Respiratory Module Histology _2024-2025_.pdf

FACULTY OF MEDICINE – MENOUFIA UNIVERSITY RESPIRATORY MODULE [ MED 201] Histology Histology & Cell Biology Department 2024 - 25  Respiratory Module (Respiratory System & Integumentary System) 2 VISION: To be academically accredited coll...

FACULTY OF MEDICINE – MENOUFIA UNIVERSITY RESPIRATORY MODULE [ MED 201] Histology Histology & Cell Biology Department 2024 - 25  Respiratory Module (Respiratory System & Integumentary System) 2 VISION: To be academically accredited college with local, regional, and international reputation for having a leading role in the field of medical education and health care provision. MISSION: The faculty of Medicine, Menoufia University is committed to graduate a physician in accordance to the National Academic Reference Standards, who is able to meet the needs of local and regional market, skilled in conducting scientific researches that participate in developing the profession and the provided health care, and keen on continuous training and education to support the service provided to community and surrounded environment in the frame of commitment to the ethics of the profession 3  Index Topic Page Overall aim of the course 5 Intended Learning Outcomes 5 Respiratory system 6 The conducting portion 8 The respiratory portion 19 The Integumentary System 29 The thick skin or non-hairy skin 31 The thin skin or hairy skin 44 Skin appendages 46 References 53 4 Overall aims of the course: o To provide the basic histological knowledge of the normal microscopic structure of upper and lower respiratory system. o To provide the basic histological knowledge of the normal microscopic structure of skin & its appendages Intended Learning Outcomes:  Distinguish histological structural features of upper and lower respiratory tracts and cell types present in each of them and relate the structure to function.  Compare between structure of different parts of respiratory tract and their function.  Identify microscopic structure of skin and its appendages and cell types present in each of them and relate the structure to function.  Draw diagrams showing different component of respiratory system seen under light microscope during practical classes.  Differentiate between trachea, bronchi, bronchioles and alveoli in histological slides.  Differentiate adult, fetal and injected lungs in histological slides.  Draw diagrams showing the thick and thin skin.  Differentiate between the thick and thin skin in histological slides. 5  RESPIRATORY SYSTEM The respiratory tract consists of two portions: I- The conducting portion: It is composed of:  Nasal cavity  Nasopharynx,  Larynx  Trachea  Bronchi  Bronchioles  Terminal bronchioles. 6  ❖The function of this part 1- The conduction of air to respiratory portion (characterized by rigid walls that keep the airways open and prevent collapse). 2- These structures filter, moisten and warm the inspired air before it reaches the respiratory portion II- The respiratory portion: It is composed of:  Respiratory bronchioles  Alveolar ducts  Alveolar sacs  Alveoli ❖The function of this part These structures are concerned with gas exchange between blood and inspired air (respiration). 7 I- The conducting portion Nasal Cavities The nasal cavity consists of the vestibule and the nasal fossae. A- The vestibule: the anterior dilated part of the nasal cavity lined by skin. It contains thick short hairs called vibrissae which filter large particles from inspired air. B- Nasal fossae: two cavities separated by nasal septum containing 3 bony projections; superior, middle and inferior conchae. ❖ The middle and inferior conchae are covered by respiratory epithelium (pseudostratified columnar ciliated epithelium with goblet cells) ❖ The superior conchae are covered by olfactory epithelium. - Lamina propria of conchae is highly vascular and contains mucous and serous glands for warming, moisture and catching dust.  The respiratory epithelium It lines most of the conducting portion and is composed of pseudostratified columnar ciliated epithelium with goblet cells including five cell types: 1- Ciliated columnar cells The most abundant type. Each cell has about 300 cilia. Beneath the cilia, are numerous small mitochondria that supply ATP for ciliary beating. 2- Goblet cells The next most abundant cells. Form & secrete mucous. extend through the full thickness of the epithelium between the ciliated cells 3- Brush cells Columnar cells with numerous apical microvilli. They have afferent nerve endings on their basal surfaces and are considered to be sensory receptors. 8 4- Basal cells Short pyramidal cells that lie on the basal lamina but do not extend to the surface. They are considered to be stem cells. 5- Diffuse neuroendocrine cells (DNES) or small granule cells Columnar cells with basal dense granules. These cells belong to the diffuse neuroendocrine system. They are difficult to distinguish in the light microscope without special stain such as silver. Synthesize different polypeptide hormones (Serotonin & Calcitonin). 