Epidermis, Dermis, and Basement Membrane Flashcards
What is the epidermis derived from?
Ectoderm
What are the layers of the epidermis?
- Stratum corneum/Cornified layer
- Stratum granulosum/granular layer
- Stratum spinosum/Spinous layer
- Stratum Basale/Basal layer
Which layer contains keratinocyte stem cells?
Stratum Basale
What are some of the functions of the skin?
- Maintenance of body temperature
- Recognition of outer enivronment
- Defense against microorganisms
- Protection from harmful materials in the external environment
What layer of the epidermis is only on the palms and soles and what two layers is it located between?
Translucent layer (Stratum Lucidum) - present between the granular layer and the cornified layer
How do the stem cells of the basal layer form keratinocytes?
- Each stem cell divides into a daughter stem cell and a transient amplifying cell
- The transient amplifying cell undergoes a few more clel division cycles before separating from the basement membrane
- Now known as a keratinocyte, the cell moves upward to join the stratum spinosum
Which layer of the skin contains the most keratinocytes?
The spinous layer (stratum spinosum)
What holds together the keratinocytes of the spinous layer?
Desmosomes
What types of junctions are responsible for keratinocyte communication and adhesion?
Gap junctions
Adherens junctions
Tight junctions
Desmosomes are protein complexes that connect _________ and their ________ ________ ________ ________
Keratinocytes; keratin intermediate filament network
What type of proteins are keratins?
alpha helical proteins that make up the intermediate filaments of the skin
What are the two types of keratins and how do they eventually form intermediate filaments?
Type I (acidic) and Type II (basic) keratins heterodimerize - two heterodimers form a tetramer that is further organized into keratin intermediate filaments
Keratin intermediate filaments connect to _______ and __________ to form the cytoskeleton network of the epidermis
Desmosomes; hemidesmosomes
What are the two types of granules secreted by keratinocytes in the granular layer? What is the function of each?
Keratohyalin granules - filled with proteins that are important for formation of the cornified envelope (profilaggrin)
Lamellar granules - Contain lipids such as ceramides and cholesterol that are important in forming the lipid barrier of the cornified layer
What type of granules are responsible for promoting the desquamation of the cornified layer?
Lamellar granules containing hydrolytic enzymes
What type of cells make up the cornified layer?
Corneocytes (anuclear)
Which sites lack a cornified layer?
Where are the thickest cornified layers?
Mucosal sites such as the mouth lack a cornified layer
Thickest cornified layer is present on the palms and soles
Where are melanocytes present? What is their main function?
Melanocytes are present in the basal layer - responsible for producing melanin, the pigment that determines skin color
Where are Langerhans cells mostly found?
Spinous layer (but present throughout the dermis and epidermis)
What is cornification/keratinization
The process of keratinocyte migration and maturation
What changes occur as the keratinocyte migrates to the skin surface?
It flattens out and loses its water content - progressively loses its cellular organelles and nucleus and releases its intracellular granules - eventually shed in the process of desquamation
What is the transit time of keratinocyte through the epidermis?
How long does it take the keratinocyte to migrate from the basal layer to the granular layer?
28 days; 14 days
The main protein that makes up the cornified envelope is _______ which is processed from __________ and ________
Filaggrin; profilaggrin and involucrin
The main lipid that makes up the cornified envelope is ________
ceramide
What are two disorders of the epidermis?
Pephigus Vulgaris
Ichthyosis Vulgaris
What causes Pemphigus Vulgaris? What proteins are affected?
Autoantibodies against desmosomal proteins, specifically Desmoglein 1 and 3
Pemphigus Vulgaris
What happens as a result of weakened desmosomes?
Intraepidermal blistering occurs
What areas does Pemphigus Vulgaris affect?
Affects mucosal sites such as the mouth nose and genitalia as well as any cutaneous site on the body
How is Pemphigus Vulgaris treated?
What can happen if it is not treated?
Treatment is with immunosuppressive medications such as prednisone, azathioprine and mycophenolate mofetil (Rituximab has been increasingly used in recent years)
It can be fatal when not treated
Who is most at risk for Pemphigus vulgaris?
Elderly
What type of inheritance does Ichthyosis Vulgaris have?
What gene is mutated?
