# Lecture 7: Skin Structure and Function ## Unit 2.10: Musculoskeletal System/Dermatology --- ## Learning Objectives By the end of this lecture, students will be able to: 1. Describe the layers and structure of the skin 2. Explain the functions of the epidermis and dermis 3. Describe the skin appendages and their functions 4. Explain the immune function of the skin 5. Describe wound healing processes 6. Explain the terminology used in dermatologic description --- ## Lecture Outline ### I. Skin Overview The skin is the largest organ of the body, serving as the critical interface between the internal milieu and the external environment through a remarkable array of physiologic functions. As a barrier, the skin provides protection against pathogens, chemicals, and ultraviolet radiation, shielding underlying tissues from the constant environmental insults encountered in daily life. Thermoregulation is accomplished through sweating and adjustments in cutaneous blood flow via vasodilation and vasoconstriction, allowing the body to maintain core temperature within a narrow physiologic range. The skin serves as a sensory organ through an elaborate network of receptors for touch, pain, and temperature, and plays a central role in immune function as the body's first-line defense against microbial invasion. Additional vital functions include vitamin D synthesis through UVB-mediated conversion of 7-dehydrocholesterol in the epidermis and regulation of fluid and electrolyte balance by preventing transepidermal water loss. The skin is organized into three principal layers that work in concert to fulfill these diverse functions. The epidermis is the outermost layer and is composed of keratinocytes, melanocytes, Langerhans cells, and Merkel cells, forming a stratified squamous epithelium that provides the primary barrier function. The dermis lies beneath the epidermis and is a connective tissue layer containing collagen, elastin, blood vessels, nerves, and skin appendages that provides structural support, nutrition, and sensation. The hypodermis, or subcutaneous fat layer, is the deepest layer and serves as insulation, energy storage, and cushioning for underlying structures. Skin characteristics vary considerably across the body surface and among individuals. Skin thickness ranges from 0.5 to 4 millimeters, with the thinnest skin found on the eyelids and the thickest on the palms and soles where mechanical stress is greatest. The total surface area of adult skin is approximately 2 square meters, and it accounts for roughly 15% of total body weight, making it the heaviest single organ. Skin color is determined by the interplay of three chromophores: melanin produced by melanocytes provides brown-black pigmentation, hemoglobin in dermal blood vessels contributes red tones, and carotene in the subcutaneous fat adds yellow hues. The embryologic origins of skin components reflect its complex structure and diverse cell populations. The epidermis, hair, nails, and sweat glands are all derived from ectoderm, reflecting their epithelial nature and shared developmental pathway. The dermis and hypodermis arise from mesoderm, consistent with their connective tissue composition including fibroblasts, collagen, and vascular elements. Melanocytes originate from the neural crest, migrating during embryonic development to take up residence in the basal layer of the epidermis, a fact that explains their unique biology and susceptibility to particular diseases such as melanoma and vitiligo. Panel A: Cross-sectional view of full skin thickness showing the three main layers - epidermis at surface, dermis in middle, and hypodermis (subcutaneous fat) at bottom. Panel B: Detailed view of skin appendages including hair follicles extending through dermis, sebaceous glands attached to follicles, and eccrine sweat glands with coiled secretory portions. Panel C: Vascular supply diagram showing superficial and deep dermal plexuses with capillary loops extending into dermal papillae. Panel D: Nerve distribution showing free nerve endings in epidermis, Meissner corpuscles in dermal papillae, and Pacinian corpuscles in deep dermis. --- ### II. Epidermis The epidermis is a stratified squamous keratinizing epithelium organized into distinct layers that progress from deep to superficial, each representing a stage in the differentiation and maturation of keratinocytes. The stratum basale is a single layer of cuboidal cells resting on the basement membrane that contains stem cells responsible for continuous epidermal renewal as well as melanocytes interspersed among the basal keratinocytes. The stratum spinosum lies above and consists of polyhedral cells connected by prominent desmosomes that give them a characteristic "spiny" appearance on histologic examination. The stratum granulosum is defined by the presence of keratohyalin granules within the cells and is the level at which the lipid barrier is assembled through extrusion of lamellar bodies into the intercellular space. The stratum lucidum is a thin, translucent layer found only in thick skin of the palms and soles, while the stratum corneum is the outermost layer composed of anucleate corneocytes that constitute the primary physical barrier of the skin. Keratinocytes are the predominant cell population of the epidermis, arising from stem cells in the basal layer and undergoing a carefully orchestrated program of terminal differentiation. These cells originate from basal layer stem cells and progressively differentiate as they migrate superficially through the epidermal layers over a turnover time of approximately 28 days from the basal layer to the stratum corneum. Their primary function is the production of keratin, a family of intermediate filament proteins that provides structural integrity to the epidermis and assembles into increasingly dense networks as differentiation progresses. The end result is the