Physiology Lectures: Skin and Locomotor System 2024/2025 - Lecture 1

2 Physiology Lectures- Skin and Locomotor System- 2024/2025 Prof.Shaimaa Nasr Amin Lecture 1 I-Physiology of The Skin SKI Skin and Home...

2 Physiology Lectures- Skin and Locomotor System- 2024/2025 Prof.Shaimaa Nasr Amin Lecture 1 I-Physiology of The Skin SKI Skin and Homeostasis: Skin homeostasis refers to the steady state of the body's internal environment. Maintaining skin homeostasis is an important prerequisite for maintaining the stability of the entire internal environment. At the same time, skin ten homeostasis is also the basis for maintaining the function of the skin barrier. The skin barrier is the first line of defense of the human body, and its main function is to prevent water loss and harmful substances from invading the body. Only when skin homeostasis is well maintained can the skin barrier function properly and protect the body from external threats. Therefore, maintaining skin homeostasis is of great significance for maintaining human health. Skin Functions: 1-PROTECTIVE FUNCTION The skin forms a protective covering over the entire body, safeguarding underlying parts from physical trauma and pathogen invasion. The skin has a variety of components that participate both innate and adaptive immune responses. A-The innate immune system: The innate immune system comprises mechanisms of immediate host defense, including (1) physical barriers system, which a variety of in I (epithelia) and (2) soluble factors such as antimicrobial peptides, chemokines, cytokines, and the complement resident cells can produce (e.g., keratinocytes, fibroblasts) and infiltrating leukocytes such as polymorphonuclear leukocytes (PMNs), monocytes/macrophages, dendritic cells (DCs), and natural killer (NK) cells. B-Adaptive immune responses of the skin: Effective immune response in human skin is usually initiated by dendritic antigen-presenting cells (APC) in the epidermis Langerhans Cells (LCs), and dermal DCs (DDCs) in the dermis and is finally executed by T lymphocytes or B-cell–derived antibodies, or both. Induction of a sufficient adaptive immune response requires the recognition of a given antigen by lymphocytes. C-The melanocytes in the skin protect it from UV radiation (providing chemical barrier) and Melanocytes express functional toll-like receptors (TLRs), and innate immune stimulation via TLRs affects melanin synthesis The major types of melanin are: 00 Pheomelanin –orange to red pigment expressed in the hair and skin. Low protective properties against DNA damage induced by UV radiation. 00 Eumelanin – a brown to black pigment expressed in the hair and skin. Higher protective properties against DNA damage induced by UV radiation. Neuromelanin – expressed in several regions of the brain. Its loss is associated with several neurological disorders including Parkinson's disease (PD). Melanin formation and the functional interaction between melanocytes and Keratinocytes: The cellular site of melanin synthesis, storage, and transportation is a membrane-bound subcellular organelle 0 0 known as melanosome produced by melanocytes. While in the perinuclear region of melanocytes, melanosomes are immature and non-pigmented. As they migrate to dendrites, they undergo conformational changes and become mature and pigmented. Ten cytoplasm aroundthenuclear Melanocytes are inserted into the keratinocytes in the epidermis due to their long and fine prolongations. j towA melanocyte is surrounded by approximately 36 keratinocytes, with which it forms the epidermal unit, whose me activity is paracrine-regulated. The synthesized quantity of melanin pigments at the melanocyte level is influenced (stimulated or inhibited) by a series of factors secreted by the keratinocytes. On the other hand, melanocytes secrete a series of substances that act upon keratinocytes. Through extensions, the melanosomes of melanocytes are transferred to the surrounding keratinocytes, where they distribute uniformly to achieve a homogeneous pigmentation and create a screen covering the keratinocytes' nucleus. Keratinocytes take over melanosomes 2 3 Physiology Lectures- Skin and Locomotor System- 2024/2025 Prof.Shaimaa Nasr Amin through a phagocytosis process, dependent on ultraviolet radiation and regulated by the alpha-melanocyte- stimulating hormone (α-MSH). Cells communicate by a variety of mechanisms. One mechanism is gap junctions. Keratinocytes and melanocytes have gap junctions in addition to cytokines release that act on the surrounding cells by paracrine mode of action. Endothelin-1 (ET-1) and basic fibroblast growth factor (bFGF) are secreted by keratinocytes, stimulating proliferation, chemotaxis, and pigment production in melanocytic cells. Ultraviolet irradiation (UVR) increases ET-1 and bFGF secretion by keratinocytes. D-The sebaceous glands secret acidic oily secretions, which retards the growth of bacteria. 2-SKIN HELPS REGULATE WATER LOSS: In the skin's epidermis, a water gradient exists, with the moisture content of the stratum corneum being lower than that of the deeper dermal layers. Due to this gradient, passive diffusion of water occurs from the inner layers towards the stratum corneum. Most water evaporates from the skin surface, while a fraction of the water is retained within the stratum corneum. This insensible water loss from the skin due to evaporation (in the absence of sweat) is referred to as transepidermal water loss(TEWL). ISIS In healthy skin, the stratum corneum acts as a protective barrier against water loss due to the presence of layers of keratin and glycolipids. Since outer skin cells are dead and keratinized, the skin is waterproof, preventing water loss. A fully functioning stratum corneum closely controls the water diffusion gradient, and any damage to the skin due to chemical or mechanical insult would impair the skin barrier. In effect, the skin loses some of its efficiency in retaining water within the stratum corneum, and due to a higher volume of water being lost through evaporation, an increase in TEWL will be detected. *Hydration refers to the skin's water content. Aquaporins (AQPs) and skin