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Summary

Dermatology Summary Part 1

Dermatology and Venerology Contributing Authors: Linus Kutup, Eric Hoffmeister, Benjamin Kersch, Niclas Samirae, Tobias Verdegem, Alexander Wolff, Lara Afaneh, Joana Strzlkowski, Nadine Fernandez, Katharina Weitzel Epidermis- anatomical, histological organization and ultrastructure. Keratinocytes...

Dermatology and Venerology

Contributing Authors:

Linus Kutup, Eric Hoffmeister, Benjamin Kersch, Niclas Samirae, Tobias Verdegem, Alexander Wolff, Lara Afaneh, Joana Strzlkowski, Nadine Fernandez, Katharina Weitzel

  1. Epidermis- anatomical, histological organization and ultrastructure.
  • Keratinocytes – produce keratin as a protective barrier
  • Langerhans cells – present antigens and activate T-lymphocytes for immune protection
  • Melanocytes – produce melanin, which give pigment to the skin and protects the cell nuclei from ultraviolet radiation-induced DNA damage
  • Merkel cells – contain specialized nerve endings for sensation
  • Structure:

• Stratum corneum

• Stratum lucidum

• Stratum granulosum

• Stratum spinosum

• Stratum basale

  • Composition of each epidermal layer
    • Stratum corneum(Horny layer) – layer of keratin, most superficial layer, barrier against water loss and exogenous trigger
    • Stratum lucidum – exists only on thick epidermal areas. Consist of paler, compact keratin
    • Stratum granulosum (Granular cell layer) – epidermal keratogenic zone, cells lose their nuclei and contain granules of keratohyaline. They secrete lipid into the intercellular spaces
    • Stratum spinosum (Prickle cell layer) – consists of polygonal, differentiating, cells related with desmosomal contacts
    • Stratum Basale – actively dividing cells, deepest layer. Consists of one layer of cylinder-like cells that contain melanin from the neighbouring melanocytes and have high mitotic rate
  • Dermal-epidermal junction
  • Functions:
    • Connects epidermis and dermis
    • Regulates the epidermal-dermal metabolism
    • Enhance keratinocytes migration
    • A transport medium for inflammatory cells in different conditions
  • Ultrastructure – 4 layers:
    • Basal keratinocytic membrane
    • Underneath light zone (lamina lucida)
    • Osmophilic zone (lamina densa)
    • Sub basal filamental zone of lineal protein structures going to the papillary dermis (anchoring fibres)
  1. Dermis and hypodermis- anatomical, histological organization and ultrastructure.
  • Dermis (Corium)
  • The dermis is made up of collagen (mainly), elastin and glycosaminoglycans, which are synthesized by fibroblasts. Collectively, they provide the dermis with strength and elasticity.
  • The dermis also contains immune cells, nerves, skin appendages as well as lymphatic and blood vessels.
  • Layers
    • Papillary (superficial) dermis
    • Reticular dermis
  • The hypodermis consists of connective tissue and lipocyte. The fat content depends on body site and sex. There is no hypodermis on eyelids, nails and scrotum.
  • Skin appendages
  • Sweat glands (glandulae sudoriferae)

• eccrine

• apocrine

  • Sebaceous glands (glandulae sebaceae)
  • Pilo-sebaceous units

3.Adnexal structures- sweat and sebaceous glands. Histological organization.

  • Sebaceous (fat) glands
  • multilobular holocrine gland
  • Sebaceous glands produce sebum via hair follicles (collectively called a pilosebaceous unit). They secrete sebum onto the skin surface which lubricates and waterproofs the skin.
  • Sebaceous glands are stimulated by the conversion of androgens to dihydrotestosterone and therefore become active at puberty.
  • Found throughout skin except palms and soles
  • Always associated with follicles except following locations (‘free’ sebaceous glands):
    • Gland of Zeiss → found on superficial eyelid margin (near Moll’s gland)
    • Meibomian gland → tarsal plate of eyelids (behind Moll’s gland)
    • Montgomery tubercle → nipple and areola
    • Tyson’s gland → external fold of prepuce (genitalia)
    • Fordyce spot → vermilion border of the lips and buccal mucosa
  • Gland under adrenergic hormonal control; enlargement at puberty due to ↑ androgens
  • Sweat glands
  • Eccrine Sweat glands regulate body temperature and are innervated by the sympathetic nervous system.
  • They are divided into two types: eccrine and apocrine sweat glands.
    • Tubular exocrine glands
    • Produce sweat – mixture of salts and water
  • Regulate body temperature – cool the body via evaporation of water
  • Natural detoxicators
  • Universally distributed in the skin with the exception of lips and glans penis
  • Apocrine Sweat Glands Belong to the pilo- sebaceous unit
  • Their discharge has a specific individual odor, regulated by the sex glands
  • Activate in puberty
  • Distributed in the axillae, areolae, genitalia and anus, and modified glands are found in the external auditory canal

