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General histology of the skin.

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When we think of the organs of the body, we tend to think of structures inside of us. But did you know that the largest and probably one of the most vital organs of your body is something you see every day. I am, of course, referring to your skin.

In this Kenhub tutorial, we will be looking closer at the skin and its histology. In this tutorial, we'll be covering an overview of the skin and its function, the different types of skin we have, the layers of skin, the cells that it's composed of, and the accessory structures which help it to carry out its functions. We'll also mention a clinical scenario where knowledge of the skin is important.

Skin is amazing. It's the largest organ in the human body, covering us from head to toe and has several functions. It protects our squishy insides from trauma, infection and UV radiation; regulates our temperature and water content and keeps us waterproof in the rain, synthesizes the hormone vitamin D in daylight, and lets us sense and interact with the world around us. Without skin, you would perish pretty quickly. It's, therefore, a vital organ.

Not all skin is the same, however. It changes depending on the whereabouts of this in the body adapting to the specific requirements of that area. Broadly, however, there are two types of skin – thick skin and thin skin.

First, let's look at the layers of skin. We'll use thick skin as our example and then explain the difference between thick and thin skin later on. There are three main layers of thick skin – the epidermis which is the outermost layer, the dermis which is the middle layer, and the hypodermis which can also be called the subcutaneous tissue is the deepest layer directly overlying the fascia covering the muscles. These layers are subsequently divided into separate sublayers which we'll cover as we go through each in turn.

We'll start with the outermost layer – the epidermis – first looking at its compositions and then its five sublayers. This image is a magnified view of thick skin with the epidermis highlighted in green. The epidermis is composed of keratinized stratified squamous epithelium, but what does that mean? Let's break it down.

Epithelium means that it's lining an organ or cavity. In this case, the skin is that organ. Squamous refers to the type of cells. Squamous cells have a stretched, flattened appearance. This makes them efficient at covering a large area. Stratified describes the arrangement of these cells. Stratified meaning that the cells are layered up. This image shows the stratified keratinocytes of the epidermis. Keratinized means that the top layers of cells contain keratin. That's where the name keratinocyte that we just mentioned comes from.

Keratinization provides greater resilience to abrasion and makes the cells waterproof, however, this also means that water and nutrients can't get into the cells so they subsequently die. This results in a need for high production rate of skin cells. In fact, the skin cells lifespan is around ten to thirty days.

The epidermis can be split into five distinct layers in thick skin and four in thin skin. This is based on the types of cells observed at these levels. A heads up before we list the layers. The term "stratum" is just Latin for layer. Going from superficial to deep, the layers are the stratum corneum roughly indicated here, the stratum lucidum, the stratum granulosum, the stratum spinosum, and the stratum basale. Deep to the stratum basale is the basement membrane. This is a layer of connective tissue that separates the epidermis and the dermis. It is the deepest part of the epidermis although it is not classically counted as one of the layers.

The epidermis is avascular – that is, it has no blood supply. It, therefore, has to receive all of its nutrients and remove its waste by diffusion through the basement membrane. This results in the superficial layers of the epidermis being deprived of nutrients.

Now that we've reached the base of the epidermis, we'll go back up the layers from deep to superficial to discuss each layer and how they differ. Going from deep to superficial allows us to follow the life cycle of a skin cell. As we go through, we'll underline the features which you can use to identify skin cells in each layer and, in turn, identify the cells that will allow you to identify the layer.

We've zoomed in a little on our image with the dermis here, the epidermis here and the stratum basale highlighted in green. The stratum basale is a one-cell thick layer of epidermis sitting on top of the basement membrane. When we say skin cells, what we really mean are keratinocytes – the most abundant cell in the skin. In the stratum basale, basal cells proliferate and differentiate into keratinocytes. Basal cells are stem cells which are columnar in shape. They can divide into more basal cells to regenerate their population in the stratum basale or into keratinocytes. The stratum basale is, therefore, the birthplace of keratinocytes.

Basal cells are bound to the basement membrane while keratinocytes are pushed superficially into the stratum spinosum. Because the epidermis is avascular, keratinocytes become progressively depleted of nutrients as they move superficially further away from the basement membrane. Other cells found in the stratum basale are melanocytes which are pigment-producing cells, Langerhans cells which are cells that stimulate the immune system in response to a pathogen, and Merkel cells which are a type of nerve ending. We'll be talking more about these toward the end of the tutorial.

