Phase 1 week 1 Flashcards
What are the three main functions of skin?
Physical and immunological barrier, physiological regulation, Sensation
In what ways does the skin act as a barrier?
Protects against; mechanical impacts, pressure, variations in temperature, micro-organisms (Lymphocytes), radiation
How is the skin involved in physiological regulation of the body?
Body temperature via sweat and hair, changes in peripheral circulation, fluid balance via sweat, synthesis of vitamin D
Describe sensation in the skin
Network of nerve cells detect and relay changes in the environment (heat, cold, touch, pain)
Itch is a unique feature of the skin
Describe vitamin D synthesis in the skin
During exposure to UV light, UVB photons are absorbed by 7-dehyrocholesterol in the skin and converted to provitamin D(3) Provitamin D(3) undergoes transformation within the plasma membrane of cells to active vitamin D(3)
What are the layers of the epidermis?
Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale
Describe Eccrine glands
Everywhere on skin apart from nail bed and lips
secrete sweat
most abundant on palms, soles and axillae
Describe apocrine glands
Scent glands, role unclear
Axillae and genitals
Describe sebaceous glands
Present everywhere except palms and soles
Enlarge greatly at puberty in response to androgens (acne)
Main function is to provide lipids which lubricate the hair shaft
What is the main type of cell found in the epidermis and what proportion does it make up?
keratinocyte - 95%
What types of cell are found in the epithelium?
keratinocytes
dendritic cells - langerhans cells
melanocytes
what are the properties of keratinocytes?
They form keratinised squamous epithelium
waterproof
protection against friction, microbial invasion and desiccation
Held together by desmosomes - intermediate filaments and cadherins
Describe melanocytes
Found in the basal layer of the epidermis
Melanin is transferred to keratinocytes via their dendritic processes
Describe normal skin regeneration
Some cells in the stratum basale are stem cells
These can divide to form new stem cells or undergo terminal differentiation as they migrate towards the surface of the skin
It takes 1 month for epidermal turnover
2 weeks from granular layer to stratum corner
2 weeks for the corneocyte to surface the stratum corneum and to be shed to the environment
The epidermis is made up at keratinocytes at different stages of development
What is a wound?
The breakdown in the protective function of the skin
What types of wounds are there?
Erosion - only epidermis lost
Ulceration - structures deep to epidermis
Partial thickness - epidermis and some dermis
Full thickness - epidermis and all of dermis and deeper structures
What are the 3 phases of wound healing?
Inflammation - platelets and WBCs gather
tissue proliferation - epithelialisation and granulation tissue formation
Tissue remodelling
Describe phase 1 of wound healing
Platelets arrive first and initiate haemostats and release growth factors
GFs attract other cells to fight infection
New cells migrating to the area cause characteristic signs of inflammation
Neutrophils and macrophages kill microorganisms and secrete more GFs
What are the two part in phase 2 of wound healing?
re-epithelialisation and neovascularisation
Describe re-epithelialisation
Within 1-2 days of the wound, keratinocytes move from the skin appendages and near the edge of the wound
the cells adapt - they lose their adhesion properties and become flatter
Re-epithelialisation occurs either by the “leap frog” method or the “train method”
Describe neovascularisation
Chemotactic factors cause cells to migrate and proliferate
Fibroblasts multiply and lay down collagen in a haphazard way to form a fibrous network that supports new capillary loops
This tissue formed is called granulation tissue
Fibroblasts contract to pull the edges of the wound together
Describe phase 3 of wound healing
The collagen is organised into thick bundles and extensively cross-linked to form a mature scar
What factors affect wound healing?
size of wound blood supply to area presence of microorganisms age and health of the patient Drugs patient takes nutritional status of the patient
Describe the most common form of staining
Haematoxylin and eosin
Most commonly used stain
Basic dye (haematoxylin) to differentiate nuclei
Followed by acidic eosin to highlight everything else
How can epithelia be classified in terms of layers?
Simple -single layer
stratified - 2 or more layers
pseudo stratified - one layer with a mixture of cell shapes
What are different shapes of epithelial cells?
squamous - flat
Cuboidal - cube shaped
columnar - tall cylindrical shape
transitional - readily changes shape
What are the components of the plasma membrane?
Phospholipid bilayer cholesterol lipid rafts carbohydrates proteins
What is the structure of the phospholipid bilayer?
Hydrophilic heads towards the extracellular space and the cell lumen. Hydrophobic tails face inwards.
