IA MVST – HISTOLOGY TEXT FOR CAL MODULE ON EPITHELIUM AND SKIN EPITHELIUM INTRODUCTION Epithelium refers to sheets of cells that cover the outer surface of the body and line spaces and tubes within it. Epithelial cells are closely attached to each other by specialised intercellular junctions. All epithelia rest on a basement membrane, a specialised extracellular matrix that marks a boundary between epithelial cells and the underlying supporting tissue. Because blood vessels do not cross the basement membrane, epithelial cells rely on the diffusion of oxygen and metabolites from capillaries in the underlying supporting tissue. Epithelial cells show polarity. Their luminal (or apical), lateral and basal surfaces have different membrane constituents, which is reflected in different functions. The distribution of organelles in the cytoplasm may contribute to the cell polarity. Epithelial cells serve as a selective permeability barrier, separating compartments that have different chemical compositions. Epithelia exhibit a variety of functions such as protection, absorption and secretion. Epithelia are classified according to both the number of cell layers and cell shape (as seen in sections perpendicular to the surface membrane): a) Simple epithelium consists of one layer of cells, b) Stratified epithelium consists of two or more cell layers. The cell shape may be described as squamous (thin, scale-like, flattened cells), cuboidal or columnar. Simple epithelia Simple epithelium consists of one layer of cells. All cells make contact with the basement membrane. There are four types of simple epithelia: Simple squamous epithelium Simple cuboidal epithelium Simple columnar epithelium Depending on the height of the cells, epithelium can be described as high cuboidal or low columnar. Pseudostratified epithelium is a special category of simple epithelium. The nuclei of cells lie at different levels giving the false impression of more than one cell layer. However, all cells rest on the basement membrane. Stratified epithelia Stratified epithelium consists of more than one cell layer. Only the basal cell layer is in contact with the basement membrane. Stratified epithelia are classified on the basis of the shape of cells in the surface layers, i.e. Stratified squamous epithelium Stratified columnar epithelium Transitional epithelium is a special category of stratified epithelium. It is capable of stretching to accomodate changes in surface area. Because of the changes in appearance between the stretched and unstretched states (from stratified squamous to stratified cuboidal or stratified columnar), this epithelium is called 'transitional'. Transitional epithelium lines the renal pelvis, ureters, urinary bladder and part of the urethra. Simple epithelium LM of alveolar wall – Lung: Simple squamous epithelium is made of thin, flattened, scale-like cells, difficult to distinguish under the light microscope. Their nucleus is sometimes the only visible structure that helps their identification. Simple squamous epithelium lines most of the surface of the alveoli. In this location, the cells are known as pneumocyte type-I cells. Simple squamous epithelium also lines the lumen of blood vessels (referred to as endothelium). EM of lung – Diffusion barrier: Electron microscopy enables a clear distinction between the simple squamous epithelium of the alveolar lining and the endothelium of capillaries in the alveolar wall. In the alveoli, both epithelia are apposed to each other and their basement membranes are fused, representing a minimal barrier for diffusion of gases between blood and alveolar air. Simple cuboidal epithelium – Thyroid follicles: An example of simple cuboidal epithelium can be found in the follicles of the thyroid gland. Thyroid follicles are round, spheroidal structures made of a single layer of cuboidal secretory cells. Thyroid hormones are stored within the follicles lumen. You will learn more about the thyroid gland in future classes. Simple cuboidal epithelium with microvilli – Proximal convoluted tubule: Simple cuboidal epithelium is also found lining the proximal convoluted tubules (PCT) of the kidney. Under LM, the PCT epithelium shows a brush border on the luminal side of the cells. The brush border is a specialisation of the cell luminal surface. Under EM, it is evident that the brush border consists of extensions of the plasma membrane known as microvilli. Microvilli EM – proximal convoluted tubule : Microvilli are found in the luminal (or apical) surface of cells specialised in absorption. Microvilli can be resolved by EM, as shown in this micrograph of a proximal convoluted tubule (PCT) of the kidney. In the PCT, microvilli increase the luminal surface area for reabsorption of the glomerular filtrate. Simple columnar epithelium – EM of the small intestine: Simple columnar epithelium with a brush border (microvilli) lines the luminal surface of the small intestine. Mucus-secreting epithelial cells, known as goblet cells, are found scattered amongst the columnar absorptive cells of the intestinal epithelium. Lymphocytes (cells with a round, darkly stained nucleus) are sometimes seen amongst the epithelial cells. Lymphocytes play a role in the immune defence system. Simple columnar epithelium with goblet