Moving up a layer, we have the stratum spinosum highlighted here in green. The stratum spinosum, also known as the prickle cell layer, is around eight to ten cells thick. As a keratinocyte is pushed upwards through the stratum spinosum, its cytoskeleton starts to shrink and the cells start to flatten. You might also notice that the nuclei in this layer are paler than they were in the stratum basale. This is down to an increase in keratin synthesis, a process known as keratinization.

Keratin is a fibrous protein which gives epidermal cells their higher tolerance to damage. The keratinocytes camp with other keratinocytes which means that keratinocytes have a spiny, prickly appearance. This is where the name spinosum and prickle cell layer come from. The numerous interconnections between keratinocytes form a network which provides protection to underlying tissues particularly from abrasive forces and gives elasticity and flexibility to the epidermis. You might also find a few Langerhans cells hanging out in the stratum spinosum doing their mean thing.

Going up another level, we arrive at the stratum granulosum. This is actually the deep pink layer of skin you see when a wound is healing. It's around three to five cells thick. Keratinocytes have darker cytoplasms in this region due to the presence of keratohyaline granules which stain dark purple on a hematoxylin and eosin stain. The keratohyaline granules seen highlighted in green on this callout image bind keratin filaments together to increase the tensile strength of the cells. The darkened keratinocytes on this layer lose their nuclei and organelles as they start to die and become the keratinized squames of the superficial epidermal layers. They also secrete lamellar bodies.

The word "lamellar" comes from the Latin meaning thin plate. You can see a good example of the word lamellar in lamellar armor which is a type of body armor worn in ancient Japan and features panels of leather tightly packed together in horizontal rows. The oblong-shaped lamellar bodies are also tightly packed, forming an impermeable membrane so you can see how they might contribute to waterproofing. Owing to their granular content and appearance, keratinocytes in this layer are sometimes called granular cells, but be careful because these are not the same as granulocytes which are immune cells in the blood.

Moving on up, we have the stratum lucidum, also known as the clear cell layer. This is only present in thick skin, not thin skin. At around three to five cells thick, you might think it should be easily visible as the stratum granulosum but although it is the same number of cells thick, these keratinocytes are flatter and the layer does not stain well on hematoxylin and eosin so it's difficult to see. We've highlighted it in green to make it clearer.

The main way of recognizing the stratum lucidum is that the keratinocytes do not have clear boundaries and do not have a dark granular appearance and the layers are slightly brighter, clearer shade of pink which is uniform in color. This shade difference in uniformity is easier to see if we zoom out a little. A part of the stratum lucidum is still highlighted in green, but if we follow along here above the dark cells of the stratum granulosum, there is a thin layer of uniform pink color which is a slightly brighter shade than the layer above. If you can't see this, don't worry, but come back and try again as distinguishing between fine color differences is an important skill in histology and can be improved a lot with practice.

The keratinocytes are nearing the end of their journey. Now they're pushed out into the stratum corneum. In thin skin, the stratum corneum is only a few cells thick but in thick skin, as we have here, can be over thirty cells thick. In this layer, the keratinocytes are dead and fully keratinized but this makes them perfect for their functions of protection and waterproofing. The more abrasive forces an area of skin is subjected to, the thicker the stratum corneum.

Here we've highlighted some of the skin cells. In this layer of epidermis, the keratinocytes can also be called corneocytes which identifies them as being biologically dead with no ability for further synthetic functions. These features differentiate corneocytes from keratinocytes. As corneocytes are pushed further towards the surface, they squame off the skin, leaving the body. The next time you see them will probably be when you're dusting your room.

We followed keratinocytes from their formation in the stratum basale to their desquamation from the skin surface but what goes on underneath? Now, we'll return to the deep part of the epidermis and work our way down, starting at the dermo-epidermal junction. The dermo-epidermal junction simply refers to the level where the epidermis and dermis meet. At this junction, the epidermis folds around a series of papillae from the surface. "Papilla" is Latin for nipple and refers to the shape of these protrusions.

On histology slides, these look like ridges and, therefore, are named epidermal ridges or Rete ridges, which can be seen clearly here highlighted in green. The functions of the ridges are to increase the surface area at the junction which enhances nutrient transfer and increases resistance to shearing forces. The ridges are deeper in thick skin than thin because as you might expect, thick skin needs to be more resistant to abrasion.

