Page 19 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 1-4 Anatomy, Physiology, and Embryology

Bricks (keratinocytes)
Mortar (intercellular space
of the stratum corneum)
Cornified layer
SKIN PHYSIOLOGY: THE PROCESS Corneodesmosomes
OF KERATINIZATION

Keratinization, also known as cornification, is unique to
the epithelium of the skin. Keratinization of the human
skin is of paramount importance; it allows humans to
live on dry land. The process of keratinization begins
in the basal layer of the epidermis and continues upward
until full keratinization has occurred in the stratum Granular layer
corneum. The function and purpose of keratinization
is to form the stratum corneum.
The stratum corneum is a highly organized layer that
is relatively strong and resistant to physical and chemi- Cornified cell envelope
cal insults. This layer is critically important in keeping Spinous cross linked with ceramides
out microorganisms; it is the first line of defense against layer replaces plasma membrane
ultraviolet radiation; and it contains many enzymes
that can degrade and detoxify external chemicals. The Filaments
stratum corneum is also a semipermeable structure that Corneodesmosome of keratin
selectively allows different hydrophilic and lipophilic
agents passage. However, the most obvious and most
studied aspect of the stratum corneum is its ability to LM
protect against excessive water and electrolyte loss. It Corneocyte
acts as a barrier to keep chemicals out, but more impor- Basal layer
tantly, it keeps water and electrolytes inside the human SG cell LB
body. Transepidermal water loss (TEWL) increases as LB
the stratum corneum is damaged or disrupted. The
main lipids responsible for protection against water loss LB
are the ceramides and the sphingolipids. These mole-
cules are capable of binding many water molecules.
As keratinocytes migrate from the stratum basale
and journey through the layers of the epidermis, they Dermis Keratohyalin
undergo characteristic morphological and biochemical granules
changes. The keratinocytes flatten and become more
compacted and polyhedral. The resulting corneocytes Golgi
become stacked, like bricks in a wall. These corneocytes apparatus
are still bonded together by desmosomes, which are
now called corneodesmosomes. Lamellar bodies (LB) that are seen today
The stratum granulosum gets its name from the as part of a branched tubular structure
appearance of multiple basophilic keratohyalin granules like the trans-Golgi network migrate to
present within the keratinocytes. These granules are the surface of the cell of the stratum
largely composed of the protein profilaggrin. Profilag- The dashed lines ( ) granulosum (SG) and release their content
grin is converted into filaggrin by an intercellular endo- show the tortuous intercellular into the intercellular space (ICS). The
proteinase enzyme. Filaggrin is so named because it is penetration pathway within the released lipids are rearranged into lamellar
a filament-aggregating protein. Over time, filaggrin is stratum corneum taken by water- membrane (LM)
broken down into natural moisturizing factor (NMF) soluble substances when the permeability
and urocanic acid. NMF is a breakdown product of of the skin barrier is activated
filaggrin that slows water evaporation from the
corneocytes.
The intercellular space is composed of lipids and
water. The lipids are derived from the release of the
lamellar bodies (Odland bodies). Ceramides make up
the overwhelming majority of the contents of the lamel-
lar bodies. Other components include free fatty acids, membrane. As the keratinocyte migrates upward, the desquamation. Shedding is achieved by the final degra-
cholesterol esters, and proteases. The lamellar bodies cell membrane is lost, and the ceramides that are dation of the corneodesmosomes by proteases that
fuse with the cell surface and release their contents into released begin cross-linking with the CCE proteins. destroy the desmoglein-1 protein.
the intercellular space. The fusion of the lamellar body The cells continue to move toward the surface of the Keratinization is especially important in the diseases
with the cell surface is dependent on the enzyme trans- skin and begin to lose their nucleus and cellular organ- of cornification. Many skin diseases have been found to
glutaminase I. elles. The loss of these organelles is mediated by the involve defects in one or more proteins that are critical
Concurrently. the cornified cell envelope (CCE) activation of certain proteases that can quickly degrade in the process of cornification. Examples are lamellar
develops. The CCE proteins envoplakin, loricrin, peri- protein, DNA, RNA, and the nuclear membrane. ichthyosis, which is caused by a defect in the transglu-
plakin, small proline-rich proteins, and involucrin are Once the cells reach the outer layers of the stratum taminase I enzyme, and Vohwinkel’s syndrome (kera-
cross-linked in various arrangements by transglutamin- corneum, they begin to be shed. On average, a kerati- toma hereditarium mutilans), which results from a
ase I and transglutaminase III, forming a sturdy scaf- nocyte spends 2 weeks in the stratum corneum before genetic mutation in the loricrin protein and a resultant
folding along the inner surface of the keratinocyte cell being shed from the skin surface in a process called defective CCE.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 5