cell – Intestine More details of the simple columnar epithelium lining the small intestine are shown in Ems of intestinal cells. Numerous microvilli are present on the apical surface of the columnar absorptive cells. Microvilli increase the luminal surface membrane area for absorption. Mucus-secreting goblet cells are scattered between the absorptive cells. Their name is due to their resemblance to a drinking goblet. Pseudostratified columnar ciliated epithelium – Trachea: Pseudostratified epithelium is a special type of simple epithelium that gives the false impression of having more than one cell layer. This is because the cell nuclei are disposed at different levels. All cells make contact with the basement membrane but not all cells reach the surface. Pseudostratified epithelium is found lining the upper respiratory airways and parts of the male reproductive tract. In mammals, the pseudostratified epithelium lining the upper airways consists mostly of columnar ciliated cells, amongst which there are scattered mucussecreting goblet cells. Cilia are motile structures. In the respiratory tract, cilia propel fine particles that may have entered with the inspired air to the pharynx . Simple cuboidal ciliated epithelium – EM: The EM of a small bronchiole shows an example of simple cuboidal ciliated epithelium. Cilia consist of extensions of the plasma membrane containing a central core of microtubules arranged in a characteristic fashion. Cilia are much larger than microvilli and can be resolved by light microscopy. EM of bronchial epithelial cells: Cilia are motile structures containing microtubules and are inserted into basal bodies. Mitochondria provide energy for ciliary movement. Stratified epithelium Stratified squamous epithelium – Oesophagus Stratified epithelium consists of two or more layers of cells. Only the basal layer is in contact with the basement membrane. The cells of the basal layer are generally cuboidal in shape. Stratified epithelia are classified on the basis of the shape of the cells in the surface layers. The main function of stratified squamous epithelium is protection. Cell division continuously occurs in the germinal basal layer. The new cells are pushed upwards to replace the continuous loss of cells at the top layer. As the cells migrate, there is a progressive change in cell shape (from cuboidal to squamous) and cell deterioration. Stratified cuboidal epithelium – Sweat glands Stratified cuboidal epithelium occurs in the excretory ducts of some exocrine glands such as sweat and salivary glands. The epithelium of the sweat glands excretory ducts consists of two layers of cuboidal cells. Epithelial junctions EM of a junctional complex – Bile duct Epithelial cells are linked by several types of specialised junctions. These junctions enable intercellular mechanical attachment, prevent the passage of macromolecules through the intercellular space and allow metabolic cell coupling. The main types of junctions present in mammalian epithelium are: 1) Tight junction (or zonula occludens), a belt-like zone that runs around the intercellular region immediately below the cells luminal surface. It holds cells together, functions as a permeability barrier between the two compartments separated by the epithelium, and prevents the diffusion of membrane proteins along the plasma membrane, from one pole of the cell to the other. 2) Intermediate junction (or zonula adherens), located below the tight junction, forms an anchoring belt around the cells. 3) Desmosome (or macula adherens), located deeper, below the intermediate junction, is a circular spot (or macula) of strong mechanical attachment. There can be a variable number of desmosomes binding two adjacent cells in epithelia. Hemidesmosomes (not shown in this EM) are a variant of desmosomes that provide points of attachment to the basement membrane. The combination of a tight junction, intermediate junction and desmosome is known as a junctional complex. 4) Gap junctions (or communicating junctions) are also present in epithelia (not shown here). Gap junctions allow the passage of small molecules directly from one cell to the other. Their physiological significance in epithelia is not clear. Please see your Histology handbook for more information on the various types of cell junctions. EM of a bile duct It shows, at lower magnification, several junctional complexes. EM of intestinal epithelium The epithelial cells of the small intestine are connected by junctional complexes. A junctional complex is the combination of a tight junction, intermediate junction and desmosome. SKIN The skin, or integument, is the largest organ of the body. It consists of two main layers: 1) The epidermis, made of keratinised stratified squamous epithelium. 