Dermis Flashcards
Rate limiting step for collagen synthesis
Prolyl hydroxylase
How does hyperbaric oxygen affect the dermis?
Promotes collagen formation (prolyl hydroxylase)
How does vitamin C affect the dermis?
Promotes collagen formation (reducing agent for prolyl hydroxylase)
What element is needed for lysyl hydroxylase oxidation?
Copper
Mode of secretion of epitrichial sweat glands
MEROCRINE (not apocrine)
-Secretion via exocytosis
Which species do NOT have epitrichial sweat glands?
Rodents, ferrets
Which part of hair follicle has the entrance for the epitrichial sweat gland?
Infundibulum
Where are epitrichial sweat glands largest on the body?
Glaborous areas
What sweat gland change occurs in anhidrosis?
Downregulation of aquaporin 5 (water channel for rapid fluid movement)
What medication can downregulate aquaporin 5?
Macrolides (horses treated for Rhodococcus)
What cell surrounds equine sweat glands? #Unique
Myoepithelial cells (all animals), but in a loose basket-weave pattern with a rich surrounding blood supply!!
Are epitrichial sweat glands directly innervated in horses?
No. Neural control via adrenergic agonists is MAIN control.
ALSO: humoral control via adrenergic agonists from adrenal medulla during exercise
How are epitrichial sweat glands innervated?
NOT directly
Neural control via adrenergic agonists
Humoral control via adrenergic agonists
What part of the dermis contributes to its tensile strength?
Collagen, elastin
What part of the dermis contributes to its compressive resistance?
Proteoglycans, hyaluronan
Which immune cells are residents in the dermis?
1) Macrophages
2) Mast cells
3) Melanocytes
4) Dendritic cells
What is unique about the scrotal dermis?
Numerous smooth muscle bundles
Does the superficial dermis have more tightly or loosely woven collagen/elastin compared to the deep dermis?
Looser
What is the Ross-Spiegel layer?
“Horse mirror” layer in equine dermis
-collagen fibers in a “tree-like” arrangement that appears shiny on gross exam
Where on the body is the Ross-Spiegel/ Horse Mirror layer?
Rump, back, upper half of chest
Major cell type in the dermis
Fibroblasts
Embryonic origin of fibroblasts
Mesenchymal
Cell that makes glycosaminoglycans, glycoproteins, procollagen, elastin
Fibroblasts
ECM products of fibroblasts
1) Glycosaminoglycans
2) Glycoproteins
3) Procollagen
4) Elastin
Functions of fibroblasts (4)
1) Produce ECM proteins
2) Mitosis after tissue damage –> wound healing
3) Degrade matrix proteins
4) Synthesize cell mediators for cell growth, differentiation, migration, inflammation (TGF-β, MMP-1)
Collagen types in adult dermis
Types I (majority!), III, V
Collagen types in fetal dermis
Type III
First collagen type made during wound healing
Type III
Collagen types around blood vessels
Types III, V
Collagen that stabilizes/organizes larger fibrils of ECM
Type VI
FACIT collagens (fibril-associated collagens with interrupted triple helices); organize/stabilize fibril-forming collagens (I, III, V)
Types XII, XIV
Collagen types in the BMZ
Types IV, VII, XVII
Which amino acids are required for cross-linking between collagen α-chains; stabilize triple helix
Proline, hydroxyproline
(Also glycine)
Which amino acids are required for cross-linking between collagen fibrils?
Lysine, hydoxylysine
Stimulate or Inhibit collagen synthesis:
Vitamin C!!
