1 - SKIN: BASIC STRUCTURE AND FUNCTION Flashcards
Skin is composed of three layers:
the epidermis, dermis, and subcutaneous fat (panniculus)
The outermost layer, the epidermis, is composed of viable keratinocytes covered by a layer of keratin, the stratum corneum. The principal component of the dermis is the fibrillar structural protein collagen. The dermis lies on the panniculus, which is composed of lobules of lipocytes separated by collagenous septa that contain the neurovascular bundles.
The epidermis is thickest where? What is the measurement?
Palms and soles
1.5 mm
The dermis is thickest where? what is the measurement?
Back
30 - 40x as thick as the overlying epidermis
During the first weeks of life, the fetus is covered by a layer of nonkeratinizing cuboidal cells called the
Periderm
The adult epidermis is composed of three basic cell types:
Keratnocytes, melanocytes and langerhans cells
An additional cell, the ______\_ , can be found in the basal layer of the palms and soles, oral and genital mucosa, nail bed, and follicular infundibula.
Merkel cells
Merkel cells contain intracytoplasmic dense-core neurosecretorylike granules and, through their association with neurites, act as slow-adapting touch receptors. They have direct connections with adjacent keratinocytes by ________ and contain a paranuclear whorl of intermediate keratin filaments.
Desmosomes
Both polyclonal keratin immunostains and monoclonal immunostaining for keratin 20 stain this whorl of keratin filaments in a characteristic _______
Paranuclear dot pattern
Merkel cells also label for neuroendocrine markers such as
Chromogranin and synaptophysin
_______ are of ectodermal origin and have the specialized function of producing keratin, a complex filamentous protein that not only forms the surface coat (stratum corneum) of the epidermis but also is the structural protein of hair and nails.
Keratinocytes
Mutations in the genes for _____ are associated with epidermolysis bullosa simplex
Keratins 5 and 14
mutations are associated with epidermolytic hyperkeratosis.
Keratin 1 and 10
The epidermis can be divided into ____
- the innermost basal layer (stratum germinativum),
- the malpighian or prickle layer (stratum spinosum),
- the granular layer (stratum granulosum),
- the horny layer (stratum corneum)
- On the palms and soles, a pale clear to pink layer, the stratum lucidum, is noted just above the granular layer
When the skin in other sites is scratched or rubbed, the _____ thicken, a _______ forms, and the ______ becomes thick and compact.
malpighian and granular layers thicken
stratum lucidum forms
stratum corneum becomes thick and compact.
regulate epidermal differentiation
Histones
suppresses expression of profilaggrin
Histone deacetylation
Sites rich in stem cells include
deepest portions of the rete, especially on palmoplantar skin, as well as the hair bulge
Stem cells divide infrequently in normal skin, but in cell culture they form active, growing colonies. They can be identified by their high expression of
Ξ²1-integrins and lack of terminal differentiation markers
Stem cells can also be identified by their low levels of
desmosomal proteins, such as desmoglein 3
Abnormal keratinization can manifest as
- parakeratosis (retained nuclei),
- as corps ronds (round, clear to pink, abnormally keratinized cells), or
- as grains (elongated, basophilic, abnormally keratinized cells).
During keratinization, the keratinocyte first passes through a what phases on its way to becoming a horn cell.
synthetic and then a degradative phase
Identify the phase of keratinization.
within its cytoplasm the keratinocyte accumulates intermediate filaments composed of a fibrous protein, keratin, arranged in an Ξ±-helical coiled pattern. These tonofilaments are fashioned into bundles, which converge on and terminate at the plasma membrane, where they end in specialized attachment plates called desmosomes.
synthetic phase
characterized by the disappearance of cell organelles and the consolidation of all contents into a mixture of filaments and amorphous cell envelopes.
degradative phase of keratinization
programmed process of maturation resulting in death of the cell
terminal differentiation
Terminal differentiation is also seen in the involuting stage of keratoacanthomas, where the initial phase of proliferation gives way to terminal keratinization and involution.
Degradation of the mitochondrial network within keratinocytes occurs with ____
aging
Oxidation injury to keratinocytes occurs with environmental exposure and thermal burns, and can be partially prevented by ______
vitamin C in the form of L-ascorbic acid
appears in hematoxylin and eosin (H&E)βstained sections as scattered brightred cells, some of which may contain small, black pyknotic nuclei. These cells are present at various levels of the epidermis, because this form of cell death does not represent part of the normal process of maturation.
Premature programmed cell death, or apoptosis
Widespread apoptosis is noted in the
verrucous phase of incontinentia pigmenti.
It is also a prominent finding in catagen hairs, where apoptosis results in the involution of the inferior segment of the hair follicle.
appear in the intercellular space (separates plasma membranes of adjacent cells), primarily at the interface between the granular and cornified cell layers.
Lamellar granules (Odland bodies or membrane-coating granules)
Lamellar granules contribute to skin cohesion and impermeability.
Conditions such as ______ and ______demonstrate abnormal lamellar granules.
lamellar ichthyosis and Flegel hyperkeratosis
contribute a water-barrier function to skin and are typically found in topical products meant to restore the epidermal barrier.