9  The olfactory area - Extends over superior conchae functioning as the organ of smell. - It is lined by olfactory mucosa which consists of olfactory epithelium and underlying CT corium. a- Olfactory Epithelium Tall pseudostratified columnar epithelium (no cilia and no goblet cells) composed of three types of cells; 1- Olfactory cells (neurons) Bipolar neurons that respond to odors. A single dendrite extends to the surface to form a swelling, the olfactory vesicle from which stereocilia extend over the surface to increase surface area exposed to odors. The axon passes to CT corium to form olfactory nerve. 2- Supporting (sustentacular) cells Tall columnar cells. Narrow base and wide apex. Microvilli on the apex. Oval nucleus near apex. Cytoplasm contains yellow pigment that gives the olfactory mucosa yellow colour. Functioning as supporting cells. 3- Basal cells Short pyramidal cells. 10  Rounded basal nucleus. Basophilic cytoplasm. Serve as reserve cells for the olfactory and supporting cells. b- The CT corium (lamina propria) Contains serous glands (Bowman’s glands), bundles of olfactory nerves, blood vessels and lymphatics. The secretion of Bowman’s glands moistens the olfactory epithelium and serves as a solvent which dissolves odorous substances and thus stimulates the cilia of olfactory cells. 11 Paranasal Sinuses They are lined with a thinner respiratory epithelium with few goblet cells. The lamina propria contains only a few small glands and is continuous with the underlying periosteum. Nasopharynx It is lined by respiratory epithelium. The lamina propria contains mucous and serous glands as well as lymphoid tissue; the pharyngeal tonsil. Larynx 1. The wall is supported by: * hyaline cartilages ( thyroid , cricoid & arytenoid) * elastic cartilages ( epiglottis , corniculate & cuneiform) 2. Vestibular folds (false vocal cords): Lie superior to the vocal cords. These folds of loose connective tissue contain glands, lymphoid aggregations, and fat cells. They are covered by respiratory epithelium. 3. The true vocal cords: Consist of skeletal muscle, the vocal ligament (formed by a band of elastic fibers), and a covering of non-keratinized stratified squamous epithelium. Inferior to the vocal cords, the lining epithelium changes to respiratory epithelium. 12 Trachea - Trachea is a flexible fibroelastic cartilaginous tube allowing expansion in width during inspiration. It is 10 cm long and 2 cm wide. - Structure of trachea: The trachea is made of four coats. 1. Mucosa It is composed of epithelium and lamina propria. The epithelium is thick and is formed of pseudostratified columnar ciliated with goblet cells (respiratory epithelium). The lamina propria consists of fibroelastic vascular connective tissue with abundant lymphocytes and mast cells. Elastic membrane with many elastic fibers separating the lamina propria from the submucosa 2. Submucosa It is made of loose connective tissue found deep to lamina propria, containing muco-serous gland (Tracheal glands). 3. Cartilage and smooth muscle layer It is formed by C-shaped hyaline cartilaginous rings. The posterior free ends of the cartilage ring are bridged by smooth muscle (trachealis muscle) and fibroelastic ligament. 4. Adventitia It is made of fibro-elastic connective tissue containing neurovascular structures. 13 14 Bronchi ❖Extrapulmonary bronchi  Trachea divides into two primary bronchi (extrapulmonary bronchi) which have the same structure as trachea.  Primary bronchi enter the lung at the hilum, giving rise to secondary bronchi (intrapulmonary bronchi). ❖ Intrapulmonary bronchi  Intrapulmonary bronchi divide in the lung, forming tertiary one. The tertiary bronchi give rise to smaller and smaller bronchi, whose terminal branches are called bronchioles.  The wall of the intrapulmonary bronchi is formed of 3 layers: 1- Mucosa: Highly folded mucosa formed of: a- Epithelium: pseudostratified columnar ciliated with few goblet cells. b- Lamina propria: contains numerous, longitudinally arranged elastic fibers. 2- Muscle layer: Spirally arranged smooth muscle fibers surrounding the mucosa. 3- Adventitia: C.T. which contains mucoserous glands, plates of hyaline cartilage and lymph follicles. 15  Items Trachea/Extrapulmonary Intrapulmonary bronchi (Large) bronchi Lumen Wide lumen Narrow lumen Mucosa - Less folded - Highly folded  Epithelium - Pseudostratified columnar - Pseudostratified columnar ciliated with goblet cells. ciliated with few goblet cells.  Elastic - Has elastic membrane in - No elastic membrane in membrane mucosa mucosa, but lamina propria contains numerous elastic fibers. Submucosa Present Absent Muscle layer smooth muscle (trachealis Spirally arranged smooth muscle muscle) extends between the the fibers surrounding the mucosa. posterior free ends of the cartilaginous rings. Supporting layer C-shaped hyaline plates of hyaline cartilaginous rings in its wall cartilage in the adventitia Mucoserous Present in submucosa Present in adventitia between glands cartilaginous plates Lymphatic Absent Present in adventitia nodules 16 CLINICAL HINT  The respiratory epithelium of people chronically exposed to irritants such as cigarette smoke and coal dust undergoes reversible alterations known as metaplasia, associated with an increase in the number of goblet cells relative to ciliated cells.  