Dermatology

What is the largest organ in the body?

Skin

What are the major divisions of the skin?

Epidermis and dermis

What is the function of the skin?

Defense, heat exchange, water barrier, sense environment

Thick skin is made of how many layers?

5

Skin turns over in how many days?

40-50

Thin skin contains ______,__ while thick skin ______

hair follicles; does not

What are the layers of the skin? (From bottom to top)

Stratum basale (germinativium)

Stratum Spinosum

Stratum Granulosum

Status Lucidum

Stratum Corneum

What is the layer only in thick skin?

Stratum Lucidium

Stratum basale

Layer of stem cells with high degree of mitotic activity

Where are keratinocytes born?

Stratum basale

Stratum Spinosum

Several layers of cells, highly attached to neighbors via desmosomes; cell morphology begins to undergo change

Where is keratin produced?

Stratum Spinosum

Stratum Granulosum

Most superficial layer of non-keratinized cells; cells go through apoptosis and then aggregate and form keratin filaments

How many layers thick is the stratum granulosum?

1-3 layers thick

Stratum Lucidum

Only in thick skin; contains flattened cells with advanced keratinization with no cellular organelles visible

How do stratum lucidium stain?

Pink- highly eosionphilic

Stratum Corneum

Thick keratin filled plates, no cellular organelles

What is the stratum corner coated with?

Lipids

Skin type

Stratified keratinized squamous epithelium

Fingerlike projections projecting up into the under surface of epidermis?

Dermal papillae

What epidermal layer projects into dermis?

Epidermal ridges

When there are higher forces in an area, what happens to the epidermis/dermis border?

More interdigitation

What are the predominant cell of the integumentary system?

Keratinocytes

What influences keratinocyte differentiation?

Calcium

Where is calcium the concentration the lowest and highest?

Basale and granulosum

What is exfoliation controlled by?

Decreasing pH of the epidermis

What is the pH of the epidermis regulated by?

LETKI and KLKs

What degrades desmosomes in the epidermis?

KLKs 4,5,7

What inhibits KLKs?

LETKIs

When do LETKIs release KLKs?

Low pH = exfoliates skin

Where is the water barrier located?

Between granulosum and corenum

What is the function of the water barrier?

Prevents dehydration of the organism in a dry environment

what do keratinocytes produce? Where?

Lamellar bodies; in the Golgi

What are lamellar bodies composed of?

Phospholipids, glycophingolipids, and ceramides

What is in the inner surface of keratinocyte plasma cell envelope?

Layer of insoluble proteins involucrin, elafin

What does the water barrier help protect against?

Desiccation (lipid) and microorganism invasion (protein)

What layer do keratinocytes aid in production of Vitamin D?

Stratum basale and spinosum

What is the pathway of Vitamin D?

7-Dehydrocholesterol in keratinocytes→cholecalciferol (vitamin D3) transported to liver for hydroxylation into Calcifediol → Calcitriol in kidneys (active vitamin D2)

UV radiation causes dimerize via covalent bonding forming either

Cyclobutane pyrimidine dimer or 6-4 photoproduct

What enzyme repairs DNA?

Photolyase- destroys TT dimers via nucleotide excision

what causes sunburn?

UVA and UVB rays

What is the cell response launched when the epidermis is exposed to radiation?

Induced apoptosis of irreparably damaged cells

What is released during induced apoptosis in sunburn?

Prostaglandins, reactive oxygen species, and bradykinins

What physical reaction occurs from sunburn? What causes it?

Vasodilation and edema; degranulation of mast cells

UBV causes increase in ______

Chemokine CXCL5

What does Chemokine CXCL5 activate?

Nociceptors (pain)

Prolonged sun exposure results in the process known as

photoaging

UV radiation causes reduction in

Type I and Type III collagen production

UV exposure causes an increase in

abnormally thick and non function elastic fibers and MMP1 and 9

Increased expression of MMP1 and 9 is done by

fibroblasts and neutrophils

What are MMP1 and 9 ket in check by?

TIMPS, but TIMPS decrease in UV exposed skin

What is the autosomal recessive condition of mutation of several genes that encode for nuclear excision repair enzymes?

Xeroderma Pigmentosum

What is the most common xeroderma pigmentosum?