4.Hair. Hair follicle- histological organization. Hair cycle.

  • There are 3 main types of hair:
    • lanugo hair (fine long hair in fetus)
    • vellus hair (fine short hair on all body surfaces)
    • terminal hair (coarse long hair on the scalp, eyebrows, eyelashes and pubic areas)
  • Each hair consists of modified keratin and is divided into the hair shaft (a keratinized tube) and hair bulb (actively dividing cells, and melanocytes which give pigment to the hair)
  • Each hair follicle enters its own growth cycle.
  • This occurs in 3 main phases:
    • Anagen (long growing phase)
    • Catagen (short regressing phase)
    • Telogen (resting/ shedding phase)

5.Nails- histological organization.

  • Nails (ungues, onyx)
  • Nails
  • The nail is made up of a nail plate (hard keratin) which arises from the nail matrix at the posterior nail fold, and rests on the nail bed.
  • The nail bed contains blood capillaries which gives the pink color of the nail.
  • The matrix, sometimes called the matrix unguis, keratogenous membrane, nail matrix, or onychostroma, is the tissue (or germinal matrix) which the nail protects. It is the part of the nail bed that is beneath the nail and contains nerves, lymph and blood vessels. The matrix is responsible for producing cells that become the nail plate. The width and thickness of the nail plate is determined by the size, length, and thickness of the matrix, while the shape of the fingertip itself shows if the nail plate is flat, arched, or hooked. The matrix will continue to grow as long as it receives nutrition and remains in a healthy condition. As new nail plate cells are made, they push older nail plate cells forward; and in this way older cells become compressed, flat, and translucent. This makes the capillaries in the nail bed below visible, resulting in a pink color.
  • The lunula (“small moon”) is the visible part of the matrix, the whitish crescent-shaped base of the visible nail. The lunula can best be seen in the thumb and may not be visible in the little finger.
  • The nail bed is the skin beneath the nail plate. Like all skin, it is made of two types of tissues: the deeper dermis, the living tissue which includes capillaries and glands, and the epidermis, the layer just beneath the nail plate, which moves toward the fingertip with the plate. The epidermis is attached to the dermis by tiny longitudinal “grooves” called matrix crests (cristae matricis unguis). In old age, the nail plate becomes thinner, and these grooves become more visible.
  • The nail sinus (sinus unguis) is where the nail root is; i.e. the base of the nail underneath the skin. It originates from the actively growing tissue below, the matrix.
  • The nail plate (corpus unguis) is the hard part of the nail, made of translucent keratin protein. Several layers of dead, compacted cells cause the nail to be strong but flexible. Its (transverse) shape is determined by the form of the underlying bone. In common usage, the word nail often refers to this part only.
  • The free margin (margo liber) or distal edge is the anterior margin of the nail plate corresponding to the abrasive or cutting edge of the nail. The hyponychium (informally known as the “quick”) is the epithelium located beneath the nail plate at the junction between the free edge and the skin of the fingertip. It forms a seal that protects the nail bed. The onychodermal band is the seal between the nail plate and the hyponychium. It is just under the free edge, in that portion of the nail where the nail bed ends and can be recognized in fair-skinned people by its glassy, greyish color. It is not visible in some individuals while it is highly prominent on others.
  • Together, the eponychium and the cuticle form a protective seal. The cuticle is the semi-circular layer of non-living, almost invisible dead skin cells that “ride out on” and cover the back of the visible nail plate while the eponychium is the fold of skin cells that produces the cuticle. They are continuous, and some references view them as one entity; in this classification, the names eponychium, cuticle, and perionychium are synonymous. It is the cuticle (nonliving part) that is removed during a manicure, but the eponychium (living part) should not be touched due to risk of infection. The eponychium is a small band of living cells (epithelium) that extends from the posterior nail wall onto the base of the nail. The eponychium is the end of the proximal fold that folds back upon itself to shed an epidermal layer of skin onto the newly formed nail plate.[contradictory] The perionyx is the projecting edge of the eponychium covering the proximal strip of the lunula.
  • The nail wall (vallum unguis) is the cutaneous fold overlapping the sides and proximal end of the nail. The lateral margin (margo lateralis) lies beneath the nail wall on the sides of the nail, and the nail groove or fold (sulcus matricis unguis) are the cutaneous slits into which the lateral margins are embedded.
  • The paronychium is the soft tissue border around the nail, and paronychia is an infection in this area.

