Integumentary System

Integumentary System: Skin and Derivatives

Introduction to Skin

  • The skin is the largest organ in the body.
  • Functions of the skin include:
    • Protection: physical, chemical, bacterial, UV radiation.
    • Waterproof barrier.
    • Gland secretion.
    • Thermoregulation.
    • Reception of sensory stimuli.
    • Immune defense.
  • Skin layers vary in thickness and presence of epidermal appendages (glands, hairs) throughout the body.
  • Classification: Broadly categorized as thick or thin skin.

Epidermis

  • An ectodermal derivative.
  • Composed of stratified squamous epithelial cells called keratinocytes.
  • Divided into distinct strata (layers) based on the structure and differentiation stage of keratinocytes.
  • Keratinocytes undergo a life cycle from birth in the basal layer to being sloughed off as dead bags of keratin at the surface.
  • The cycle length is approximately 2828 days, but can be as short as 77 days in conditions like Psoriasis.
  • Keratin: A fibrous structural protein that provides protection from chemical and mechanical damage.
  • Waterproof layer: Produced along the keratinocyte differentiation pathway, also functions as a permeability and microbial barrier.
Layers of the Epidermis (from deep to superficial)
  • These layers are more easily observed in thick skin:

  1. Stratum Basale (Stratum Germinativum)

    • Location: Deepest layer, next to the connective tissue (dermis).
    • Cells: Contains mitotic (dividing) keratinocytes, responsible for producing new cells.
    • Junctions: Hemidesmosomes link the cell membrane of basal keratinocytes to the basement membrane, firmly attaching the epidermis to the dermis.
    • Tonofilaments: Bundles of intermediate filaments (keratin filaments) are present.

  2. Stratum Spinosum

    • Cells: Often called "prickle cells" due to their appearance from numerous desmosomes.
    • Junctions: Strong spot junctions (macula adherens) called desmosomes hold cells tightly together.
    • Tonofilaments: Bundles of keratin tonofilaments terminate in desmosomes, strengthening intercellular adhesion.

  3. Stratum Granulosum

    • Appearance: Granulated cells.
    • Keratohyalin granules: Contain proteins that cross-link keratin tonofilaments to form large bundles, a necessary step for keratinization (cornification).
    • Lamellar bodies: Small, membrane-bound organelles containing lipids that are exocytosed (secreted).
      • Function: Upon secretion, these lipids form an impermeable barrier to water and act as an antimicrobial barrier, contributing to the skin's waterproofing and protection.

  4. Stratum Lucidum

    • Location: Only present in thick skin (e.g., palms, soles).
    • Appearance: Clear, translucent layer.
    • Cells: Consists of flattened, dead cells.

  5. Stratum Corneum

    • Location: Topmost layer.
    • Cells: Stack of flattened, dead, anucleated cells (squames) filled with keratin.
    • Process: Loss of organelles, nuclei, and junctions signifies the final stage of keratinocyte differentiation.
    • Function: Provides a strong protective barrier.
Other Cells Present in the Epidermis
  • Besides keratinocytes, a small number of other specialized cells are found:

  1. Merkel Cell

    • Location: Stratum basale.
    • Type: Epithelial cell, modified to function as a sensory touch receptor (mechanoreceptor).
    • Associated with: A nerve ending called a Merkel disc.

  2. Langerhans Cell

    • Location: Predominantly in the stratum spinosum (also in dermis).
    • Type: Antigen-presenting cell (APC), a type of dendritic cell.
    • Function: Searches for pathogens attempting to invade the body via the skin. Captures, phagocytoses, and processes antigens into peptides. These cells then travel from the epidermis to the connective tissue, are carried by lymph vessels to lymph nodes, and present antigens to T lymphocytes.
    • Involvement: Involved in contact allergic dermatitis and cutaneous hypersensitivity.
    • Clinical relevance: Increased in mycobacterium infections.

  3. Melanocyte

    • Location: Spider-like cell in the stratum basale, with processes extending up into the stratum spinosum.
    • Origin: Derived from neural crest.
    • Function: Synthesizes the dark brown pigment melanin from tyrosine in membrane-bound organelles called melanosomes.
    • Melanin transfer: Melanosomes are extruded at the tips of cell processes and transferred to nearby keratinocytes. (Note: in H&E stains, pigmented cells are keratinocytes, not melanocytes themselves).
    • Protection: Within keratinocytes, melanosomes congregate around the nucleus, forming a protective "umbrella" that shields keratinocyte DNA from UV damage.
    • Tanning: Reflects an increase in melanin in the skin due to sun exposure.
Selected Diseases of the Epidermis

  1. Psoriasis

    • Type: Inflammatory disease.
    • Pathology: Characterized by increased proliferation and accelerated development of keratinocytes.
    • Histology: Immature cells still containing their nuclei (parakeratosis) accumulate at the surface (stratum corneum). The stratum granulosum layer is lost, resulting in a poor water barrier. Hyperplasia of the spinosum occurs with elongated epidermal ridges.
    • Clinical Features: Most patients develop thick, raised plaques with silvery or white surfaces, commonly dry patches.
    • Cycle: Normal keratinocyte cycle approx. 2828 days; in psoriasis, it can be as little as 77 days.