Let's move on now to talk about the dermis. Delving below the basement membrane, we can see the dermis highlighted in green on our lovely illustration here. In this section, we'll look at the overall composition of the dermis followed by its sublayers which are the stratum papillare and the stratum reticulum. This layer is mostly connective tissue and, as such, the most abundant cell is the fibroblast. The junction of the dermis and the hypodermis does not have a distinct tissue barrier like the basement membrane and so it is more of a blurry transition rather than a sharp line.

Let's take a closer look at the layers of the dermis. The stratum papillare, seen in this image here, is the more superficial layer of the dermis. It lies directly beneath the basement membrane and represents around twenty percent of the thickness of the dermis. The name stratum papillare comes from the fact that this layer forms ridges underneath the epidermis and can be seen here. These are, otherwise, known as papillae. This refers to their shape as the term "papilla" is Latin for nipple. They interlink with the epidermal ridges just here.

The function of the papillae is to increase the surface area of the dermo-epidermal junction. This results in increased capacity for diffusion and increased resistance to abrasive forces. Some papillae contain Meissner's corpuscles which, like the Merkel cells of the stratum basale, are a type of nerve ending. The papillary dermis is composed of loose areolar connective tissue. This is a type of loose connective tissue which contains many open spaces. "Areolar" is Latin meaning little open space. These spaces are filled with interstitial fluid. This tissue binds structures together while being flexible. The fluid spaces provide cushioning.

Blood vessels are abundant in the stratum papillare, forming capillaries in the papillae. These capillaries are responsible for nutrients supplied to the epidermis via diffusion across the basement membrane. These functions are all taken care of by the papillary dermis. So, what's going on in the other layer of the dermis?

The stratum reticulare or reticular dermis is the deep layer of the dermis, which is seen here. It actually accounts for approximately eighty percent of the dermis. The stratum reticulare contains all three types of dense irregular connective tissue which are collagenous, elastic and reticular. These fibers all help to give the reticular dermis tensile strength and elasticity. The percentage of each type present varies by location allowing some areas of skin to be more elastic or more resistant to tension.

It can be difficult to distinguish between the two layers of dermis on histology. The main way is by identifying that the reticular dermis has comparatively less cells and more fibers than the papillary dermis. The reticular dermis also contains types of nerve endings namely Pacinian corpuscles, Meissner's corpuscles, Ruffini's corpuscles, and end bulbs of Krause; larger blood vessels, sebaceous and sweat glands, and hair and nail roots. These can be identified and used to help locate the reticular dermis.

That's us done with the dermis. Now, let's take a bit of a closer look at the hypodermis which is the layer highlighted in green on our illustration here. Here, we'll take a look at connective tissue septae and deep investing fascia which is not technically considered to be part of the skin but we'll be covering it nonetheless so that you can get a clearer picture of how the skin actually transitions to the rest of the body's structures.

The hypodermis all the way down here on our micrograph goes by multiple names sometimes called subcutis, the subcutaneous layer, the superficial fascia or the subcutaneous fascia but as I said, it's not always necessarily included as being part of the skin. Zooming in, we can see that this layer is composed primarily of adipose tissue which is arranged around loose connective tissue like this. The adipose tissue, in green here, is fat tissue and is made up of fat cells known as adipocytes.

The hypodermis has four main functions. It increases the mobility of skin, it provides insulation, and it acts as a shock absorber, and works as an energy store. The hypodermis contains blood vessels such as the venule here, lymphatics, nerves and nerve endings, specifically, Pacinian corpuscles. The hypodermal layer is identifiable on histology by the presence of these structures and by its paler pink color. The general paleness refers the high fat content as adipose tissue does not stain on hematoxylin and eosin. Given its connective tissue component, the hypodermis is sometimes referred to as the subcutaneous or superficial fascia. It's connected to the deep investing fascia below and sends connective tissue septae up through the dermis like this septa highlighted here. These septae provide anchor points for the connective tissue fibers of the dermis further increasing the resilience of tissue.

