derm A 2 Flashcards
pilosebaceous unit
-hair shaft
- Hair follicule
- sebaceous gland
Sebaceous glands
- throughout the epidermis EXCEPT THE PALSM AND SOLES
- face and scalp have hte highest denisty and size variation
- empties into upper hair folecule
- sebum production stimulated by androgens
- secretion via holocrine process
- replicating cells (mitotic) at gland perimeter replace those lost
- sebaceous gland cells have nuclei and clear lipid/sebum around
holocrine process
-> entire cell breaks down to release contents (all of the cell breaks open to release sebum contents –> secretion from constantly dying cells)
pilosebaceous unit - acne
sebocytes & KCs
- hypersecretion & hyperproliferation, respectively, blocks duct and/or hair follicle (keratinocytes lining hair follicle hyperproliferate, plugging follicle and increasing infection)
- accutane (13-cis retinoic acid) decrease KC proliferation and decreases sebum production (slows chance of plugging opening)
pilosebaceous unit - hair growth cycle
ranges from few months to years depending on body site
- hair shaft = packed keratinocytes specialized
- length depends on body site
epidermis KC replication - normal
-cells build physical strata & functional barrier
- physiological requirement to maintain a lifetime replacement of upper layers
- normal turnover
- wound healing
LOOK AT PICTURE SLIDE 14
interfollicular stem cells (between hair follicles)
- normal site of replication in basal layer only (basal layer stem cells replicate)
- responsible for routine replacement of epidermis & minor wounds (filling in the void)
LOOK AT PICTURE SLIDE 14
follicular stem cells (“bulge”) –> hair follicle
- important for healing of 2 degree burns (incredibly important for major wound healing)
- progeny contribute to epidermis and hair
- stem cell “bulge” gives rise to keratinocytes
- fibroblasts in dermal papilla “instruct” bulge daughter KCs to follow hair KC maturation –> instruct incoming KCs to change their gene patterns to make keratins specific to the hair shaft (push tip of hair out of the hair follicle)
- re-epithelialize –> recover what was stripped away from the epidermis surface
LOOK AT SLIDE 14
epidermal KC replication diseases: benign - psoriasis
- ~3% of US population –> genetic component?: first degree relative of patient more likely to develop symptoms
- presentation - varying severity
- symmetric, well-demarcated, plaques often on elbows, knees, scalp, & lower back
- plaques –> over-replication of keratinocytes in large areas
- reddened, inflamed, itch (characteristic of hyperplastic disease)
epidermal KC replication diseases: benign - psoriasis HISTOLOGY
- hyperproliferation (overaccumulation of keratinocytes)
- hyperkeratosis - increased but immature SC layers
- parakeratosis - nuclei retained in SC incomplete maturation (nuclei normally broken down from granular to cornified)
- SG may be reduced
- very poor barrier function; “more” isn’t better –> incompletely matured keratinocytes
- immune cell infiltration
- infection, fluid leakage
- missing stratum granulosum layer and thicker epidermis layer
- still basal separation between the dermis and epidermis
epidermal KC replication diseases: possible precursors to keratinocyte malignancy. 1
actinic keratoses (AK)
- chronic sun exposure
- chiefly on face, ears, & forearms (overexposure to the sun)
- individual or multiple sites, scaly, red
- ~20% develop malignancy over 10-25 years
- does not go away without treatment
epidermal KC replication diseases: possible precursors to keratinocyte malignancy. 2
keratoacanthoma (KA)
- usually solitary nodule often same areas as AK
- rapidly growing; 2.5cm in only 3-8 weeks
- frequently, spontaneously regress
- some later develop malignancy at same site
- THE TOMATO ON THE FACE
epidermal KC replication diseases: AK and KA therapy
- physical: surgery, dermabrasion, laser resurfacing
- drug: topical cyto-toxic drug (short-term) –> target and stop mitosis of hyperplastic cells
epidermal KC replication diseases: skin malignancies - keratinocyte (non-melanoma)
skin cancers
- ~3 million TOTAL cases diagnosed in US per year are unevenly distributed among types
- ~80% BCC - basal cell carcinoma vs. ~20% SCC - squamous cell carcinoma
- ~95% cure rate for both if detected & treated early
- commonly diagnosed but relatively high cure rate
- most occur in pts >60 yo –> “cancer”: a time-dependent accumulation of multiple mutations? (progressive series of mutations can lead to cancerous KC phenotype)
BCC & SCC: shared risk factors
- sun, indoor tanning, fair-skin (UV exposure)
- chemical exposure, ex. arsenic (contaminated drinking water)
- immunosuppression or compromised immune system (AIDS/organ transplant ~20-200x) –> may not remove tumor cells with altered antigens otherwise recognized as NON-self
epidermal KC replication diseases: BCC PRESENTATION AND HISTOLOGY
basal cell carcinoma
- presentation: pearly nodule, central depression, rolled edge
- histology: look like immature or “basal” cells of epidermis, slow growing (rarely metastasize)
epidermal KC replication diseases: BCC etiology and treatment
