Integumentary System

I. SKIN. The skin consists of two layers: the outer layer, or epidermis, and the deeper, connective tissue layer, or dermis. Skin functions as a barrier against infection, serves thermoregulation, and protects the body against dehydration.

A. Epidermis. The epidermis is derived from the ectoderm.

1. Early development a. Initially, the epidermis consists of a single layer of ectodermal cells that give rise to an overlying periderm layer.

b. The epidermis soon becomes a three-layered structure consisting of the stratum basale (mitotically active), the intermediate layer (progeny of stratum basale), and the periderm.

C. Peridermal cells are eventually desquamated; they form part of the vernix caseosa, a greasy substance of peridermal cells and sebum from the sebaceous glands that protects the embryo's skin.

2. Later development. The definitive adult layers are formed through the inductive influence of the dermis. The ectodermal cells give rise to five cell layers:

a. Stratum basale (stratum germinativum)

b. Stratum spinosum C. Stratum lucidum d. Stratum granulosum e. Stratum corneum. This layer is associated with the expression of 56.5-kda keratin, 67-kda keratin, and filaggrin (a binding protein).

3. Other cells of the epidermis a. Melanoblasts are derived from neural crest cells that migrate into the stratum basal of the epidermis. These cells differentiate into melanocytes by mid-pregnancy, when pigment granules called melanosomes are observed.

b. Langerhans cells are derived from the bone marrow (mesoderm) and migrate into the epidermis. These cells are involved in antigen presentation.

C. Merkel cells are of uncertain origin. They are associated with free nerve endings and probably function as mechanoreceptors.

B. Dermis. The dermis is derived from both the somatic mesoderm, which is located just beneath the ectoderm, and mesoderm of the dermatomes of the body. It is derived from neural crest cells in the head and neck region (see Chapter 11).

1. Early development. The dermis initially consists of loosely aggregated mesodermal cells that are frequently referred to as mesenchymal cells (or mesenchyme). The mesenchymal cells secrete a watery type of extracellular matrix that is rich in glycogen and hyaluronic acid.

2. Later development a. Mesenchymal cells differentiate into fibroblasts, which secrete increasing amounts of collagen and elastic fibers into the extracellular matrix.

b. Vascularization occurs.

C. Sensory nerves grow into the dermis.

d. The dermis forms projections into the epidermis called dermal papillae, which contain tactile sensory receptors (e.g., Meissner's corpuscles).

C. Clinical correlations

1. Albinism a. Oculocutaneous albinism (classic type) is an autosomal recessive trait in which melanocytes fail to produce melanin in the skin, hair, and eyes. The cause is an absence of tyrosinase activity, b- Piebaldism, an autosomal dominant disorder, is a localized albinism in which there is a lack of melanin in isolated patches of skin or hair. C. Albinism predisposes to basal and squamous cell carcinoma and also to malignant melanoma.

2. Ichthyosis is an X-linked disorder of keratinization characterized by dryness and scaling of the skin.

3. Psoriasis is a skin disease characterized by excessive cell proliferation in the stratum basale and stratum spinosum, resulting in thickening of the epidermis and shorter regeneration time of the epidermis.

4. Ehlers-Danlos syndrome (Figure 16-1 A, B) is characterized by extremely stretchable and fragile skin, hypermobile joints, aneurysms of blood vessels, and rupture of the bowel. It is caused by a defect of the gene for peptidyl lysine hydroxylase, which is an enzyme necessary for the hydroxylation of lysine residues of collagen. Type I and type III collagen are mainly affected.

5. Hemangiomas (Figure 16-1 C, D) are vascular malformations, that is, benign tumors of endothelial cells. They produce "birth marks" on the skin. A port-wine stain is a birth mark covering the area of distribution of the trigeminal nerve (CN V) that is frequently associated with a hemangioma of the meninges called Sturge-Wcbcr syndrome.