If we return briefly to our illustration of the skin layers, we can see the deep fascia often called the investing fascia highlighted in green. This is a fascial plane separating the hypodermis from the underlying structures. In the case we can see here, the underlying structure is muscle, however, it could also be bone, a blood vessel, a nerve or any other structure or tissue located directly under the skin. Remember, the deep fascia is not part of the skin. The reason we've included it is for continuity so that you know where the skin meets other tissues of the body. The deep fasciae envelop all muscles, bones, blood vessels and nerves in the body. They are continuous with the connective tissue layers of all these structures, for example, the epimysium, the perimysium and the endomysium of muscles and the periosteum and the endosteum of bone. Subsequently, fibers of deep fascia gather and form ligaments, tendons and aponeurosis.

Fascia is avascular but it has a rich nerve supply, therefore, it's been implicated in causing pain in both acute and chronic injuries. It also appears to be able to sense proprioception which is the ability to sense the position of our bodies without looking. Retraining proprioception of the fascia, tendons and ligaments which we've just heard are all connected is a major aim of physiotherapy after injury and is vital to avoid re-injury.

That's us gone deeper than the bottom of the skin. Great job following so far.

Now, let's talk about the different types of skin. As I mentioned briefly at the beginning of the tutorial, the two types of skin are thick skin and thin skin. It's useful to note that skin can actually be categorized as thick or thin as we mentioned before and hairy or glabrous meaning hairless. Generally, this categorizations overlap. Thick skin is usually hairless while thin skin is usually hairy. Hairs are often barely visible to the naked eye. If you don't believe me, look closely at the back of your hand. For the purposes of this tutorial, we'll discuss the types as thick or thin.

Let's start off with thick skin, which is the type of skin we've been using as an example throughout the tutorial so far, and here you can see the histology section of thick skin that we've used for most of this tutorial. Thick skin is found on areas of the body where abrasive forces are common. For example, thick skin is present on the soles of the feet, the fingertips and the palms of the hands. It also has more nerve endings and is therefore better than thin skin in detecting sensations. This make sense when you consider that areas of thick skin are on the parts we used most to interact with the world around us.

Thick skin is so called because its outermost layer, the stratum corneum, is significantly thicker than that of thin skin and because it contains an additional layer, the stratum lucidum. The stratum spinosum is also thicker to give additional protection and elasticity. Another difference is that thick skin has a thinner dermis but more pronounced dermal papillae and epidermal ridges. If that's not enough, then you can also tell thick skin apart by the structures present. For example, thick skin contains much more nerve endings and many more eccrine glands – one of the two types of sweat gland. Thick skin does not contain apocrine glands – the other type of sweat gland – hairs or sebaceous glands. Let's now look at thin skin for comparison.

This section which is again stained with hematoxylin and eosin shows thin skin. Thin skin covers the rest of the body. Compared with thick skin, it is better at controlling temperature given its hairiness and greater concentration of sweat glands, however, it's not as well innervated. When we look at the image right away, we can see that the pink outer layer – the stratum corneum – is much thinner, only a couple of cells thick in most places.

The dermis is much thicker. The hypodermis isn’t even visible on this section because of this. Also, the dermal papillae and epidermal ridges are much smaller or not present at all as is the case here. Thin skin also has only four layers in the epidermis as it is missing the stratum lucidum. The stratum spinosum is visibly thinner too. Thin skin contains hairs and the muscles associated with them, apocrine sweat glands and sebaceous glands. In fewer numbers than in thick skin but still present are eccrine glands and nerve endings. Now, you should be well-equipped to differentiate between thick and thin skin.

Now, let's have a look at the types of cells found in each layer. Again, we'll start with the outermost layer, the epidermis, and work down. Let's start by looking at the types of cells found in the epidermis which include keratinocytes, basal cells, melanocytes and Langerhans cells.

Keratinocytes, which we can see here, are the most abundant. They make up ninety percent of the cells of the epidermis. We've highlighted a few in the stratum spinosum but most of the cells on the screen are keratinocytes. At different stages of their life cycle, keratinocytes can be called two other names. Granular cells captured here in green is the name given to keratinocytes as they ascend through the stratum granulosum. This is in reference to their granular appearance which is caused by the presence of keratohyaline granules within their cytoplasm. These granules as discussed earlier are what will help the cells to become the next type of keratinocyte, also known as the corneocyte shown here.

