Integumentary System

11.1

Overview

The integument, the largest organ of the body, is composed of skin and skin appendages — nails, hair, sweat glands, and sebaceous glands. The total weight and overall surface area of skin in the adult are 3-5 kg and 1.5-2 m ² , respectively. Skin thickness, between 0.5 and 3 mm, varies regionally; skin is thickest on the back and thinnest on the eyelid. At mucocutaneous junctions, skin is continuous with mucous membranes lining digestive, respiratory, and urogenital tracts. As well as serving as a protective barrier against injury (e.g., abrasions, cuts, burns), infectious pathogens, and ultraviolet (UV) radiation, skin assists in body temperature regulation, vitamin D synthesis, ion excretion, and sensory reception (touch and pain), and it has a remarkable regenerative capacity. It consists of stratified squamous keratinized epithelium on its outer part, called the epidermis, and an inner layer of fibrous connective tissue, called the dermis. A loose layer of subcutaneous connective tissue, the hypodermis, attaches skin to underlying structures and permits movement over most body parts. Skin has a dual embryologic origin: Epidermis and its appendages derive mostly from surface ectoderm; dermis originates from mesoderm. The epidermis consists primarily of cells called keratinocytes, which make up more than 90% of the cell population. Other epidermal cells are melanocytes and Merkel cells, which derive from neural crest, and Langerhans cells, which have a monocytic origin. During embryonic development, skin appendages deriving from the epidermis grow down into the dermis.

11.2

Histology of Thick and Thin Skin

On the basis of the structural complexity and thickness of the epidermis, skin is classified into thick or thin. Thick skin, which is glabrous, is found on palms of the hands and soles of the feet; thin skin covers most of the remaining body surface. Whereas the multilayered epidermis of thick skin is 0.8-1.5 mm thick, the epidermis of thin skin is 0.07-0.15 mm thick, with fewer cellular layers. The junction between the avascular epidermis and richly vascularized dermis —the dermoepidermal border—is usually highly corrugated and has many downward, ridge-like extensions of epidermis, called epidermal, or rete, ridges that project between alternating, upward projections of dermis, the dermal papillae. The contour of this border resembles the undersurface of an egg carton and is more complex in thick than in thin skin. A basement membrane separates epidermis from dermis. The thick dermis is divided into two layers: a superficial papillary layer of loose connective tissue containing type I and III collagen fibers interspersed with elastic fibers, connective tissue cells, and rich network of capillaries; and a deeper reticular layer of dense irregular connective tissue consisting of coarse, interlacing bundles of collagen fibers, mostly type I. Aside from fibroblasts, other connective tissue cells in the dermis include macrophages, mast cells, adipocytes, plasma cells, and lymphocytes.

11.3

Histology of the Epidermis

The epidermis consists of cells that undergo mitosis, differentiation, maturation, and keratinization as they are displaced outward toward the skin surface to be shed. Four or five distinct layers, or strata, constitute the epidermis. The stratum basale, or germinativum, is the deepest; it consists of a single layer of closely packed, basophilic cuboidal to columnar epithelial cells, known as keratinocytes, resting on a basement membrane. These cells have oval nuclei that often show mitotic figures; they continuously undergo cell division to replace cells that move outward through the epidermis. The next layer, the stratum spinosum, is several cells thick and has polyhedral cells that become progressively flatter toward the surface. Processes of adjacent cells are attached by desmosomes. Cell shrinkage caused by a fixation artifact accentuates the processes and creates spines or prickles—thus the name prickle cells. The next layer, the stratum granulosum, consists of three to five layers of flattened cells, their axes aligned parallel to the epidermal surface. They contain numerous basophilic granules, the keratohyalin granules. Superficial to this layer is a thin, translucent, lightly eosinophilic layer, known as the stratum lucidum. Absent in thin skin but present in thick skin, it consists of a few layers of tightly packed squamous cells that lack organelles and nuclei. The outermost layer, the stratum corneum, is made of dead, anucleate cornified cells; its thickness varies regionally. The protein keratin replaces cytoplasm in its cells. The most superficial cells are continuously shed in a process known as desquamation.

