The epidermis is a multilayered epithelial structure composed of keratinocytes that produce the structural protein keratin. Histologically, the epidermis is composed primarily of four tightly-adherent layers of squamous epithelium organized into distinct vertical zones by stages of differentiation.
The epidermis is reminiscent of a brick wall, with the keratinocytes representing bricks, and intercellular matrix representing the mortar. From innermost to outermost the layers are: stratum basale, stratum spinosum, stratum granulosum, and stratum corneum.
The deepest/innermost layer of the epidermis is the stratum basale. Histologically, the stratum basale is a single layer of cuboidal keratinocytes that directly abut and attach to the dermis. The two primary functions of the stratum basale are 1) proliferation and 2) attachment of the epidermis to the dermis.
Cells of the stratum basale essentially represent germinal cells (“brick generators”) responsible for the generation of all cells of the epidermis. As such, these cells are the most mitotically active keratinocytes (apparent in histologic sections) and are the least differentiated. Stratum basale keratinocytes divide and then “push up” towards the surface, differentiating into cells of the stratum spinosum.
Histologically, the stratum spinosum is located directly above (superficial to) the stratum basale. Cells of the stratum spinosum have prominent cell-to-cell junctions, termed desmosomes, that appear as spiky membrane projections on histology. For this reason, these are referred to as “prickle cells”. Desmosomes are protein complexes that firmly attach keratinocytes to their surrounding cells (intercellular, between cells), thereby providing significant structural integrity. Tonofilaments are intracellular (within cells) protein complexes that anchor desmosomes to the cell membranes.
The thickness of the stratum spinosum can vary dramatically depending on the anatomic location on an animal. For example, the stratum spinosum of canine inguinal skin is 1-2 cell layers thick, whereas the stratum spinosum of the canine footpad is often >20 cell layers thick! The reason for this is clear when the primary function of skin is considered: protection.
The stratum granulosum, where present, sits above the stratum spinosum and directly below the stratum corneum. Histologically, the stratum granulosum is a thin layer of keratinocytes containing dense, basophilic (blue/purple) cytoplasmic structures called keratohyalin granules. Keratohyalin granules contain components responsible for keratinization, including fibrous proteins (keratohyalin) and a lipid-rich secretory product.
It should be noted that the stratum granulosum is not apparent in all regions of the skin, particularly in regions of thin skin (e.g. canine inguinal and axillary skin).
The stratum corneum is the variably thick (10-20 layers) outermost layer of the skin. Histologically, cells of the stratum corneum, or corneocytes, are flattened eosinophilic keratinocytes that lack nuclei (anuclear). Corneocytes, often considered “dead”, retain some metabolic and signaling functions despite having no organelles or nuclei.
Keratinocytes of the stratum corneum have a thickened, insoluble, hydrophobic, cell membrane and contain abundant keratin. In addition, the corneocytes are surrounded by a hydrophobic phospholipid secretory product (produced by stratum granulosum). Together, these combine to provide the hydrophobic and structural properties that serve to protect the epidermis from physical insults as well as water loss. Desmosomal attachment become more sparse in superficial layers, resulting in sloughing of keratinocytes, a process known as desquamation.
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