Corneocytes, as you can, see are keratinocytes which have died and gone to the great layer above. In other words, they are keratinocytes in the stratum corneum. They are terminally differentiated keratinocytes which means that they are the keratinocyte's final form. A corneocyte is actually biologically dead in that it has no synthetic activity. This is because it has lost its nucleus and organelles. Corneocytes are linked by specialized cell-to-cell junctions which degrade as they are pushed superficially. Eventually, the cells undergo desquamation where they detach from the skin squaming off into the environment.

And so ends the tale of the keratinocyte. Now, let's talk about the keratinocyte's parent cell – the basal cell – some of which are highlighted in green here. These exist exclusively in the stratum basale of the epidermis bound to the basement membrane. They are actually stem cells which are columnar in shape. Basal cells are able to proliferate which means one basal cell can divide into two basal cells and differentiate into keratinocytes meaning a basal cell can become a keratinocyte. Proliferation gives the skin capacity for regeneration which is what allows us to heal without scarring after minor skin injuries. Since the epidermis is avascular, the basal cells can only receive nutrients and remove waste by diffusion across the basement membrane.

The next cell to discuss is the melanocyte which can be seen in this image. These cells also hang out in the stratum basale but have dendrites – long projections of the cell membrane – which reach throughout the stratum spinosum and stratum basale. As is demonstrated in the image, they are rarer than keratinocytes and basal cells. Melanocytes are responsible for melanin secretion which is the pigment that gives you a tan. You might, therefore, expect melanocytes to stain brown, however, this is not the case. As melanocytes produce and release melanin, therefore, the cells which stain brown are the cells that have received melanin from the melanocytes. In fact, a melanocyte has a pale cytoplasm and dark nucleus in hematoxylin and eosin staining.

Melanin can dissipate almost all UV radiation which hits it allowing it to protect the DNA in our skin cells from being damaged by UV light. Melanocytes deliver melanin to basal cells and nucleated keratinocytes in the epidermis throughout the dendrites. When melanin reaches these cells, it collects in the protective barrier on the side of the nucleus closest to the skin's surface protecting the nucleus from UV radiation.

Freckles such as these which we found in our histology slide of thin skin are flat, hyperpigmented areas of skin like the ones on this individual here that are the result of increased melanin deposition. Important to remember is that the number of melanocytes is normal in a freckle, it is the melanin production and deposition which is increased. Naevi or moles as they're more commonly known are different to freckles as they're raised lesions involving melanocytes. Moles are what are created by an increased number of abnormal or normal melanocytes. Lentigines, the plural of lentigo, are flat, hyperpigmented areas of skin similar in appearance to freckles. The difference is that lentigines arise from an increased number of melanocytes but that's for dermatologists to learn more about.

Now to the other protective cell of the epidermis known as the Langerhans cell seen in this image here. This cell type is actually an immune cell more accurately known as an antigen-presenting cell similar to the dendritic cells of other tissue. Their function is to sample antigens and present them to the immune system for analysis. A Langerhans cell can be recognized on the hematoxylin and eosin stain section by its pale cytoplasm and dark, well-defined nucleus. These features are in stark contrast to the surrounding keratinocytes with their pink cytoplasms and lighter purple nuclei.

These ones here are in the stratum spinosum but they can live in any layer of the epidermis except the stratum corneum. This feature allows us to distinguish Langerhans cells from melanocytes as melanocytes are only present in the stratum basale.

That's all the cell types the epidermis has to offer but what about the dermis? The dermis has three main cell types which are fibroblasts, adipocytes and macrophages. Let's talk briefly about each one in turn.

The fibroblasts are the most abundant cell of the dermis. They create a connective tissue skeleton connecting the basement membrane of the epidermis to the hypodermis. This network of fibers that they weave offers a structure for the cells, vessels and nerves of the dermis to attach to and is highly resistant to pulling forces and is flexible and so allows the skin to slide to a certain degree while resisting abrasion. Adipocytes or fat cells arrange themselves around the connective tissue. They provide a small degree of padding and insulation. As with all fat cells, the adipocytes of the dermis also act as an energy store. Like the Langerhans cells of the epidermis, macrophages are antigen-presenting cells of the immune system. They are scattered throughout the dermis to sample anything that enters the layer.

