Dermatology Flashcards
Know the structure and functions of the skin
- Decoration/Beauty
- Barrier
• Physical (keratinocytes)
• Light (Melanocytes)
• Immunologic (Langerhans cells) - Vitamin D synthesis (keratinocytes)
- Water Homeostasis (keratinocytes, eccrine glands)
- Thermoregulation (eccrine glands, blood vessels)
- Insulation/Calorie Reservoir (Subcutaneous fat)
- Touch/Sensation (nerves)
- Grasp (Nails)
- Lubrication of skin (sebaceous glands)
Be familiar with the functions of the different layers of the epidermis and cells in this region.
stratum basalis (germinativum) = Basal cell Layer
stem cells of epidermis, source of new keratinocytes/proliferation
attach via hemidesmosomes to the dermis
stratum spinosum
kerattinocytes adhere to each other via desmosomes to form barrier
stratum granulosum
cells of this layer contain Keratohyalin granules with Profilaggrin (filaggrin precursor). Filaggrin cross-links keratin tonofilaments and is important in the barrier function of the skin.
stratum lucidum
cells of this layer no longer have nuclei or organelles
stratum corneum
outermost layer, tighlty packed and filled with keratin
Understand the proteins involved in cell attachments.
- Hemidesmosomes: attach basal cells are firmly to the basal lamina of the dermal epidermal junction
- Desmosomes: attach keratinocytes to each other
- Tonofilaments: protein structures (keratin filaments) that insert into the dense plaques of desmosomes on the cytoplasmic side of the plasma membrane
Recognize regional variation of skin with regard to skin thickness and adnexal structures.
Epidermis is primary a protective barrier of keratinocytes.
The dermis contains blood capillaries and more adnexal structures (glands, encapsulated touch receptors). The dermis is thicker than the epidermis
Be familiar with Fitzpatrick Skin Types
Understand the differences in melanin in dark and light skin
V. SKIN COLOR VARIATION
Not due to the number of melanocytes in the skin
• Due to the type of melanin produced
– Eumelanin: black to brown pigment
– Pheomelanin: yellow to red-brown pigment
• Due to the distribution melanosomes
– Light Skin: melanosomes distributed in clusters above the nucleus
– Dark Skin: melanosomes distributed individually throughout the cytoplasm
How to perform a skin exam
Patient needs to be in gown, under good illumination.
Be systematic in inspection.
When describing findings, describe the morphologic appearance of individual lesions, their distribution, their arrangements, and how many are present.
To appreciate the biological role and importance of the epidermis
Outermost layer of the skin
Acts as barrier against infection, also retains body water/moisture
To know the types of cells that normally inhabit the epidermis
Epidermis:
keratinocytes - form fibrous barrier layer
melanocytes - contain melanin to protect DNA from UV damage
Langerhans cells - participate in immune reactions, APCs
To understand the structure and function of the basement membrane zone, the cellular epidermis, and the stratum corneum.
cornified layer (stratum corneum)
Composed of 10 to 30 layers of polyhedral, anucleated corneocytes (differentiated keratinocytes). water-retaining keratin proteins, attached together through corneodesmosomes and surrounded in the extracellular space by stacked layers of lipids.[10] Most of the barrier functions of the epidermis localize to this layer
Middle layers connect the keratinocytes through desmosomes and as they progress towards the surface they lose their nuclei. Langerhan cells in this middle layer for immune purposes.
basal/germinal layer (stratum basale/germinativum).
Composed mainly of proliferating and non-proliferating keratinocytes, attached to the basement membrane by hemidesmosomes (bp180 proteins). Melanocytes are present, connected to numerous keratinocytes in this and other strata through dendrites. Merkel cells are also found in the stratum basale with large numbers in touch-sensitive sites such as the fingertips and lips. They are closely associated with cutaneous nerves and seem to be involved in light touch sensation.[10]
List the layers of the epidermis and associated structural elements that make up the layers (i.e. keratin, desmosomes, hemidesmosomes).
stratum basalis (germinativum) = Basal cell Layer
• Consists of a single layer of columnar or cuboidal cells (keratinocytes)
• Basal keratinocytes are the stem cells of the epidermis (the source of new keratinocytes and thus a site of intense proliferation)
• Cell attachments:
- Hemidesmosomes: attach basal cells are firmly to the basal lamina of the dermal epidermal junction
- Desmosomes: attach keratinocytes to each other
- Tonofilaments: protein structures (keratin filaments) that insert into the dense plaques of desmosomes on the cytoplasmic side of the plasma membrane
stratum spinosum
• Has a “prickly” or spiny appearance due to desmosome attachments between cells
• intercellular adhesion depends upon the tonofilament-desmosome interaction in the distribution of stress
• synthesis of involucrin and membrane coating granules begins in this layer (see below)
stratum granulosum
• the cells of this layer contain different types of granules
• Keratohyalin granules contain Profilaggrin (filaggrin precursor). Filaggrin cross-links keratin tonofilaments and is important in the barrier function of the skin. Filaggrin is mutated in dry skin conditions including ichthyosis and atopic dermatitis.
stratum lucidum
• under the light microscope, a thin, light staining band seen only in thick skin
• cells of this layer no longer have nuclei or organelles
stratum corneum
• the outermost layers of epidermis
• keratinocytes have lost their nuclei and organelles and the entire cell is filled with keratin
• desmosomes still connect tightly packed adjacent cells
Understand the concept of stem cells, and the location and functions of the stem cells for the epidermis.