formation of tough, resilient corneocytes in the stratum corneum that are embedded in a lipid matrix, creating the "bricks and mortar" architecture essential for barrier function. The epidermis contains four major cell types, each contributing distinct functional capabilities to this tissue. Keratinocytes comprise approximately 90% of epidermal cells and are responsible for producing keratin and assembling the structural framework of the epidermis. Melanocytes reside in the basal layer and are responsible for melanin production and transfer of melanosomes to surrounding keratinocytes for photoprotection. Langerhans cells are bone marrow-derived dendritic cells located primarily in the stratum spinosum that function as professional antigen-presenting cells, serving as sentinels of the cutaneous immune system. Merkel cells are found at the dermal-epidermal junction and function as slowly adapting mechanoreceptors that detect light touch and pressure, with particular density in tactile-sensitive areas such as the fingertips. The epidermal barrier is a multi-component system that prevents transepidermal water loss and blocks penetration of environmental agents. The lipid matrix occupying the intercellular spaces of the stratum corneum is composed of ceramides, cholesterol, and free fatty acids organized into lamellar sheets that create a waterproof seal between corneocytes. Tight junctions between keratinocytes in the granular layer provide cell-cell connections that regulate paracellular permeability. The cornified envelope, formed by extensive cross-linking of structural proteins including involucrin, loricrin, and small proline-rich proteins, creates a rigid protein shell surrounding each corneocyte. Antimicrobial peptides such as defensins and cathelicidins are produced by keratinocytes and secreted into the intercellular space, providing innate antimicrobial defense against bacteria, fungi, and viruses that contact the skin surface. Panel A: Epidermal layers from deep to superficial showing stratum basale with cuboidal cells attached to basement membrane, stratum spinosum with polyhedral cells connected by desmosomes, stratum granulosum with keratohyalin granules, and stratum corneum with anucleate corneocytes. Panel B: Keratinocyte differentiation pathway showing progression from basal stem cells through spinous and granular layers with increasing keratin content and loss of organelles. Panel C: Distribution of epidermal cell types showing keratinocytes (90%), melanocytes in basal layer with dendritic processes, Langerhans cells in spinous layer, and Merkel cells at dermal-epidermal junction. Panel D: Epidermal barrier components including lipid matrix between corneocytes, tight junctions, and antimicrobial peptide secretion. --- ### III. Melanocytes and Pigmentation Melanocytes are specialized pigment-producing cells that reside in the basal layer of the epidermis at a ratio of approximately one melanocyte for every ten keratinocytes. These cells originate from the neural crest during embryonic development and migrate to the epidermis where they extend long dendritic processes between adjacent keratinocytes. Their primary function is the synthesis of melanin within specialized organelles called melanosomes, which are membrane-bound structures that serve as the site of melanin production and storage. Once melanosomes are fully melanized, they are transferred from the melanocyte's dendritic tips to surrounding keratinocytes, where they accumulate in a supranuclear cap that shields the nucleus from ultraviolet radiation-induced DNA damage. Melanin synthesis is a tightly regulated enzymatic pathway that begins with the amino acid tyrosine. Tyrosinase is the rate-limiting enzyme in this pathway, catalyzing the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine (DOPA), which serves as a key intermediate in the biosynthetic cascade. DOPA is subsequently oxidized to dopaquinone, from which the pathway diverges to produce two forms of melanin: eumelanin, which is brown to black in color and provides the most effective photoprotection, and pheomelanin, which is red to yellow and is less photoprotective while potentially generating more reactive oxygen species upon UV exposure. The relative amounts and distribution of eumelanin and pheomelanin determine an individual's constitutive skin color and contribute to their susceptibility to UV-induced skin damage and skin cancer. Multiple factors regulate melanin production and influence cutaneous pigmentation. Ultraviolet radiation is the most important environmental stimulus, increasing melanin synthesis through direct effects on melanocytes and indirect signaling from UV-damaged keratinocytes via alpha-melanocyte-stimulating hormone and other paracrine factors. Hormonal influences include melanocyte-stimulating hormone (MSH) and estrogen, both of which increase melanin production and explain the hyperpigmentation seen during pregnancy, particularly of the areolae, linea alba, and facial melasma. Inflammation can result in either post-inflammatory hyperpigmentation from increased melanin deposition in the epidermis and dermis or post-inflammatory hypopigmentation from melanocyte damage, with darker skin types being particularly susceptible to post-inflammatory pigmentary changes. Genetic factors determine the baseline type and amount of melanin produced, influencing constitutive skin color and response to UV exposure across different populations. Disorders of pigmentation reflect dysfunction at various points in the melanin synthesis and distribution pathway. Vitiligo is an autoimmune condition in which melanocytes are selectively destroyed, resulting in sharply demarcated depigmented patches that can be disfiguring and profoundly impact quality of life. Albinism results from genetic defects in tyrosinase or related enzymes, leading to absent or markedly reduced melanin production