Essentials in Dermatology, Venereology & Leprology Ramesh Bansal
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1DERMATOLOGY
SECTION OUTLINE
  1. Structure of Human Skin
  2. Approach to Diagnosis in Dermatology
  3. Skin Diseases Caused by Protozoa, Arthropods and Parasitic Worms
  4. Cutaneous Infections
  5. Eczemas
  6. Genetics and Genodermatoses
  7. Vesiculobullous Diseases
  8. Papulosquamous Disorders
  9. Disorders of Connective Tissue
  10. Disorders of Skin Appendages
  11. Disorders of Pigmentation
  12. Leg Ulcers and other Disorders of Vascular Insufficiency
  13. Urticaria, Mastocytosis, Pruritus and other Vascular Responses
  14. Disorders due to Cold, Light, Heat and Radiation
  15. Drug Reactions
  16. Nevi and Skin Tumors
  17. Cutaneous Manifestations of Internal Diseases
  18. Miscellaneous Cutaneous Diseases
  19. Glucocorticoids
  20. Dermatotherapeutics
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Structure of Human SkinCHAPTER 1

CHAPTER OUTLINE
  • ◆ Functions
  • ◆ Structure
  • ◆ Epidermis
    • • Stratum Basale or Germinativum (Basal Cell Layer)
    • • Stratum Spinosum (Prickle Cell Layer)
    • • Stratum Granulosum (Granular Cell Layer)
    • • Stratum Lucidum (Transitional Cell Layer)
    • • Stratum Corneum (Horny Cell Layer)
  • ◆ Epidermal Cell Kinetics
    • • Epidermal Turnover Time
    • • Epidermal Cell Cycle
    • • Growth Fraction
    • • Mitotic Index
  • ◆ Dermal-Epidermal Junction
    • • Hemidesmosomes
  • ◆ Dermis
  • ◆ Hypodermis
  • ◆ Cutaneous Receptors of Skin
    • • Nerves
    • • Receptors
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INTRODUCTION
Skin is the largest organ* in human body and has a surface area of about two square meters. A human body has two main kinds of skin:
  1. Nonhairy skin (glabrous skin):
    • It is seen on palms and soles.
    • It has thick epidermis with an additional layer of stratum lucidum below stratum corneum.
    • This part is devoid of hair follicles and sebaceous glands but is rich in encapsulated sense organs in the dermis.
  2. Hair-bearing skin:
    • It covers the larger part of our body and has both hair follicles and sebaceous glands.
    • It is devoid of encapsulated sense organs.
 
FUNCTIONS
  • It acts as a barrier against all harmful elements.
  • Through sweating it acts as an excretory organ and regulates body temperature.
  • It absorbs ultraviolet (UV) radiation and synthesizes vitamin D.
  • Subcutaneous fat is a storehouse of energy and helps in thermal regulation.
  • It mediates various sensations.
  • It also acts as a reservoir of blood which is provided to main pool at the time of need.
  • Immune surveillance: Langerhans cells in the epidermis act as first line defense against any kind of epidermal invasion.
  • Cosmetic function: It adds attractiveness in both sexes.
 
STRUCTURE
  • Human skin consists of continuously renewing stratified squamous epithelium known as epidermis.
  • Epidermis is about 0.05–0.1 mm thick (total thickness of skin, 1.5–4 mm).
  • Beneath the epidermis there is underlying dermal connective tissue. The ratio between epidermis and dermis is about 1:20.
  • Between dermis and epidermis there is a dermal-epidermal junction (DEJ) which provides mechanical support and resistance against external shearing forces.
  • Below the dermis, there is a subcutaneous fatty tissue.
 
EPIDERMIS
  • Embryology:
    • Epidermis originates from surface area of early gastrula.
    • Dermis is derived from mesoderm.
    • Neural crest contributes pigment cells.
  • Structurally: Epidermis is largely composed of keratinocytes which are formed by division of basal layer cells. After division, cells move outwardly toward skin surface and get differentiated to form well defined different layers of epidermis (Fig. 1.1). Following layers have been recognized in the epidermis.
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Fig. 1.1: Diagrammatic representation of epidermal cell layers
 
Stratum Basale or Germinativum (Basal Cell Layer)
Generally, it is one cell thick continuous layer. Cells are small, columnar having dark staining nuclei and dense cytoplasm. These cells are mitotically active and give rise to cells of epidermal layers.
  • Melanocytes:* Among the basal cells, there are pigment synthesizing, dendritic cells known as melanocytes. They transfer pigment to the associated keratinocytes. Melanocytes are derived from neural crest and appear to have ovoid nucleus and pale staining cytoplasm as seen light microscopically.
  • Merkel cells: They are also present among basal keratinocytes of the skin of certain regions of body having high tactile sensitivity. They are found in hairy skin, glabrous skin of digits, lips, oral cavity and outer root sheath of hair follicle. These cells are in contact with nerve fibrils and function as mechanoreceptors. They are also pale staining and have lobulated nuclei.
 