Immotile cilia syndrome: a disorder that causes immotile spermatozoa and infertility in men and chronic respiratory-tract infections in both sexes. It is caused by immobility of cilia and flagella induced in some cases by deficiency of dynein, a protein normally present in the cilia. Dynein participates in the ciliary movement and has ATPase activity. Bronchioles  Bronchioles are airways that are usually less than 1 mm in diameter.  The wall of bronchioles consists of: 1- Mucosa: simple columnar ciliated epithelium with Clara cells. The cells decrease in height and cilia gradually decrease as the bronchiole gets smaller (Clara cells increase in number as the ciliated cells decrease along the length of the bronchiole) Clara cells: Tall, dome-shaped, non ciliated cells. Have numerous secretory granules. Have various functions, including the following: 1- Secretion of surfactant like substance to reduce surface tension of the terminal bronchioles. 2- Protection of bronchiolar epithelium by their glycoprotin secretion. 3- Detoxification of inhaled airborne toxins by SER. 4- Act as stem cells for replacement of other bronchiolar cell types. 2- Musculosa: circularly arranged smooth muscles. 3- Adventitia: Connective tissue with no glands, cartilage or lymphatic nodules. 17  Terminal bronchioles  The last part of the conducting portion  Similar to larger bronchioles, but they are lined with cubical ciliated cells with Clara cells. Differences between bronchus and bronchiole Items Bronchus Bronchiole Mucosa - Less folded - Highly folded - lined by pseudostratified - lined by simple columnar ciliated columnar ciliated with goblet cells epithelium with Clara cells. The cells decrease in height and cilia gradually decrease as the bronchiole gets smaller. NO goblet cells Muscle layer Less developed spirally smooth more developed circularly smooth muscle muscle Adventitia Cartilage plates, lymphatic NO Cartilage plates nodules and mucoserous glands NO lymphatic nodules are present NO mucoserous glands 18 CLINICAL HINT The smooth muscle layers of bronchioles are controlled by the parasympathetic nervous system. Normally, the smooth muscle coats contract at the end of expiration and relax during inspiration. In persons with bronchial asthma, the smooth muscle coat undergoes prolonged contraction during expiration; thus, these individuals have difficulty in expelling air from their lungs. Steroids and β2- agonists relax bronchiolar smooth muscle and are frequently used to relieve asthmatic attacks. II- The respiratory portion: It is composed of: Respiratory bronchioles Respiratory bronchioles constitute a transitional zone in the respiratory system; they are involved in both air conduction and gas exchange. The wall is formed of simple cubical ciliated epith & Clara cells, connective tissue and smooth muscles. The epithelium of the initial segments of the respiratory bronchioles contains both ciliated cells and Clara cells. Distally, Clara cells predominate. Their walls are interrupted by some alveoli, the sites where gas exchange occurs and hence the name of respiratory bronchioles. Alveolar ducts Their walls consist of adjacent alveoli, which are separated from one another only by an interalveolar septum. They are lined by simple cubical non ciliated epithelium between alveoli. Smooth muscle fibers are very few. Alveolar sacs A group of alveoli which open into a common central space, located at the distal ends of alveolar ducts They are lined by simple squamous epithelium. Muscle fibers are absent. 19 Pulmonary alveoli - They are structural & functional unit of the lung. - They are minute air spaces that unit with each other & form air sacs. - There are pores in between lung alveoli that allow communication. - The alveoli are separated from each other by thin interalveolar septum. - The alveoli are lined by two types of cells called pneumocytes type I & type II. 20 21 Type I Pneumocytes: * They represent about 97% of the lining epithelium. * They are squamous flat cells with flat densly stained nuclei. * They contain minimal cytoplasm that contains few cell organelles. * The cells are connected together by tight junctions to avoid escape of tissue fluids within the alveoli. * The cells cannot divide. * The main function of pneumocyte type I is gas exchange as they form a very thin layer. Type II Pneumocytes: * Only 3% of the lining epithelium. * They are cuboidal cells with large rounded nuclei and prominent nucleoli. Their apical surface carries microvilli. * They have abundant vacuolated cytoplasm rich in Golgi apparatus, rER, mitochondria & characteristic multilamellar bodies (cytosomes) that contain phospholipids. * Pneumocytes type II secretes pulmonary surfactant that forms a thin film over the epithelial lining. Surfactant reduces the surface tension of alveoli which prevent their collapse during expiration and allows alveoli to be inflated with less inspiratory force, thus easing the work of breathing * They can divide and give the two types of pneumocytes. 