Phase 1 - Week 1 (Skin) Flashcards
List the functions of skin
- Protection - physical and immunological barrier
- Regulation - temperature, fluid, Vitamin D
- Sensation - nervous
Describe how skin acts as a protective barrier
- Keratin and lipids strengthen and protect from mechanical impacts
- Langerhan’s cells (macrophages) protect from pathogens
- Eccrine glands secrete acidic sweat with antimicrobial properties
- Melanocytes have melanosomes which produce melanin - pigment which protects skin from UV damage
- Lipids waterproof to prevent water loss
Describe how skin regulates processes within the body
- Body temp via eccrine glands producing sweat, movement of hairs via errector pilli muscles, changes in peripheral circulation (vasodilation/constriction)
- Fluid balance via eccrine glands producing sweat
- Synthesis of Vitamin D
Describe the skin’s nervous function
- Merkel cells - sensory receptors, relay signals to sensory nerves
- In the dermis
- Detect changes in temperature, pressure, pain etc.
List the layers of the skin
- Epidermis
- Dermis
- Hypodermis
Describe the general structural features of the epidermis
- Stratified squamous epithelium with keratinisation
- Avascular
- Varies in thickness - thick skin (palmoplantar) up to 1mm, thin skin (w/ hair) 50-100 micrometers
List the layers of the epidermis
- Stratum corneum
- Stratum lucidum
- Stratum granulosum
- Stratum spinosum
- Stratum basale
Describe the structure and function of the stratum corneum
- 15-30 layers of cells
- Dry, dead layers of keratinised cells
- Prevents dehydration, penetration of microbes, mechanical protection against abrasion, insulation
- Cells shed periodically + replaced in 4 weeks - cells called corneocytes
Describe the structure and function of the stratum lucidum
- Thin layer only in palmoplantar skin
- Keratinocytes are dead + squamous
- Densely packed with eleiden - clear protein rich in lipids, derived from keratohyalin - waterproofs
Describe the structure and function of the stratum granulosum
- ‘Grainy’ appearance due to changes in keratinocytes - become flatter, cell membranes thicken, generate large amounts of keratin + keratohyalin which accumulate as lamellar granules within cells
- Nuclei + organelles disintegrate as cells die - leaving keratin, keratohyalin + cell membranes to form lucidum, corneum + accessory structures e.g. hair, nails
Describe the structure and function of the stratum spinosum
- Spiny appearance due to protruding cell processes that join cells via desmosomes (interlock to strengthen bond between cells)
- 8-10 layers of keratinocytes, formed due to mitosis in basal cells
- Langerhan’s cells (dendritic, antigen presenting cells)
- Keratinocytes begin synthesis of keratin and release water - repelling glycolipid which prevents water loss from body
Describe the structure and function of the stratum basale
- Single layer, mostly basal cells - cuboidal stem cells, precursor to keratinocytes
- Also contains melanocytes + merkel cells
- Melanocytes - produce pigment melanin to protect from UV
- Merkel cells - sensory receptors, stimulate sensory nerves which send impulses the brain perceives as touch. Most concentrated on hands and feet
- Attaches the epidermis to the basal lamina, below which lies the dermis
- Cells bond to dermis via basement membrane
Describe the structure and function of the dermal-epidermal junction
- Holds dermis to epidermis
- Basement membrane - keratinocytes of basal layer bind to proteins of dermis via hemidesmosomes
- Failure causes blistering/ulceration - epidermolysis bullosa
Describe the general structural features of the dermis
- Much thicker than epidermis
- Contains blood/lymph vessel, nerves, hair follicles, glands
- 2 layers of connective tissue of an interconnected mesh of elastin + collagenous fibres, produced by fibroblasts
List the layers of the dermis
- Papillary
2. Reticular
Describe the structure and function of the papillary layers of the dermis
- 1st layer of dermis made of loose areolar connective tissue - mesh of collagen and elastin
- Projects into basal layer as finger-like dermal papillae - helps adhesion to epidermis
- In palmoplantar skin dermal papillae push to surface of epidermis - papillary ridges (fingerprints)
- Contains fibroblasts, small number of adipocytes + many small BVs, phagocytes (engulf pathogens)
