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
What two unusual amino acids does collagen contain?
Hydroxylysine and 4-hydroxyproline
What IHC stains reticular fibers (i.e. reticulin)?
Special silver stains
What IHC stains elastin?
Verhoeff and van Gieson elastin stains
What are elastin fibers composed of?
- Amorphous elastin and microfibrils
What two unique cross-linked amino acids are found in elastin that are not found in any other mammalian proteins?
Desmosine and isodesmosine
What are dermal microfibrils composed of?
Type VI collagen and Fibrillin
What is the predominating type of collagen found in the dermis?
Type I collagen
What stimulates collagen synthesis?
- Vitamin C (i.a. ascorbic acid)
- TGF-B
- IL-1
- IGF-1
- IGF-2
- Superoxide generating systems
- Bleomycin
What inhibits collagen synthesis?
- Glucocorticoids
- Retinoids
- Vitamin D3
- Parathormone
- Prostaglandin E2
- IFN-Y
- D-penicillamine
- Minoxidil
Collagenases
- Members of the matrix metalloproteinase gene family
- Dermal fibroblasts are the major source
What are elaunin and oxytalan fibers?
Elastic fibers that are organized in an arcade-like arrangement (Elaunin fibers) in the superficial dermis with thinner elastic fibers (oxytalan fibers) vertically ascending to terminate at the dermoepidermal junction
- Elaunin = microfibrils/elastin
- Oyxtalan = microfibrils
Dermal dendrocytes
- mostly bone marrow derived
- Express CD45, MGC Class II, various adhesion molecules (LFA-1, ICAM-1)
- antigen-presenting cells
- Phagocytic
- Variably factor XIIIa and CD34 positive
- Immunophenotype variation based on location
- In dogs: CD1, factor XIIIa, MHC class II and Thy-1 positive
What is dermal ground substance composed of?
- glycosaminoglycans (formerly called mucopolysaccharies)
- proteoglycans
What are the major proteoglycans and glycosamingoclycans?
- Hyaluronate and heparin sulfate in the epidermis (synthesized by keratinocytes)
- Heparin sulfate and chondroitin 6 sulfate in the basement membrane
- Hyaluronic acid, keratin sulfate, dermatan sulfate (i.e. chondroitin sulfate B), chondroitin 6 sulfate, chondroitin 4 sulfate, versican, syndecan, decorin, glypican and serglycin in the dermis
What special stains highlight mast cells?
- Toluidine blue
- Acid orcein-Giemsa
What are the three subtypes of mast cells seen in the skin?
1) Those that contain tryptase (i.e. T-mast cells)
2) Those that contain chymase (i.e. C-mast cells)
3) Those that contain both tryptase and chymase (i.e. TC mast cells)
What layer of the hair shafts contain the pigment that give the hair its colour?
Primarily in the cortex; can be in medulla but it has little influence on color of the hair shaft itself
Where does trichilemmal keratinization begin?
The infundibulum: the segment from the entrance to the sebaceous duct (i.e. where trichilemmal keratinization begins) to the skin surface
Where do trichohyalin granules containing cells begin?
At the attachment of the arrector pili muscle to the hair follicle, found in the inner root sheath.
What are the layers of the inner root sheath?
From inside to outside: the inner root sheath cuticle, layer of huxley, layer of henle.
- Inner root sheath contain eosinophilic granules called tricohyalin granules
- Inner root sheath keratinizes and disintegrates when it reaches the level of the isthmus
- Telogen hairs contain no inner root sheath
What is the function of tricohyalin?
Major protein found in the granules of the inner root sheath and medullory cells of the hair follicle
- keratin-associated protein that promotes the lateral alignment and aggregation of parallel bundles of intermediate filaments in the inner root sheath
- Found in other parts of the epithelium where it is expressed in conjunction with filaggrin (the major keratohyalin granule)
Which amino acid is concentrated in hair and tricohyalin granules?
Citrulline; used as a marker for hair follicle differentiation
Where does trichilemmal keratinization occur?
In the hair follicle starting in the isthmus where the outer root sheath is not covered by the inner root sheath. Keratohyalin granules are NOT formed here.
