CHAPTER 2

BASIC ANATOMY, STRUCTURE, AND FUNCTION OF THE SKIN

 

I. Introduction

The skin covers whole body.

The area of adult skin is 1.6 m² and it weighs 3 Kg.

The skin consists of a cellular layer called epidermis, and a connective tissue layer called dermis.

The skin consists of three major
components:

A. stratified epithelium of the epidermis; less than 0.1 mm

B. a connective tissue sheet of the dermis; 1.5 - 4.0 mm

C. the fatty tissue

The epidermis and dermis are separated by a basement membrane (or called basal lamina because it is not the true membrane). In comparison to the total thickness of the skin, 1.5 mm to 4.0 mm, the epidermis is remarkably thin, less than 0.1 mm. Three major cell types comprise the epidermal cells:

A. keratin-forming -  85-90%

B. melanin-forming melanocytes -  5-10%

C. immune-response cells of Langerhans cells -  5%

The dermis is composed of superficial papillary and deep reticular layers.  The connective tissue bundles of papillary dermis are fine, whereas reticular dermis is made of course connective tissue bundles.

 

II. Anatomy of Skin

A. Epidermis

The epidermis consists of four different types of cells called keratinocytes, melanocytes, Langerhans cells, and Merkel cells.

Outermost layer of epidermis called stratum corneum plays a key role as a barrier to the outer environment.

1. Thickness

The epidermis is a stratified epithelium which differentiates in the direct exposure to the environment to produce a keratinized surface membrane (stratum corneum) comprising the rate-limiting barrier to diffusion of water, electrolytes, and non-polar substances.

Alteration of the epidermis occurs in almost all of the common skin diseases. The altered epidermal structure in many of these diseases is often of key diagnostic importance. The epidermis is a non-vascular epithelium and consists of two principal anatomic layers:

 a. the stratum malpighii or germinativum (wet living epidermis)

 b. the stratum corneum or a horny layer (dried, keratinized, "dead" outermost layer).

Keratinocytes undergo cellular differentiation.  The end product of the process is a thin layer of cells called the stratum corneum.

2. The Living System

The germinative layer may be further subdivided (and usually is in the older texts) from the dermo-epidermal junction upward, into:

 a. the basal layer

 b. the prickle layer, and

 c. the granular layer

These layers simply reflect the sequence of growth stages through which basal cells of the stratum germinativum pass in their gradual conversion into dried, keratinized horny cells.

The epidermis contains two distinct cell types:

 a. Keratinocytes（角化細胞）:  the primary structural cells composing 90 - 95% of the epidermis - the keratin synthesizing cells.

 b. Melanocytes（色素細胞）:  the melanin synthesizing cells composing 5 - 10% of the cell population - normally found in the basal layer (white skin and black skin do not differ in the number of melanocytes; the darker skin does contain more melanin; this reflects the greater activity of the melanocytes that are there).

 c. Mitosis and differentiation:  The epidermis is constantly being renewed.  All of the cells in the epidermis are replaced about once every month and about 20% of the protein requirement of an adult are used for this purpose.  The replacement process is not a periodic event (as it is in snakes) but occurs continuously; the epidermis at any one time has cells in each stage of development.

 d. Basal Cell Layer （基底細胞層）:  The basal cell layer is the progenitor of all the other cell layers in the epidermis.  Cells of the basal layer multiply rapidly and rise progressively to the surface.  In so doing, they have progressive changes in structure and function, which is accompanied by drastic changes in cell organelles and the molecular species within them. 

This process of differentiation of epidermal keratinocytes requires 28 days.  About 14 days are required to migrate through the entire malphighian layer (the wet living epidermis), and about 14 more days to reach the outermost stratum corneum cells where they are sloughed away.

3. Microanatomy and Histology of Differentiation

From their arrangement as a fairly uniform single layer of columnar cells, the dividing cells of the basal layer give rise to the prickle layer（有棘層）.

With the light microscope, the intercellular attachments can be seen particularly well in this layer.  Cells appear to be joined to each other by numerous "spines" or "prickles".  The electron microscopy clarified that these spines or prickles derive from desmosome complexes.

Disk-like structures where plasma membranes of two cells firmly attach each other.

