Structure, Function and Disorders of Epidermis, Dermis and Adnexa 12% Flashcards
Describe Vitamin D production in the epidermis
- Provitamin D3 (7-dehydrocholesterol) forms Vitamin D3 (cholecalciferol) via Previatmin D3 on exposure to sunlight
- Vitamin-D binding protein in plasma translocates Vitamin D3 from the skin to circulation
- Vitamin D3 is then hydroxylated in the liver to 25-hydroxyvitamin D3
- 25-hydroxyvitamin D3 is then hydroxylated in the kidney to form 1, 25-dihydroxyvtamin D3
Fetal skin contains a large percentage of type a)_____ collagen whereas adult skin contains a large percentage of type b)______ collagen
a) III
b) I
Transglutaminase
- Marker of early anagen hair follicles
- important in protein cross-linking that contributed to shape and strength of hair
In dogs and cats, which hairs are medullated?
Both primary (outercoat, guard) and secondary (undercoat)
Lanugo
non-medullated hair shaft
What are the three types of hairs seen in cats?
1) Guard hairs (thickest, straight, evenly tapered to a fine tip)
2) Awn hairs (thinner, possessing subapical swelling below the hair tip)
3) Down hairs (thinnest, evenly crimped or undulating)
Trichoglyphics
The study of hair tract patterns.
List how the trophic effects of cutaneous nerves are exerted on follicular growth
- regulation of vascular tone (and nutrient/oxygen supply)
- neuropeptide stimulation of receptors on follicular keratinocytes and dermal papilla fibroblasts
- modulation of macrophages and mast cells activities
List several factors that control the hair cycle
- Photoperiod (hair growth responds predominately to photoperiod)
- Ambient temperature
- Nutrition
- Hormones
- General state of health
- Genetics
- Poorly understood intrinsic factors (growth factors, cytokines produced by the hair follicle, dermal papilla and other cells)
- Sinus hairs are not subjected to a seasonal shedding and are shed continuously as single hairs
What are the transient portions of the hair follicle?
- Matrical cells
- dermal papilla cells (mesenchymal component)
What is an agouti-type hair?
Seen in the German Shepherd or Norwegian elkhound
- the tip is white or light
- The heavy body is pigmented brown or black
- The base is light yellow or red-brown
Eumelanin
- The black-brown pigment
- Activation of the melanocortin 1 receptor (MC1R) on melanocytes leads to production of eumelanin
- The shade of eumelanin is controlled by tyrosinase related protein 1 gene (TYRP1)
Pheomelanin
- The red-brown pigment
- Inhibition of the melanocortin 1 receptor (MC1R) on melanocytes leads to production of pheomelanin
List the 13 genes involved in coat coloration of dogs
1) A - agouti; agouti signaling protein (ASIP)
2) B - brown; tyrosinase related protein 1 gene (TYRP1)
3) C - colored/albino
4) D - blue dilution; melanophilin (MLPH)
5) E - extension; melanocortin 1 reception (MC1R)
6) G - graying
7) H - Harlequin
8) I - phaeomelanin dilution
K - black; beta defensin 103 gene
9) M - merle, SILV
10) P - dilute
11) R - roaning
12) S - white spotting, micropthalmia-associated transcription factor (MITF)
13) T - ticking
What is the underlying mechanism of pointed hair coats seen in Siamese, Himalayan-Persian, Balinese and Burman cats?
- There is a temperature dependent enzyme that converts melanin precursors into melanin by a process of oxidation.
- With high temperatures, the hair coat is lighter
- With low temperatures, the hair coat is darker
- Inflammation and hyperemia cause more lightly colored new hair
- Poor peripheral circulation the accompanies senility and shaving to remove hair often results in more darkly colored new hair
- Expression of this enzyme is controlled by the colorpoint restriction gene (C, tyrosinase gene, TYR)
Tortoioseshell pattern
occurs in females or in males with two XX chromosomes
What breeds of cat are characterized by a curly hair coat?
- Devon Rex: has primary hairs that resemble secondary hairs; whiskers are either absent or stubbled
- Cornish (German) Rex: lacks primary hairs, whiskers are often short and curly
- Both breeds partially or completely molt during estrus or pregnancy that result in a symmetric alopecia that may be mistaken for an endocrine alopecia
What are voight lines?