with associated increased susceptibility to UV-induced skin damage and skin cancer. Melasma is an acquired hyperpigmentation disorder with a strong hormonal component, presenting as symmetric brown to gray-brown patches most commonly on the face in women during pregnancy or oral contraceptive use. Lentigo is characterized by a focal increase in the number of melanocytes in the basal layer, producing flat, pigmented macules that are distinguished histologically from freckles (ephelides) by this melanocyte hyperplasia rather than simply increased melanin production. Panel A: Melanin synthesis pathway showing tyrosine conversion to DOPA by tyrosinase enzyme, then to dopaquinone and finally to eumelanin (brown/black) or pheomelanin (red/yellow). Panel B: Melanosome transfer process with melanocyte dendritic processes extending between keratinocytes, melanosome-containing vesicles, and uptake by adjacent keratinocytes forming supranuclear cap. Panel C: Factors affecting pigmentation including UV radiation stimulating melanogenesis, hormonal influences (MSH, estrogen), and inflammatory changes. Panel D: Comparison of pigmentation disorders showing vitiligo (depigmented patches from melanocyte destruction), albinism (absent melanin), and melasma (hyperpigmented patches). --- ### IV. Dermis The dermis is the connective tissue layer of the skin that provides structural support, nutrition, and a scaffold for skin appendages, vessels, and nerves. Collagen constitutes approximately 80% of the dry weight of the dermis, with type I collagen being the predominant form and providing tensile strength that resists mechanical deformation. Elastin fibers account for 2-4% of dermal dry weight and are responsible for the elastic recoil that allows skin to return to its original configuration after stretching. Ground substance composed of glycosaminoglycans including hyaluronic acid fills the spaces between collagen and elastin fibers, attracting water to maintain dermal hydration and turgor. Fibroblasts are the primary cellular component responsible for producing and maintaining the extracellular matrix, while the dermis also contains an extensive network of blood vessels for nutrition and thermoregulation and nerve fibers providing cutaneous sensation. The dermis is organized into two structurally distinct layers that differ in their connective tissue architecture and functional properties. The papillary dermis is the superficial layer composed of loose connective tissue with thin collagen bundles and numerous fibroblasts, forming finger-like projections called dermal papillae that interdigitate with epidermal rete ridges to increase the surface area of the dermal-epidermal junction. The reticular dermis is the deeper and thicker layer composed of dense irregular connective tissue with thick, interwoven collagen bundles that provide the bulk of the skin's mechanical strength. The transition between these layers is gradual, but their distinct structural properties are clinically relevant as wounds extending into the reticular dermis heal with scarring rather than complete regeneration. The dermal-epidermal junction is a specialized basement membrane zone that anchors the epidermis to the dermis and serves as a selective barrier between the two compartments. Hemidesmosomes anchor basal keratinocytes to the basement membrane through transmembrane proteins including bullous pemphigoid antigens 1 and 2, which are targets of autoantibodies in bullous pemphigoid. The basement membrane itself is composed of the lamina lucida (a clear zone adjacent to the basal cells) and the lamina densa (a dense layer containing type IV collagen and laminin). Anchoring fibrils composed of type VII collagen extend from the lamina densa into the papillary dermis, providing additional structural integrity to the junction. Disruption of any component of this complex can result in blistering diseases; for example, antibodies against type VII collagen cause epidermolysis bullosa acquisita, while mutations in the same protein cause the inherited dystrophic form of epidermolysis bullosa. The dermal blood supply is organized into two interconnected horizontal plexuses that support skin metabolism and participate in thermoregulation. The superficial plexus lies in the papillary dermis and sends capillary loops into the dermal papillae where they are positioned immediately beneath the avascular epidermis, allowing nutrient and gas exchange to occur via diffusion. The deep plexus is located at the junction of the reticular dermis and the hypodermis, receiving blood from perforating arteries that traverse the subcutaneous tissue. Glomus bodies are specialized arteriovenous shunts found in the reticular dermis, particularly in the fingers, toes, ears, and nose, that allow blood to bypass the capillary network for rapid thermoregulation by shunting large volumes of warm blood directly from arterioles to venules. Notably, the epidermis contains no lymphatic vessels and relies entirely on diffusion from dermal lymphatics and capillaries for fluid homeostasis. Panel A: Dermal structure showing papillary dermis with loose connective tissue and dermal papillae interdigitating with epidermal rete ridges, and reticular dermis with dense irregular connective tissue. Panel B: Collagen fiber organization with type I collagen bundles providing tensile strength, interspersed elastin fibers for recoil, and ground substance filling spaces. Panel C: Dermal-epidermal junction components including hemidesmosomes anchoring basal keratinocytes, lamina lucida and lamina densa of basement membrane, and type VII collagen anchoring fibrils. Panel D: Dermal blood supply showing superficial plexus in papillary dermis, deep plexus at dermal-subcutaneous junction, and connecting vessels with glomus bodies for thermoregulation. --- ### V. Skin Appendages - Hair The hair follicle is a complex structure