Desmogleins and desmocollins are major transmembrane components, members of cadherin supergene family.

Desmoplakin and plakoglobin are cytoplasmic plaque proteins.

Desmogleins bind to plakoglobin

Keratin filaments (historically called tonofilaments) anchor at the plaque of desmosome via desmoplakin.

As the cells ascend, they change from small columnar cells to larger, more symmetrical polyhedral forms.

Near the surface, the prickle layer quite abruptly seems to accumulate a dense collection of darkly staining, basophilic granules, thereby becoming the granular layer（顆粒層）.  These so-called keratohyaline granules stain intensely with haematoxylin and are possibly an intermediate stage in the degradation of some of the cellular components.

At this stage most of the cellular organelles have fragmented and all synthesis is presumably stopped.

Some of the cellular material apparently coalesces, fuses with the cell membrane, and is discharged into the extracellular space where it spreads over the outer surfaces of the cell walls.  These are called membrane-coating granules（被膜顆粒）, MCG.

Immediately above the granular layer the first, squamous and dehydrated cells of the stratum corneum appear.

The most apparent change at this stage is the compaction of the intracellular material due to the loss of most of the intracellular water.  The final development of this complex sequence is the formation of the stratum corneum（角層）.

4. Keratinization（角化）

All the living, metabolic processes in each epidermal cell are devoted either to the manufacture of lipids or protein.  Most of these substances reach the stratum corneum, polymerized and associated into a highly complex intracellular substance called "keratin".

Keratin (diameter 10 nm) is a member of intermediate filaments (diameter 6-25 nm) Keratin maintains shape of epidermal keratinocytes.

Type I (small acidic, K9-K20) and type II (large neutral-basic, K1-K8) keratins make coiled-coil heterodimers

Basal keratinocytes express K5/K14.

Spinous layers express K1/K10.

Hyperproliferative keratinocytes express K6/K16.

Keratinization of the epidermis, i.e. that part of the differentiation process leading to "keratin"-containing stratum corneum cells, apparently begins in the basal layer with the synthesis of "-keratin protofibrils.

These gradually associate into the larger fibrils as the cells migrate upward, but the details are not yet clear.

5. The stratum corneum（角層）

The stratum corneum (or horny layer) can be regarded as the final secretory product of the epidermis, and its formation as the principal biological function of the epidermis.  Some important features of the structure of the stratum corneum, notably its relative uniformity and lack of porosity, have only quite recently been settled.

The histologic custom of viewing skin in transverse section after dehydration, fixation, and staining might have tended to confirm the erroneous notion of a porous stratum corneum.  The stratum corneum is in fact quite impermeable, compact, and coherent, and these characteristics endow it with its singular effectiveness as the skin's major protective barrier.

The much greater thickness of the palmar and plantar stratum corneum suggests the underlying chemical and structural disparities between these areas and other parts of the body.  In particular, the differentiation of the horny layer of the palms and soles is so unlike that of the rest of the skin that it deserves separate status.

6.  Cornified Cell Envelope (CCE) Formation

Terminally differentiated keratinocytes form 15 nm thick CCE underneath the cell membrane.

CCE is important for barrier function.

Loricrin, cysteine-rich protein, filaggrin, small proline rich proteins, involucrin constitute CCE.

Transglutaminase cross-bridges the constituents of CCE.

7. Epidermal lipids

Stratum corneum lipids are essential for the barrier function of epidermis.

Lamellar granules of keratinocytes contain phosphoglycerides, sphingomyeline, glucosylceramides, ceramides fatty acids, sterols, and serolesters.

Strutum corneum lipids are released from lamellar granules and make lipid layers surrounding corneocytes.

 

B. Basement Membrane (BM)（基底膜）

1. Epidermo-dermal junction

This important structure can only be resolved using the electron microscope, but its microscopic stature betrays a very complex organization of macromolecules which is strategic to maintenance of epidermal-dermal cohesion.

It is resolved into 2 layers, the superficial lamina lucida and the electron-dense lamina densa.  An understanding of the most basic structural features of the BM is important in the discussion of bullous diseases.