- boundaries of the areas of distribution the main cutaneous nerve stems
What are langer lines?
Reflect the course of blood vessels or lymphatics
What are blaschko lines?
- Form the pattern assumed by many different nevoid and acquired skin disease
- reflect a mosaic condition deriving from either a single mutated clone of cells originating from a post zygotic mutation or from an x-linked mutation made evident by lyonization
- These lines form a V shape or the spine, S shape on the abdomen, and axial distribution on the limbs and a wavy pattern down the forehead, over and below the eyes, over the upper lip and behind the eyes
- The black lines in a Brindle coat follow Blaschko lines
What are the four cell types found in the epidermis?
- Keratinocytes (85%)
- Merkel cells (~2%): associated with tylotrich pads
- Melanocytes (~5%)
- Langerhans cells (3-8%)
From outside to inside, label the layers of the epidermis
- Stratum corneum
- Stratum lucidum
- Stratum granulosum
- Stratum spinosum
- Stratum basale
What kind of keratinocytes make up the stratum basale?
Single row of columnar - cuboidal cells
Where are the presumed sited of epidermal and hair follicle stem cells in humans and rodents?
- The tips of the deep epidermal rete ridges in glabrous skin
- The bulge (Wulst) region of the hair follicle (i.e. the site attachment of the arrector pili muscle
- Dogs and cats do not have a hair follicle bulge
The cells of the stratum basale are define by what keratin filaments?
K5 and K14
What are the major gene families that make up the desmosome?
- plakins (i.e. desmoplakin)
- armadillo proteins (i.e. plakoglobin and plakophilin)
- desmosomal cadherins (i.e. desmogleins and desmocollins)
What are hemidesmosomes composed of?
- Distributed along inner aspects of basal keratinocytes, major role in epidermal-dermal adhesion
- linkage of keratin intermediate filaments (i.e. cytokeratin network) to hemidesmosomes and basal keratinocyte plasma membrane involves
1) Plaque proteins
2) Bullous pemphigoid antigen 1 ( BPAG 1, pr BP230) and plectin
3) Transmembrane proteins: alpha 6 beta 4 intern and BPAG II (Collagen XVII) and laminin 332a (i.e. laminin 5)
Intergrins
- Large family of cell surface adhesive receptors
- Surface glycoproteins are important in cell-cell and cell-matrix interactions
- Act as signal transducers through which extracellular and intracellular signals compartments can influence and modify one another
- Heterodimers consisting of an alpha and beta subunit
- Integrin expression limited to the basal cell layer
What are the four major types of keratinocyte adhesions?
1) Desmosomes
2) Hemidesmosomes (basal surface of basal cells)
3) Adherens junctions
4) Focal adhesions (basal surface of basal cells)
What do desmosomes consist of?
1) Keratin intermediate filaments and their attachment plaques (i.e. desmoplakin I and II, plakoglobin, plakophilin)
2) Keratinocyte plasma membrane
3) Desmosomal core (desmoglea; i.e. desmogleins I, II, III and desmocollin I, II, III) interposed between two adjacent keratinocyte plasma membranes
Keratin pairs
All epithelia express a keratin pair: one keratin from the acidic subfamily (type I keratins, cytokeratin 9-20) and one chain from the neutral-basic subfamily (type II keratins, cytokeratin 1-8)
What cytokeratins define the stratum spinosis
1) K5 paired with K14
AND 2) K1 paired with K10
1) Where are the lamellar granules first produced,
2) What do they contain?
3) Where are they secreted
1) Stratum spinosum
2) Primarily phospholipids, ceramides, free fatty acids, hydrolytic enzymes and sterols; I.E. glycoproteins, glycolipids, phospholipids, free sterols, glucosylceramides, and a number of acid hydrolyses
3) Into the intercellular space at the interface of stratum granulosum and stratum corneum
1) Where are keratohyalin granules produced?
2) What are keratohyalin granules composed of?
- Not true granules as they lack a membrane, better described as insoluble aggregated.
1) Stratum granulosum
2) Profilaggrin, keratin filaments, loricrin
What is the function of filaggrin?
Aggregate, pack and and align keratin filaments into macrofilaments
What are the filaggrin degradation products?