Stem cells located in the basal layer - stratum basalis
They produce the keratinocytes which mature and form the layers of the epidermis as they migrate toward the surface
Describe the structural characteristics of the differentiated cells in various layers of the epidermis.
stratum basalis (germinativum) = Basal cell Layer
• Consists of a single layer of columnar or cuboidal cells (keratinocytes)
• Cell attachments:
- Hemidesmosomes: attach basal cells are firmly to the basal lamina of the dermal epidermal junction
- Desmosomes: attach keratinocytes to each other
- Tonofilaments: protein structures (keratin filaments) that insert into the dense plaques of desmosomes on the cytoplasmic side of the plasma membrane
stratum spinosum
• Has a “prickly” or spiny appearance due to desmosome attachments between cells
• intercellular adhesion depends upon the tonofilament-desmosome interaction in the distribution of stress
• synthesis of involucrin and membrane coating granules begins in this layer (see below)
stratum granulosum
• the cells of this layer contain different types of granules
• Keratohyalin granules contain Profilaggrin (filaggrin precursor). Filaggrin cross-links keratin tonofilaments and is important in the barrier function of the skin. Filaggrin is mutated in dry skin conditions including ichthyosis and atopic dermatitis
stratum lucidum
• under the light microscope, a thin, light staining band seen only in thick skin
• cells of this layer no longer have nuclei or organelles
stratum corneum
• the outermost layers of epidermis
• keratinocytes have lost their nuclei and organelles and the entire cell is filled with keratin
• desmosomes still connect tightly packed adjacent cells
keratin
the major intracellular fibrous protein of the skin
desmosomes
cell-to-cell adhesion junctions, provide some of the tensile strength in squamous epithelium. Contains interlinkage proteins called desmogleins
hemidesmosomes
epidermal-to-dermal junctions, anchor the epidermis down
Identify the structural components of the dermis
Dermis contains all the blood vessels, nerves, glandular structures, etc– it keeps the epidermis alive, since the epidermis has none of these structures (except the very ends of free nerve endings). It is much thicker than the epidermis. It lies under the epidermis and above the subcutaneous tissue.
Contains hair follicles, sweat glands, vessels, nerves.
Divided into a papillary layer and a reticular layer.
The papillary layer interlocks with the epidermal base to provide shear strength and increase area available for diffusion.
The reticular layer contains everything else.
Components:
Collagen: provides most of the tensile strength in the skin. Note that the tensile strength doesn’t, mainly, come from the epidermis.
Collagen is secreted as procollagen by fibroblasts and assembled into collagen extracellularly– requires vitamin C as cofactor (which is why vitamin C deficiency causes a skin disease called scurvy).
Scurvy: easy bruising, abnormal hair structure, bleeding gums, delayed wound healing. Easy bleeding due to lack of collagen sheath around blood vessel.
Collagen stains eosinophilic.
Ground substance: between collagen, allows for diffusion in dermis.
Elastic fibers: allow resiliency (elasticity).
Much thinner than collagen fibers.
Can’t usually see these without special staining.
All of these are made by fibroblasts.
Distinguish between the types of collagen relevant to the skin
Collagen I: 85% of adult dermis; also a major component of bone.
Collagen III: large part of the fetal dermis.
Evidently, this is why fetal skin doesn’t scar like adult skin.
Collagen IV: found in basement membrane zone. Prominent around some vessels in the dermis.
Collagen VII: anchoring fibrils between dermis and epidermis.
Understand the function of elastic fibers in the skin
elastic fibers provide the skin with resiliency. Roughly put, resiliency is the ability of the skin to be distorted but then return to its original shape. Elastic fibers are much smaller than collagen fibers
Be familiar with the ground substance components of the dermis
Ground substance is a gelatinous material intercalated between and amongst the collagen bundles, elastic fibers, and appendageal structures of the dermis. It consists principally of two glycosaminoglycans: hyaluronic acid and dermatan sulphate. Remember that glycosaminoglycans are complex molecules made up of proteins and sugars, and are capable of absorbing >10,000x their weight in water.