that extends from the skin surface deep into the dermis or hypodermis and is composed of several distinct anatomic components. The hair bulb is the expanded base of the follicle containing rapidly dividing matrix cells that represent the active growth zone responsible for producing the hair shaft. The dermal papilla is a mesenchymal condensation nestled within the concavity of the bulb that provides inductive signals controlling hair growth, cycling, and differentiation. The inner root sheath surrounds the growing hair shaft and guides its trajectory through the follicle, while the outer root sheath forms the external wall of the follicle and is continuous with the surface epidermis. The bulge region, located at the insertion point of the arrector pili muscle, is a critically important stem cell niche harboring multipotent stem cells capable of regenerating the follicle, sebaceous gland, and even the interfollicular epidermis following wounding. Hair growth proceeds through a precisely regulated cycle of three main phases that vary in duration depending on the body site. Anagen is the active growth phase lasting 2 to 6 years on the scalp, during which matrix cells in the bulb rapidly proliferate and differentiate to produce the hair shaft at a rate of approximately 0.3 to 0.5 millimeters per day. Catagen is a brief regression phase lasting 2 to 3 weeks during which apoptosis of the lower follicle occurs, the dermal papilla retracts, and the hair shaft becomes a club hair. Telogen is the resting phase lasting 2 to 3 months during which the club hair is retained in the follicle while the dermal papilla rests in proximity to the bulge stem cells before being reactivated by signals initiating a new anagen phase. Exogen refers to the active shedding process by which the old club hair is released from the follicle, a process that may be independent of telogen-to-anagen transition and normally results in loss of 50 to 100 scalp hairs daily. Three major types of hair are recognized based on their size, pigmentation, and distribution. Vellus hair is fine, short, and unpigmented, covering most of the body surface and functioning primarily as a sensory organ for detecting light touch. Terminal hair is thick, long, and pigmented, found on the scalp, eyebrows, eyelashes, and after puberty in the axillae, pubic region, and beard area in males. Lanugo hair is a fine, soft hair produced by the fetus beginning around the third month of gestation and normally shed before birth, though it may persist in premature infants or reappear in severe malnutrition or certain malignancies as a paraneoplastic phenomenon. Hair disorders encompass a variety of conditions affecting hair growth, cycling, and retention. Alopecia areata is an autoimmune condition in which T-cell-mediated destruction of hair follicle bulb cells produces well-circumscribed patches of non-scarring hair loss, with exclamation point hairs at the periphery being a characteristic finding. Androgenetic alopecia is the most common cause of hair loss, resulting from the effects of dihydrotestosterone (DHT) on genetically susceptible follicles that undergo progressive miniaturization from terminal to vellus-like hairs in a pattern distribution. Telogen effluvium is a diffuse, non-scarring hair shedding that occurs 2 to 3 months after a physiologic stress such as childbirth, high fever, major surgery, or severe illness, resulting from premature synchronized transition of numerous follicles from anagen to telogen. Hirsutism refers to excess growth of terminal hair in women in a male-pattern distribution and may be caused by androgen excess from conditions such as polycystic ovary syndrome, adrenal hyperplasia, or androgen-secreting tumors. Panel A: Hair follicle structure showing hair bulb with matrix cells surrounding dermal papilla, inner and outer root sheaths, and hair shaft emerging through epidermis. Panel B: Hair growth cycle phases with anagen (active growth with mitotic matrix cells), catagen (regression with apoptosis), and telogen (resting phase with club hair). Panel C: Stem cell niche in the bulge region located at arrector pili muscle insertion, showing multipotent stem cells capable of regenerating follicle and epidermis. Panel D: Hair types comparison showing vellus hair (fine, unpigmented) versus terminal hair (thick, pigmented) with cross-sectional differences in medulla and cortex. --- ### VI. Skin Appendages - Glands Eccrine sweat glands are the most widely distributed glands in the skin, found over virtually the entire body surface with the highest density on the palms, soles, and forehead. Their primary function is thermoregulation, accomplished through the production and secretion of hypotonic sweat that cools the body surface through evaporation. Despite being innervated by sympathetic nerve fibers, eccrine glands are unusual in that they respond to cholinergic (acetylcholine) rather than adrenergic neurotransmitters, a unique exception among sympathetic effectors. The eccrine duct opens directly onto the skin surface through a spiral intraepidermal channel, and these glands begin functioning at birth, producing up to several liters of sweat per hour during maximal stimulation by heat or exercise. Apocrine sweat glands have a much more limited distribution, being confined to the axillae, groin, areolae, and periumbilical region where they are associated with hair follicles. These glands produce a protein-rich, lipid-containing secretion that is initially odorless but acquires its characteristic scent when metabolized by resident skin bacteria, particularly Corynebacterium species, on the skin surface. Apocrine glands do not become active until puberty, reflecting their regulation by sex hormones, and are stimulated primarily by emotional stimuli and adrenergic signaling rather than thermal stimuli. Their duct opens into the hair follicle above the