Now to our last layer – the hypodermis – which we can see here highlighted. You'll be glad to hear that the hypodermis has the same cells as the dermis which are, as we just saw, fibroblasts, adipocytes and macrophages. The difference is that adipocytes are the most abundant cell type in this layer instead of fibroblasts. This reflects that the hypodermis is primarily a fat storage tissue. The actual composition of the hypodermis varies with region and person. The more fat a person has increases the size of the adipocytes but they still have the same number of adipocytes.

But enough about cells, let's move on to discuss the accessory structures in the skin. These include venules and arterioles, lymphatic vessels, hair follicles, sebaceous glands, sweat glands, skin pores, connective tissue septae, nerves and nerve endings which we can split into five different types – Merkel cells, Meissner's corpuscles, Ruffini's corpuscles, end bulbs of Krause, and Pacinian corpuscles. This sounds quite a lot to get through but it's not and once we have, you'll have a much more complete picture of what is going on in your skin. So starting from the beginning of our list, we have venules.

These are small veins that carry blood from the capillaries. Multiple venules join together to form veins. This image is showing a venule caught in cross-section which is actually a part of the histology specimen of thin skin we used earlier. Here is the lumen of the venule, where the blood flows and these are the cells of the vessel wall which create this well-demarcated line at the lumen. In fact, there are even some red blood cells still inside the lumen here at the top. Venules reside in the hypodermis. Can you remember how to identify the hypodermis and recognize it here? Feel free to pause and have a go. That's right, if you recall, the hypodermis is mainly a fat storage site so you should be able to identify the hypodermis through its abundance of adipocytes.

Arterioles carry blood from arteries to capillaries and are similar in diameter to venules. Arterioles have a thicker vessel wall but as we can see in our illustration here also travel in the hypodermis, so, generally very difficult to differentiate from venules on histology slides.

Now to look at another vessel. Lymphatic vessels carry lymph from the extracellular space in tissues which is the extracellular fluid that has served its time in the tissue and has now drained into a lymphatic vessel and is on its way to return to the bloodstream. Again, this image is from a different area of the same histological section, this time showing a lymphatic vessel in the dermis in green. We know this is a lymphatic vessel because it is a relatively large diameter vessel in the dermis. Lymph is often overlooked but without adequate lymphatic drainage, your veins could not cope and your peripheries would swell up like a big water balloon but more on that in another tutorial.

Next stop, hair. Hair is, unsurprisingly, present in hairy skin. This is the actual scientific name and is the opposite of glabrous or hairless skin. We're looking, of course, again at our diagrammatical representation of skin with the hair follicles highlighted. Hair follicles are the part of the hair fiber beneath the skin. Hair shafts highlighted here in green are the part of the hair fiber above the skin. Hair is made up of keratin strands. The visible shaft contains only biological dead tissue while the hair follicle houses the hair matrix. This is where the specialized hair forming stem cells known as trichocytes are kept. The matrix is present around the papilla which provides a rich blood supply. The lumen of the hair follicle is where the hair strand passes up through the skin layer. The lumen is lined by epidermis and dermis. The papilla sits deep within the skin at the level of the dermis or the hypodermis.

If we take a look at a micrograph of the hair follicle, we can see how in histology, hair has a few distinguishing features. In this image, we've caught a hair in cross-section and are looking down into the follicle. Firstly, it just looks very different. Starting at the edge of the region, it's a well-demarcated area caught and off by a surrounding ring of cells and connective tissue. We said that the lumen is lined by epidermis. This is the epidermis. The connective tissue ring is the basement membrane and the ring of cells is the stratum basale. The cells are less keratinized than at the skin surface so the stratum corneum is less thick.

Now to deal with this strange structure in the middle. This is a hair follicle, identified by the pale core surrounded by pigmented cells with smeared nuclei. These smeared nuclei indicate the cells are fibrous in nature. The pigment is melanin which comes in three types and the different types account for the different colors of hair. Another way to identify hair fibers is to look for the arrector pili muscles which are highlighted in green on our illustration here. These are muscles in the dermal layer which attach from the basement membrane to the base of the hair fiber. They are smooth muscle innervated by sympathetic nerves and are responsible for making our hair stand on end.

Now, let's move on but not too far to the sebaceous glands. These glands which we see in green here are usually associated with a hair follicle and are, therefore, found more in hairy skin. However, they are present in some glabrous skin in smaller numbers. On histology, they resemble a big bowl of cells as seen here. Their role is to secrete sebum. Sebum is made from cells produced in the sebaceous gland which have burst. It is an oily waxy substance designed to protect and waterproof the skin surface and hair fibers. Have you ever thought you have greasy or dry hair? These glands are the culprits.