22 CLINICAL HINT At birth, the infant's lungs expand upon the first intake of breath, and the presence of pulmonary surfactant permits the alveoli to remain patent. Immature infants (those born before 7 months of gestation) who have no surfactant or an inadequate supply of surfactant suffer from the potentially fatal respiratory distress of the newborn. These newborns are treated with a combination of synthetic surfactant and glucocorticoid therapy. 23 Regions of Airway within lung Epithelium Bronchi Respiratory Bronchioles Simple ciliated columnar, with Clara cells Terminal bronchioles Simple cubical, ciliated cells and Clara cells Respiratory bronchioles Simple cubical, ciliated cells and Clara cells, with scattered alveoli Alveolar ducts and sacs Simple cubical non ciliated between alveoli Alveoli Types I and II alveolar cells (pneumocytes) The alveolar septum * Separates adjacent alveoli in lung tissue. * Formed of blood capillaries, type I collagen, interstitial cells, smooth muscle cells, mast cells, lymphocytes and monocytes. * Alveolar septum also contains elastic fibers to allow the expansion of alveoli and contains also reticular fibers to prevent over expansion, thus protect the capillaries from ruptures 24 Blood air barrier Definition: It is the wall through which gas exchange occurs. It is present in between blood in blood capillaries & air within the lung alveoli. Structure: 1- Thin film of pulmonary surfactant. 2- Cytoplasm of pneumocyte type I. 3- Fused basement membrane of type I pneumocyte & capillary endothelium. 4- Capillary endothelium. 25 Alveolar phagocytes Definition:-They are phagocytic cells which are present in the cavities of lung alveoli or in the interalveolar septum. Origin:-They arise from blood monocytes. Staining:- They are demonstrated by vital stain as trypan blue. Fate:-They may be coughed in sputum or they may die & remain in the interalveolar septum or nearby lymph nodes. Types:- 1- Dust cells: these cells phagocytosed dust &carbon particles that appear as black particles in their cytoplasm. 2- Heart failure cells: They are not present in normal person; they can only be seen in patient suffering from heart failure. Congestion of blood capillaries will lead to their rupture & escape of RBCs to alveolar cavities. Macrophages phagocytose HB & destroy it to red colored haemosiderin granules that appear within them. Fetal Lung 1. Clear lobes and lobules due to thick CT septa. 2. It is similar to a gland where bronchial tree branches resemble ducts and alveoli resemble acini. 3. Collapsed alveoli, lined by simple cubical epithelium. 4. Presence of cartilage plates around bronchi will differentiates the lung from gland. 5. The bronchi and bronchioles are folded. 6. Blood vessels are full of blood. 7. Fetal lung sinks in water, so it helps to know whether the infant has died before or after delivery (Medico-legal importance). 26 THE PLEURA  The pleura is the serous membrane covering the lung.  It consists of 2 layers, parietal and visceral, that are continuous in the hilum.  The visceral layer covers the lung and the parietal layer lines the thoracic cavity  Both membranes are composed of mesothelial cells (simple squamous epithelium) resting on fine connective tissue that contains collagen & elastic fibers, blood & lymph capillaries and nerve fibers.  A thin film of fluid separates the two layers and permits free movement between them. 27 28 THE INTEGUMENTARY SYSTEM 29  THE INTEGUMENTARY SYSTEM - It is the largest and the heaviest organ of the body, constituting 16% of the total body weight. -The integument is composed of skin and its appendages (sweat glands, sebaceous glands, hair and nails). Skin The skin consists of two layers l-The epidermis  Derived from ectoderm  Composed of stratified squamous keratinized epithelium. 2 -The dermis  Derived from mesoderm.  Composed of dense, irregular collagenous connective tissue. The hypodermis  A loose connective tissue containing fat underlies the skin.  It is not part of the skin but it is the superficial fascia that cover body immediately deep to the skin. Classification of the skin Based on the thickness of the epidermis, skin is classified as: I. Thick skin II. Thin skin 30  I. The thick skin or non-hairy skin - Covers the palms of hands and soles of feet. - It is formed of epidermis and dermis. A- Epidermis  The thickness of epidermis is 0.8 mm in palms and1.4 mm in the soles.  It is composed of stratified squamous keratinized epithelium containing 4 types of cells: 1- Keratinocytes, keratin forming cells. 2- Melanocytes, pigmentary system. 3- Langerhans cells, immune system. 4- Merkel cells, sensory system. 1- Keratinocytes  Represent 85% of cells in epidermis.  Keratinocytes are continually renewed because they are continually sloughed from the surface of the epidermis.  