Where are keratohyalin granules found in the hair follicle?
In the infundibulum; keratinization of the hair follicle is the same as the epidermis in this portion of the hair follicle.
What is the hair follicle’s “glassy membrane”?
The basement membrane zone
Where are sinus hairs (vibrissae, whiskers) found?
Muzzle, lip, eyelid, face, throat and palmar aspect of the carpus in cats
Sinus hairs
Characterized by an endothelium-lined blood sinus interposed between the external root sheath of the follicle and an out connective tissue capsule
- The sinus is divided into a superior nontrabecular ring (or annular) sinus and an inferior cavernous (or trabecular) sinus
- Thought to function as slow-adapting mechanoreceptors
Tylotrich hairs
Scattered throughout ordinary body hairs
- larger hair follicles and contain single, stout hair and an annular complex of neurovascular tissue that surrounds the follicle at the level of the sebaceous glands
- Thought to function as rapid-adapting mechanoreceptors
- Each tylotrich follicle is associated with a tylotrich pad
Tylotrich pads
Thickened and distinctive epidermis underlaid by convex areas of fine connective tissue that is highly vascularized and well-innervated
- Unmyelinated nerve fibers end as flat plaques in associated with Merkel cells, which serve as slow-adapting touch receptors
What is the best morphologic feature of catagen?
Partial replacement of the inner root sheath by trichilemmal keratinization;
CATAGEN
- Retraction of the hair follicle towards the surface
- increased number of apoptotic keratinocytes
- Smaller hair bulb and an ovoid or round dermal papilla
- Hair follicle srhinks from the position of the hair bulb to just below the entry into the sebaceous duct
- TGF-beta pathway is involved in induction of catagen, caspases play an essential role execution of apoptosis
- Melanogenesis stops and the proximal hair shaft is depigmented
Telogen hair follicle
- Reduced to 1/3 of its former length
- Small dermal papilla that is separated from the matrix cells, no hair bulb, lack of melanin and mitotic activity, absence of inner root sheath, presence of club-like hair
Exogen
Shedding of the hair from its follicle.
Anagen hair follicle
- well-developed, spindle-shaped dermal papila capped by the hair matrix (ball and claw appearance) to form hair follicle bulb
- Hair matrix cells often heavily melanized and show mitotic activity
- Hair follicle extends deep into deep dermis and subcutis
What are the four different morphologic patterns of keratinization in the hair follicle?
1) Infunfibular ( like epidermis, basket weave, presence of keratohyalin granules)
2) Trichilemmal (serrated, more closely backed, eosinophilic keratin with scant or no keratohyalin granules)
3) Hair matrix or trichogenic
4) Inner root sheath and hair shaft medullary (compact, opaque keratin with blue-gray to eosinophilic and red tricohyalin granules)
Plucked anagen vs. telogen hair shaft
Anagen: larger expanded root, moist, glistening, often pigmented and square at the bottom
Telogen: tapered club root with little or no pigment
Where are 1) sebaceous glands located and 2) largest and most numerous?
3) What species do not have sebaceous glands?
4) Where are sebaceous glands NOT found?
1) Throughout all haired skin in mammals
2) Near mucocutaneous junctions, in the interdigital spaces, on the dorsal neck and rump, on the chin, and on the dorsal tail
3) Whales and porpoises
4) Footpads and nasal planum
What kind of glands are sebaceous glands?
Holocrine glands, they make sebum by rupturing/disintegrating; appear to be innervated and under hormonal control (androgens cause them to become larger, estrogens and glucocorticoids cause them to become smaller)
What two different receptors do sebaceous glands carry that are involved in uptake of circulating lipids?
1) FATP4 (fatty acid transporter 4
2) LDL (low-density lipoprotein)
Epitrichial sweat glands
- Not present in foot pads or nasal planum
- Empty into hair follicle in the infundibulum, slightly above where the sebaceous duct empties
- Do not appear to be innervated
- Sweat probably has pheromonal and antimicrobial properties
- Positive for cytokeratin, associated myoepithelial cells are both cytokeratin and S-100 protein positive
What does freshly liberated sebum primarily contain?