6.Blood and lymphatic vessels of skin. Innervation of skin.

  • NERVES
  • Two main types of corpuscular endings: nonencapsulated (merkel cells) and encapsulated (Meissner’s and Pacinian corpuscles)
  • Nonencapsulated endings
  • Free nerve endings – terminal endings within epidermis and papillary dermis; mainly detects touch, pressure, and pain
  • Merkel cells – found in basal layer and makes close contact with sensory nerve terminal (Merkel disc), detects touch
  • Encapsulated endings
    • Vater-Pacini (Pacinian) corpuscle – found in deep dermis/subcutis, detects deep pressure and vibration; increased concentration in palms/soles, nipples, and anogenital region
  • Meissner’s corpuscle – elongated mechanoreceptor detecting light touch (resembles pine cone); located just below DEJ (dermal papillae) and highest density in palmoplantar skin
  • Ruffini corpuscle – found in deep dermis and detects continuous pressure
  • Mucocutaneous end organs (Krause end bulbs) – mucocutaneous receptors found on vermilion lip, perianal region, glans penis, clitoris, and labia minora
  • Skin vasculature
  • Two major horizontal plexus
    • The deep plexus is close to dermo-hypodermic area
    • Superficial plexus is the boundary between the papillary and reticular dermis and paid to any dermal papilla vascular loop → up of ascending precapillary arterioles and descending capillary venules

7.Anatomy and organization of mucous membranes.

  • Structure of the mouth
  • Like the skin, mucous membranes consist of three layers: the superficial epithelial (tunica epithelialis), medium (tunica s. lamina propria) and deep (tunica submucosae)
    • Tunica epithelialis does not contain granular and stratum corneum
    • Tunica s. lamina propria is composed of fine collagen and reticular and less elastic fibers
    • Tunica submucosae consists of fatty lobules separated by connective tissue strands
  • The mouth contains numerous salivary glands buccal swabs emit three pairs of major salivary gland
    • glandulae parotes
    • glandulae sublinguales
    • glandulae submandibulares
  • Tongue – on its surface there are four types of papillae
    • papillae filiformes
    • papillae fungiformes
    • papillae foliate
    • papillae circumvallate

8.Keratinocytes. Synthesis of keratins.