- Lymphatic capillaries, nerve fibres, touch receptors called Meissner corpuscles
Describe the structure and function of the reticular layer of the dermis
- Much thick than papillary
- Composed of dense, irregular connective tissue
- Well vascularised, rich sensory + sympathetic nerve supply
- Appears reticulated (net-like) due to tight meshwork of fibres
- Elastin fibres give elasticity, enabling movement
- Collagen fibres give structure + tensile strength - extend into papillary and hypodermis
- Binds water to keep hydrated
Describe the structure and function of the hypodermis of the skin
- Connects skin to underlying fascia of bones + muscles
- Consists of well-vascularised, looser areolar connective tissue and adipose tissue - functions as a mode of fat storage + provides insulation and cushioning
List the glands found in skin
- Eccrine
- Apocrine
- Sebaceous
Eccrine glands
- Sweat glands, control temperature
- Everywhere in skin except nail beds, lips, external auditory meatus and some of genitals
- Most concentrated on palms, soles of feet and axillae
Apocrine glands
- Scent glands - role unclear in humans
- Axillae, genitals
Sebaceous glands
- Formed from hair follicle
- Everywhere except palmoplantar skin
- Enlarge during puberty due to sex hormones
- Produce lipids to lubricate hair shaft
Describe the structure of hair in skin
- Ectoderm derived
- Infundibulum = epidermis -> sebaceous gland opening
- Isthmus = sebaceous gland opening -> bulge at errector pilli muscle insertion
- Errector pilli responsible for movement of hair - helps to regulate body temperature
List the stages of hair growth
- Anagen - growth
- Catagen - transitional
- Telogen - resting
Describe the structure and growth of nails
- Nail matrix - specialised epithelium, produces plate, high concentration of melanocytes
- Cuticle holds nail plate to proximal nail fold
- Growth rate - fingernails, 2-3 mm per month, toenails, 1 mm per month
Keratinocyte structure and function
- Epidermal cells
- Produce keratin and lamellar glands
- Keratin - tough fibrous protein that protects the skin
- Lamellar granules - release water repelling glycolipid to waterproof skin
- Found in epidermis
- Go from cuboidal basal keratinocytes in stratum basale (highly metabolically active) to stratified squamous keratinised epithelium in stratum corneum (dead corneocytes)
Melanocytes
- Produce melanin granules - pigment absorbs UV radiation protecting skin from damage
- Found in stratum basale
- Have protrusions that transfer melanin granules to keratinocytes
- Granules surround the external side of the keratinocyte nucleus protecting it from harmful UV rays
Langerhans cells
- Dendritic antigen-presenting cells
- Found in epidermis - most prominent in stratum spinosum
- Originate in bone marrow, migrate to epidermis
- Able to engulf, destroy and present the antigens of pathogens
- Travel via lymphatic vessels to lymph nodes to activate lymphocytes
Merkel cells
- Found at border between epidermal and dermal layers
- Have small dendrites that protrude between nearby keratinocytes in the stratum spinosum
- Each merkel cell associated with a sensory nerve, called a Merkel disc and together, they act as a slowly-adapting touch receptor
Describe the process of normal skin regeneration
- Dead keratinocytes in stratum corneum shed regularly due to everyday wear and tear
- New keratinocytes formed from basal stem cells at same rate as they are lost - maintain epidermal thickness
- As cells in stratum basale multiply, existing cells are pushed out towards surface
- As cells move out they undergo keratinisation in stratum granulosum - keratin proteins become longer keratin filaments
- Eventually, nucleus + organelles of the cells disappear, metabolism stops + cells undergo apoptosis to become fully keratinised - takes 4 weeks
- Become less metabolically active as less nutrients are available - dermis contains Bv which supplies oxygen + other nutrients only to deep epithelial cells
Define wound
- Breakdown in protective function of skin
- Loss in continuity of epithelium
- With/without loss of connective tissue
- Caused by injury from surgery, blow, cut, chemicals, extreme temperatures, friction, sheer force, pressure or as result of disease e.g. ulcers
List the types of wounds
- Erosion/abrasion - only epidermis
- Ulceration - deep to epidermis
- Partial thickness - epidermis and parts of dermis