  2. Blistering Diseases of Skin

    • A. Pemphigus Vulgaris
      • Type: Autoimmune disease.
      • Pathology: Antibodies target desmosomes.
      • Result: Separation and lysis of cells in the stratum spinosum. Fluid-filled blisters form between the stratum basale and spinosum.
      • Adhesion: The stratum basale remains attached to the basement membrane via hemidesmosomes, giving a "tombstone appearance" to the basal layer.
    • B. Bullous Pemphigoid
      • Type: Autoimmune disease.
      • Pathology: Antibodies target hemidesmosomes.
      • Result: Blisters form by separating the stratum basale from its basement membrane and the dermis.

  3. Skin Malignancies

    • Association: Often associated with sun and UV damage.
    • Treatment: Commonly removed by Mohs micrographic surgery.
    • Types of skin cancer:
      • A. Basal Cell Carcinoma: Most common type of skin cancer. Resembles basal cells. Grows slowly and rarely spreads (metastasizes), but can enlarge locally.
      • B. Squamous Cell Carcinoma (cutaneous): Second most common skin cancer. Characterized by atypical keratinocytes throughout the epithelium. Can become invasive if not treated. Often preceded by precancerous lesions like actinic keratosis.
      • C. Melanoma: Highly aggressive neoplasm originating from melanocytes. Associated with UV damage, it is the deadliest form of skin cancer. Exhibits irregular edges and coloration.
      • D. Merkel Cell Carcinoma: Rare, aggressive form of skin cancer, allegedly stemming from Merkel cells.

Dermis

  • Composition: Consists of connective tissue, containing epidermal derivatives (glands, hair follicles), nerves, sensory receptors, blood, and lymphatic vessels.
  • Layers: Divided into two main layers:

  1. Papillary Layer

    • Composition: Composed of dermal papillae with loose connective tissue, many capillaries, and sensory nerve endings.
    • Junction: The epidermal-dermal junction is strengthened by interdigitations of dermal papillae and downward extensions of the epidermis, known as epidermal ridges or rete.

  2. Reticular Layer

    • Composition: Dense irregular connective tissue.
    • Contents: Can contain hair follicles, arrector pili muscle, sebaceous and sweat glands, nerves and nerve endings, blood vessels, and numerous arteriovenous shunts.
    • Arteriovenous Shunts: Direct links between arteriolar and venous blood, bypassing capillary beds. These shunts play a crucial role in thermoregulation.

Hypodermis

  • Location: A layer of loose connective tissue with abundant adipose (fat) tissue, located deep to the dermis.
  • Classification: Although not considered part of the skin proper, it may contain portions of hair follicles, sweat glands, and Pacinian corpuscles.
  • Alternative Names: In gross anatomy, this layer is called the subcutaneous layer or superficial fascia.

Sensory Innervation of Skin

  • The skin is richly innervated by various sensory receptors:

  1. Meissner's Touch Corpuscles

    • Type: Encapsulated sensory receptors.
    • Location: Found in the dermal papillae of thick skin.
    • Function: Specialized for two-point tactile discrimination.

  2. Pacinian Corpuscles

    • Type: Large, encapsulated sensory receptors.
    • Location: Found in the reticular layer of the dermis or the hypodermis.
    • Function: Respond to vibration and deep pressure.

  3. Free Sensory Nerve Endings

    • Location: Present in connective tissue (CT), around each hair follicle, and extend into the epidermis between keratinocytes.
    • Function: Respond to pain, temperature, and crude touch.

  4. Merkel Cells

    • Type: Touch receptor.
    • Location: Stratum basale of the epidermis.
    • Associated with: A nerve ending called a Merkel disc.

Epidermal Skin Derivatives or Appendages

Glands

  • Modes of Secretion for Exocrine Cells in Skin:

    • Eccrine or Merocrine: Releases product with little or no loss of cytoplasm (e.g., common sweat glands).
    • Apocrine: Releases product with loss of some apical cytoplasm (e.g., apocrine sweat glands).
    • Holocrine: Releases product when the entire cell dies and disintegrates (e.g., sebaceous glands).

  • Types of Skin Glands:

  1. Eccrine Sweat Glands (Merocrine)

    • Prevalence: Common throughout the skin of the body.
    • Structure: Simple coiled tubular glands.
    • Appearance in sections: Nest of cut tubules with pale-staining secretory cells and darker ducts.
    • Accessory cells: Myoepithelial cells assist in squeezing the secretion into the ducts.
    • Emptying: Empty their watery secretion directly onto the surface of the epidermis.
    • Ducts: Initially carried by ducts, then merge with the stratum basale and appear as spaces in the epidermis.
    • Function: Play a major role in thermoregulation; evaporation of sweat from the skin surface cools the body.