Autosomal dominant
Mutations in the profilaggrin gene
What is the presentation of Icthyosis Vulgaris and where does it preferentially occur?
Presents with large scales on the body
The extremities, primarily the shins are preferentially affected
What are the three types of UV light?
- UVA (200-280 nm)
- UVB (280-320 nm)
- UVC (320-400 nm)
Which two types of UV light penetrate the skin?
Which is responsible for erythema and sunburn?
Which is responsible for tanning and photaging?
UVA and UVB penetrate the skin
UVB is responsible for erythema and sunburn
UVA causes tanning and photoaging
What type of skin cancers are associated with UV light?
What skin diseases are treated by UV phototherapy?
Skin cancers: Basal cell carcinoma; squamous cell carcinoma; melanoma
UV phototherapy: Psoriasis; atopic dermatitis; mycosis fungoides
What is SPF?
MED?
How is SPF calculated?
SPF (sun protection factor) provides a measur of protection against UVB exposure and sunburns (not UVA)
MED (minimal erythema dose) is the minimum amount of UVB tha tcauses skin redness at 24 hours
SPF = MED protected/MED unprotected
Sunscreen should be applied at least __ minutes prior to sun exposure
An adult will need __oz of sunscreen to cover the entire body
Reapply sunscreen every __ hours
15; 1; 2
The dermis is derived embyrologically from the _______
mesoderm
What are functions of the dermis
- Provide the skin with structure and flexibility
- Vascular support for th eskin
- Immunologic protection
- Nerve sensation
What adnexal structures are contained in the dermis?
- Eccrine (sweat) glands
- Sebaceous (oil) glands
What are the two layers of the dermis? Describe their appearance
- The superficial layer - the papillary dermis
- More cellular and has fine, loosely woven collagen
- The lower layer - the reticular dermis
- Fewer cells and contains coarse tightly packed collagen
What is the main component of the dermis?
ECM
What functions does the ECM regulate in the Dermis?
Adhesion
Migration
Division
Apoptosis
Main components of the ECM in dermis
Colagen, elastic fibers, and extrafibrillar matrix
Collagen makes up ___% of the skin’s volume and __% of the skin’s dry weight
20%; 75%
How many types of collagen are there?
How many types are in the skin?
What are the top two most abundant types of collagen in the skin?
There are 28 types of collagen with 12 types present in the skin
Collagen I is the most abundant collagen of the skin followed by collagen III
What is the function of elastic fibers in the dermis?
What are they composed of?
Elastic fibers are responsible for skin elasticity and the ability to be stretched and still return to the original form
They are composed of microfibrils, primarily made up of fibrillin, and amorphous elastin
What is the non-collagen, non-elastin component of the dermis? What are its components?
Ground substance - composed of water, electrolytes, plasma proteins and proteoglycans
What is the most prominent GAG in skin? What is unique about it?
Hyaluronic acid - unique for not being covalently linked to a protein
What are the predominant cells of the dermis and what are they derived from?
Fibroblasts are the predominant cells of the dermis and are derived from mesoderm
What is the main role of the fibroblast in the dermis?
The main role of the fibroblast is the production and secretion of the components of the extracellular matrix
Endothelial cells in the dermis are arranged in a _______ ________
vascular network
The _______ ______ ______ in the papillary dermis and the _____ _______ in the lower reticular dermis are composed of arterioles and venules
Interconnected superficial plexus
Deep plexus
Aside from circulation, what other functions do the blood vessels of the dermis have?
Temperature regulation
Leukocyte trafficking
Wound healing
What do the autonomic nerves of the dermis innervate - what is the result of each innervation?
Endothelial cells - control vascular tone
Smooth muscles of the hair follicle - control the pilomotor response
Eccrine glands - mediate sweating
What are the special sensory receptors in the skin?Where are they present and what are their functions?
Pacinian corpuscles - present in weight-bearing surfaces (as well as lips, nipples, penis and clitoris) - located in deep dermis and subq tissue - detect pressure
Meissner’s corpuscles - Located just below the peidermis in the dermal papillae - sensitive to light touch and are concentrated on palms and soles
The collagen molecule contains 3 nucleotide repeats where every third amino acid is _______
What are the other two residues that commonly make up the other positions?