11.4

Ultrastructure of the Epidermis

In upper layers of the stratum spinosum, keratinocytes contain irregular, non–membrane-bound, electron-dense keratohyalin granules with diameters of 100-150 nm. These granules consist of the protein filaggrin, which cross-links with keratin. In the stratum granulosum, almost all cytoplasmic organelles and nuclei disappear because of lysosomal enzyme activity. The residual cellular profiles are filled with tightly packed filaments and are enclosed by a thickened cell membrane—the horny cell membrane. The protein involucrin binds to the inner cell membrane. Round to oval membrane-bound granules in keratinocytes in upper layers—the lamellar bodies —are 300-500 nm in diameter, are derived from Golgi complex, and are rich in glycolipids. They are eventually released from and deposited between keratinocytes, most likely forming an intercellular barrier to water. Unique keratin packing probably accounts for the presence of a stratum lucidum in plantar and palmar skin. The stratum corneum is made of interlocking cells arranged in orderly vertical stacks. These cells have thickened cell membranes and lack desmosomes, which allows cells to dissociate and desquamate easily. The normal time for turnover of keratinocytes from stratum basale to uppermost stratum corneum varies from 20 to 75 days. Turnover and transit times may be even more rapid in some diseases, such as psoriasis, in which transit time is about 8 days.

11.5

Ultrastructure of Keratinocytes

Cells of the stratum basale have relatively euchromatic nuclei compared with those of more superficial layers. Their cytoplasm contains many ribosomes, mitochondria, and an extensive cytoskeleton of 10-nm intermediate filaments known as tonofilaments. These are made of the keratin family of intermediate filament proteins. All epithelial cells contain keratins, and almost 50 different types of keratins are found in skin. Keratinocytes of the strata basale and spinosum are connected by desmosomes. These complex intercellular junctions mediate and enhance cell adhesion by anchoring keratin filaments to keratinocyte plasma membranes. By linking tonofilament bundles of adjacent cells, desmosomes provide the epidermis with structural continuity and mechanical strength. To further counteract mechanical forces, basal aspects of keratinocytes are firmly attached to underlying basement membrane by hemidesmosomes. Hemidesmosomes have only one intracytoplasmic attachment plaque to which tonofilaments from the cell interior attach. Fine anchoring filaments radiate from the outer aspect of the plasma membrane into the basal lamina. The basement membrane at the dermoepidermal junction usually requires special light microscopic techniques to be visible. This specialized supporting zone of extracellular matrix consists of several layers. A lamina lucida and lamina densa together constitute the basal lamina, which contains type IV collagen, laminin, fibronectin, and proteoglycans. A deeper reticular lamina, made mainly of type I collagen fibers, merges with underlying connective tissue.

11.6

Histology and Function of Epidermal Melanocytes

Melanocytes are melanin pigment-producing cells that determine color of skin and hair. The major determinant of color is not melanocyte number but activity, which is affected by corticotropin from the pituitary. Derived from the neural crest, melanocytes migrate to the basal layer of the epidermis and hair matrices as early as 8 weeks in the embryo, and to eyes, ears, and brain meninges. Typically, 1000-2000 melanocytes occur per 1 mm ² of epidermis. Instead of being linked by desmosomes, each melanocyte establishes contact via dendritic processes with about 30 nearby keratinocytes. Melanin is produced in membrane-bound organelles known as melanosomes. They rearrange themselves within cells in response to external cues such as UV rays; they usually cluster near cell centers and can rapidly redistribute along microtubules to ends of dendritic processes. Keratinocytes then phagocytose the dendritic tips. Melanosomes are pinched off into keratinocyte cytoplasm, where they are often packaged in secondary lysosomes. Darkly pigmented skin, hair, and eyes have melanosomes that contain more melanin. Two major forms of melanin are found in humans, eumelanin, which is brown to black, and pheomelanin, which is yellow to red; both are derived from tyrosine. Tanning of the skin caused by UV exposure represents an increased eumelanin content of the epidermis. Its major purpose is enhanced protection against damaging effects of UV radiation on DNA. With aging, melanocyte numbers decline significantly in skin and hair.

11.7