sebaceous gland duct, and their function in humans is considered vestigial, though they are homologous to scent-producing glands that serve important communication functions in other mammals. Sebaceous glands are found in association with hair follicles across nearly all skin surfaces except the palms and soles, with the highest density on the face and scalp. Their primary function is the production of sebum, a complex lipid mixture containing triglycerides, wax esters, squalene, and cholesterol that lubricates the skin and hair, contributes to the epidermal barrier, and has antimicrobial properties. Sebaceous glands employ holocrine secretion, in which the entire cell disintegrates to release its lipid contents into the follicular canal, and new cells are continuously generated from the peripheral basal layer of the gland. Androgen hormones, particularly dihydrotestosterone, stimulate sebaceous gland growth and sebum production, which explains the onset of oily skin and acne during puberty. Disorders related to sebaceous glands include acne vulgaris, which results from excess sebum production combined with follicular hyperkeratinization and bacterial colonization, and sebaceous hyperplasia, a benign condition presenting as yellowish papules on the face of older adults. The nail unit is a specialized keratinized appendage that protects the dorsal aspect of the distal phalanx and enhances fine touch and grasping ability. The nail plate is a hard, translucent structure composed of tightly packed, heavily keratinized cells that grows continuously from the nail matrix at a rate of approximately 3 millimeters per month for fingernails and 1 millimeter per month for toenails. The nail matrix is the germinative tissue located beneath the proximal nail fold from which the nail plate is produced, and damage to the matrix can result in permanent nail dystrophy. The nail bed lies beneath the nail plate and provides attachment through a system of longitudinal ridges and grooves, while the visible portion of the matrix seen through the proximal nail plate appears as the lunula, the white crescent at the base of the nail. The cuticle, or eponychium, is the extension of the proximal nail fold that seals the space between the nail plate and the nail fold, providing a barrier against infection of the nail matrix. Panel A: Eccrine sweat gland showing coiled secretory portion in deep dermis with clear and dark cells, straight dermal duct, and spiral intraepidermal duct opening directly to skin surface. Panel B: Apocrine sweat gland with larger secretory coil, duct emptying into hair follicle above sebaceous gland, and location in axillae and groin. Panel C: Sebaceous gland structure showing acini filled with lipid-laden cells undergoing holocrine secretion, duct connecting to hair follicle, and sebum composition. Panel D: Nail anatomy with nail matrix (growth zone) under proximal nail fold, nail plate overlying nail bed, lunula (visible matrix), and hyponychium at distal attachment. --- ### VII. Skin Immune Function The skin provides a multilayered physical barrier that constitutes the first line of defense against microbial invasion and environmental insults. The stratum corneum serves as a mechanical barrier, with its densely packed corneocytes and intercellular lipid matrix creating an impermeable shield that most microorganisms cannot penetrate. The lipid matrix composed of ceramides, cholesterol, and fatty acids creates a waterproof seal that not only prevents transepidermal water loss but also blocks penetration of water-soluble pathogens and toxins. The skin surface maintains a low pH of approximately 4.5 to 5.5, often referred to as the acid mantle, which directly inhibits the growth of many pathogenic bacteria while supporting the resident commensal flora. The normal microbial flora of the skin provides an additional layer of protection through competitive exclusion, occupying niches and consuming nutrients that would otherwise be available to pathogenic organisms. The innate immune system of the skin provides rapid, non-specific responses to microbial threats through both humoral and cellular mechanisms. Antimicrobial peptides, including defensins and cathelicidins, are produced by keratinocytes and constitute a chemical barrier that directly kills bacteria, fungi, and enveloped viruses through disruption of microbial membranes. Keratinocytes themselves are active participants in innate immunity, expressing Toll-like receptors (TLRs) that recognize pathogen-associated molecular patterns and responding by producing pro-inflammatory cytokines including interleukin-1, tumor necrosis factor-alpha, and chemokines that recruit inflammatory cells. Mast cells are resident dermal cells that release preformed inflammatory mediators including histamine, proteases, and cytokines upon activation, playing central roles in allergic reactions and early antimicrobial defense. Dermal macrophages perform phagocytosis of microorganisms and cellular debris, produce cytokines that amplify the inflammatory response, and present antigens to activate adaptive immune responses. The adaptive immune system of the skin is composed of specialized antigen-presenting cells and lymphocyte populations that provide targeted, long-lasting immunity. Langerhans cells are dendritic cells residing in the stratum spinosum that capture and process antigens encountered at the skin surface, then migrate through dermal lymphatics to draining lymph nodes where they present these antigens to naive T cells to initiate adaptive immune responses. Dermal dendritic cells represent a second population of antigen-presenting cells positioned deeper in the skin that complement Langerhans cell function and may preferentially activate different arms of the adaptive response. Resident memory T cells patrol the skin and provide rapid recall responses upon re-exposure to previously encountered