Keratinocytes of basal layer undergo mitosis at night; get pushed toward the surface, passing from one layer to another until reaching the surface, a process that takes 20 to 30 days. On their way, the cells accumulate keratin filaments in their cytoplasm. Eventually, the cells die and sloughed off near the surface.  Keratinocytes are arranged in five layers: 31  a-The stratum basale (Germinativum) or Basal cell layer b-The stratum spinosum (Spinous layer or prickle-cell layer) c-The stratum granulosum (Granular layer) d- The stratum lucidum (Clear layer) e-The stratum corneum (Horny layer) a-The Stratum basale (Germinativum) or Basal cell layer: - consists of a single layer of mitotically active low columnar cells resting on a clear wavy basement membrane. - The cells have basophilic cytoplasm and basal oval nucleus. - Electron micrographs reveal a few mitochondria and rough endoplasmic reticulum (RER), a small Golgi complex, and abundant free ribosomes. - The cells are attached to each other and to cells of the stratum spinosum by many desmosomes -The Basal cells attached to basement membrane by hemidesmosomes. - Mitotic figures are common in this layer because this layer is responsible for cell renewal in the epidermis. - All keratinocytes in the stratum basale contain intermediate filament made of protein keratin (known as keratin filament or tonofilament). - Melanocytes and Merkel's cells are present in this layer. 32 b- The stratum spinosum (spinous layer or prickle-cell layer) -The thickest layer of the epidermis. - Composed of 4 -8 layers of polyhedral cells having central rounded nuclei and cytoplasm actively synthesize more tonofilaments so it has abundant tonofilaments which are grouped in bundles called tonofibrils. - Tonofilament bundles (tonofibrils) radiate from perinuclear region and terminate in desmosomes. -The basally located cells in this layer showed also, mitotic figures as basal layer, so both layers are responsible for renewal of epidermal keratinocytes. - The cells are less basophilic than those of the stratum basale. - The cells are attached tougher by numerous desmosomes. - The cells appear to have numerous short spiny projections (intercellular bridges) that extend between adjacent cells. These projections are sites of desmosomes. As a result of these spiny projections, it is called the stratum spinosum. - Both Stratum spinosum and basale are called malpighian layer. - Langerhans Cells are present in the upper part of this layer. 33 c- The stratum granulosum (granular layer) - Consists of 3-5 layers of flattened cells with flat nuclei. -Their cytoplasm contains two types of granules * Keratohyaline granules - Intense basophilic non membranous masses - cause aggregation of bundles of tonofibrils * Membrane-coated lamellar granules -Lamellar ovoid granules surrounded by membrane and discharge their lipid- rich contents into the intercellular spaces of this layer by exocytosis which acts as seal of skin. -The contents act as a barrier: 1- Preventing water loss and entrance of foreign substances. 2- It prevents nutrition to the cells lying superficial to this region leading to their death. d- The stratum lucidum (clear layer) - It is clear, homogeneous, lightly staining thin layer, superficial to the stratum granulosum. - Consists of four to six rows of extremely flattened eosinophilic cells. - The cells lack organelles and nuclei. - The cytoplasm consists of densely packed keratin filaments and eleidin (transformation product of keratohyaline granules). - This layer is present only in thick skin. 34 e- The stratum corneum (Horny layer) -The most superficial layer of skin - Composed of numerous layers of flattened, keratinized dead cells. -These cells lack nuclei and organelles but have numerous keratin filaments embedded in an amorphous matrix. - Cells near the surface, called squamous or horny cells, are without desmosomes so they can be sloughed.  Clinical hints In psoriasis, a common autoimmune skin disease, there is an increase in the number of proliferating cells in the stratum basale and the stratum spinosum as well as a decrease in the cycle time of these cells. This results in greater epidermal thickness, more rapid renewal of epidermis, abnormal keratinization with a defective skin barrier. This can lead to inflammation with redness, irritation, itching, and scaling. 35 2- Melanocytes - Melanocytes produce melanin pigment that gives brown to black color to skin. -They are ectodermal in origin. -Melanocytes are not stained with H&E. -They are present in the stratum basale but not attached to the surrounding keratinocytes. -They are branched cells with rounded cell body, and numerous branching cytoplasmic processes that extend between the surrounding keratinocytes. - Melanin is formed in granules called melanosomes. - The cell body contains nucleus and organelles for protein synthesis as ribosomes, RER, Golgi apparatus and mitochondria. They also contain tyrosinase enzyme, needed for the formation of melanin granules. So they give a +ve DOPA reaction. - Melanosomes are transferred via the cytoplasmic processes to the cytoplasm of keratinocytes. 