Triglycerides and wax esters
Atrichial sweat glands
- Only found in the deep dermis and subcutis of foot pads in dogs and cats
- richly innervated with cholinesterase positive-positive nerves
- Carnivores lack atrichial sweat glands in haired skin
1) What is the critical temperature of dogs?
2) At what rectal temperature do dogs start shivering?
1) 14 C (57 F) in haired skin
25 C (77 F) when the hair has been shaved off
2) 1 C
What innervated arrector pili muscles?
Receive cholinergic innervation and contract in response to epinephrine and norepinephrine, producing piloerection. Probably function in thermoregulation and in the emptying of sebaceous glands; important in providing social signals.
Describe the blood vessel plexuses and what they supply blood to
1) Deep plexus - found at interface between deep dermis and subcutis; branches descend into subcutis and ascent to supply lower portions of the hair follicles and epitrichial sweat glands.
2) Middle plexus - blood vessels ascend from deep plexus; present at the level of the sebaceous glands; gives off branches to the arrector pili muscles, ascending and descending branches that supply the middle portions of the hair follicles and sebaceous glands and ascend to feed superficial plexuses
3) Superficial plexus - capillary loops immediately below the epidermis and supply the epidermis and upper portions of the hair follicles.
The majority of superficial dermal vessels are?
Post-capillary venules
- most physiologically reactive segment of microcirculation
- where inflammatory cells migrate from the vascular space into the tissues
List 4 characteristic features of blood vessel endothelial cells.
1) Have peripheral basement membrane with intracytoplasmic Weibel-Palade bodies (rod-shaped, tubular structures enveloped in a continuous single membrane)
2) Posses Factor VIII (i.e. von Willebrand) antigen, plasminogen activators, prostaglandins
3) CD 31 (platelet endothelial cell adhesion molecule PECAM)
4) Are phagocytic
What is a glomus and what is it composed of?
A special arteriovenous shunt located within the deep dermis; consists of both arterial (Sucquet-Hoyer canal) and venous segment.
- Arterial segment branches from arteriole; the wall shows a single layer of endothelium surrounded by a BMZ and a tunica media that is densely packed with 4-6 layers of glomus cells.
- Glomus cells considered to be modified smooth muscle cells; they are large, plump, have a clear cytoplasm, and resemble epithelioid cells.
- Acetylcholine and histamine cause dilation of shunts and improves blood flow
- Epinephrine and norepinephrine cause constriction
How can you distinguish lymph vessels from blood vessels?
1) Lymph vessels contain wider and more angular lumina
2) Lymph vessels have flatter and more attenuated blood vessels
3) Lymph vessels have no pericytes
4) Lymph vessels contain no blood (unless there’s been trauma)
How can you highlight cutaneous nerves and free nerve endings using light microscopy?
- Methylene blue staining
- Metallic impregnation
- Histochemical techniques
What is a dermatome?
The area of skin supplied by the branches of one spinal nerve
What is a meissner corpuscle?
- Rapid-acting mechanoreceptor
- located in Superficial dermis
- Layers of the large leaflife endings of two to six afferent nerve
- Respond to vibration
What is a pacinian corpuscle?
- Rapid acting mechanoreceptor
- Large, layered, onion-like structure enclosing an afferent neuron
- Sensitive to pressure and vibration
What is a ruffini corpuscle?
- Slow adapting type II mechanoreceptor
- Located in connective tissue of dermis
- Large spindle-shaped structure that interconnects with collagen matrix
- Sensitive to skin stretch
What is a tylotrich pad?
- Slow adapting mechanoreceptor
- Local area of epidermal thickening with a layer of highly vascular and well-innervated connective tissue under it
What is a tylotrich hair?
- Rapid acting mechanoreceptor
- Specialized hair that is a large primary follicle surrounded by a ring of neurovascular tissue
- Associated with a tylotrich pad
What is a merkel cell?