pathogens, persisting for years in the absence of continued antigen exposure. Innate lymphoid cells (ILCs) are tissue-resident cells that bridge innate and adaptive immunity, producing cytokines that shape the immune response and participate in tissue homeostasis and repair. The concept of skin-associated lymphoid tissue (SALT) describes the integrated immune network within the skin that coordinates cutaneous immune responses. Keratinocytes function as sentinels, detecting danger through pattern recognition receptors and initiating immune cascades by producing alarm cytokines such as IL-1 and thymic stromal lymphopoietin. Professional antigen-presenting cells, including both Langerhans cells and dermal dendritic cells, capture antigens and migrate to lymph nodes to prime adaptive responses while also presenting antigens locally to resident memory T cells. T cells within the skin include effector populations that mediate antimicrobial defense, regulatory T cells that prevent autoimmunity and limit excessive inflammation, and memory T cells that provide rapid recall immunity. The cytokine network coordinating these responses includes IL-1 and TNF-alpha for initiating inflammation, IL-17 for antimicrobial defense particularly against extracellular bacteria and fungi, and numerous other mediators that fine-tune the balance between protective immunity and pathologic inflammation. Panel A: Physical barriers of skin immunity showing stratum corneum as mechanical barrier, lipid matrix creating waterproof seal, acidic pH inhibiting pathogens, and normal flora providing competitive exclusion. Panel B: Innate immune components including keratinocytes with Toll-like receptors producing antimicrobial peptides (defensins, cathelicidins), dermal macrophages, and mast cells releasing inflammatory mediators. Panel C: Langerhans cell function showing antigen capture in epidermis, migration through dermis via lymphatics, and presentation to T cells in draining lymph node. Panel D: Skin-associated lymphoid tissue (SALT) network with resident memory T cells, dermal dendritic cells, and cytokine signaling pathways coordinating immune responses. --- ### VIII. Wound Healing Wound healing is a dynamic, highly coordinated process that proceeds through four overlapping phases, each characterized by distinct cellular and molecular events. Hemostasis occurs within minutes of injury as platelets adhere to exposed subendothelial collagen, aggregate to form a platelet plug, and activate the coagulation cascade to generate a fibrin clot that stops bleeding and creates a provisional matrix for subsequent cellular infiltration. The inflammatory phase begins within hours and extends through approximately the first four days, during which neutrophils are the first inflammatory cells to arrive and perform phagocytosis of bacteria and debris, followed by macrophages that clear apoptotic neutrophils, continue debridement, and secrete growth factors that transition the wound to the proliferative phase. The proliferative phase spans approximately days 4 through 21 and is characterized by formation of granulation tissue composed of new blood vessels, fibroblasts depositing type III collagen, and keratinocytes migrating from wound edges to re-establish the epithelial barrier. The remodeling phase begins around week 3 and continues for months to over a year, during which the provisional type III collagen matrix is gradually reorganized and replaced by stronger type I collagen, though the final scar achieves only approximately 80% of the tensile strength of unwounded skin. Each phase of wound healing is orchestrated by specific cell populations that are recruited, activated, and eventually cleared in a carefully regulated temporal sequence. Platelets dominate the hemostasis phase, not only forming the physical plug but also releasing alpha granule contents including platelet-derived growth factor and transforming growth factor-beta that recruit inflammatory and mesenchymal cells. Neutrophils are the predominant cells during early inflammation and arrive within hours of injury, but they are rapidly succeeded by macrophages that assume the central regulatory role and are considered indispensable for normal wound healing. During the proliferative phase, fibroblasts produce extracellular matrix and eventually differentiate into myofibroblasts that contract the wound, keratinocytes proliferate and migrate to restore the epithelial surface, and endothelial cells undergo angiogenesis to establish new blood vessel networks within the granulation tissue. The remodeling phase is dominated by fibroblasts and myofibroblasts that reorganize collagen fibers along lines of mechanical stress and undergo apoptosis as the scar matures. Growth factors are the molecular signals that coordinate the transitions between healing phases and direct the behavior of participating cells. Platelet-derived growth factor (PDGF) is released from platelet alpha granules and serves as a potent chemotactic factor for fibroblasts and smooth muscle cells, recruiting them to the wound site. Transforming growth factor-beta (TGF-beta) stimulates collagen synthesis by fibroblasts and is the primary mediator of extracellular matrix deposition, with its excess activity contributing to hypertrophic scar and keloid formation. Vascular endothelial growth factor (VEGF) is produced by macrophages and keratinocytes in the hypoxic wound environment and is the principal driver of angiogenesis, promoting endothelial cell proliferation and new vessel formation. Epidermal growth factor (EGF) stimulates keratinocyte proliferation and migration to promote re-epithelialization, while fibroblast growth factor (FGF) promotes fibroblast proliferation and also contributes to angiogenesis, illustrating the redundancy built into this critical repair process. Numerous local and systemic factors can impair wound healing