  • The primary function of keratinocytes is the formation of a barrier against environmental damage by pathogenic bacteria, fungi, parasites, viruses, heat, UV radiation and water loss. Once pathogens start to invade the upper layers of the epidermis, keratinocytes can react by producing proinflammatory mediators, particularly chemokines such as CXCL10 and CCL2 which attract leukocytes to the site of pathogen invasion.
  • Structure
  • A number of structural proteins (filaggrin, keratin), enzymes (proteases), lipids and antimicrobial peptides (defensins) contribute to maintain the important barrier function of the skin. Keratinization is part of the physical barrier formation (cornification), in which the keratinocytes produce more and more keratin and undergo terminal differentiation. The fully cornified keratinocytes that form the outermost layer are constantly shed off and replaced by new cells.
  • Epidermal stem cells reside in the lower part of the epidermis (stratum basale) and are attached to the basement membrane through hemidesmosomes. Epidermal stem cells divide in a random manner yielding either more stem cells or transit amplifying cells.Some of the transit amplifying cells continue to proliferate then commit to differentiate and migrate towards the surface of the epidermis. Those stem cells and their differentiated progeny are organized into columns named epidermal proliferation units.
  • During this differentiation process, keratinocytes permanently withdraw from the cell cycle, initiate expression of epidermal differentiation markers, and move suprabasally as they become part of the stratum spinosum, stratum granulosum and eventually become corneocytes in the stratum corneum.
  • Corneocytes are keratinocytes that have completed their differentiation program and have lost their nucleus and cytoplasmic organelles. Corneocytes will eventually be shed off through desquamation as new ones come in.
  • At each stage of differentiation, keratinocytes express specific keratins, such as keratin 1, keratin 5, keratin 10, and keratin 14, but also other markers such as involucrin, loricrin, transglutaminase, filaggrin, and caspase 14.
  • In humans, it is estimated that keratinocytes turnover from stem cells to desquamation every 40–56 days. whereas in mice the estimated turnover time is 8–10 days.
  • Factors promoting keratinocyte differentiation are:
  • A calcium gradient, with the lowest concentration in the stratum basale and increasing concentrations until the outer stratum granulosum, where it reaches its maximum. Calcium concentration in the stratum corneum is very high in part because those relatively dry cells are not able to dissolve the ions. Those elevations of extracellular calcium concentrations induces an increase in intracellular free calcium concentrations in keratinocytes. Part of that intracellular calcium increase comes from calcium released from intracellular stores and another part comes from transmembrane calcium influx, through both calcium-sensitive chloride channels and voltage-independent cation channels permeable to calcium. Moreover, it has been suggested that an extracellular calcium-sensing receptor (CaSR) also contributes to the rise in intracellular calcium concentration.
  • Vitamin D3 (cholecalciferol) regulates keratinocyte proliferation and differentiation mostly by modulating calcium concentrations and regulating the expression of genes involved in keratinocyte differentiation. Keratinocytes are the only cells in the body with the entire vitamin D metabolic pathway from vitamin D production to catabolism and Vitamin D receptor expression.
  • Cathepsin E.
  • TALE homeodomain transcription factors.
  • Hydrocortisone.
  • Since keratinocyte differentiation inhibits keratinocyte proliferation, factors that promote keratinocyte proliferation should be considered as preventing differentiation. These factors include:
  • The transcription factor p63, which prevents epidermal stem cells from differentiating into keratinocytes.
  • Vitamin A and its analogues.
  • Epidermal growth factor.
  • Transforming growth factor alpha.
  • Cholera toxin.
  • Within the epidermis keratinocytes are associated with other cell types such as melanocytes and Langerhans cells. Keratinocytes form tight junctions with the nerves of the skin and hold the Langerhans cells and intra-dermal lymphocytes in position within the epidermis. Keratinocytes also modulate the immune system: apart from the above-mentioned antimicrobial peptides and chemokines they are also potent producers of anti-inflammatory mediators such as IL-10 and TGF-β. When activated, they can stimulate cutaneous inflammation and Langerhans cell activation via TNFα and IL-1β secretion.
  • Keratinocytes contribute to protecting the body from ultraviolet radiation (UVR) by taking up melanosomes, vesicles containing the endogenous photoprotectant melanin, from epidermal melanocytes. Each melanocyte in the epidermis has several dendrites that stretch out to connect it with many keratinocytes. The melanin is then stored within keratinocytes and melanocytes in the perinuclear area as supranuclear “caps”, where it protects the DNA from UVR-induced damage
  • Wounds to the skin will be repaired in part by the migration of keratinocytes to fill in the gap created by the wound. The first set of keratinocytes to participate in that repair come from the bulge region of the hair follicle and will only survive transiently. Within the healed epidermis they will be replaced by keratinocytes originating from the epidermis.
  • At the opposite, epidermal keratinocytes, can contribute to de novo hair follicle formation during the healing of large wounds.
  • Keratinocytes migrate with a rolling motion during the process of wound healing.
  • Functional keratinocytes are needed for tympanic perforation healing.
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