- Slow-adapting type I mechanoreceptor
- Located in basal layer of the epidermis
- Unmyelinated ending of afferent nerve
- Touch receptor and respondes to pressure, edges and curves
What is a sinus hair?
- i.e. Vibrissae, whiskers
- Slow-adapting mechanoreceptor
- Loinger, thicker and stiffer than normal hairs
- Have an endothelium-lined blood sinus between the external root sheath of the follicle and the outer connective tissue capsule
- Pacinian corpuscles are located close to the sinus hair follicle
What is typically the thickest layer of the skin?
Subcutis
What is subcutis primarily composed of?
Its 90% triglyceride by weight
What are veil cells?
- Flat, adventitial, fibroblast-like cells that surround all dermal microvessels
- Stain for factor XIIIa, indicating they are a component of the dermal dendrocyte system
- Entirely external to the vascular wall
- Demarcated blood vessel from surrounding dermis
What are pericytes?
- Fusiform to club like in appearance
- aligned parallel to blood vessels on their dermal side
- Contractile cells with actin-like and myosin-like filaments
- Important in regulating capillary flow
What are Toll-like receptors?
Pattern-recognition receptors that recognize molecular patterns (i.e. PAMPS; pathogen associated molecular patterns) that are common to invading organisms
What are some examples of PAMPS?
Peptidoglycan, lipopolysaccharides (LPS), glycolipids, and mannan-rich carbohydrates, lipoproteins, double-stranded RNA, viral nucleic acids, lipoteichoic acid, flagellin, CpG motifs
What is transferrin?
Iron-binding protein, main effect is to prevent the buildup of free iron which can predispose to bacterial infection. Found in the intercellular lipid layer. Also reduces the binding of gram-negative and positive bacteria to surfaces.
What are defensins?
- Cysteine-rich proteins containing 29-34 amino acids
- Synthesis upregulated in response to IL-1 and TNF
- A type of antimicrobial peptide
What are adhesins and what are some examples?
Molecules on the surface of bacteria that allow them to adhere to the skin. Examples include: teichoic acid, lipoteichoic acid, fibronectin-binding proteins, and laminin-binding proteins
What are the three distinct complement pathways?
1) The classical pathway
2) The alternative pathway
3) The lectin pathway
What is the membrane attack complex and what is it composed of?
Part of the complement pathways, a cylindrical structure composed of complement components 4, 5 , 6 , 7, 8 and 9
- It can punch holes in the membranes of certain types of bacteria
What activates the classical complement pathway?
Antigen-antibody complexes
What activates the alternative complement pathway?
Direct interaction between the surface of a microbe and C3b
What activates the lectin pathway?
Plasma lectin binds to a mannose residue on the surface of a microbe and activates C1 in the absence of antibodies; this pathway is subsequently the same as the classical pathway.
What leads to upregulation of adhesion molecules (i.e. selectins and integrins) on blood vessel walls?
IL-1, TNF-alpha
E-selectin
- Binds to carbohydrate ligands on phagocytic cell surface with low affinity
- Causes cells to slow down and roll along the endothelium
What are some examples of integrins on the vascular endotheliym?
ICAM-1 (intercellular adhesion molecule 1)
VCAM-2 (vascular cell adhesion molecule 2)
What are some examples of integrin ligands on the inflammatory cells?
- leukocyte function-associated antigen 1 (LFA-1 or CD11a/CD18)
- Macrophage activation complex 1 (Mac-1 or CD11b/CD18)
What are chemokines?
Chemotactic cytokines that stimulate movement and migration of leukocytes from the blood into tissues.
List 5 signaling molecules involved in melanoblast migration and differentiation into melanocytes.
1) Wnt
2) Endothelin-3 (ET3)
3) Bone morphogenetic proteins (BMPs)
4) Steel factor (stem cell factor) - binds to C-KIT
5) Hepatocyte growth factor
How do epidermal and follicular melanocytes differ?
- Epidermal melanocytes are typically found in the basal layer
- Follicular melanocytes are located in the outer root sheath and the hair matrix of the hair follicles
What adhesion molecules do melanocytes predominately express?
E and P-cadherin
Where are melanocytes located?
