for exploration, promising a future where skin health is prioritized and maintained with the utmost care and precision.
The Closing of A Skin Saga
The human skin is the largest organ in the body, which serves as a protective barrier between our internal systems and the external environment. It is not merely a covering; it is a complex and dynamic structure that plays numerous vital roles in maintaining overall health and well-being. Comprised of two (2) primary layers: the Epidermis and Dermis, with an underlying Hypodermis, not regarded as part of the Skin layer classification. The outermost layer, the Epidermis, is primarily responsible for protection. It contains Keratinocytes, resident skin cells that produce Keratin, a protein that helps waterproof the skin and provides a physical barrier against environmental threats such as pathogens, chemicals, and physical abrasions. The Epidermis also houses Melanocytes, which produce Melanin, the pigment responsible for skin colour and protection against some forms of Ultraviolet Radiation (UVR). Beneath the Epidermis lies the Dermis, a thicker layer that contains a rich supply of blood vessels, nerves, and connective tissue. This layer is essential for Thermoregulation, Sensation, and providing Structural Support. It contains Hair follicles, Sweat glands, and Sebaceous glands, all of which contribute to the skin's functions. The dermis is also where Collagen and Elastin fibres reside, giving the skin its strength and elasticity. The skin also plays a significant role in the Immune System. It contains specialized cells, such as Langerhans cells, which help detect and respond to pathogens. This immune function is critical in preventing infections and maintaining overall health. Additionally, the skin is instrumental in Sensations of Fine Touch, Pressure, Pain, and Temperature.
Another fascinating aspect of our skin is the Skin Microbiota, a diverse community of microorganisms that reside on the skin's surface. The Skin Microbiota is a component part of our whole body Microbiome and plays a crucial role in protecting against foreign microbes, supporting the immune response, and maintaining balanced skin health. As we age, our skin undergoes various changes, including a decrease in collagen production, reduced elasticity, and a slower cell turnover rate. These changes can lead to wrinkles, sagging, and a dull appearance. Factors such as sun exposure, pollution, and lifestyle choices can accelerate these ageing processes. Therefore, understanding how to care for our skin, including proper hydration, nutrition, and sun protection, is essential for maintaining its health and appearance over time. In closing, the marvel of our skin extends far beyond its appearance. Understanding the intricacies of our skin can lead to better care practices, ultimately enhancing our overall health and well-being. Embracing and nurturing this remarkable organ is essential for a vibrant and healthy life.
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