Also referred to as moisturizing factors, urocanic acid and pyrrolidone carboxyclic acid.
- Important for normal stratum corneum hydration and also help filter UV radiation
What is loricrin?
- A cystine-rich protein synthesized in the stratum granulosum in assocation with keratohyalin granules
- Involved in binding keratin filaments together in the corneocyte and anchoring them to the cross-linked envelope
1) What is the stratum lucidum?
2) How does it differ from the stratum corneum
3) Where on the body is it found?
4) What is another name for it?
1) Fully keratinized, compact, thin layer of dead cells; anuclear, homogeneous, hyaline like, contains refractile droplets and a semifluid sustance called eleidin
2) It is rich in protein-bound lipids
3) Best-developed in the footpads; less well developed in nasal planum and absent from other locations.
4) Stratum conjunctum
List the protein components of the cornified envelope
loricrin, involucrin (bings ceramides covalently, forming a back bone of attachment of intracellular lipids), filaggrin, elafin, cystatin A, cornifelin, small proline-rich proteins and “late-envelope” proteins
Cornified envelope
- Develops beneath plasma membrane of stratified epidermal cells, cells of the inner root sheath and medulla of the hair follicle and cuticle of the claw
- Formation associated with increased activity of calcium-dependant epidermal or hair-follicle transglutaminases that catalyze cross-linking of soluble and particulate protein precursors into large, insoluble polymers
- Provides structural support and resists invasion by microganisms and deleterious environmental agents.
Transglutaminases
- superfamily of enzymes involved in keratinization and hair follicle formation
- Two members of the superfamily: keratinocyte transglutaminase and epidermal transglutaminae - mediate sequential cross-linking of the cornified cell envelope precursor proteins (involucrin, cytostan A, elafin, and loricin)
- Chiefly expressed in stratum granulosum and upper stratum spinosum and require catalytic amino acids and calcium
What are the four distinct cellular events that occur in the process of cornification?
1) Keratinization (synthesis of the principal fibrous proteins of the keratinocytes)
2) Keratohyalin synthesis (including the histidine-rich protein filaggrin)
3) Formation of the highly cross-linked insoluble stratum corneum cornified cell envelope (including the structural protein, involucrin)
4) Generation of neutral lipid-enriched intercellular domains resulting from secretion of distinctive lamellar granules
Ceramide
Amide-linked fatty acids containing a long-chain amino alcohol (sphingoid base)
Linoleic acid is found in which three ceramides?
Ceramide 1, 4 and 9
Which ceramides bind to involucrin and other proteins of the cornified envelope?
Ceramides 1 and 2
Describe how polyunsaturated fatty acids turn into eicosanoids?
- Polyunsaturated fatty acids are liberated from phospholipids by phospholipase A2
- Subsequently metabolized by cycloxygenase and lipoxygenase enzymes into prostaglandins and leukotrienes
Where are melanocytes found in the skin?
- Basal layer of the epidermis
- Outer root sheath
- Hair matrix of hair follicles
- Ducts of sebaceous and sweat glands
- Superficial dermis
Aside from the skin, where else are melanocytes found?
- Derived from neural crest and migrate into epidermis in early fetal life
- Also found in eyes (retinal pigment epithelium), cochlea (stria vascularis) and meninges
Epidermal melanin unit
- Typically 1 melanocyte per 10 - 20 keratinocytes that transfer melanosomes to keratinocytes via dendrites
How do pheomelanins differ from eumelanins?
Pheomelanins contain a higher proportion of sulfur
What is the key intermediate of all the melanins?
Dopaquinone
What enzyme catalyzes the conversion of tyrosine to DOPA?
Tyrosinase; the rate-limiting step in the melanin pathway, it is a copper-containing enzyme found exclusively in melanocytes
List two melanocyte specific enzymes
Tyrosinase and dopachrome tautomerase
What is the ultrastructural hallmark of the melanocyte?
The melanosome; the location of melanogenesis.