and must be recognized and addressed to optimize outcomes. Nutritional deficiencies significantly compromise healing, with protein malnutrition impairing fibroblast proliferation and collagen synthesis, vitamin C deficiency preventing proper collagen cross-linking, and zinc deficiency impeding cell division and immune function. Diabetes mellitus impairs wound healing through multiple mechanisms including peripheral neuropathy, peripheral vascular disease, impaired neutrophil function, and advanced glycation end-product accumulation that stiffens the extracellular matrix. Wound infection delays healing by perpetuating the inflammatory phase and can convert an acute wound to a chronic non-healing wound if not controlled. Adequate blood supply is critical for delivering oxygen, nutrients, and immune cells to the wound, and vascular insufficiency from atherosclerosis, venous hypertension, or vasculitis significantly impairs all phases of repair. Medications, particularly systemic corticosteroids, impair healing by suppressing inflammation, inhibiting fibroblast proliferation, and reducing collagen synthesis, effects that must be weighed against the therapeutic benefits of these agents in individual patients. Panel A: Hemostasis phase showing platelet aggregation at wound site, fibrin clot formation, and vasoconstriction followed by vasodilation. Panel B: Inflammatory phase with neutrophil infiltration (days 1-2) followed by macrophage predominance (days 2-4), debris clearance, and cytokine release. Panel C: Proliferative phase showing granulation tissue formation with fibroblasts producing collagen, angiogenesis creating new blood vessels, and keratinocyte migration for re-epithelialization. Panel D: Remodeling phase with collagen reorganization from type III to type I, myofibroblast contraction, and scar maturation over weeks to months. --- ### IX. Dermatologic Terminology - Primary Lesions Accurate description of skin lesions using standardized dermatologic terminology is an essential clinical skill that enables precise communication between providers and guides differential diagnosis. Flat lesions represent changes in skin color without alteration in surface texture or elevation. A macule is a flat, non-palpable lesion less than 1 centimeter in diameter that is defined solely by a color change, such as a freckle (brown macule) or a small patch of vitiligo (depigmented macule). A patch is the larger counterpart of the macule, measuring greater than 1 centimeter in diameter, and similarly represents a color change without elevation, as exemplified by large areas of vitiligo, cafe-au-lait spots, or port-wine stains. Elevated solid lesions are palpable and represent increases in tissue mass through cellular infiltration, edema, or deposition of material in the skin. A papule is a raised, solid lesion less than 1 centimeter in diameter that can be felt as a small bump and may be caused by epidermal hyperplasia, dermal infiltrate, or dermal deposits. A plaque is a raised, flat-topped lesion greater than 1 centimeter in diameter that is often formed by the coalescence of multiple papules, as seen characteristically in psoriasis. A nodule is a solid, raised lesion greater than 1 centimeter in diameter that extends deeper into the dermis or subcutaneous tissue than a papule, while a tumor refers to a particularly large nodule. A wheal is a distinctive lesion characterized by dermal edema that produces a transient, pale or pink, often pruritic elevation that resolves within hours, as seen in urticaria. Fluid-filled lesions are defined by their content and the plane of cleavage within the skin. A vesicle is a small, circumscribed elevation less than 1 centimeter containing clear serous fluid, as seen in herpes simplex and early varicella lesions. A bulla is the larger counterpart of a vesicle, measuring greater than 1 centimeter and containing clear fluid, as exemplified by the tense bullae of bullous pemphigoid or the flaccid bullae of pemphigus vulgaris. A pustule is a circumscribed elevation containing purulent material and may arise within a follicle, as in folliculitis and acne, or may be non-follicular, as in pustular psoriasis. A cyst is a closed, epithelial-lined cavity within the dermis or subcutaneous tissue that contains fluid or semi-solid material and is typically felt as a mobile, round, firm-to-fluctuant nodule. Additional primary lesion types include vascular lesions defined by hemorrhage into the skin. Purpura is the general term for hemorrhage within the skin that does not blanch with pressure, distinguishing it from erythema caused by dilated blood vessels. Petechiae are small purpuric lesions measuring less than 3 millimeters in diameter that suggest thrombocytopenia, platelet dysfunction, or vasculitis. Ecchymoses are larger purpuric lesions measuring greater than 3 millimeters that result from extravasation of blood into the skin from larger vessel disruption or coagulopathy, and their color evolves over days from purple to green to yellow as hemoglobin is metabolized. Panel A: Flat lesions showing macule (less than 1 cm color change without elevation) and patch (greater than 1 cm color change without elevation) with examples of freckle and vitiligo. Panel B: Elevated solid lesions comparing papule (less than 1 cm raised), plaque (greater than 1 cm flat-topped elevation), and nodule (greater than 1 cm deeper in dermis) with clinical examples. Panel C: Fluid-filled lesions showing vesicle (less than 1 cm clear fluid), bulla (greater than 1 cm clear fluid), and pustule (contains purulent material) with cross-sectional anatomy. Panel D: Other primary lesions including wheal (edematous, transient), purpura (non-blanching hemorrhage), petechiae (less than 3 mm), and ecchymosis (greater than 3 mm). --- ### X. Dermatologic Terminology - Secondary Lesions Secondary lesions result from evolution, manipulation, or