II. HAIR AND NAILS. Hair and nails are derived from the ectoderm. A. Hair (Figure 16-2)

1. At week 12, ectodermal cells from the stratum basale grow into the underlying dermis and form the hair follicle.

2. The deepest part of the hair follicle soon becomes club-shaped to form the hair bulb.

3. The hair bulbs are invaginated by mesoderm called hair papillae, which are rapidly infiltrated by blood vessels and nerve endings.

4. Epithelial cells within the hair bulb differentiate into the germinal matrix where cells proliferate, grow toward the surface, keratinize, and form the hair shaft. These cells also form the internal root sheath.

5. Other epithelial cells of the hair follicle form the external root sheath, which is continuous with the epidermis.

6. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheath and the arrector pili muscle.

Arrector Pili Muscle

Figure 16-1. (A, B) Ehlers-Danlos syndrome. Note the extremely stretchable skin of the ear and elbow region. (C, D) Sturge-Weber syndrome. Note the port-wine stain over the area of distribution of the trigeminal nerve (CN V). Hie radiograph shows calcification of die cerebral cortex closely following the cerebral convolutions (or gyri). Calcification of meningeal arteries may also be prominent. (A and B, from Smith DW, Jones Kb Recognizable Patterns of Human Malformation, 3rd ed. Philadelphia, WB Saunders, 1982, p 359. C and D, from Salmon HA, Lin-denbaum RH: Developmental Defects and Syndromes. Aylesbury, England, HM M Publishers, 1978, p 95.)

Figure 16-1. (A, B) Ehlers-Danlos syndrome. Note the extremely stretchable skin of the ear and elbow region. (C, D) Sturge-Weber syndrome. Note the port-wine stain over the area of distribution of the trigeminal nerve (CN V). Hie radiograph shows calcification of die cerebral cortex closely following the cerebral convolutions (or gyri). Calcification of meningeal arteries may also be prominent. (A and B, from Smith DW, Jones Kb Recognizable Patterns of Human Malformation, 3rd ed. Philadelphia, WB Saunders, 1982, p 359. C and D, from Salmon HA, Lin-denbaum RH: Developmental Defects and Syndromes. Aylesbury, England, HM M Publishers, 1978, p 95.)

7. The first fine hairs, called lanugo hairs, are sloughed off at birth.

8. BMP-2 (bone morphogcnctic protein), FGF-2 (fibroblast growth factor), sonic hedgehog, and Msx (a homeobox gene) appear to be important in the development of hair.

B. Nails develop from the epidermis. They first develop on the tips of the digits, then mi

Cortex

Cuticle

Melanocytes

Pattern Root Hair Development

Dermal

Figure 16-2. Diagram of a hair and its follicle. The expanded lower end of the follicle contains a hair papilla. Formation and growth of the hair depend on the continuous proliferation (note the cells in mitosis) and differentiation of cells around the rip of the hair papilla. (A) Cells that give rise to the hair medulla. (B) Cells that give rise to the hair cortex. (C) Cells that give rise to the hair cuticle. Other peripheral cells give rise to the internal and external root sheath. Melanocytes contribute to hair color. (From Junqueira LC, Cameiro J, Kelley KG: Basic Histology1, 9th ed. Stamford, CT, Appleton & Lange, 1998, p 335.)'

Medulla

Cortex

Cuticle

Dermal

Melanocytes

External root sheath

Internal

Figure 16-2. Diagram of a hair and its follicle. The expanded lower end of the follicle contains a hair papilla. Formation and growth of the hair depend on the continuous proliferation (note the cells in mitosis) and differentiation of cells around the rip of the hair papilla. (A) Cells that give rise to the hair medulla. (B) Cells that give rise to the hair cortex. (C) Cells that give rise to the hair cuticle. Other peripheral cells give rise to the internal and external root sheath. Melanocytes contribute to hair color. (From Junqueira LC, Cameiro J, Kelley KG: Basic Histology1, 9th ed. Stamford, CT, Appleton & Lange, 1998, p 335.)'

grate to the dorsal surface, taking their innervation with them; this is why the median nerve innervates the dorsal surface of three and one-half digits (I-IV).