36 -The difference in skin pigmentation is related to the amount of the melanin not to the total number of melanocytes in the skin, which is nearly the same for all races. - In whites, melanosomes are smaller, fewer and restricted to the lower zones of the epidermis. Whereas in blacks, melanosomes are larger, more numerous, and dispersed through all cells & all layers of the epidermis. - In old age, the hair turns white because melanocytes become unable to form melanin.  DOPA reaction - It is the reaction that differentiates between melanocytes and melanophores. - If DOPA (dihydroxyphenyl alanine) is added to a suitable epidermal section, * In melanocytes, tyrosinase enzyme converts the DOPA into melanin. Melanin becomes visible as dark pigment particles in the cytoplasm of melanocyte meaning +ve DOPA reaction. * In melanophores (macrophage engulfing melanin), there is no tyrosinase enzyme, so no melanin particles in their cytoplasm, meaning -ve DOPA reaction  Stimulating factors of melanin formation: -Exposure to sunlight (ultraviolet rays) increases tyrosinase enzyme. - Melanocyte stimulating hormone (MSH) from pituitary gland (pars media). - Adreno- cortico trophic hormone (ACTH) from pituitary gland. 37  Comparison between Melanocytes & Melanophores Melanocytes Melanophores l-They are present in the epidermis, 1-They are found in the dermis, between the basal columnar cells. 2-They are ectodermal in origin 2-They are mesodermal in origin 3-They give a positive Dopa reaction 3-They give a negative Dopa reaction (no due to the presence of tyrosinase enzyme). enzyme 4-They form melanin. 4-They carry melanin (macrophages which engulfed melanin).  Clinical hints * In complete albinism, there is genetic defect in tyrosinase enzyme needed for melanin formation (no absence of melanocytes), so the skin appear too white (Albino). * Addison's disease: Decreased production of cortisone from adrenal cortex leads to increase of adreno- corticotrophic hormone (ACTH) from pituitary gland. This increases tyrosinase enzyme in melanocytes and causes hyperpigmentation. 3- Langerhans Cells - They are antigen-presenting cells which are usually located in the upper part of the stratum spinosum. - They arise from precursors in the bone marrow, which are transported in the blood to the dermis and migrate into the epidermis - As melanocytes, Langerhans’ cells are not attached to surrounding keratinocytes by desmosomes. - By LM:  Stellate cells with long slender processes that radiate between keratinocytes, it has dark staining nucleus surrounded by a pale-staining cytoplasm. Functions of Langerhans cells: They are antigen-presenting cells participating in the body's immune responses and play an important role in protecting the skin against infections. 38 4- Merkel's cells - Merkel's cells are modified epidermal cells that have an important role in sensory reception. - They are found in the basal layer of the epidermis of the thick and thin skin. - They are attached to the basal cells by desmosomes. - Merkel's cells are closely associated with sensory nerve fiber, which loses its myelin sheath and its neurolemma as reaching epidermis. It terminates as a disc like expansion under Merkel's cell forming a Merkel's tactile corpuscle, which is a sensitive mechanoreceptor (reception of light touch). 39 40 B-Dermis (Corium) -The dermis is the connective tissue that supports the epidermis and binds it to the subcutaneous tissue (hypodermis). - It is thicker than the epidermis. - The surface of the dermis is very irregular and has many projections (dermal papillae) that fit into the concavities in the epidermis. - It consists of two layer layers with indistinct boundaries: 1- The superficial papillary layer. 2- The deeper reticular layer. 1- The papillary layer of the dermis (cellular layer) - It is the thinner superficial layer that forms the dermal papillae that fit into the concavities in the epidermis - It is composed of a loose connective tissue mainly formed of thin type III collagen fibers and thin elastic fibers. - It contains more cells as fibroblasts, macrophages, mast cells. - It has many capillary loops (highly vascular) that regulate body temperature and nourish the cells of the avascular epidermis. - It contains Meissner corpuscles (mechanoreceptors) located in the dermal papillae. 2- Reticular Layer of the Dermis (fibrous layer) - It is the thicker deep layer. - Composed of irregular dense connective tissue formed mainly of bundles of type I collagen that form network with thick elastic fibers. - Has more fibers and fewer cells than the papillary layer 41 - Less vascular than the papillary layer - It contains receptors (pacinian corpuscles, Ruffini corpuscles and krause's end bulb) How the epidermis is cemented to the Dermis? A-The dermal papillae fit into the concavities on the under surface of the epidermis. B-Hemidesmosomes extended from basal cells to the underlying papillae. C-Basement membrane itself fixes the basal cells to dermal papillae.  Receptors in the epidermis 1- Free nerve endings (for pain, light touch and temperature sensation): penetrate the epidermis and terminate in the stratum granulosum. 2- Merkel's Tactile Corpuscles (mechanoreceptors). 