It may be helpful to conceptualize this ground substance as “pie filling” made of long chains of sugar molecules. With the help of other compounds, called fibronectins (“glue”) this gel-like mass functions like a sponge. Crudely put, under pressure it can expel bound water and then take it up again. This process helps to facilitate nourishment of the overlying epidermis by easily allowing a water-based environment for diffusion.
Identify disorders associated with defects in collagen and elastin
Ehlers-Danlos Syndrome: A defect disease of collagen, not elastin, despite its seemingly elastic manifestations. This would make a really obvious test question.
Hyperextensible skin and joints.
“Molluscoid psuedotumors” (soft, spongy tumors, made of fat and collagen) in easily damaged locations.
Often don’t have a lingual frenula (membrane attachment of inferior surface of tongue to base of mouth).
Solar elastosis: acquired disorder of elastic fibers.
The elastic fibers are damaged due to UV exposure. This turns the elastin fibers basophilic (blue-staining), a good indication that you’re looking at the dermis of someone who’s either older or has had a lot of UV exposure.
Psuedoxanthoma elastica (PXE): genetic elastin disease; elastin becomes calcified and brittle.
Can lead to arterial rupture in the retina, can lead to blindness.
Skin also has a “plucked chicken” appearance
Know the vascular supply and innervation of the skin as well as associated disorders.
As mentioned, vascular supply and innervation are located in the dermis only, not the epidermis. Blood vessels go to the very top of the dermis, at the epidermal interface.
As should not be surprising by this point, dermal vasculature is significant for wound healing, homeostatic control, and modulation of inflammatory responses.
Dilated, torturous dermal capillaries are noted in diseases with increased epidermal turnover:
Psoriasis
Verruca (warts)
Note removal of scales in psoriasis causes pinpoint bleeding– this still doesn’t mean there are blood vessels in the epidermis, just that you’ve ripped open the capillaries right under the epidermis.
Can get vasculitis in the dermis from immune complex deposition in the dermal vasculature (standard type III immunopathology, here called “Gell and Coombs” reaction pattern). Tends to manifest, on this scale, as palpable purpura (as per “Rheumatology Review and Vasculitis” from B+L notes) and nonblanching petechiae.
Identify the major adnexal structures of the skin
Hair follicles:
“Terminal hair” (dark thick, coarse)
“Vellus hair” (fine, thin, apigmented)
Three regions of hair:
Top third = infundibulum;
Middle third = isthmus;
Bottom third = matrical area.
Sebaceous glands: next to hair follicles; lubricate the hair and prevent splitting.
Eccrine glands = sweat glands (watery, odorless). Used primarily for thermoregulation.
Numerous on forehead, palms/soles, axilla, cutaneous lips, etc.
This seems important (as emphasized twice by Dr. High): These are stimulated by acetylcholine, but are sympathetic glands. Note that acetylcholine usually stimulates the parasympathetic system.
Apocrine glands = secrete a different kind of sweat (give off body odor when acted upon by bacteria).
Called apocrine due to their method of secretion: membrane ‘blebs’ off in apical direction.
Apoeccrine glands = hybrid, produce both eccrine sweat (watery, odorless) and apocrine sweat (odiferous); located mainly in the axilla and can produce an enormous volume of sweat.
“Hyperhidrosis”: excess production of sweat. Note can use botox (botulinum toxin) to prevent acetylcholine release to treat this condition.
Macule
DEFINITION
Circumscribed change in skin color that is flush with the surrounding skin. Lesion is <1.0 cm in diameter
EXAMPLE
Solar lentigo
Traumatic purpura
Patch
Definition
Circumscribed change in skin color that is flush with the surrounding skin. Lesion is ≥1.0 cm in diameter
Example
Café au lait spot
Vitiligo
Papule
A solid or cystic elevation <1.0 cm in diameter
Example
Acne
Eruptive xanthoma
Nodule
A solid or cystic elevation >1.0 cm but <2.0 cm in diameter
Example
Dermato-fibroma
Tumor
A solid cystic elevation >2.0 cm in diameter
Example
Follicular cyst
Plaque
An elevated lesion that is >1.0 cm in diameter
Example
Psoriasis
Scale
Desiccated, thin plates of cornified epidermal cells that form flakes on the skin surface
Example
Ichathyosis
Wheal
Circumscribed, flat-topped, firm elevation of skin with a well-demarcated and palpable margin
Example
Uritacaria
Vesicle
Circumscribed, elevated lesion containing clear serous or hemorrhagic fluid that is <1 cm in diameter
Example
Contact dermatitis
Herpes simplex
Bulla
Circumscribed, elevated lesion containing clear serous or hemorrhagic fluid that is >2 cm in diameter
Example
Bullos pemphigoid
Pustule
A vesicle containing purulent exudate
Example
Folliculitis
Atrophy
A depression from the surface of the skin with underlying loss of epidermal or dermal substance
Example
Lichen sclerosis et atrophicus
Erosion
A depression from the surface of the skin with a loss of all or part of the epidermis –Burn
Can be a secondary lesion –ruptured bulla
Ulceration
A depression from the surface of the skin with a loss of the entire epidermis and at least some of the dermis
Example
Ecthyma
Lichenification
Dry, leathery thickening of the skin with exaggerated skin markings
Example
Chronic eczema
Scar
An elevated or depressed area of fibrosis of the dermis or subcutaneous tissue resulting from an antecedent destructive process
Example
healing wound
Fissure
A deep linear split in the skin extending through the epidermis
Example
traumatized eczema
Crust
Dried exudates of serum, blood, sebum, or purulent material on the surface of the skin
Example
Acute and/or secondarily infected eczema
Bullous Pemphigoid
Autoimmune, blistering disease (IgG vs. BP180 proteins in hemidesmosomes in the basement membrane zone).