healing of primary lesions, and their recognition provides important clues to disease chronicity and patient behavior. Lesions characterized by loss of skin surface include erosions, ulcers, excoriations, and fissures. An erosion is a superficial loss of epidermis that does not extend into the dermis and therefore heals without scarring, as seen in the ruptured vesicles of pemphigus vulgaris or herpes simplex. An ulcer represents a deeper loss of tissue extending through the epidermis into the dermis or subcutaneous tissue and heals with scarring, as seen in venous stasis ulcers, arterial insufficiency ulcers, and pyoderma gangrenosum. An excoriation is a superficial erosion caused by scratching and may be linear or punctate, providing clinical evidence of pruritus and the itch-scratch cycle seen in atopic dermatitis and other pruritic conditions. A fissure is a linear crack or split in the skin, typically occurring in dry, thickened, or inflexible skin at sites of mechanical stress such as the corners of the mouth, fingertips, or heel margins. Material on the skin surface provides diagnostic clues about the underlying disease process. Scale consists of flaky, dry fragments of the stratum corneum produced by abnormal keratinization, and its character varies from fine and powdery in pityriasis versicolor to thick and silvery in psoriasis to greasy and yellowish in seborrheic dermatitis. Crust is formed by the drying of serum, blood, or purulent exudate on the skin surface and indicates a disrupted epidermal barrier with serous weeping, as seen in the honey-colored crusts of impetigo or the hemorrhagic crusts of excoriated lesions. Eschar is a black, adherent, necrotic tissue that forms over areas of full-thickness skin death and is seen in deep burns, necrotizing infections, and the eschars characteristic of certain rickettsial diseases and anthrax. Changes in skin texture and thickness represent chronic adaptations to inflammation, rubbing, or disease-mediated alterations in dermal and epidermal structure. Lichenification is a thickening of the skin with accentuation of normal skin markings that results from chronic rubbing or scratching, representing epidermal hyperplasia and is characteristically seen in chronic atopic dermatitis. Atrophy refers to thinning of the skin that may involve the epidermis, dermis, or both, resulting in a tissue-paper quality with visible underlying blood vessels, and can be caused by aging, prolonged topical corticosteroid use, or inflammatory conditions such as lupus. Sclerosis is hardening of the skin due to increased dermal collagen deposition, as seen in morphea and systemic sclerosis, where the skin becomes taut, shiny, and bound down to underlying structures. A scar represents the end result of wound healing in which normal tissue is replaced by fibrous tissue, and scars may be flat, atrophic, hypertrophic, or keloidal depending on the balance of collagen production and remodeling. Descriptive terms for lesion configuration and distribution provide additional diagnostic information. Annular describes a ring-shaped configuration with central clearing, as characteristically seen in tinea corporis, granuloma annulare, and erythema migrans. Linear describes lesions arranged in a line, which may result from external contact (as in linear allergic contact dermatitis from poison ivy), dermatomal distribution (as in herpes zoster), or vascular distribution (as in linear morphea). Dermatomal distribution follows the pattern of a sensory nerve dermatome and is pathognomonic for herpes zoster. The Koebner phenomenon (isomorphic response) refers to the development of new lesions at sites of trauma or mechanical irritation and is characteristically seen in psoriasis, lichen planus, and vitiligo. The Auspitz sign describes the appearance of pinpoint bleeding when the silvery scale of a psoriatic plaque is removed, resulting from exposure of the dilated capillaries in the elongated dermal papillae characteristic of psoriasis. Panel A: Lesions with surface loss showing erosion (superficial, epidermis only), ulcer (deeper, extending into dermis), excoriation (from scratching), and fissure (linear crack). Panel B: Material on skin surface including scale (dry, flaky keratin), crust (dried serum, blood, or pus), and eschar (black necrotic tissue). Panel C: Skin texture changes showing lichenification (thickened skin with accentuated markings from chronic rubbing), atrophy (thinning with visible vessels), and sclerosis (hardening). Panel D: Distribution patterns and descriptive terms including annular (ring-shaped), linear, dermatomal, with examples of Koebner phenomenon and Auspitz sign. --- ## Summary - Skin has three layers: epidermis, dermis, hypodermis - Epidermis: keratinocytes (90%), melanocytes, Langerhans cells, Merkel cells - Stratum corneum: barrier function; lipids and cornified envelope - Dermis: collagen (type I), elastin, fibroblasts, vessels, nerves - Hair cycle: anagen (growth) → catagen (regression) → telogen (rest) - Sweat glands: eccrine (thermoregulation), apocrine (scent) - Skin immunity: physical barrier + innate + adaptive (SALT) - Wound healing: hemostasis → inflammation → proliferation → remodeling - Primary lesions: macule, papule, plaque, vesicle, bulla, pustule - Secondary lesions: scale, crust, erosion, ulcer, scar --- ## Key Terms | Term | Definition | |------|------------| | Keratinocyte | Predominant epidermal cell; produces keratin | | Melanocyte | Pigment-producing cell | | Langerhans cell | Epidermal antigen-presenting cell | | Stratum corneum | Outermost epidermal layer; barrier | | Dermis | Connective tissue layer beneath epidermis | | Anagen | Active hair growth phase | | Macule | Flat lesion <1 cm | | Papule | Raised solid lesion <1 cm | --- *This content is subject to the [MIT License](https://opensource.org/licenses/MIT). © 2024–2026 Hibbert School of Medicine.*