2) The dermis, a layer of dense, vascular supporting tissue. The dermis is connected to underlying tissues by the hypodermis, a layer of loose supporting tissue containing a variable amount of fat. Both dermis and hypodermis contain sensory receptors such as the Pacinian corpuscle. The epidermis of skin is a typical example of a stratified squamous keratinising epithelium and reflects one of its most important functions - protection. The surface epithelial layers are covered by a layer of keratin, a fibrous protein synthesized in the cells as they move upwards towards the surface. The epidermis is relatively impermeable to water, protecting against dehydration. Skin varies in thickness in different parts of the body. Thick skin is found mainly on the fingertips, palms of the hands, and soles of the feet. In thick skin both the number of epithelial cell layers and thickness of the keratin layer are greater than in thin skin. A feature of thick skin are the epidermal ridges on the surface. Each individual has a characteristic ridge pattern that determines the fingerprints. Upward extensions of the dermis interdigitate with downward projections of the epidermis strengthening the adhesion between these two layers. This arrangement is less prominent in thin skin. Sweat glands are distributed in the hypodermis and dermis of most areas of the skin. Their secretions reach the surface via excretory ducts. Epidermis cell layers: 1. Stratum germinativum or stratum basale, a layer of cuboidal cells that are anchored to the basement membrane. Active cell division occurs in this layer. 2. Stratum spinosum, made of several layers of larger cells that appear to have cytoplasmic spines extending from the surface across the intercellular space. 3. Stratum granulosum, characterised by cells with dense cytoplasmic granules containing proteins that contribute to the process of keratin formation. 4. Stratum lucidum, sometimes visible in thick skin only, as a homogenous layer of flattened dead cells rich in keratin (a transition between layers 3 and 5). 5. Stratum corneum, the outer layer, consisting of dead, flattened, non-nucleated cells and cell remnants rich in keratin. The outer part of this layer sheds continuously. At high LM magnification, the spines or prickles (arrows) of cells of the stratum spinosum, can be seen extending across the intercelullar spaces. Each prickle represents a punctate desmosome binding adjacent cells. Cells of the stratum spinosum are involved in the initial steps of keratin formation. Hair follicles Hair follicles are downgrowths of the epidermis extending into the dermis and hypodermis. Hairs are formed by the hair follicles, at the hair bulb, from proliferating epithelial cells which constitute the hair matrix. The hair follicle consists of five layers of epithelial cells: - The external root sheath, a downward extension of the epidermis, which does not contribute to hair formation. - The other four layers originate from the hair matrix. From these, the inner three layers (medulla, cortex and cuticle) undergo a process of keratinisation and form the hair shaft. The fourth layer, the inner root sheath is slightly keratinised and disintegrates before reaching the surface of the skin. (It is not always possible to see all the different hair follicle layers in tissue sections). Sebaceous glands Sebaceous glands, also a downgrowth of the epidermis, secrete sebum (an oily substance) into the hair follicles. Sebum lubricates the hair and coats the surface of the skin. Sebaceous glands are made of cells containing numerous vacuoles filled with lipid. Sebum is produced as a holocrine secretion. The cells become filled with lipid, they undergo a process of disruption and disintegration, and then they are eventually discharged together with the lipid product, as sebum. Cells at the periphery of the glands, show mitotic activity and are responsible for producing new cells. A bundle of smooth muscle called arrector pili muscle extends obliquely from the hair follicle, below the sebaceous gland, to the upper dermis, just beneath the epidermis. Upon contraction of this muscle, the hair moves to an upright position. This is a common event in certain animals as a response to fear, cold or anger. Sweat glands Sweat glands are also epidermal derivatives. There are two types: eccrine (or merocrine) glands, which produce sweat, and apocrine glands, which secrete a viscous milky secretion. In this class, we will focus on eccrine sweat glands. Eccrine sweat glands are distributed over most of the body surface with few exceptions (lips and external genitalia). They are simple coiled tubular glands, extending from the hypodermis (where the secretory portion forms a coil) to the epithelial surface. Their secretion (sweat) is discharged through a long excretory duct. Eccrine secretion involves exocytosis. Secretory granules discharge their content by fusion with the plasma membrane. The secretory portion of sweat glands is made of a single layer of columnar, or large cuboidal cells. The excretory duct consists of two layers of cuboidal cells. Myoepithelial cells, which are capable of contraction, can be found around the secretory units. They are thought to contribute to the expulsion of sweat. Sweat glands play a role in temperature regulation through the cooling which results from the evaporation of sweat. Pacinian corpuscles – Sensory receptors Pacinian corpuscles are sensory receptors located in the hypodermis. They respond to deep pressure and vibration. Pacinian corpuscles consist of a fine capsule enclosing concentric layers (lamellae) of flattened cells that give the appearance of an onion. At the centre of the corpuscle there is a non-myelinated afferent nerve fibre that becomes myelinated as it leaves the corpuscle.