Stratum Spinosum (Prickle Cell Layer)
  • This layer lies immediately above the basal cell layer and is 8–10 layers thick.
  • Its cells are polyhedral, larger, more flattened and contain lamellar granules.
  • It is named as spinous after the spine-like appearance of cell margins in histological sections. Spines are due to abundant desmosomes which provide mechanical coupling between keratinocytes. Desmosomes are one of the important intercellular junctions between adjacent keratinocytes or between keratinocytes and basement membrane. It comprises of electron dense material in the keratinocyte cytoplasm running parallel to the junctional region. Gap junctions are the sites of physiological communication between keratinocytes.
  • Sometimes, the term “malpighian layer” is used to include both the basal and spinous cells.
 
Stratum Granulosum (Granular Cell Layer)
  • Cells of spinous cell layer get differentiated into cells of granular cell layer which is 2–5 layers thick.
  • These cells consist of basophilic keratohyalin granules.
  • Langerhans cells:
    • These are other dendritic cells seen in epidermis.
    • They are found in basal, spinous and granular cell layers, preferentially at suprabasal position.
    • Found in other squamous epithelia also, e.g. oral cavity, esophagus, vagina, etc.
    • Microscopically, they are pale staining and have convoluted nuclei. These cells are stained with gold chloride and contain adenosine triphosphatase (ATPase).
    • Electron microscopically, rod and racket-shaped Birbeck granules are seen in the cytoplasm.
    • These cells are derived from bone marrow and have involvement in T-cell responses.
 
Stratum Lucidum (Transitional Cell Layer)
  • It is seen only in the skin of palms and soles.
  • The cells in this layer still have nucleus and are called as transitional cells.
 
Stratum Corneum** (Horny Cell Layer)
  • During transition from granular cell layer, these cells normally lose their nuclei, cytoplasmic organelles and desmosomal connections and get flattened and polyhedral in shape.
  • This layer provides mechanical protection and allows permeation of soluble substances and acts as a barrier to water loss.
 
EPIDERMAL CELL KINETICS
 
Epidermal Turnover Time
The amount of time taken by whole epidermal cell population to replace itself is called turnover time or epidermal turnover time.
It is also called as regeneration time or replacement time. The mean turnover time of normal skin is 47–48 days. At any time not all basal cells are in proliferative stage. So turnover time depends on cell cycle and growth fraction.
 
Epidermal Cell Cycle
The cell cycle (Tc) refers to the interval between two successive mitoses (M). A dividing cell passes through following four stages (Fig. 1.2):
  1. Mitosis (M)
  2. Postmitotic growth phase or interphase (G1)
  3. A period of active deoxyribonucleic acid (DNA) synthesis (S)
  4. Premitotic growth or resting phase (G2)
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Fig. 1.2: Cell cycle
Abbreviations: G0, quiescent phase; G1, interphase; G2, resting phase; M, mitosis; S, active DNA synthesis period; D, differentiated
Postmitotic growth phase is quite longer, while premitotic growth phase is short. After division, cells may become quiescent (G0 phase), but can reenter the cell cycle again when they are required to do so. After division, cells have another option to get differentiated (D). Duration of cell cycle varies from 13 to 14 days. It is markedly reduced to 36–48 hours in psoriasis.
 
Growth Fraction
It refers to the percentage of basal cells in proliferative stage at any time. The cell may be in any of the above four proliferative stages.
 
Mitotic Index
The percentage of cells that are in mitosis (M) phase is called as mitotic index. It is also called as proliferative index or flash labeling index. Mitotic index is always less than growth fraction because latter includes cells of all the four stages of cell division. In psoriasis, mitotic index is greatly increased, while growth fraction is 100%.
 
DERMAL-EPIDERMAL JUNCTION
 
Hemidesmosomes
These are electron dense focal thickenings which stud the trilaminar plasma membrane of basal keratinocytes at frequent intervals. Tonofilaments are associated perpendicularly with the cytoplasmic portion of hemidesmosomes.
zoom view
Fig. 1.3: Diagrammatic representation of dermal-epidermal junction
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Inner to plasma membrane is the basement membrane, which is comprised of three layers, i.e. lamina lucida, lamina densa and lamina fibroreticularis.
 
Lamina Lucida
It is an electron lucent intermembranous space which separates plasma membrane from lamina densa. In areas of lamina lucida, there are linear densities beneath each hemidesmosome. These densities are termed as sub-basal dense plaques (SBDP). Fine anchoring filaments traverse the SBDP and extend perpendicularly from plasma membrane to mesh with lamina densa. Lamina lucida is considered as the weakest zone of DEJ.
 
Lamina Densa (Basal Lamina)
It is an electron dense layer lying next to lamina lucida and is parallel to the lower border of plasma membrane. Type IV collagen is its primary component.
 
Lamina Fibroreticularis
It is a fibroreticular layer which is composed of three major structures, namely anchoring fibrils, type III collagen and dermal bundle of microfibrils.
  1. Anchoring fibrils are major constituent and are irregularly spaced cross banded fibers. Their epidermal ends mesh with lamina densa and dermal end with papillary dermis in the amorphous bodies known as anchoring plaques. But, more characteristically, they curve back to have a second insertion in lamina densa. Type VII collagen is the major component of anchoring fibrils.
  2. Type III fibers are randomly oriented type fibers.
  3. Dermal microfibrils extend perpendicularly from basal lamina to papillary dermis.
 