  2. Apocrine Sweat Glands ("Odoriferous" Glands)

    • Location: Only in specific areas, including the underarm (axilla), areola of the nipple, and perianal area.
    • Structure: Simple coiled glands with large lumens.
    • Emptying: Empty directly into hair follicles.
    • Development: Begin to secrete their slightly viscous, protein-rich sweat at puberty.
    • Odor: Initially odorless, but acquire a distinctive odor due to bacterial activity.

  3. Sebaceous Glands (Holocrine)

    • Type: Simple branched alveolar glands.
    • Location: Primarily in thin skin, emptying directly into hair follicles.
    • Secretion: Produce sebum, an oily secretion.
    • Histology: Cells have a light-staining vacuolated cytoplasm.
    • Mode of secretion: Holocrine mode of secretion (entire cell disintegrates).
    • Pathology: Inflammation of sebaceous glands results in acne.
Hairs
  • Distribution: Present throughout the body except for thick skin areas (palms and soles).
  • Composition: Filaments with tightly packed hard keratin, produced by hair follicles.

  1. Hair Shaft

    • Part: The free part sticking out of the skin (the "hair").
    • Composition: Contains dead cells.
    • Analogy: Analogous to the stratum corneum of the epidermis.

  2. Hair Root

    • Part: Portion attached to the cylindrical hair follicle.

  3. Hair Follicle

    • Structure: Cylindrical extension of the stratum basale and spinosum that produces the hair.
    • Sheaths: Divided into an internal and external root sheath. The external sheath is continuous with the stratum basale and spinosum.

  4. Hair Bulb

    • Part: Deep, growing end of the hair follicle.
    • Contents: Contains the mitotic matrix that produces differentiating keratinocytes.
    • Nutrition: The bulb surrounds the dermal papillae, a vascular connective tissue that provides nutrition and oxygen to the bulb cells.
    • Pigmentation: Pigment is added to the developing keratinocytes by melanocytes through melanosome transfer, similar to the process in the epidermis.
  • Associated Structures with Hair Follicles:
    • Sebaceous glands: Empty into hair follicles.
    • Arrector pili muscle: Smooth muscle with one end attached to the connective tissue sheath of the hair follicle and the other inserting into the papillary layer of the dermis.
      • Function: Muscle contraction results in "goosebumps" (piloerection).
Nails
  • Composition: Consist of tightly packed plates of hard keratin, forming the nail plate.
  • Location: Rests on an underlying stratified squamous epithelium called the nail bed.
  • Analogy: The nail plate (dead bags of keratin) is analogous to the stratum corneum.

  1. Nail Root

    • Location: Area at the base of the nail.

  2. Nail Matrix

    • Location: Within the nail root.
    • Function: Mitotically active area that gives rise to new keratinocytes. As cells differentiate, they become part of the hard nail plate.
    • Extension: The nail root and matrix are extensions of the stratum basale and spinosum of the epidermis.

  3. Cuticle (Eponychium)

    • Structure: Highly keratinized free edge of skin overlying the nail bed and matrix.

  4. Hyponychium

    • Structure: A thickened layer of epidermis.
    • Function: Secures the free edge of the nail plate at the fingertip.

  5. Lunula

    • Appearance: Crescent-shaped white area near the root of the nail.
    • Representation: Represents the distal extension of the nail matrix underlying the nail plate.
    • Clinical Significance: The transparency of the lunula and nail plate provides a useful window on the amount of blood oxygenation in the dermal vessels.

Skin Repair and Regeneration

  • Superficial damage of the epidermis is repaired from cells in the stratum basale.
  • Deeper skin injuries (e.g., full-thickness burns involving all of epidermis, dermis, and often hypodermis) can regenerate from remnants of hair follicles and sweat glands that extend into the dermis or hypodermis.

Laboratory Focus Topics

  • Compare thick and thin skin and describe structures and glands in each.
  • Describe the steps in keratinocyte differentiation and relate them to specific strata. Include details of cell structure, junctions, mitosis, nuclei, granules, and secretions.
  • Describe Langerhans cells and melanocytes.
  • Describe eccrine, apocrine sweat glands, and sebaceous glands in terms of their structure, mode of secretion, and where they empty.
  • Identify the basic components of hair and nails.

Sample Questions (from materials)

  1. Which stratum or layer is characterized by cells linked by many desmosomes?
  2. Which stratum has the most mitotic figures?
  3. Which stratum has cells with keratohyalin granules and lamellar bodies? What is the function of the lamellar bodies?
  4. Hemidesmosomes are present in which stratum and what is their function?
  5. Which stratum does not contain nuclei?
  6. Which stratum has "prickle" cells?
  7. Which cell in the epidermis is derived from neural crest?
  8. What is the function of Langerhans cells? Where are they located?
  9. Which gland empties into the hair follicles?
  10. Which layer contains Meissner’s corpuscles – dermis, epidermis, or hypodermis?
  11. The nail plate is analogous to which layer of the epidermis?
  12. Which gland has a holocrine mode of secretion?
  13. What is the structure of the common sweat gland – simple tubular or alveolar?
  14. Which cell produces melanosomes and which cell stores them?