How about we talk now about another type of gland which is the sweat gland. Sweat glands come in two types – eccrine like the one shown here and apocrine. This diagrammatical representation shows the three-dimensional structure of sweat glands. They consist of a tube which is coiled up on itself into a light mass. At the edge of the diagram here, we can see how this looks in cross-section which is how we are seeing it down the microscope. This collection-of-tubes appearance is in contrast to the bowl-of-cells appearance of sebaceous glands. Each type of sweat glands secretes a different solution but both release secretions into the skin via pores like this one. This is the lumen where the few sebaceous glands gathered around it and an eccrine sweat gland just down here. Notice the difference between the bowl-of-cells appearance of sebaceous glands and the collection-of-tubes appearance of the eccrine gland.

Here's another example of an eccrine gland on histology. These glands are present over the entire body and are responsible for thermoregulation. They do this by secreting dilute sodium chloride solution which also helps maintain skin pH. Eccrine glands exist in the dermis and are not associated with hair follicles whereas an apocrine gland highlighted in green here is always associated with a hair follicle which in this case can be seen up here.

Back down to our apocrine glands now, these are located at the junction between the dermis and the hypodermis and are only found in the axillae or armpits, the areolae of around the nipple, the perineum or the area between the genitals and the anus, and the ear canals and the eyelids. They only become active during puberty and are responsible for providing nutrients to our skin's microbiome – i.e. the friendly bacteria – and pheromone production. Apocrine glands are the reason for our natural scent but also for BO.

Moving swiftly on, here's a peripheral nerve in green, running in the hypodermis. Peripheral nerves carry sensations from receptors and deliver signals to muscles. They are recognizable on histology by being a well-circumscribed bundle as we can see on our image here. They are also contained within a connective tissue sheath. The connective tissue sheath is the epineurium whilst the bundle is the nerve fascicle. The fascicle is well-circumscribed due to the perineum which is intimately wrapped around the fascicle.

Larger axons are encapsulated by a myelin sheath consisting of Schwann cells. The axons can be observed as this darker dot inside a clear space. The dot is the axon and the clear space is the myelin sheath. The nuclei within the fascicle are those of glial cells or Schwann cells.

We mentioned that peripheral nerves carry sensations. In the skin, sensory signals come from specialized nerve endings. There are multitude of nerve endings in the skin so let's give each a shout out. There are five types of nerve endings in the skin. Going from superficial to deep, these are Merkel cells, Meissner's corpuscles, Ruffini's corpuscles, end bulbs of Krause and Pacinian corpuscles – each let us perceive a different aspect of touch so it's worth mentioning each in turn.

Let's start with Merkel cells. If you have a seriously keen eye, you might notice this image is the same as that for melanocytes. In practice, it is impossible to differentiate between melanocytes and Merkel cells on a hematoxylin and eosin stain, so these cells here could be melanocytes or Merkel cells. Although melanocytes are more common and, therefore, more likely, Merkel cells are oval shaped with a pale cytoplasm and dark nucleus. They're only found in glabrous skin especially in the fingertips. So if you're looking at thin skin, it will definitely be a melanocyte and not a Merkel cell. Their specialized function as nerve endings are to sense light touch.

A little deeper, there are Meissner's corpuscles. This hematoxylin and eosin stained section shows the corpuscle pretty clearly. Found almost exclusively in glabrous skin, these nerve endings are present in the dermal papillae. They're classically egg-shaped on histology with the narrow end pointing towards the skin surface. They also have a lamellar appearance which means they look layered. This is actually one or two nerve endings which coil and spiral upwards towards the tip of the dermal papilla. The nuclei we can see here are Schwann cells. The dense coiling makes the nerve ending more sensitive and so, Meissner's corpuscles also allow us to perceive light touch.

Ruffini's corpuscles detect a different sensation altogether or rather, two sensations – skin stretch and temperature. Each corpuscle is a spindle-shaped arrangement of a nerve in a dermis and are especially common in the fingertips where it is thought they allowed the detection of objects or surfaces slipping over the skin. Given their stretch detection, they also provide information about joint position and can be used when sense of proprioception to the fingers is lost.