Glycine; Proline and hydroxyproline
What are the steps of collagen synthesis?
- RER translation
- ER and Golgi modification
- Cleavage of signal peptides
- Hydroxylation
- Glycosylation
- Assocation of alpha chains and folding into procollagen triple helix
- Protease cleavage of N-and C- terminals
- Assembly and cross-linking with other collagens to form collagen suprastructure
Marfan Syndrome results from what mutation?
What type of inheritance is associated with this disorder?
Mutations in fibrillin
Autosomal dominant
Abnormalities associated with Marfan’s syndrome
- Musculoskeletal (4)
- Eye (2)
- Skin (1)
- Cardiovascular (2)
- Musculoskeletal (4)
- tall and thin body type
- long lims and fingers
- scoliosis
- flexible joints
- Eye (2)
- nearsightedness (myopia)
- ectopia lentis (dislocation of the lens)
- Skin (1)
- Striae (strech marks)
- Cardiovascular (2)
- Aortic aneurysm
- Mitral valve prolapse
Ehler Danlos syndrome is caused by mutations that interfere with…
Structure, production, processing, or assembly of collagen
Clinical features of Ehler Danlos syndrome
Fragile skin
Flexible joints (joint dislocations and early arthritis)
Severe scoliosis
Morphea is characterized by…
Sclerosis or thickening of collagen
How does morphea appear on the skin?
It appears as erythematous and indurated plaques that slowly expand
What other skin disease besides morphea is characterized by sclerosis?
Systemic sclerosis
What are the two principle forms of systemic sclerosis?
Limited systemic sclerosis
Diffuse systemic sclerosis
What are the features of limited systemic sclerosis (CREST)
- Calcinosis cutis
- Raynaud phenomenon
- Esophageal dysmotility
- Sclerodactylyl (thickening and tightening of fingers)
- Telangectasia of the face
What are the features of diffuse systemic sclerosis?
- Widespread sclerosis of the skin
- Pulmonary fibrosis
- Renal failure
- Gastrointestinal disease
- Cardiac disease
Wound healing stages?
- Hemostasis
- Inflammation
- Proliferation
- Maturation
What is the first step of hemostasis
Reflexive vasoconstriction
What induces vasoconstriction in hemostasis?
Endothelin (released from endothelium)
Circulating catecholamines (epinephrine, norepinephrine)
Prostaglandins from injured cells
Bradykinin, Serotonin, and thromboxane A2 (from platelet activation)
What are the physical signs of inflammation?
Erythema, heat, edema, and pain
What are the signs of inflammation on the cellular level?
Vessel dilation
Increased vascular permeability
Leukocyte recruitment to the site of injury
How does edema result from inflammation?
Increased permeability leads to transport of intravascular fluid, proteins and cells into the extravascular space resulting in wound edema
What do fibroblasts, smooth muscle cells and endothelial cells do to promote healing?
These cells infiltrate the wound and reesetablish tissue continuity through matrix deposition, angiogenesis and epithelialization within 4-12 days post injury
What is the last cell population to enter a wound? What attracts them?
Fibroblasts are the last cell pop. to enter a wound, they are attracted by platelet derived products (PDGF, IGF-1, TGF-ß)
How does epithelialization occur
- Epidermal thickening along the wound edges -
- Attachments between hemidesmosomes and basement membrane are broken down allowing cells to migrate
- The movement of basal cell parallels collagen orientation
- Contact inhibition signals stop cell migration
- Subsequent celular proliferation leads to a multilayer epidermis
What is maturation in wound healing?
Inflammatory cells are cleared from scar tissue
Most fibroblast undergo apoptosis
Blood vessels in the scar become more mature
Collagen maturation
What is below the dermis? What is it derived from? What is its function?
Subcutaneous fat derived from mesoderm
Function is the storage of energy in the form of fats - also provides insulation for the body and shock absorption
What are the main cells of the subcutaneous fat? How do they appear?
Adipocytes
They appear as large clear cells with the nucleus displaced to one edge
What type of disease is Erythema Nodosum (EN)? In what demographic is this disease most common?
EN is a panniculitis (inflammation of subq fat) that is most common in young women
What type of infection is most common in EN?