DERMIS
The dermis is bounded externally by DEJ and internally by hypodermis. It constitutes the major part of skin but varies in thickness. It is about 1 mm thick on eyelids and 5 mm on the back.
The cellular components of dermis consist of:
  • The fibroblasts, macrophages and mast cells constitute the usual cellular components of dermis. These are mainly found in the papillary region and around vessels.
  • Monocytes, macrophages and dermal dendrocytes represent the mononuclear cutaneous phagocytic system. The dermal dendrocyte is a stellate or spindle shaped dendritic and highly phagocytic fixed connective tissue cell in normal dermis.
  • The other cells which are present in dermis include histiocytes and lymphocytes.
 
Functions
  • It makes the skin pliable, elastic, tensile and protects the body from mechanical injury.
  • Two major regions are recognized, the upper papillary dermis which studs the epidermis and the deeper reticular dermis forming main bulk of dermal tissue. The subpapillary plexus of vessels lying in a horizontal plane forms the boundary between these regions.
  • The main bulk of dermis is formed by amorphous supporting matrix or ground substance. In ground substance, molecules of polysaccharides and proteins combine to form proteoglycan (PG) macromolecules which are hygroscopic and retain water. The ground substance is embedded by collagen fibers, elastic fibers, various cell types, blood vessels, nerves and epidermally derived appendages.
 
HYPODERMIS
Also known as subcutaneous fat or subcutis.
  • It is present almost in all regions of body surface between skin and deep fascia except in the regions of eyelids and male genitalia.
  • The main constituent is adipocytes which are organized into lobules that are separated by fibrous connective tissue septa. Histologically, the adipocytes appear as signet-ring due to the peripherally displaced oval nucleus by a large single intracellular vacuole containing fat.
  • The projections of epidermis into dermis are called rete ridges. Simultaneously, dermis also projects into epidermis as dermal papillae alternating with rete ridges.
 
Functions
  • It is the reserve source of energy.
  • It insulates and protects the body.
  • Cosmetic function: Give shape to face, breast and buttocks.
 
CUTANEOUS RECEPTORS OF SKIN
 
Nerves
Skin is innervated mainly by two types of sensory nerves— thicker rapidly conducting myelinated fibers and thinner slowly conducting unmyelinated C fibers.
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zoom view
Fig. 1.4: Cutaneous receptors
The latter contain both sensory and autonomic fibers. The sensory nerves receive sensation from sensory receptors (Fig. 1.4).
 
Receptors
Sensory receptors can be either sensory fibers itself (free nerve endings) or specialized structures (corpuscular structures).
 
Types
Corpuscular receptors can be further of two types:
  1. Encapsulated receptors: Present in dermis of glabrous skin.
  2. Nonencapsulated receptors: Present in epidermis, e.g., Merkel's touch spot.
On the basis of functional point of view, also receptors are categorized into various types:
  • Mechanoreceptors
  • Thermoreceptors
  • Nociceptors (pain receptors)
Mechanoreceptors are of two types:
  1. Slowly adapting mechanoreceptors: These types of receptors respond continuously to continuous stimulus as they adapt slowly to stimulus.
  2. Rapidly adapting mechanoreceptors: These types of receptors respond at the onset and at the end of stimulus but not throughout the stimulus as they adapt rapidly to stimulus.
Various receptors (Fig. 1.4) are as under:
  • Free nerve endings: These are rapidly adapting receptors that are present subepidermally in the papillary dermis and appear to be derived from nonmyelinated fibers.
    They perceive stimuli of touch, temperature, pain and itch. In hairy skin, they consist of overlapping innervations exhibiting generalized discrimination. In nonhairy regions, such as palms and soles, there are no overlapping innervations and hence exhibit fine discrimination.
  • Merkel's receptors: These are formed by association of Merkel cells with free nerve endings. The Merkel cell-nerve complexes are also called as touch domes or Merkel's touch spots. These are slowly adapting low threshold touch receptors and respond to vertical pressure.
  • Meissner's corpuscle: It is found only in glabrous skin and is located superficially in the dermal papillae of digital skin. They are oriented vertically to epidermal surface and are rapidly adapting receptors. It responds to light touch and slow vibrations.
  • Pacinian corpuscle: These are also rapidly adapting pressure receptors located deeply in dermis and subcutaneous tissue. Structurally, it consists of a characteristic perineural capsule made up of concentric layers (onion-like) of cells and fibrous connective tissue. The capsule surrounds the middle subcapsular zone and inner core. It rapidly adapts to vibrational stimuli and deep pressure.
  • Ruffini's corpuscle: They are slowly adapting receptors present in deeper dermis in human digits and respond to sustained pressure by maintaining stress in dermal collagen.
  • Krause end bulb: These are rapidly adapting mechanoreceptors that respond to sensation of cold. It is an encapsulated swelling on myelinated fibers located in superficial layers of dermis.
  • Golgi-Mazzoni corpuscle: These are located in subcutaneous tissue of human fingers and are rapidly adapting mechanoreceptors.