hydration: khti oni.ws Ie Aquaporins (AQPs) are components of the epidermis that impact both hydration and barrier. This family of transmembrane proteins forms water channels across cell membranes. Thirteen different AQPs have been recognized in mammals, where some are selective water channels and others transport both water and glycerol. Pyp AQP-3 (aquaglyceroporin) is detected and found to be significant in Subcutaneous (SC) hydration. Additionally, AQP3 has been shown to regulate keratinocyte proliferation, cell migration, and tumor genesis. Increased AQP3 expression increases keratinocyte proliferation and may result in increased skin hydration. Abnormalities of AQP3 expression are associated with the development of certain skin disorders. Other aquaporins have also been found in the skin epidermis: AQP10 and AQP9. Factors affecting skin hydration: I-Environmental Factors Affecting Skin Hydration: A-Ultra-Violet light (UVL): ATENI Overexposure to UVL is associated with decreased skin hydration and increased TEWL. The increased TEWL is mainly attributable to the degradation of the skin's barrier function. B-Seasonal effects: SC lipid levels decreased in winter vs. spring and summer; such reduction of lipid content impacts skin hydration by increasing the skin's susceptibility to dryness and disruptions in barrier function. C-Humidity: of Relative humidity (RH), rather than absolute humidity, is the most common way of measuring the moisture content of the air. It is the amount of water vapor (moisture) in the air compared to the maximum amount the air could hold at a given temperature and express as a percentage. TEWL C The relationship between transepidermal water loss to rising ambient humidity is not linear. With increasing humidity, the TEWL rises until it starts falling at about 30- 50% RH. II-Nutritional Factors Affecting Skin Hydration: T.it *Vitamin C as a nutritional supplement to improve skin barrier function has been extensively studied and has been reported to stimulate ceramide production in keratinocytes by modulating metabolic enzymes to improve epidermal barrier function. 3 4 Physiology Lectures- Skin and Locomotor System- 2024/2025 Prof.Shaimaa Nasr Amin *Calcium is a nutrient also responsible for maintaining the epidermal barrier due to its crucial role in regular keratinocyte differentiation. *Polyunsaturated fatty acids found in vegetable oils and fish oils have been found to contain cutaneous anti- inflammatory and antiproliferative metabolites. Deficiency in linoleic acid, a polyunsaturated acid, has been shown to cause scaly skin disorders and excessive water loss. III-Collagen: Collagen is the most abundant component of the extracellular matrix. The extracellular matrix retains water and supports smooth, firm, and strong skin. Collagen fibers are synthesized primarily by the fibroblasts in the deeper layers of the skin. The skin contains a network of collagen fibers that provide structural support and help maintain the skin's elastic properties. IV-Glycation as a Factor Impacting Skin Hydration: Glycation is a non-enzymatic process by which proteins and lipids are modified upon exposure to sugars. Glycated keratin in the epidermis is associated with a decrease in SC water levels that contributes to skin dryness; this may be due to the excess binding of glucose to skin fibers reducing skin elasticity, thereby decreasing hydration. The negative impact of glycation on skin hydration was seen in the skin of persons with diabetes mellitus. V-Aging as a Factor Affecting Skin Hydration: ceramide HE All major lipid species, especially ceramides, are significantly decreased in the SC with increasing age, suggesting a decreased skin barrier function. An age-related reduction in epidermal hyaluronic acid (HA), the key molecule involved in skin moisture. It has a unique capacity to bind and retain water molecules. Because of its importance, hyaluronic acid has been a target of pharmacological intervention in anti-aging skin treatments that are reported 0 to promote fibroblast activation and skin hydration VI-Circadian variations: (will be presented later with Biological Clocks and The Skin). 3-EXCRETION Sweat excrete some urea, apocrine and eccrine are the two types of sweat glands present. Apocrine is concentrated in the axilla, pubis, and areola of the breast. The gland cells are innervated by the sympathetic adrenergic fibers. Its secretion starts at the time of puberty, and the adrenal androgens stimulate the secretion. The gland cells are stimulated by emotional excitement and mediated through sympathetic adrenergic innervation. The eccrine glands have a coiled duct system, which opens into the skin's surface. They are distributed more in the palm, hand, chest, and forehead. The cells of eccrine glands are supplied by sympathetic cholinergic fibers. The eccrine gland is stimulated in response to the increase in the body temperature. The sweat glands are innervated by cholinergic nerve fibers (fibers that secrete acetylcholine). The eccrine glands can also be stimulated to some extent by epinephrine or norepinephrine circulating in the blood, even though the glands themselves do not have adrenergic innervation. This mechanism is important during exercise when the adrenal medullae secrete these hormones, and the body needs to lose excessive amounts of heat produced by the active muscles. Mechanism of Sweat Secretion: the sweat gland is shown to be a tubular structure consisting of two parts: (1) a deep subdermal coiled portion that secretes the sweat, and (2) a duct portion that passes outward through the dermis and epidermis of the skin. the secretory portion of the sweat gland secretes a fluid called the primary secretion or precursor secretion. The precursor secretion is an active secretory product of the epithelial cells lining the coiled portion of the sweat gland. The composition of the precursor secretion is similar to that of plasma, except that it does not contain plasma proteins. As this precursor solution flows through the duct portion of the gland, it is modified by the reabsorption of most of the sodium and chloride ions. Nath Ct 4