2. Lamina lucida（低電子板）

The basal cell is attached to the BM via hemidesmosomes which are continuous within the basal cells with the tonofilaments, structures comprised primarily of keratin.  Bullous pemphigoid（類天疱瘡） antigen is on the dermal border of basal cells and plays a role in basal cell adhesion to the BM, as do the anchoring filaments which traverse the lamina lucida.

3. Lamina densa（高電子板）

These interact via complex associations with Type IV collagen, a major constituent of the lamina densa.  Dermal anchoring fibrils, made of Type VII collagen, associate with the BM and are stabilized by dermal attachment plaques comprised of Type IV collagen.

 

4. Anchoring fibril（係留線維）

Dermal Type I and III collagen fibers provide the dermal framework for a stable anchoring structure whereby cohesive forces are sequentially transferred from dermis to BM to basal cells, and hence via desmosomes to the more superficial epidermal layers.

 

C. Dermis（真皮）

1. Components

The dermis is a composite tissue comprising fibrous and amorphous connective tissue housing nerve and vascular networks, cutaneous appendages, fibroblasts, macrophages, resident lymphocytes and mast cells.  It makes up the bulk of the skin providing pliability, elasticity and tensile strength.

The demarcation line between papillary and reticular dermis is rather arbitrary, the former consisting of less dense and smaller diameter fibrous components and being more superficially located below the BM.

2. Collagen

Collagen is the major constituent of dermis and is synthesized by dermal fibroblasts.  Collagen Types I, III and V make up 85%, 10% and 5% of dermal collagen, respectively.  Collagen fibers provide tensile strength and extensibility.

3. Elastic fiber

Elastic fibers have a complex structure and return the skin to its normal configuration following stretching.  The amorphous component of the dermis consists of proteoglycans and glycoaminoglycans which give the dermis sponge-like properties providing water binding capacity, compressibility and embed cellular elements in a biologically compatible milieu.

4. Vasculature

The cutaneous vasculature consists of musculocutaneous arteries that penetrate the subcutis and enter the deep reticular plexus where they organize into a horizontal arteriolar plexus.  Terminal vertical ascending arterioles ascend to the subpapillary plexus at the junction of papillary and reticular dermis.

Capillary loops extend from the plexus into the dermal papillae.  Collecting channels complete the circuit.  The vessels provide nutrition for the tissues and are involved in the regulation of temperature, blood pressure, wound healing and in the skin immune system.

 

D. Sweat Apparatus

1. Eccrine sweat glands （エクリン腺）

Eccrine sweat glands (ESGs) are small and distributed all over the body.

The main function of (ESGs) is the control of body temperature.

Near-isotonic primary eccrine sweat is produced in the secretory portion of ESG.

Ductal portion reabsorb NaCl from primary sweat, which makes hypotonic eccrine sweat.

2. Apocrine sweat glands（アポクリン腺）

Apocrine sweat glands (ASGs) are large sweat glands and distributed on the axillae and genital area.

ASGs secrete proteninaceous odorous sweat.

ASGs become active in adolescence.

 

E. Pilosebaceous Structures

 

F. Subcutis

The subcutaneous fat consists of fat lobules comprised of adipocytes separated into compartments by fibrous septae.  Thus, pathological processes involving the subcutis are divided into lobular and septal processes.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

G. Hair（毛髪）

Hair is present on all surfaces of the body except the palms and soles, ventral aspect of fingers and toes, prepuce, glans penis, and inner aspect of female genitalia.

Fetus is covered by a fine layer of delicate lanugo hairs.

Lanugo hair is lost before birth except on the scalp, eyebrows, and eyelashes.

Shortly after birth, a new growth of vellus hair covers the body of infants.

At around puberty, larger, pigmented terminal hairs develop in the pubic and axillary regions, and on the face and chest of males.

The hair follicle develops as an oblique downgrowth of epidermal cells into the dermis.

Proliferation of germinative cells at the base of the hair forms the inner root sheath and the hair shaft.

The inner root sheath has three concentric layers (Henle's layer, Huxley's layer, and cuticle) of which undergo keratinization.

The external root sheath is a downward invagination of the epidermis.

The external root sheath consists all layers of epidermis.

The external root sheath cells are vacuolated due to the presence of large quantity of glycogen.

The external root sheath cells show keratinization without keratohyalin granules