- Full thickness - epidermis, all of dermis, deeper structures
Describe the function of deep wound healing
- Prevents infection, dehydration and bleeding
- Plugs gap in skin integrity, re-epithelialises over defect, rapidly replace lost dermis with new matrix
List the phases of deep wound healing and when they occur
- Inflammatory phase - 1st 6-8 hours
- Proliferative phase - 5-7 days
- Tissue remodelling phase - 3 weeks to 6 months
Inflammatory phase of deep wound healing
- Platelets appear first at sight of wound to initiate haemostasis (blood clotting via fibrin) to prevent blood loss and seal injury from external environment. Clot connects interior border of wound
- Damaged tissue stimulates release of the inflammatory factor histamine, which triggers vasodilation + increases permeability of BVs, Rate at which microbes + dead tissue are cleared from wound site prior to repair is increases, as WBC have greater access
Describe the proliferative phase of deep wound healing
- Re-epithelialisation + neovascularisation
- Epithelial cells migrate across the basal surface of scab to connect borders of the wound
- Fibroblasts migrate along fibrin threads and secrete collagen to strengthen the clot, BVs begin to grow back
- Collagen strands deposited haphazardly to form fibrous network to support new capillary loops - granulation tissue (moist, translucent, red)
- Signs of inflammation disappear, fibroblasts contract to pull wound edges together. Wound contraction means less granulation tissue is required to fill wound cavity
Describe the tissue remodelling phase of deep wound healing
- Granulation forms mature scar tissue (fibrosis = formation of scar tissue), made of collagen organised in thick bundles
- Type 3 collagen becomes type 1 collagen
Compare scar tissue to normal skin
Scar tissue -
- Weaker (70-80% strength of normal skin)
- Higher density of collagen fibres
- Reduced elasticity
- Small variety of accessory structures
Normal tissue -
- Strong
- Lower density of collagen fibres
- High elasticity
- Large variety of accessory structures e.g. eccrine glands, hair follicles, nerve endings
Describe the process of epidermal wound healing
- Cells in basal layer break off from BM
- Basal epithelial cells enlarge + migrate across the wound
- Cell migration stops when two epidermal cells meet - contact inhibition - migratory phase over when epidermal cells surrounded
- During migration, epidermal growth factor is released - stimulates basal stem cells to divide + replace epithelial cells that have relocated
What controls normal skin regeneration
Epidermal growth factor
List the factors which affect wound healing
- Size
- Blood supply
- Foreign bodies + microorganisms
- Age
- Health
- Nutritional status
- Drugs
- Systemic diseases e.g. diabetes mellitus
- Oxygen/nitric oxide supply
- Cytokines/growth factors
Outline the features of consent in the patient-doctor relationship
- Have to have capacity
- Have to have all relevant information - about their condition, details of management plan and risks of proposed treatment
- Voluntary (own willing decision free to change at anytime)
- Not coerced or manipulated
- Must be lawful and valid
- Can be implied for minor/routine investigations/treatments
Outline the meaning of capacity
- Power to act, make decisions for self according to own reasoning
- Communicate decisions
- Understand implications of decisions
- Retain memory of decisions
- Presumed in adults unless there is reason to call into question
- Formally held at age 16 - under 16s can have capacity depending on individual and decision
- Not all-or-nothing - may have for some decisions, not for others
- May have at some times and not others e.g. dementia lucid periods
List the basic parts of a cell
- Plamsa membrane
- Nucleus
- Nuclear envelope
- Nuclear pore
- Rough endoplasmic reticulum
- Microtubules
- Centrosome
- Mitochondria
- Lysosome
- Perioxisome
- Golgi apparatus
Define tissues
Group of cells working together to carry out common function
- Parenchyme = working tissue
- Stroma = scaffold + nutrition
Organ
More tissues of different comprised in a morphologically recognisable structure
What is the most common stain?
Haematoxylin-Eosin (HE)
- Haematoxylin - basic, stains basophillic nucleus blue/purple
- Eosin - acidic, stains acidophillic proteins in cytoplasm + ECM pink
Is the nucleus basophillic or acidophillic? Why?