3- Plexus of Bonnet around hair follicles (mechanoreceptors). 2 3 1  Receptors in the dermis 1- Free nerve endings (pain receptors or thermoreceptors). 2- Meissner's corpuscles (mechanoreceptors) in dermal papillae. 3- Krause's end bulb (cold receptors). 4- Ruffini corpuscles (heat receptors & mechanoreceptors). 5- Pacinian corpuscles (deep touch and pressure; detect vibration, changes in the position and sense of movement.) in deep dermis and hypodermis. 42 43  II. The thin skin or hairy skin - It covers all the body except the palms of hands and soles of feet - It has the same structure as the thick skin but with some differences Differences between the thick and thin thick Item Thick skin Thin skin Site palms of hands and soles of feet The rest of the body Epidermis Thicker Thinner Malpighian layer Thicker Thinner Granular layer Thicker Thinner Clear layer Present Absent Horny layer Thicker Thinner Dermal papillae Numerous and regular Fewer and irregular Sweat glands Numerous (eccrine) Fewer (eccrine and apocrine) Hair follicles Absent Present Sebaceous glands Absent Present Arrector pili Absent Present muscles Plexus of Bonnet Absent Present 44 45  Skin appendages - Skin appendages are derived from down growths of epidermal epithelium into the dermis during development. - They include the following: sweat glands, sebaceous glands, hairs, and nails. The sweat glands of the skin - They are merocrine, simple coiled tubular glands located deep in the dermis or in the underlying hypodermis. - They are classified on the bases of their structure and the nature of their secretion into two types: A- Eccrine or ordinary sweat glands B- Apocrine glands A) Eccrine Sweat Glands - They are the most numerous (about 3 million) distributed all over the body except at the lips, glans penis, glans clitoris and labia minora. - They are most numerous in the palms and soles - They are formed of a secretory portion and an excretory duct  The secretory portion - This part is of highly coiled tube situated in the deep dermis. - Small in size with narrow lumen - It is lined by a single layer of cuboidal epithelium containing three cell types: clear cells, dark cells (both are secretory cells) and myoepithelial cells (contractile cells) 1- Clear cells (Pale-staining): - have a narrow apex and a wide base that extends to the basal lamina - Larger in size and more numerous than dark cells - In routine H&E preparations, the cytoplasm of clear cells stains poorly. - It has numerous mitochondria, little RER, and a small Golgi apparatus, microvilli and basal infoldings. No secretory granules - They secrete sodium chloride, urea, uric acids, ammonia, and water. 2-Dark cells - Have a narrow base and a wide apex and do not contact the basal lamina. - Smaller and less numerous than the clear cells. 46 - Dark cells has abundant RER, large Golgi and secretory granules (containing glycoproteins), feature c of glycoprotein secreting cells. 3-Myoepithelial cells: - They are spindle shaped cells located between the secretory cells and their basement membrane.Their cytoplasm contains numerous contractile actin filaments, their contraction help squeeing secretion from the gland.  The excretory duct - It is continuous with the secretory portion and passes in a spiral course through the dermis to open on epidermal surface. - It is lined by two layers of cuboidal cells (st. cuboidal epithelium). - As the duct reaches the epidermis, it loses their lining epithelium and passes as a tunnel between the epidermal cells. 47 B) Apocrine Sweat Glands - Are enlarged, modified eccrine sweat glands, present in the skin of the axilla, the areola of the breast, pubic region and the anal region. - less numerous than eccrine glands. - It is similar to eccrine glands but : - The secretory portion is larger in size and has wider lumen. - The secretory portion is mainly formed of (dark cells) with numerous secretory granules. - The ducts of apocrine glands are similar to those of the eccrine glands, but they usually open into the upper part of hair follicles, above the opening of the sebaceous gland. - Apocrine glands are merocrine not apocrine according to mode of secretion. - Slightly viscous secretion is initially odorless but may acquire a distinctive odor as a result of bacterial activity. - Apocrine glands do not become functional until puberty. 48  The sebaceous glands - The sebaceous glands are found in the dermis over most of the body, except in the thick skin of the palms and soles. - These glands are most abundant on the face, scalp, and the forehead. - They are simple acinar (alveolar) or simple branched acinar glands (holocrine glands) with several acini that are connected to a broad short duct that usually opens into the upper portion of a hair follicle. - In certain hairless regions, such as the eyelids, glans penis, labia minora, and nipples, sebaceous ducts open directly onto the epidermal surface. - Each acinus is pear shaped and has a basal layer of fattened epithelial cells on the basal lamina, which proliferate and differentiate into large rounded pale staining cells (lipid-producing cells) that fill the acinus and contain small fat droplets and abundant smooth ER. -The large rounded cells undergo degeneration and break down releasing the lipids as the main secretory product. New rounded cells are produced by proliferation of the basal cells. - It secretes sebum (a complex mixture of lipids). Its oily nature helps to keep the skin and hair soft. It prevents dryness of the skin (prevent skin cracking). - The secretion from sebaceous glands begins at puberty and is under the influence of sex hormones.  