- etiology: UV exposure induces DNA mutations ex. in p53 tumor suppressor gene (normal p53 arrests cell cycle, allows time for DNA repair)
- treatment therapy: no single method ideal –> surgical excision (may be difficult to remove all of the islands), radiation, retinoids (vitamin A derivative) to suppress cell replication
- retinoic acid (acidic form of vitamin A)
epidermal KC replication diseases: SCC PRESENTATION AND HISTOLOGY
squamous cell carcinoma
- presentation: early stage vs. late stage
- early stage: indurated (hardened), erythematous plaque
- late stage: ulceration/crusting often indicating invasion of underlying tissue
- histology: cells look like squame KCs, irregular masses of proliferating KCs extend into dermis, “keratin pearls” in differentiated tumors
epidermal KC replication diseases: SCC etiology and treatment
- etiology: similar to BCC, UV exposure
- treatment/therapy: surgery, usually followed by radiation or chemotherapy (ex. retinoids to suppress replication of anything the surgery did not remove)
malignant melanoma (ABCDEs) –> skin cancer derived from melanocytes
- incidence: ~100,000 cases yr (~ 7,000) deaths /yr
- etiology/risk factors: fair skin & congenital nevi already present (moles), family history of melanoma, history of chronic sun exposure (UV)
- presentation: greatly variable in size, shape, color, atypical ABCDE (especially >5-6mm)
treatment/therapy:
- excision of lesion and nearby uninvolved skin and evaluation of lymph nodes for possible spread, often followed with interferon (suppress growth)
ABCDE - good
- symmetry, smooth border, light/med/dark brown, no bigger than a pencil eraser, slight dome or flat
ABCDE - bad
- no symmetry, change in pigmentation, raised
- some parts of the malignant melanoma might have no pigment because there were so many mutations that it lost its function to make melanin but is still growing
dermis - organization & cell types
- extracellular matrix (ECM) protein - mostly collagen, some laminin,multiple cell types
- fibroblasts produce collagen & other ECM proteins
- macrophages & mast cells peripheral immune function, some antigen processing (langerhans from blood vessels traveling to/from the epidermis)
- endothelial cells walls of blood vessels
- sensory nerve endings
dermis: 2 histological compartments
- papillary dermis - undulating projections at the interface, more organized collagen, finer capillaries
- reticular dermis - the bulk of the dermis, extra extracellular matrix, thicker collagen fibrils
- overall, similar
dermis: papillary dermis
-Immediately under basal lamina
-fine mesh of collagen fibrils - small vessels & capillary beds supply the dermis AND epidermis and sensory nerve endings
- undulating arrangement - more contact area between epidermis & dermis per unit of surface provides stronger attachment
dermis: reticular dermis
- dense collagen fibrils - larger blood vessels and dilation/constriction promote / restrict heat loss
- nerves, base of hair follicles & sweat glands
1st degree (mild sunburn)
- damage within epidermis
- transient dermal erythema
- heals 4-5 days; no scarring
- redness = expansion of vasculature
- only damage to a few KCs in the epidermis
2nd degree (note depths - varying)
- in dermis
- blister fluid may separate epidermis from dermis
- painful; nerve endings viable
- heals in ~2 weeks
- regrowth: KCs w/in follicles
- always leaves a bit of hair follicle
3rd degree (eschar)
- follicles, glands destroyed dermis may be lost (base of hair follicle lost)
- under lowest part of hair follicle –> lost reservoir of healing cells (bulge)
- injury depth kills nerves; less pain than 2nd degree
- wounds <5cm diameter heal from edge
- wounds > or = ~5cm diameter require grafting (if diameter is too big, KCs cannot replicate and migrate to wider diameter)
skin surface area: rule of nines - adults
9% of each of 11 sites
- all of head & neck
- R & L anterior trunk
- R & L posterior trunk
- R & L arm
- R & L anterior leg
- R & L posterior leg
- 1% - groin
skin surface area: critical burns
burns critical if
- >25% of body has 2nd degree burns
- >10% of body has 3rd degree burns
- area affects amt of fluid loss & increases infection rate
- adverse drug reactions (ADR) –> estimating involved skin area w/ blistering, rash, etc. from medication reaction
skin wound healing - stages
get HIP-R (often overlap) –> next stage usually begins before prior stage is complete
- hemostasis
- inflammation
- proliferation
- remodeling
skin wound healing: hemostasis
minutes-hours
- vasoconstriction; platelet aggregation & blood clotting
skin wound healing: inflammation
hrs-days/weeks (depending on the wound size)
- early acute phase: vasodilation & capillary permeability chemotaxis of leukocytes
- late acute (possibly chronic) phase: macrophages infiltration
skin wound healing: proliferation
days-weeks
- KCs, fibroblasts, endothelial cells
- synthesis & deposition of matrix; excess matrix & fibroblasts lead to keloid (hypertrophic scar)
skin wound healing: remodeling
weeks-years
- scar contraction: myofibroblast cells
- scar maturation: collagen cross-linking
skin ADR - MP rash/SJS/TEN
skin-manifested ADR - a continuum of 3 individual pathologies?