Nucleus is basophillic due to nucleic acid
List the steps in tissue processing
- Fixation
- Embedding
- Sectioning - slicing sample to give thin section, thinner the slice = higher resolution, allows light from microscope to skin through and structures to be seen
- Staining
List the types of epithelium
- Covering - simple (squamous, cuboidal, columnar), stratified (squamous keratinised or non-keratinised), pseudostratified, transitional
- Glandular
List the types of cell junctions
- GAP
- Tight
- Adherens
- Focal adhesion
- Desmosome
- Hemidesmosome
GAP junctions
Function = metabolic and electrical coupling
Components = connexins
E.g. cardiac tissue
Tight junctions
Function = barrier, selective permeability, cell polarity
Components = claudins
Cytoskeleton = actin
E.g. Epidermis
Adherens junctions
Function = tissue integrity, contractility, motility Components = cadherins Cytoskeleton = actin Example = morphogenesis
Focal adhesion junctions
Function = cell anchorage, mechanical and biochemical signalling
Components = integrins
Cytoskeleton = actin
E.g. cell migration
Desmosome junctions
Function = strong adhesion, resist mechanical stress
Components = desmosomal cadherins
Cytoskeleton = intermediate filaments
E.g. epidermis (keratins), myocardium (desmin)
Hemidesmosome junctions
Function = cell anchorage
Components = integrins
Cytoskeleton = intermediate filaments
E.g. dermal-epidermal junction
Give an example of a cell whose structure is adapted to its function
Muscle cell - sarcoplasmic reticulum which releases calcium for muscle contraction
Give an example of an organelle found in specific cells and not in others
Cillia:
- Found in respiratory epithelial cells
- Not found in most cells
What is the effect of dysfunction in mitochondria?
Mitochondrial cytopathies - defects in oxidative phosphorylation
What is the effect of dysfunction in lyososomes?
Tay-sachs disease - lysosomal storage disorders - destroys neurones
What is the effect of dysfunction in microtubules?
Kartagener’s syndrome
- Mutation in dynein motor protein - immotile cilia
- Recurrent respiratory infections (ineffective mucus clearance)
- Male infertility (immotile sperm)
What is the effect of dysfunction in GAP junctions?
Recessive mutation in Cx26 leads to sensorineural hearing loss
What is the effect of dysfunction in hemidesmosomes?
Lack of integrity at dermo-epidermal junction - epidermolysis bullosa simplex (blistering + ulceration of skin)
Where can proteins go after assembly in ribosomes?
- ER -> Golgi -> outside cell/plasma membrane/lysosomes
2. Cytosol -> stays/nucleus/mitochondria/perioxosomes
Explain how the letter analogy can be used to explain protein targeting to specific locations within the cell
Letter = protein
Address label = Signal peptide
Postman = Signal recognition particle (SRP)
Name-plate on door = SRP receptor in ER membrane
Letterbox = Translocon (pore in ER)
- Protein is threaded through translocon
- Signal peptidase cleaves off signal peptide
- Finished protein ends up in lumen of ER
- Transport vesicles contain protein in lumen bud from ER
- Then -> golgi apparatus
Describe the post office function of the Golgi apparatus in direction proteins to specific sub-cellular locations (protein trafficking)
- Proteins sent from ER to golgi in vesicles
- Vesicles fuse to become cis cisterna
- According to cis maturation model, proteins move through golgi stack
- As they do, the undergo enzymatic changes/modifiction - labels them for specific cell destination
What is responsible for protein degradation
Lysosomal:
- Long half-life
- Membrane proteins
- Extracellular proteins
Proteosomal:
- Short half-life
- Key metabolic enzymes
- Defective proteins
Lysosomal enzymes
- Lipases, nucleases, proteases/proteolytic enzymes
- Activated by acidic environment (pH 4.8)
Used for
- Protein with long half lifes
- Membrane proteins brought into cell via endocytosis
- Extracellular proteins brought into cell via receptor-mediated endocytosis
- Pathogenic proteins brought into cells via phagocytosis
Proteasomal degradation
- Cytosolic
- Takes place at proteasomes - cylindrical protein complexes
- Binding, unfolding, translocation
- ATP dependent
Used for:
- Proteins that need to be removed quickly - short half-life, key metabolic enzymes, defective proteins
- Proteins covalently tagged w/ ubiquitin