Dermis Flashcards by Treasa Clifford

Rate limiting step for collagen synthesis

Prolyl hydroxylase

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How does hyperbaric oxygen affect the dermis?

Promotes collagen formation (prolyl hydroxylase)

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How does vitamin C affect the dermis?

Promotes collagen formation (reducing agent for prolyl hydroxylase)

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What element is needed for lysyl hydroxylase oxidation?

Copper

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Mode of secretion of epitrichial sweat glands

MEROCRINE (not apocrine)
-Secretion via exocytosis

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Which species do NOT have epitrichial sweat glands?

Rodents, ferrets

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Which part of hair follicle has the entrance for the epitrichial sweat gland?

Infundibulum

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Where are epitrichial sweat glands largest on the body?

Glaborous areas

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What sweat gland change occurs in anhidrosis?

Downregulation of aquaporin 5 (water channel for rapid fluid movement)

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What medication can downregulate aquaporin 5?

Macrolides (horses treated for Rhodococcus)

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What cell surrounds equine sweat glands? #Unique

Myoepithelial cells (all animals), but in a loose basket-weave pattern with a rich surrounding blood supply!!

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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

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How are epitrichial sweat glands innervated?

NOT directly

Neural control via adrenergic agonists

Humoral control via adrenergic agonists

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What part of the dermis contributes to its tensile strength?

Collagen, elastin

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What part of the dermis contributes to its compressive resistance?

Proteoglycans, hyaluronan

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Which immune cells are residents in the dermis?

1) Macrophages
2) Mast cells
3) Melanocytes
4) Dendritic cells

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What is unique about the scrotal dermis?

Numerous smooth muscle bundles

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Does the superficial dermis have more tightly or loosely woven collagen/elastin compared to the deep dermis?

Looser

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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

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Where on the body is the Ross-Spiegel/ Horse Mirror layer?

Rump, back, upper half of chest

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Major cell type in the dermis

Fibroblasts

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Embryonic origin of fibroblasts

Mesenchymal

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Cell that makes glycosaminoglycans, glycoproteins, procollagen, elastin

Fibroblasts

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ECM products of fibroblasts

1) Glycosaminoglycans
2) Glycoproteins
3) Procollagen
4) Elastin

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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