Stimulate
Stimulate or Inhibit collagen synthesis: TGF-β
Stimulate
Stimulate or Inhibit collagen synthesis: IL-1
Stimulate
Stimulate or Inhibit collagen synthesis: IL-4
Stimulate
Stimulate or Inhibit collagen synthesis: IGF-1
Stimulate
Stimulate or Inhibit collagen synthesis: IGF-2
Stimulate
Stimulate or Inhibit collagen synthesis: superoxide generating system
Stimulate
Stimulate or Inhibit collagen synthesis: bleomycin
Stimulate
Stimulate or Inhibit collagen synthesis: PDGF
Stimulate
Stimulate or Inhibit collagen synthesis: glucocorticoids
Inhibit
Stimulate or Inhibit collagen synthesis: retinoids
Inhibit
(*Although quiescent cells can be stimulated to activate collagen gene expression)
Stimulate or Inhibit collagen synthesis: vitamin D3
Inhibit
Stimulate or Inhibit collagen synthesis: Parathormone
Inhibit
Stimulate or Inhibit collagen synthesis: Prostaglandin E2
Inhibit
Stimulate or Inhibit collagen synthesis: IFN-γ
Inhibit
Stimulate or Inhibit collagen synthesis: D-penicillamine
Inhibit
Stimulate or Inhibit collagen synthesis: minoxidil
Inhibit
Prolyl and lysyl hydroxylase enzyme requirements to function (4)
1) Oxygen
2) Ferrous iron
3) α-ketoglutarate
4) Vitamin C– reducing agent
Clinical outcomes of scurvy
Poor wound healing
Decreased tensile strength of dermis
Mechanism by which hyperbaric oxygen can help wound healing
Increase activity of prolyl hydroxylase
Effect of glucocorticoids on wound healing? Why?
DECREASED
Inhibit prolyl hydroxylase
Type of bond between triple helix alpha chains in collagen synthesis
Disulfide bonds
Intracellular pathway for collagen synthesis
Nucleus (transcription) -> rER (translation) -> cytoplasm (triple helix formation) -> Extracellular (protease cleaves procollagen to collagen)
Disease from deficiency of a protease to cleave procollagen’s terminals off
Dermatosparaxis
Enzyme that crosslinks collagen fibrils via covalent bonds
Lysyl oxidase
Requirements of lysyl oxidase
Copper
Cause of lathyrism (spastic paraparesis)
β-aminopropionitrile from legumes inhibits lysyl oxidase (cross links collagen fibrils)
Enzyme to degrade collagen
Matrix metalloproteinase
Requirements for MMP function
Calcium, Zinc
Denatured collagen product
Gelatin
What can you measure to indicate amount of collagen turnover?
Hydoxylysine and hydroxyproline levels in urine
-> these amino acids are specific to collagen
Histopathology stain for collagen
Masson-Trichrome
3 types of elastic fibers in dermis
1) Elastin
2) Elaunin
3) Oxytalan
What surrounds mature elastic fibers?
Microfibrils (fibrillins, fibulins) + type VI collagen
Which fibers anchor the deep dermis to the superficial?
Vertically- arranged oxytalan fibers
(elastin is horizontal)
Which fibers anchor the superficial dermis to the BMZ?
Oxytalan
Fiber with an arcade-like arrangement in the superficial dermis
Elaunin
Small, amorphous
Cross linked to elastin w/microfibrils
Precursor to elastin
Tropoelastin
Where in cells is tropoelastin converted to elastin
Extracellularly
Which enzyme cross links desmosine/isodesmosine to elastin?
Lysyl oxidase
(same as collagen fibril cross link! Needs Copper, Oxygen)
Name the enzymes related to collagen/elastin synthesis/degredation, and their mineral requirements
1) Lysyl oxidase: copper, oxygen
2) Propyl/lysyl Hydroxylases: iron, oxygen, alpha-ketoglutarate, vitamin C
3) MMP: Calcium, zinc
4) Elastase: some need Ca, most are serine proteases
What makes elastin insoluble?