C. Clinical correlations

1. Alopecia is baldness resulting from an absence or faulty development of the hair follicles.

2. Hypertrichosis is an overgrowth of hair. It is frequently associated with spina bifida occulta, where it is seen as a patch of hair overlying the defect.

3- Pili torti is a familial disorder characterized by twisted hairs. It is seen in Menkes* (kinky-hair) disease, an X-linked recessive neurologic disorder.

III. MAMMARY, SWEAT, AND SEBACEOUS GLANDS. These glands are all derived from the surface ectoderm.

A. Mammary glands develop from the mammary ridge, a downgrowth of the epidermis (ectoderm) into the underlying dermis (mesoderm). Canalization of these epithelial downgrowths results in formation of alveoli and lactiferous ducts; the latter drain into an epithelial pit, the future nipple.

B. Eccrine and apocrine sweat glands develop from downgrowths of the epidermis into the underlying dermis.

Epithelial Mammary Ridge

Figure 16-3. Successive stages in the development of a tooth. (A) Week 8. (B) Week 28. Note the formation of enamel (En) by ameloblasts and dentin (Den) by odontoblasts. (C) Month 6 postnataily. Note the early tooth eruption. (D) Month 18 postnataily. Note the fully erupted deciduous tooth. Ameloblasts are no longer present, which means that further enamel formation is not possible. (Modified from Dudek RW, Fix JD: BRS Em-bryology, 2nd ed. Baltimore, Williams & Wilkins, 1998, p 197.)

Cementoblasts

Figure 16-3. Successive stages in the development of a tooth. (A) Week 8. (B) Week 28. Note the formation of enamel (En) by ameloblasts and dentin (Den) by odontoblasts. (C) Month 6 postnataily. Note the early tooth eruption. (D) Month 18 postnataily. Note the fully erupted deciduous tooth. Ameloblasts are no longer present, which means that further enamel formation is not possible. (Modified from Dudek RW, Fix JD: BRS Em-bryology, 2nd ed. Baltimore, Williams & Wilkins, 1998, p 197.)

Epithelial Mammary Ridge

Cementoblasts

C. Sebaceous glands develop from the epithelial wall of the hair follicle and elaborate sebum into the hair follicles. The tarsal (meibomian) glands of the eyelids do not communicate with hair follicles.

D. Clinical correlations

1. Gynecomastia is a condition in which there is excessive development of the male mammary glands. It is frequently associated with Klinefelter^ syndrome (47,XXY).

2. Polymastia is a condition in which supernumerary breasts occur along the mammary ridge.

3. Polythelia is a condition in which supernumerary nipples occur along the mammary ridge.

IV. TEETH (Figure 16-3). Teeth develop from ectoderm and an underlying layer of neural crest cells.

A. The dental lamina develops from the oral epithelium (ectoderm) as a downgrowth into the underlying neural crest layer. It gives rise to tooth buds, which develop into the enamel organs.

B. Enamel organs are derived from ectoderm. These organs develop first for the 20 deciduous teeth, then for the 32 permanent teeth. They give rise to ameloblasts, which produce enamel.

C. Dental papilla is formed by neural crest cells that underlie the enamel organ. It gives rise to the odontoblasts (which produce predentin and dentin) and dental pulp.

D. The dental sac is formed by a condensation of neural crest cells that surrounds the dental papilla. This sac gives rise to cementoblasts (which produce cementum) and the periodontal ligaments.

E. Clinical correlations

1. Defective enamel formation (amelogenesis imperfecta) is an autosomal dominant trait.

2. Defective dentin formation (dentinogenesis imperfecta) is an autosomal dominant trait.

3. Discoloration of teeth is caused by the administration of tetracycline, which stains and affects the enamel of both deciduous and permanent teeth.

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