Activates complement, get subepidermal blister.
Pemphigus vulgaris
Autoimmune, blistering disease (IgG vs. desmoglein 3 proteins in intercellular desmosome junctions).
Results in intraepidermal blister due to loss of keratinocyte cohesion with each other.
More serious than BP- the patient can lose a large amount of epidermis.
Epidermolysis bullosa simplex
[EBs in general: blistering diseases due to minor trauma to the skin. “Epidermolysis”: lysis of the epidermis. “Bullosa”: blistering.]
EB simplex is a genetically-mediated disease due to mutations within one of the keratin proteins (K5 or K14) of basal cell keratinocytes. Fragile skin, recurrent blister formation.
Blisters formed ‘through’ the basal cell layer (Wiki says they’re formed ‘in keratinocytes,’ which is about as unhelpful).
How to compare Cellulitis, Errysipelas, and Dermatitis
They are diagnosed based on clinical appearance which differs due to the area of inflammation.
Dermatitis is typically more superficial in the epidermis.
Erysipelas are sharply demarcated plaques primarily in the dermis
Cellulitis can be patches or plaques and involve dermis and subcutaneous tissue.
Recognize common types of skin cancer including:
BCC
Basal Cell Carcinoma
Incidence: 2.8 million per yr in US, most common malignancy in US
Clinical: Pearly shiny papules/nodules that can have talectasias, often sore and difficult to heal if bleed, very superficial on epidermis as they arise from basal cells
Genetics: BCC caused by loss of fxn of patch gene which normally blocks smoothened, a transmembrane protein
Causes: most common cause is UV radiation (esp. faired skinned people in sunny areas), also occurs after ionizing radiation, arsenic or polycyclic hydrocarbon exposure
Malignancy? rare
Tx: Vismodegib can help shrink tumors, they can also be surgically removed (Moh’s)
Subtypes:
- Superficial
- Nodular (75%)
- Micronodular (69% of the 75%)
- Pigmented
- Infiltrative
- Sclerosing/Morpheaform
Recognize common types of skin cancer including :
SCC
Squamos Cell Carcinoma
Clinical: tend to be hyper-keratotic
Epidemiology: 2nd most common skin malignancy, occur more commonly in immune suppressed patients (esp. organ transplant pts.)
Risk Factors:
- UV damage
- thermal injury (burns and burn scars)
- radiation
- HPV
- Chronic Injury
Subtypes:
- SCC in situ (Bowen’s Disease)
- Keratoacanthoma (volcano w/ crater)
- Invasive SCC
Malignancy? Metastasis is rare but in SCC of the lip ranges 10-30%
Know the difference in Breslow depth and Clark’s level used in staging of melanoma as important prognostic factors of melanoma
Discuss the role of ultraviolet radiation effects on the skin.
-Damage to DNA, RNA, lipids, proteins
- UVB causes: Thymine dimer, pyrimidine-6-4 pyrimidone
- UVA causes: Hydroxyguanosine
- mostly repaired by Nuclease Excision Repair
-Pro-inflammatory effects
- cytokines: IL-1, TNFalpha
- Mast cells release histamine
-Immunosuppressive effects
- Langerhan cells move out of the skin induced by TNFalpha, PGE2,GM-CSF
- Dangerous b/c can allow non-melanoma cancers opportunity to develop
-Induction of innate defenses
- WBC are recruited to the skin
- Peroxidases, catalases, superoxide dysmutase all protect against reactive oxygen species
- Induction of apoptosis
- keratinocytes are more susceptible to apoptosis
- Vitamin D synthesis
- the sun induces the non-enzymatic sythesis and then the active forms are made in the liver
Know which types of ultraviolet radiation cause various conditions (i.e. sunburn, photoaging, corneal burns etc).
UVC radiation causes corneal burns.
UVB radiation causes sunburn.
UVA radiation causes photoaging.