What do integral plasma membrane proteins do?
Allow the transfer of small molecules across the membrane through pumps, carriers and channels
What do plasma membrane receptors do?
They interact with specific chemical signals (ligands) to initiate a cascade of chemical signals in the cell. e.g. EGF receptor
How is genomic DNA stored?
Packaged as chromatin
Describe features of the structure of the nucleus
bound by a double membrane, supported by a network of nuclear lamins, contains nuclear pores
Describe the compartments within the mitochondria
Outer membrane - selective permeability - e.g. pyruvate
Inner membrane - folded into numerous cristae - electron transport chain
Matrix - enzymes for citric acid / TCA cycle
Inter membrane space - important in electron transport chain and other enzymatic reactions
Describe the role of the mitochondria in apoptosis
Cellular injury / stress leads to the release of Bcl2
release of cytochrome c into the cytoplasm
activation of caspases “proteolytic cascade”
Destroy nuclear lamins
activates DNases
Destroy cell adhesion properties
what is the difference between RER and SER?
Rough endoplasmic reticulum is associated with ribosomes and is for protein synthesis
Smooth endoplasmic reticulum is not associated with ribosomes and is involved in lipid synthesis and calcium storage
Explain the role of the Golgi apparatus
Proteins are sent from the ER to the Golgi
They are carried in vesicles and fuse to become the cis cisterna
According to the cis maturation model, the proteins move through the Golgi stack
They undergo enzymatic modification which labels them for their destination
e.g mannose - 6-phosphate is the “address label” for proteins for the lysosome
What are lysosomes?
Vesicles containing proteolytic enzymes
What are endosomes?
Vesicles involved in the transport of molecules from the plasma membrane to the lysosomes
What are peroxisomes?
compartment for enzymes involved in oxidative reactions: biosynthesis of bile acids, fatty acid metabolism, detoxification
What are the key differences between lysosomal and proteasomal degradation of proteins?
Lysosomal - long half life, membrane proteins, extracellular proteins
Proteasomal - short half life, key metabolic enzymes, defective proteins
Give examples of lysosomal enzymes
lipases, nucleases, proteases (all of which are activated by an acidic environment )
Describe lysosomal degradation
Used for proteins with a half-life of >20 hours
membrane proteins via endocytosis
extracellular proteins via receptor-mediated endocytosis
pathogenic proteins via phagocytosis
Describe proteosomal degradation
Proteins to be removed quickly
Proteins covalently tagged with ubiquitin in a 3-step pathway
What does phosphorylation do?
Alters the activity of a protein
What does acetylation do?
In histones - regulation of gene expression
What does farnesylation do?
targets protein to the cytoplasmic face of the plasma membrane
What does ubiquitination do?
Targets protein for degradation
what are the main function of the cytoskeleton?
organise cell structure and to maintain the shape of the cell
supports fragile plasma membrane
provides mechanical linkages that let the cell / tissue bear stress
allows cell to adopt specific behaviours
What are the 3 types of cytoskeletal filament?
microtubules
Microfilaments
intermediate tubules
Give examples of microtubules
Tubular (dynein, kinesin)
Give examples of microfilaments
actin (myosin)
Give examples of intermediate filaments
keratin, vimentin, desmin, lamins
What are the key functions of intermediate filaments?
structrural integrity
keratin in epidermis
vimentin in fibroblasts of the dermis
nuclear lamina - nuclear organisation and membrane support
What are the key functions of microfilaments?
Movement and structural
cell projections - microvilli, stereo cilia
cytoplasm - cell contraction, shape change
Membrane extensions (lamellipodia) cell motility
contractile ring - cytokinesis
What are the key functions of microtubules?
Mitotic / meiotic chromosomal movement
intracellular vesicle / organelle transport
axonemes composed of microtubules and dyne
Kinesics move cargo away from centrosome
Dyneins move cargo towards the centrosome
what are the three types of cell junction?
Anchoring
occluding / tight
communication / gap
Describe anchoring junctions
cell - cell cytoskeleton
adherens - actin
desmosomes - intermediate filaments
cell - ECM contacts
focal adhesions - actin
hemidesmisomes - intermediate filaments
Descrive tight junctions
cell - cell contact
connect to the actin cytoskeleton
maintain polarity of epithelial cell
form a barrier e.g. blood-brain
Describe gap junctions
cell-cell contact
composed of hexamers of connexins
allows passage of small molecules