- Epidermis and hair follicle
- Ducts of sebaceous and sweat glands
- Superficial dermis
- Uvea of the eye
- Cardiovascular system
- Cochlea (stria vascular)
- The central nervous system
- Adipose tissue
What are melanosomes?
Subcellular lysosome-like organelles in which melanin pigments are synthesized and stored
What is an epidermal melanin unit?
One melanocyte that transfers melanosomes with 10-20 keratinocytes in the basal layer of canine skin
As melanocytes do not stain well with hematoxylin and eosin, what a) special stains and b) immunocytochemistry could be used to visualize melanocytes?
a) DOPA oxidase reaction; Fontana-Masson stain; Schmorl’s method
b) Vimentin and S-100 protein positive
What pigmentation of normal skin dependent on?
- Melanin
- Carotene
- Oxyhemoglobin
- Reduced hemoglobin
- Location of pigments within the subcutis, vessels, dermis, epidermis and hair
How are eumelanins and pheomelanins different?
- Eumelanines are brown-black pigments
- Pheomelanins are yellow-red pigments; contain cysteine thiol groups that react to form 5-S-cysteinyl dopa
What are the main enzymes involved in melanin production?
- Tyrosinsane
- Tyrosinase-related protein 1
- Tyrosinase-related protein 2
What does a mutation in tyrosinase-related protein 1 results in?
Results in black melanin appearing brown or chestnut ; or brown to becoming red/cinnamon
What cytokines inhibit melanogenesis in humans?
- IL-1
- IL-6
- IL-7
What are 7 genes involved in coat color in dogs
1) Agouti signal peptide
2) Beta-defensin 103
3) Melanocortin 1 receptor
4) Melanophilin
5) Microphthalmia-associated transcription factor
6) Tyrosinase related protein 1
7) SILV (formerly PMELB17)
What is feline acromelanism?
- A form of albinism that has been genetically selected for in Siamese, Himalyana, Balinese, Birman, Burmese and Singapura cats
- These cats have a temperature sensitive hair bulb tyrosinase that is inactivated at temperatures of 35-37 C
- If skin is cool enough, such as seen normally on the extremities (pinnae, tail, legs) or in areas following shaving , pigment production may in occur in the hairs and cause a darker hair coat.
- Changes in hair coat color following shaving is temporary and normal color returns with the next hair cycle
What are different etiologies for comedones?
- Hypercortisolemia
- Constant pressure/trauma (i.e. as seen in callus)
- Demodicosis
- Idiopathic primary seborrhea
- Vitamin A responsive dermatosis
What pigmentary changes can o,p’-DDD result in?
hyperpigmentation and melanotrichia, may also be a resolution of the disease being treated ; this change is typically transient
What breeds are primarily affected by pigmented viral plaques?
Pugs, miniature schnauzers, Shar-Peis
What is the pathomechanism behind albinism?
- Hereditary lack of pigmentation transmitted by an autosomal recessive trait, resulting in mutation of the tyrosinase gene.
- Siamese and Burman have their coat color as a result in the tyrosinase gene
- Albino individuals have normal number of melanocytes, but their lack of tyrosinase for melanin synthesis leaves them with a biochemical inability to produce melanin
What is piebaldism?
- Genetically determined white spotting
- Transmitted as completely dominant trait
- Melanocytes are absent or incompletely differentiated in these location
What is Waardenburg-Klein syndrome?
- A autosomal dominant trait with incomplete penetrance
- There is a defect in the migration and differentiation of melanoblasts; affected skin has no melanocytes present
- Affected animals have blue to heterochromic irides, amelanotic skin and hair, and are deaf
- Reported in cats, bull terriers, sealyham terriers, collies and dalmations.
What is Waardenburg-Klein syndrome?
- A autosomal dominant trait with incomplete penetrance
- There is a defect in the migration and differentiation of melanoblasts; affected skin has no melanocytes present
- Affected animals have blue to heterochromic irides, amelanotic skin and hair, and are deaf
- Reported in cats, bull terriers, sealyham terriers, collies and dalmations.