Melanosomes
- Site of melanogenesis
- Originate from the golgi apparatus where the tyrosinase enzyme is formed
- Melanocytes transfer stage IV melanosomes to keratinocytes by a unique process called cytocrinia
Continent melanocytes
Dermal melanocytes that do not transfer melanin
Microphthalmia transcription factor (MITF, also called master transcriptional regulator of pigmentation)
A pivotal transcription factor in expression and differentiation of many enzymes involved in melanin synthesis
Melanocortin 1 receptor (MC1R)
- A major determinant of melanogenesis
- A G protein-coupled receptor that regulated pigment phenotype
- Agonists of this receptor include: MSH, corticotropin
- Agouti gene encodes an anatagonist to MC1R
What histochemical stains stain melanin, albeit unexclusively?
- Argentaffin stains (Fontana-Masson, Gomori methenamine silver)
- Argyrophil stains (Grimelius stain)
Merkel Cells
- dendritic epidermal clear cells occurring in the basal cell layer or just below, predominately in tylotrich pads and hair follicle epithelium
- Slow-adapting type 1 mechanoreceptors
- Contain large cytoplasmic vacuole that displaces nuclear dorsally
Name immunohistochemical markers for Merkel cells
K8, K18, K19, K20 peptides
Where are keratohyalin granules located within the hair follicle?
- Keratohyalin granules are present in the stratum granulosum of the epidermis and infundibulum of the hair follicle.
- The outer root sheath of hair follicle joins the epidermis and cannot be differentiated from the epidermis in the infundibulum
1) Define the isthmus
2) What type of granules are present in the isthmus
1) Portion of the hair follicle between the entrance of the sebaceous glands and attachment of the arrector pili muscle
2) Neither trichohyalin granules nor keratohyalin granules are present in the isthmus
What is the only mesenchymal portion of the hair follicle?
The dermal papilla
Where are tricohyalin granules noted?
Within the layers of Huxley and Henley of the inner root sheath in the inferior portion of the hair follicle.
1) What are the permanent portion(s) of the hair follicle
2) What are the transitory portion(s) of the hair follicle?
1) Infundibulum and isthmus
2) Inferior segment
What is a stem cell marker for the bulge region?
Keratin 15
Outer root sheath
Defined by cytoplasmic glyogen storage during anlagen phase
Langerhans cells
- mononuclear dendritic antigen processing and presenting cells located basally or supra basally
- Epidermal clear cells, do not stain for melanin with dopa (like Merkel cells)
- Contain characteristic intracytoplasmic organelles called “Birbeck” or “Langerhans granules” that are identified via electron microscopy; these are inconsistently found in dog Langerhans cells
- They are aureophilic (i.e. stain with gold chloride)
- In dogs and cats, are S100 protein and adenosine triphosphatase (ATPase) NEGATIVE
- bone marrow origin and monocyte-histiocyte lineage
- Decreased in number / function have UVL exposure
What cell type do Birbeck granules identify?
- Langerhans cells
- Birbeck granules described as being zipper, rod, flask or tennis racket like in appearance.
- form by invagination of the plasma membrane and bound antigen
What receptors do Langerhans cells carry?
- Fc fragment immunoglobulin (Ig) G
- Complement 3 (i.e. C3)
- High affinity receptors for IgE
- In the dog, CD1a, b, c; CD11a,c; CD18; CD45; ICAM-1, MHC class II and vimentin positive
- In the cat: CD1a, CD4, CD18 and MHC class II positive
- CD4 and CD 90 negative (distinguishes them from dermal dendritic cells)
How can you immunohistochemically differentiate an epidermal langerhans cell from a dermal dendritic cell?
Langerhans cells are CD4 and CD 90 (i.e. Thy-1_ negative in the dog
What stain can be used to highlight the basement membrane zone?
Periodic acid-schiff
What are the four components that comprise the basement membrane zone?
1) The basal cell plasma membrane
2) The lamina lucida (lamina rara)
3) The lamina densa (basal lamina)
4) The sublamina densa area (lamina fibroreticularis) containing the the anchoring fibrils and the dermal microfibril bundles
What is the dermis composed of?
- Mesodermal origins
- Insoluble fibers (collagen and elastin)
- Major soluble macromolecules (proteoglycans and hyaluronan)
- Dermis of the scrotum is unique in that in contains numerous large smooth muscle bundles
- Collagen accounts for 90% of all dermal fibers and 80% of the extracellular matrix
- Most of the dermal extracellular matrix (fibers and ground substance) is synthesized by fibroblasts
What IHC stains collagen?
Masson trichrome