Upper respiratory streptococcal infection
What is the classic presentation of EN
Tender red nodules that arise on the shins
What are the ultrastructues of the basement membrane zone (BMZ)?
- Hemidesmosomes (BP 230, BP 180)
- Lamina Lucida (BP 180)
- Lamina Densa (laminin 332, collagen IV)
- Sublamina densa (collagen VII)
What are Hemidesmosomes?
Small structures on the inner surface of basal keratinocytes that are composed of many structural proteins - similar to desmosomes except only attach one cell (vs. two) to extracellular matrix
What is BP 230 (Bullous Pemphigoid Antigen 1)
BP 230 belongs to the plakin family of proteins - has cytoplasmic localization and is important for the organization of the cytoskeletal architecture
What is BP 180 (Bullous Pemphigoid Antigen 2)?
Also referred to as type XVII collagen - transmembrane protein connecting basal keratinocytes and cytoskeleton to dermal collagen VII
What is the Lamina Lucida
Thin structure underlying hemidesmosomes - may be an artifact of tissue preparation and dehydration
What type of collagen is the lamina densa composed of? What else is a component?
Type IV collagen
Laminins
What is the most abundant colagen of the BMZ?
Collagen Type IV - comprises more than half its mass
Collagen IV is a _______ which polymerizes into a ______ _______ and lattic formation
heteropolymer; triple helix
What is the key BMZ laminin and what does it do?
Laminin 332 binds to transmembrane protein of the hemidesmosome integrin α6β4 using the G domain on its α chain as well as to type VII collagen using its NC-1 domain, bridging the BMZ
What type of collagen is in the sublamina densa and what does it do?
Type VII collagen is necessary to maintian epidermal-dermal cohesion sinci it binds to both type I and type IV collagens which futher allows the type VII collagen to join the lamina densa to the papillary dermis
Explain a Routine biopsy
Taken from the edge of blister and processed by regular histologic staining to determine blister level and inflammatory infiltrate
Direct Immunofluorescence (DIF) vs. Indirec immunofluorescence (IIF)
DIF - detects IgGs and complement within biposy speciments - skin samples from peilesional skin (detect in situ)
IIF - detects circulating antibodies against BMZ in patients serum - patient serum applied to foreign substrate - antigen antibody complex detected by fluorescein-conjugated antibody
Two ways in which diseases can target the BMZ
- Inherited mutations in the genes that encode for their various protein components
- Acquired autoantibodies that attack specific proteins
Bullous Pemphigoid
Most common demographic:
Antibodies directed against:
Treatment:
The most common autoimmune bullous dermatosis
Most common demographic: Elderly
Antibodies directed against: BP230 and BP180
Treatment: high potency steroids; oral steroids and immunosuppresants used for severe disease
Blisters in Bullous Pemphigous
Starts with highly pruritic utricaria without blistering
Tense blisters with serous or hemorrhagic conent appear in phases
Roof of the blister consists of entire epidermis (extremely stable compared to pemphigus group)
Mucous Membrane Pemphigoid
Most common demographic:
Antibodies against:
Most common demographic: elderly
Antibodies against: Majority of patients have antibodies against BP180 but some have antibodies targeting BP230, integrin ß4 and laminin 332
Characteristics of MMP (Mucous membrane pemphigoid)
Recurrent blistering of mucous membranes and also the skin
Patients develops scars, strictures, synechiae and in 20% of cases - blindness
Epidermolysis Bullosa Acquisita (EBA)
Target antigen:
Characteristics:
Target antigen: Type VII collagen
Characteristics: Slight trauma elicits blistering and erosions of the skin - sites of predilection are mechanically-stressed areas such as hands, feet, elbows and knees
Epidermolysis Bullosa characteristics
Congenital absence or malfunction of structural proteins leads to erosions and blisters after minimal mechanical trauma
Type of inheritance and Targeted proteins for…
Epidermolysis bullosa simplex:
Junctional EB:
Dystrophic EB:
Epidermolysis bullosa simplex: inherited in autosomal dominant manner - target proteins are keratins 5 and 14
Junctional EB: Inherited in an autosomal recessive manner - target proteins are laminin 332 and BP 180 and BMZ
Dystrophic EB: Inherited in both autosomal dominant and recessive - target protein is type VII collagen of the dermis