Cross link to desmosine, isodesmosine
Stimulate or Inhibit elastin synthesis: TGF-β a
Stimulate
Stimulate or Inhibit elastin synthesis: IGF-1
Stimulate
Stimulate or Inhibit elastin synthesis: TNF-α
Inhibit
Stimulate or Inhibit elastin synthesis: vitamin D3
Inhibit
Stimulate or Inhibit elastin synthesis: Colchicine
inhibit
Enzyme that degrades elastin
Elastase
Mineral requirement of some elastases
Calcium (but most are serine proteases)
Histopathology stains for elastin fibers (2)
1) Verhoeff van Gieson
2) Acid orcein-Giemsa
Contents of diffuse and filamentous matrix
1) proteoglycans (PG)
2) glycoproteins
3) glucosaminoglycans (GAG)
Contents of ground substance
Proteoglycans
Glucosaminoglycans
Function of ground substance
1) Water storage
2) Wound healing
3) Resists compressive forses
*Allows nutrients, electrolytes, cells to pass
Name a proteoglycans that bind to hyaluronic acid in dermis
Versican
Name a proteoglycan that aggregates on type I collagen
Decorin
Name 4 glucosaminoglycans
-Heparan sulfate
-Chondroitin sulfate
-Keratan sulfate
-Dermatan sulfate
Only glucosaminoglycan WITHOUT a core (proteoglycan)
Hyaluronic acid
Which component of the dermis is high in fetal skin, which allows healing without scarring
Hyaluronic acid
Which glycoprotein is the main component of hyaluronic acid?
Mucin
Name 6 glycoproteins
1) Fibrillin
2) Fibulin
3) FIbronectin
4) Vitronectin
5) Tenascin
6) Mucin
Where are the glycoproteins
Bound to elastin, collagen
*Can modify cell interactions, vascular permeability, development of collagen, wound healing.
Where in the body are mucin levels highest?
Around appendages
Etiology of increased mucin in Shar-Peis
Increased hyaluronan synthase
Histopathology stain for mucin
Alcian blue
Cause of dermatoparaxis
Defective protease, unable to cleave amino-terminal from procollagen
Species with dermatoparaxis
cattle
sheep
doberman pinscher
himalayan cat
Histopathology stain for Ehlers-Danlos
masson trichrome
On histopathology for Ehlers-Danlos: in addition to irregular collagen bundles, what other change is present?
Increased mucin
Other than the skin, what other organs can be affected by Ehlers-Danlos
Eyes
Ligaments
Tendons
Blood vessels
Which breed gets Hereditary equine regional dermal asthenia?
Quarter horses
Gene for Hereditary equine regional dermal asthenia?
Mode of inheritance?
Cyclophilin
B/ peptidylprolyl isomerase B (PPIB)
Autosomal Recessive
–> impaired collagen synthesis and folding
–age of onset 1.5 yr
Which body regions are primarily affected by Hereditary equine regional dermal asthenia?
Dorsum
Lateral thorax
Withers
Croup
Age of onset of Hereditary equine regional dermal asthenia?
1.5 years old
Where should you biopsy a horse with suspected Hereditary equine regional dermal asthenia?
back, croup, neck
Fewer false negatives
Treatment of ehlers-danlos
Reduce trauma
Possibly vitamin C
Disease with nonfunctional lysyl hydroxylase
Warmblood fragile foal syndrome
Mode of inheritance Warmblood fragile foal syndrome
Autosomal recessive
Clinical signs of warmblood fragile foal syndrome
Still born with fragile skin, skin defects, flexible joins, incomplete closure of abdominal wall
Breed with genetic nonfunctional lysyl hydroxylase disease
Warmbloods
Cause of solar elastosis
Degradation of collagen/elastin 2’ UV radiation
How does UV light affect collagen levels
UV light upregulates collagenase by fibroblasts –> Collagen and elastin degeneration
Histopathology stain for solar elastosis
Verhoff van Gieson stain
Species with scleroderma
Humans, horses
Localized scleroderma
Morphea
Other organs affected by generalized scleroderma
Fibrosis of skin, lungs, GI, kidneys, heart
Diseases that cause excess mucin (6)
1) Hypothyroid
2) Acromegaly
3) DLE
4) Dermatomyositis
5) Alopecia mucinosa
6) Idiopathic- shar pei mucinosis
Treatment for shar pei mucinosis
Corticosteroids