Glycolipids such as ceramides
Lamellar bodies form abnormally in the absence of
critical ceramides such as glucosylceramide, or there is disproportion of critical lipids.
Desmosomal adhesion depends on
cadherins, including the calcium-dependent desmogleins and desmocollins.
Antibodies to these molecules result in immunobullous diseases, but desmogleins function not only in adhesion but also in differentiation. The binding of the desmoglein 1 cytoplasmic tail to the scaffoldingprotein Erbin downregulates the Ras-Raf pathway to promote stratification and differentiation of keratinocytes in the epidermis.
Keratinocytes of the granular zone contain, in addition to the keratin filament system, keratohyaline granules, composed of amorphous particulate material of high
ulfur-protein content.
This material is a precursor to filaggrin, so named because it is thought to be responsible for keratin filament aggregation
profilaggrin
Conversion to filaggrin takes place in the ______, and this forms the electron-dense interfilamentous protein matrix of mature epidermal keratin.
granular layer
a serine protease secreted from lamellar granules, appears to function in profilaggrin cleavage
Kallikrein-related peptidase 5
hygroscopic, and repeated cycles of hydration and dehydration contribute to normal desquamation of the stratum corneum.
Keratohyalin
characterized by a diminished or absent granular layer, contributing to the retention hyperkeratosis noted in this disorder.
Ichthyosis vulgaris
results in the formation of soft, flexible keratin.
Keratohyalin
Keratin that forms in the absence of k tohyaline granules is typically
hard and rigid.
Hair fibers and nails are composed of hard keratin.
______ secrete a wide array of cytokines and inflammatory mediators, including tumor necrosis factorβalpha (TNF-Ξ±). They also can express molecules on their surface, such as ntercellular adhesion molecule 1 (ICAM-1) and major histocompatibility complex (MHC) class II molecules, suggesting that keratinocytes actively respond to immune effector signals.
Keratinocytes
During wound healing, epithelial cell migration occurs before dermal remodeling. Tight junction proteins _____ and _____ are critical for effective migration.
claudin-1 and occludin
Downregulation of claudin-1 expression results in
delayed migration and reduced epithelial proliferation.
downregulation impairs wound healing when cells are also subjected to mechanical stress
occludin
Wound healing occurs best in a _____ environment but can be impaired by excessive maceration.
moist
Melanocytes are derived from
neural crest
Melanocytes can be found as early as what AOG within the fetal epidermis?
8th week
In normal, sun protected trunk epidermis, melanocytes reside in the basal layer at a frequency of
about 1 in every 10 basal keratinocytes
in heavily sun-damaged facial skin, Mart-1 immunostaining can demonstrate ratios of melanocytes to basal keratinocytes that approach
1 : 1
Recognition of the variation in melanocyte/keratinocyte ratio is critical in the interpretation of biopsies of suspected lentigo maligna (malignant melanoma in situ) on sun-damaged skin.
What determine differences in skin color?
the number, size, and distribution of the melanosomes or pigment granules within keratinocytes.
Racial differences in skin color are not caused by differences in the number of melanocytes
Chronic sun exposure can stimulate melanocytes to produce ______, thereby making the distribution of melanosomes within keratinocytes resemble the pattern seen in dark-skinned individuals.
larger melanosomes
Pale skin has fewer melanosomes, and these are smaller and packaged within membranebound complexes. Dark skin has more melanosomes, and these tend to be larger and singly dispersed.
How does melanocyte appear in histologic sections of skin routinely stained by H&E?
cell with ample amphophilic cytoplasm or as a clear cell in the basal layer of the epidermis.
The apparent halo is an artifact formed during fixation of the specimen. This occurs because the melanocyte, lacking tonofilaments, cannot form desmosomal attachments with keratinocytes.
The actual hair shaft, as well as an inner and an outer root sheath, is produced by
matrix portion of the hair bulb
The sheaths and contained hair form concentric cylindrical layers. The hair shaft and inner root sheath move together as the hair grows upward until the fully keratinized, inner root sheath sheds at the level of the isthmus. The epidermis of the upper part of the follicular canal is contiguous with the outer root sheath. The upper two portions of the follicle (infundibulum and isthmus) are permanent; the inferior segment is completely replaced with each new cycle of hair growth.
Active growth phase of the hair.
This phase lasts for how many years?
Anagen phase
3 - 5 years
Normally, about 85%β90% of all scalp hairs are in the anagen phase, a figure that decreases with age and decreases faster in individuals with male-pattern baldness (as length of anagen decreases dramatically). Scalp anagen hairs grow at a rate of about 0.37 mm/day.
Involution phase of the hair.
This lasts for how long?
Catagen phase
2 weeks
Resting phase of the hair.
This lasts for how long?
Telogen Phase
3 - 5 months
Where are capillaries and postcapillary venule found in the skin?
The dermal vasculature consists principally of two intercommunicating plexuses. The subpapillary plexus, or upper horizontal network, contains the postcapillary venules and courses at the junction of the papillary and reticular dermis (Fig. 1.7). This plexus furnishes a rich supply of capillaries, end arterioles, and venules to the dermal papillae.