What is the proposed pathomechanism behind graying?
- Rediction in melanocyte replication through senescence
- Age-related change seen in GSH, Irish setters, Labrador retrievers, golden retrievers
What are the proposed pathomechanisms underlying vitiligo?
- Acquired disease associated with melanocyte destruction resulting in areas of leukoderma and/or leukotrichia
- Exact cause is still being determined; multiple pathologic mechanisms
- Genetic variations appear to make melanocytes more susceptible to damage from immune system and oxidative damage from free radicals.
- Autoimmunity and genetics pay a major role in disease development in humans; melanocyte damage from oxidative stress associated with excessive free radical production and/or ineffective antioxidant production appears involved with production of vitiligo lesions.
- Possibly hereditary in Belgian Tervurens, Rottweilers, Old English Sheepdogs; only been described in siamese cats
- Symmetric macular leukoderma and leukotrichia, especially of the nose, lips, buccal mucosa and facial skin.
- Footpads, claws and hair coat may be affected; lesions are not typically inflammatory; no alteration in nasal markings nor do crusts/erosions occur unless secondary solar dermatitis occurs
What is aguirre syndrome?
- Described in siamese cats
- Unilateral periocular depigmentation
- Condition associated with Horner’s syndrome or corneal necrosis with uveitis and upper
Dudley nose
Used to describe dogs that have no nasal pigment and generally present from birth.
- Flesh coloring
- May represent a focal vitiligo
Seasonal nasal hypopigmentation
- Seen in Siberian huskies, golden retrievers, Labrador retrievers, Bernese mountain dogs
- referred to as “snow nose” or “winter nose”
- Decrease in nasal pigmentation typically during winter months.
- Pigment is darks in summer months, although some cases may not have a cyclic change.
- Not the same as nasal depigmentation, and has also been referred to as Dudley nose.
Tyrosinase deficiency
- Extremely rare; reported in Chow chows
- Puppies exhibit a dramatic color shnage
- Their bluish-black tongue turns pink and portions of the hair shaft turn white; buccal mucosa may depigment
- Change in color is a result of a deficiency of tyrosinase
Tyrosinase deficiency
- Extremely rare; reported in Chow chows
- Puppies exhibit a dramatic color shnage
- Their bluish-black tongue turns pink and portions of the hair shaft turn white; buccal mucosa may depigment
- Change in color is a result of a deficiency of tyrosinase
Ketoconazole and procainamide may cause what?
Diffuse lightening of their hair coats
What endocrinopathies can cause lightening of the hair coat?
- dark hair can turn red
- Hypothyroidism, hypercortisolemia and in cases of hyperestrogenism or hyperprogesteronism
What can cause claws to turn red-brown?
- Licking and salivary staining
- Malassezia dermatitis
- Bacterial paronychia
What family of regulatory proteins influence pattern formation at many levels and have roles in the development of certain skin diseases?
Homebox genes
What is diascopy?
Pushing either tape or a glass slide over an erythematous lesions. If the lesion blanches on pressure, the erythema is due to vascular engorgement; of it does not, there is hemorrhage in the skin.
What is a Nikolsky sign?
Elicited by applying pressure on a vesicle of at the edge of an ulcer. It is possible when the outer layer of the skin is easily rubbed off or pushed away. It indicated poor cellular cohesion as found in pemphigus complex, toxic epidermal necrolysis and erythema multiforme major. +=
List 7 primary skin lesions
1) Macule or patch
2) Papule or plaque
3) Pustule
4) Vesicle for Bulla
5) Wheal
6) Nodule
7) Cyst
List 7 secondary skin lesions
1) Epidermal collarette
2) Scar
3) Excoriation
4) Erosion or ulcer
5) Fissure
6) Lichenification
7) Callus
List 6 skin lesions that could be either primary or secondary, depending on the inciting disease
1) Alopecia
2) Scale
3) Crust
4) Follicular casts
5) Comedo
6) Pigmentary abnormalities 02
What is the pH of dog skin?
Roughly neutral 7.0-7.4
Human skin is generally below a pH of 5.0
