The skin is the largest of the body’s organs and provides an immediate barrier between the internal tissues and the environment. It protects the body from the effects of temperature and chemical and microbial attack. At the same time as preventing harmful substances from entering the body, the skin also prevents the loss of nutrients. This article explains how the skin’s structure helps to protect the body.

INTRODUCTION
This short report describes the six aspects of skin biology that combine to create the skin barrier, which protects the internal tissues from potentially harmful environmental effects.

These are:

• Epithelial regeneration
• Epidermal differentiation
• Formation of tight junctions
• Lipids
• Microbial flora
• Antimicrobial peptides

This article also provides key tips for practice in relation to managing periwound skin.

EPITHELIAL REGENERATION
All epithelia are constantly regenerating. This constant turnover of cells results in a loss of superficial cells together with any microbes present on the skin's surface. Thus, as well as preventing microbes from gaining a foothold, continued epidermal regeneration also means that minor breaches in the skin's barrier function are automatically repaired [Fig 1].

The process of epidermal regeneration is interesting because only the adult tissue stem cell, known as the keratinocyte stem cell, is a permanent resident cell - the remaining keratinocytes (the name given to cells in the skin's epidermis) are eventually shed. The keratinocyte stem cell resides at the bottom of the epidermis on top of a thin layer of basement membrane and is depicted in Fig 1 as the cell with the yellow nucleus.

The keratinocyte stem cell divides infrequently, but when it does so it splits to form another keratinocyte stem cell (in a process called self-renewal) and a transient amplifying cell (depicted in Fig 1 with a green nucleus - this division is demonstrated by the yellow arrows). In turn, these transient amplifying cells subsequently divide to populate the basal cell layer (demonstrated by the green arrows in Fig 1), but they do so for a finite period of time; after which they are no longer able to divide. Eventually, the transient amplifying cells and their progeny rise into the suprabasal layers as new transient amplifying cells occupy the basal cell layer beneath them - in so doing they progress up the epidermis until they are also eventually shed from the surface. Thus, during normal epidermal homeostasis, only the keratinocyte stem cell survives intact and all other cells are eventually shed over a period of approximately 28 days.

EPIDERMAL DIFFERENTIATION
In common with all epithelia tissues that are responsible for lining the body against the environment, the skin's epidermis relies upon a highly regulated process called terminal differentiation to form an impenetrable outer layer.

Proliferation at the basal layer, including among the slow-dividing keratinocyte stem cells, gives rise to some suprabasal cells that are programmed to terminally differentiate and no longer proliferate. These terminally differentiated (committed) keratinocytes undergo epigenetic changes that set them apart from cells in the basal layer.Consistent with the process of terminal differentiation, keratinocytes in the basal layer change their cytoskeletal protein (keratin intermediate filament) expression pattern as they move into the suprabasal layer, in contrast to the basal keratins (these are rigid and contribute to the structural integrity of the skin in the same way that the bony skeleton provides support and integrity to the rest of the body).

As the committed keratinocytes are pushed further up the epidermis, multiple small proteins are secreted that collapse and harden their cell membrane (termed the cornified envelope [Fig 2]), so that the surface keratinocytes become similar to bricks in a wall. Thus the skin epidermis forms a hardened barrier to the environment, which is dependent upon this highly regulated process of terminal differentiation.

FORMATION OF TIGHT JUNCTIONS
The uppermost viable cell layer is held firmly together by a complex of small cell surface membrane proteins. These proteins form bonds called tight junctions [Fig 3], which hold the keratinocytes at this layer together so tightly that they prevent water from leaking out of the skin and microbes from entering.

LIPIDS
In addition to the multiple small proteins that are released near the skin surface to form the cornified envelope (as discussed above), small fatty acids are also released into the extracellular space in the upper layers of the skin. These lipids [Fig 4] surround and fix the brick-like keratinocytes on the skin's surface, rather like cement in a wall. These lipids also repel water while their acidic pH is hostile to bacteria (normal tissue pH is 7.4 while on the surface of the skin the pH is 6.5).