- MP rash - maculo-papular rash
- SJS - steven johnson’s syndrome = skin erosion of keratinocytes
- TEN - toxic epidermal necrolysis = huge sheet of epidermis peels off
- use rule of 9s
MP rash/SJS/TEN
3 names may be different extent of same pathology
- diagnosis dependent on physical, histological, biochemical criteria
- erythematous –> skin loss; severity associated with nomenclature
- MP does NOT necessarily progress to SJS/TEN; TEN is NOT necessarily preceded by MP
drugs associated with MP/SJS/TEN
~100 different drugs associated with MP/SJS/TEN
- triggers degradation of the skin in predisposed populations
- minimum number of drugs associated w/ majority of cases
principals
- antibacterial sulfonamides & antibiotics (ex. penicillin-related)
- aromatic anticonvulsants (ex. phenobarbital)
- NSAIDs (ex. piroxicam
SJS/TEN - tissue & cellular levels
- histopathology: KC apoptosis & necrosis, blistering at dermal junction
- apoptotic signals
- reactive oxygen species (ROS) production secondary to electrophilic drug metabolites –-> cell membrane damage & necrosis
- ROS stimulates production of NO (nitric oxide)
- NO stimulates keratinocyte apoptosis
SJS/TEN - mechanism
uncertain mechanism
- ~50:1 medline hits for incidence vs. mechanism
- genetic predisposition? (HLA, CYP SNPs)
- other predisposing factors: subacute viral infection, low level auto-immune disease (stimulation of immune system already)
- novel antigen of drug/protein combination
- the “perfect storm” combo of factors (whole cluster of co-presenting events)
primary therapy for SJS/TEN
- identification & cessation of suspect drug –
- problems: drug half-life, slow metabolizers, compromised excretion; symptoms can occur weeks after initial exposure
- usually admitted to burn unit
- monitor airways for involvement
secondary therapy for SJS/TEN
- plasmapheresis: patient’s blood cells + donor plasma reinfused into patient to remove nondialyzable drug, metabolite etc.
- remove the patient’s serum and add donor serum (serum is the one causing ADR)
therapy - severe cases: supportive care
- pain management
- hydration, occlusion to prevent drying
- nutrition: hypercaloric & high-protein diet
- cyclosporin & glucocorticoids to decrease inflammation BUT may decrease ability to fight infection
- antibiotics controversial: aggravating adverse drug reaction?
sweat glands: eccrine & apocrine
differ
- in distribution, association (or not) with hair follicle, innervation, stimulus, and type of sweat produced
sweat glands: eccrine
- distribution: across body surface
- opening: skin surface
- innervation: cholinergic nerves
- stimulus: increases body temp
- product: dilute electrolyte
sweat glands: apocrine
- distribution: axillary & perineal
- opening: hair follicle
- innervation: adrenergic nerves
- stimulus: emotion or pain
- product: electrolyte & lipid
adnexal structures - nails
- nail plate - on nail bed, specialized epidermal area –> extensive underlying vascular supply responsible for pink color of nails
- matrix - mitotically active keratinocytes in nail bed –> produce the nail plate
- lunula - thickened area in nail plate distal to cuticle –> high mechanical strength but low lipid & high water loss