Type 1 XP

What is the protein that is dysfunctional in Type 1 XP?

Protein A which ensures appropriate excision

How does XP present?

Sunburn, freckles, large number of skin cancers, blistering, dry scaly skin, corneal ulceration, and eye sensitivity

What percentage of XP patients live beyond 20?

Less than 40%

Organic compound sunscreens

Allows for the absorption of UV light and converts and releases lower energy rays

What is an example of organic sunscreen?

Oxybenzone and Avobenzone

Inorganic Compound Sunscreens

Act as a physical sun block, scattering or reflecting UV light

What are examples of inorganic sunscreens?

Zinc oxide and titanium dioxide

What type of disease is psoriasis?

Complex immune mediated disease

How does psoriasis work?

Antigenic stimuli activates dendritic and innate immune cells of the skin causing pro inflammatory IFNa to activate migration of immune cells to the skin

What do macrophages and dendritic cells produce in psoriasis?

Cytokine IL-23 which stimulate attraction, differentiation, and activate of effector T cells

What do the recruited T cells produce in psorasis?

IL-17A which syngergizes with other cytokines to stimulate keratinocyte proliferation

Cytokines produced by immune cells and keratinocytes perpetuate what?

The inflammatory process via participation in positive feedback loops

what are the types of psoriasis?

Plaque, nail, guttate, inverse, pustular, erythrodermic

What vitamin is retinol?

Vitamin A1

Retinol is _____ soluble

fat

What are needed to transport retinoids?

Retinal binding protein (RBP) and cytosolic retinol binding proteins (CRBP)

What is retinol active form and how is is produced?

Retinoic acid; two step oxidation of retinol

What do RBP and CRBP activate?

Retinoid nuclear receptors

What do retinoid nuclear receptors act as?

Steroid thyroid hormone receptor

How do retinoids work?

Regulate cell apoptosis, differentiation, and proliferation, restrain trans-epidermal water loss, protect collagen against degradation, and inhibit metalloproteinases activity

What type of disorder is pemphigus?

Inflammatory autoimmune blistering disorder

What are in the pemphigus family?

Vulgaris (80%), vegetans, foliacets, erythematosus, and paraneoplastic

What causes pemphigus?

IgG autoantibodies produced against desmogleins which causes a tear at the stratum spinosum

What causes pemphigoid?

IgG autoantibodies produced against BPAG2 which causes a separation between the dermis and epidermis

What are melanocytes?

Dendritic cells found in the stratum basale which produces the pigment melanin

Where is melanin contained in?

Melanosome

What is the function of melanin?

Protection from UV radiation by scattering the UV radiation and absorbing it, preventing deep penetration of UV radiation into the epidermis

What does exposure to UVB cause in melanocytes?

Melanogenesis = tan

What amino acid do melanocytes use to produce melanin?

Tyrosine

What enzyme is needed to convert tyrosine to melanin?

Tyrosinase

What type of cells are melanocytes classified as?

Immune cells

What are the three types of melanin?

Eumelanin (black), eumelanin (brown), pheomelanin (yellow/red)

What is melanoma the result from?

DNA damage caused by UV; typically thymine dimers and ROS damage

If DNA is unreported, DNA replication can lead to what mutations?

Cytosine to thymine mutations

What is the most frequent gene mutation that occurs in melanoma?

BRAF (cell growth)

What is the order of melanoma growth phase?

Radial then vertical

What are the ABCs of melanoma?

Asymmetry, Border, Color, Diameter

what is the congenital absence of melanin?

Oculocutaneous albinism

What mutation causes albinism?

Mutation in TRP-1 gene that results in deregulation of tyrosinase

What is the condition with a loss of skin pigmentation as a result of the immune system?

vitiligo

What other diseases is vitiligo associated with?

Autoimmune diseases

What is the condition in which patches of dark pigmentation, typically on the face occur?

Melasma

What is melanoma associated with?

Birth control, pregnancy, and thyroid disease

What is the cell that is responsible for cutaneous sensation (mechanoreceptor) in the stratum basale?

Merkel’s cell

What is the immune cell of the integumentary system?

Langerhan’s cells

Where do langerhan’s cells originate?

Bone marrow

What are the causes of Merkel cell carcinoma?

Merkel cells polyomavirus (MCV; 80%) and sun exposure (20%)