Clinical hints *Acne - It is chronic inflammation of sebaceous glands, common during and after puberty due to obstruction of its duct by impaction of sebum or disturbance in the normal secretion. - The disease is most severe in boys; with onset commonly from age 9 to 11 years old when increasing levels of sex hormones begin to stimulate the sebaceous glands. 49  Comparison between the glands of the Skin Sweat glands Sebaceous glands l- They are found in both hairy and non- hairy l- They are found only in hairy skin. skin 2-They are found deep in dermis. 2- They are found in the superficial part of the dermis. 3-They are simple coiled tubular glands. 3- They are simple alveolar or simple branched alveolar glands. 4- Secretion of both eccrine and apocrine 4- Secretion is of holocrine type and involves glands is of merocrine type and involves no loss of cellular structure. loss of cellular structure. Apocrine glands are found in skin of axilla, pubic region, anal region and areola of breast 5- Eccrine glands open on the surface of the 5- They open into the upper part of the hair skin, while the apocrine glands open into the follicles by short ducts, except in eyelids, hair follicles above the sebaceous gland glans penis, labia minora, and nipples where opening. they open on to skin surface. 6- They secrete sweat. 6- They secrete sebum (protects skin from cracking). 7- Their secretory parts are lined by two types 7- Their secretory parts are composed of acini of cells, clear and dark. filled with large rounded pale-staining cells containing lipid droplets and a basal layer of fattened epithelial cells for renewal of the cells. 50  Hairs - Hairs are elongated filamentous keratinized structures found within epidermal invaginations called the hair follicles. - The hair follicle is an epidermal invagination responsible for the production and growth of hair. Structure of hair: - Shaft of hair: Project from surface of skin - root of hair: embedded in dermis of skin, lower part of root is dilated forming dilatation called hair bulb, it is filled with mass of cells called cellular matrix or germinatum matrix which is responsible for growth of hair it contain also melanocyte. There is invagination of C.T dermis into hair bulb forming dermal papillae for hair nutrition. Microscopically, the hair is formed of 3 layers. Beginning with the innermost layer, they are as follows: l- Medulla: a central core of cornified cells free from pigment. It may be absent in fine hairs. 2- Cortex: cornified melanin-containing cells which gives the color of hair. 3- Cuticle: one layer of flat dead cells containing hard keratin surrounding the cortex. - The shaft and the upper part of the root consist of keratin (soft in medulla and hard in cortex and cuticle). - The structure of the hair follicle - The hair follicle surrounds the root of the hair. - The wall of the hair follicle is formed of 3 sheaths. Beginning with the innermost layer, they are as follows: 1- Inner root sheath: present only in the lower part of the follicle up to the level of opening of the sebaceous gland. It is further divided into the following i) Cuticle: The innermost layer. It lies against the cuticle of the hair, and consists of one layer of cornified squamous dead cells. ii) Huxley's layer: l-3 layer of cuboidal cells. iii) Henle's layer: one layer of flat non-nucleated cornified cells. 51 2- Outer root sheath: It is continuation of malpighian layer of the epidermis in its upper part. At the bottom of the follicle, it consists only of one layer of the cells (stratum basale). 3- Connective tissue sheath: C.T that surround the hair follicle. It is derived from the dermis. * The outer root sheath is separated from the connective tissue sheath by a basal lamina called the glassy membrane. This membrane is strongly eosinophilic and PAS positive. * The zone of transition between the cells and keratin is called keratogenous zone where keratin of the hair is produced. Arrector Pili Muscles - Are smooth muscles which extend from the connective tissue sheath of hair follicle to the papillary layer of the dermis touching the base of the sebaceous gland. - The contractions of these muscles causes the hair to become erected, forming tiny goose bumps "goose-skin " on the surface of the skin. - Also, it squeeze secretion of the sebaceous gland. 52 References:  Wheater's Functional Histology : a Text and Colour Atlas. Edinburgh ; New York :Churchill Livingstone, 2000.  Junqueira's Basic Histology: Text and Atlas. Fourteenth edition. 53