Staying in the same skin layer, the end bulbs of Krause are also situated in the dermis. Unlike Ruffini's corpuscles, the end bulbs of Krause are found all over the body. They're not even confined to the skin. This micrograph is actually from the epiglottis in the throat. End bulbs of Krause are also called bulboid corpuscles, being given these names for their bulb-like shape. On histology, the shape will depend on how they were caught when the section was cut and they may appear bulb shaped or circular as is more the case here.

They detect temperature being more sensitive to cold. Here's a fun fact. End bulbs of Krause are thought to be responsible for a cool or fresh taste sensation such as the taste you get when you eat a mint. They also may modulate our sense of taste and contribute to why some foods taste better at different temperatures.

Now for the last type of nerve ending, the Pacinian corpuscle. These are the deepest nerve endings located in the deep dermis and hypodermis. They are also the largest but fewest in number although they are present across the entire skin. Here is where the dermis is meeting the hypodermis so we can see that the Pacinian corpuscle is very deep in the dermis. Pacinian corpuscles can be difficult to notice but can be identified by its oval shape and this lamellar appearance with the whole structure enclosed within a capsule highlighted in green on our micrograph here. Remember earlier we talked about lamellar bodies and how the word "lamellar is Latin for thin plate. Pacinian corpuscles appear lamellar because they have this similar appearance and arrangement.

In this drawing of a Pacinian corpuscle, we can see that it consists of a single nerve ending which is covered by concentric layers of connective tissue. Why this complex structure? It makes the corpuscle exceedingly sensitive. As such, it senses vibration of the skin and one Pacinian corpuscle is able to detect fine vibrations many centimeters away. Impressive, given that it's only around one millimeter in size. Detection of vibration is what lets us distinguish between textures.

Before we end, let's run through a clinical condition where knowledge of the skin is important for a pathologist.

Melanoma is a type of skin cancer. It arises due to uncontrolled growth of melanocytes in the stratum basale. In life, it looks like a mole, raised and pigmented. Before we look at a clinical image of it, let's see how the pathologist would see it. This is a section from the skin in the thigh. The whiter, well-demarcated area here seems to be distorting the shape of the tissue around it – a bit like a wormhole or something. This is the melanoma. It's not pigmented on histology because if we remember back, we said that melanocytes are the producers of pigment but are not pigmented themselves. Instead, any of these melanocytes which is still producing melanin will release melanin into the surrounding keratinocytes and basal cells and this is what gives rise to the pigmented appearance which would be seen on the skin with the naked eye. The overgrowth of melanocytes causes the area to be raised and form the mole shape.

Here's the appearance we're talking about. This is a photo of a melanoma which is about to be removed. This line, making it look like an eye, is marking where the surgeon will cut. This shape is chosen as it is easier to stitch close after the melanoma has been removed and will leave a neater scar and, hopefully, a potentially life-threatening condition has been cured.

So, in summary, today, we discussed the histology of skin.

Now that we've come to the end of the tutorial, let's summarize all the things we've talked about today. We covered the functions of skin which include protection from trauma, infection and UV radiation; regulation of our temperature and water content, synthesizing the hormone vitamin D, and letting us sense and interact with the environment. We then introduced the layers of the skin namely the epidermis – the outermost layer, the dermis, and the hypodermis – the innermost layer.

We also talked about the layers within each of these layers. In the epidermis of thick skin, there's the stratum corneum, the stratum lucidum, the stratum granulosum, the stratum spinosum, and the stratum basale – all piled on top of the basement membrane. Diving into the dermis, we saw the two layers – the stratum papillare which is roughly everything above this line and the stratum reticulare which is roughly everything below down the hypodermis. Additionally, we looked at how the skin is attached to the underlying tissue through the deep investing fascia down here.

We also looked at two types of skin – thick here and thin here – and the cells found in skin. In the epidermis, we have keratinocytes, corneocytes, granular cells, basal cells, melanocytes, Langerhans cells, and then in the dermis and hypodermis, there are fibroblasts, adipocytes and macrophages. We then discussed the multitude of accessory structures within the skin including venules and arterioles, lymphatic vessels, hair follicles, sebaceous glands, sweat glands, skin pores, connective tissue septae, nerves, and nerve endings.

So that's us done! Great job getting through it all. Thanks for watching this Kenhub histology tutorial and all the best for your studies. See you next time!

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