Week 1 Cells and Tissues Flashcards
What are the three layers of skin?
Epidermis, Dermis, Hypodermis
What is the basement membrane composed of?
Extracellular matrix proteins
What is the stratum basale composed of and its function?
Cuboidal, mitotically active stem cells that regenerate other layers of the epidermis
What type of junction connects the stratum basale to the basement membrane?
Hemidesmosomes
What are the four layers of the epidermis?
Stratum basale, spinosum, granulosum, corneum
What is the stratum spinosum?
A layer of keratinocytes
What holds the stratum spinosum (keratinocytes) together?
Desmosomes
What happens in the stratum granulosum?
Cells become flattened and are starting to lose nuclei and cytoplasm. Contain keratohyalin granules.
What is the stratum corneum?
Large plate - like envelopes filled with keratin and are all linked together. It also contains some lipids
What are the layers of the epidermis?
Basement membrane, Stratum basale, Stratum spinosum, Stratum granulosum and the Stratum corneum.
what happens as cells move up the epidermis?
They become keratinised and begin to die as they can’t get enough nutrients
Is the epidermis vascular or avascular?
Avascular
How many layers of keratin are there?
20-30 layers
How does the epidermis get its nutrients?
Supplied by the dermis
What are the layers of the dermis?
The papillary and the reticular layer
Where is the papillary layer?
The upper portion of the epidermis
What is in the papillary layer?
Connective tissue
What is connective tissue?
Tissue that connects, supports, binds or separates other tissues or organs
Where is the reticular layer found?
The lower portion of the dermis
What is the reticular layer made of?
Highly dense connective tissue
What is the connective tissue in the reticular layer made up of?
Collagen type 1 and elastin fibers
What property does collagen give the skin?
Strength
What property does elastin give the skin?
Stretchiness
What are some additional feature of the dermis?
Blood vessels, Glands, Hair follicles, receptors and muscles.
Where is the subcutis?
Below the dermis and the epidermis. It is the lowest layer of the skin.
What does the subcutis contain?
Cells such as macrophages and fat cells and a network of protein fibers.
What are some functions of skin?
Protection - the skin forms a barrier
Thermoregulation - 80% of body heat is lost through the skin
Cutaneous sensation - including touch and pressure
Excretion - metabolic waste products can be released in the sweat
Absorption - lipid - soluble substances enter the body via the skin
Vit. D synthesis - starts in the skin triggered by uv light
Where are keratinocytes found?
In the epidermis - Aprox. 90% of epidermal cells are keratinocytes
What is keratin?
A tough fibrous protein
What else (apart from keratin) do keratinocytes produce?
Lamellar granules
What is the function of Lamellar granules?
To help waterproof the skin
Where are melanocytes found?
In the epidermis - Aprox. 8% of epidermal cells are melanocytes
What do melanocytes produce?
Melanin granules
What is the function of melanin?
To absorb UV radiation so protects the skin from sun damage
It is also partly responsible for skin colour
What are Langerhans cells?
They are part of the immune system that originate in the bone marrow and move to the epidermis
What are the functions of Langerhans cells?
To recognise foreign microbes and engulf them.
They can then present antigens to the immune system for further action.
Where are merkel cells found?
At the border of the epidermis
What feature do merkel cells possess?
Small dendrites that pass in between nearby keratinocytes
What is each merkel cell associated with?
A nerve ending called a merkel disc.
What does the combination of the merkel disc and the merkel cell function as?
A slow adapting touch receptor
What are the functions of fibroblasts?
To synthesise collagen, elastin and other extracellular components.
They also play a critical role in wound healing as a connective tissue.
Where can most of the lymphocytes in the skin be found?
The dermis
What are the functions of the lymphocytes?
Part of the immune response
Carry out immuno-surveillance
What are the functions of mast cells?
Producing substances that cause inflammation e.g. histamine
How often does the skin renew?
Every 24hrs the skin sheds a layer of dead cells with the skin renewing completely every 28 days
How does renewal of the skin benefit the immune system?
It removes any potentially harmful pathogens from the surface of the skin
What happens as epidermal skin cells move up towards the surface of the epidermis?
They become keratinised - becoming flatter and gradually losing their nucleus and cytoplasm. They eventually die
What is another reason for the death of cells as they move towards the surface?
There is a lack of nutrients and oxygen they receive as they get higher up since the epidermis is receiving its nutrients from the dermis
What are the three overlapping stages of wound healing?
Inflammatory, proliferative, and remodelling
How are clots formed?
Fibrin and platelets combine to seal the wound from the external environment
What is the formation of the clot known as?
Haemostasis
What is inflammation triggered by?
The changes in microvasculature.
when does inflammation resolve?
after the neutrophils have finished clearing out the dead tissue
What are the main purposes of inflammation?
-expel any foreign bodies
-isolate the damaged area
-mobilise cells and molecules
-promote healing and tissue repair
What happens during the proliferative phase?
A lot of cell proliferation and the movement of epithelial cells to the injury site
How do fibroblasts move to the injury site?
Along fibrin threads
How do the fibroblasts contribute to clotting?
They secrete collagen which strengthens the clot
What is granulation tissue?
Delicate tissue that grows under the scab
How is the collagen deposited?
In a random arrangement
What is the change in type of collagen in the remodelling phase?
Type 3 to Type 1
What happens when the collagen changes?
The granulation tissue becomes scar tissue
What does the amount of scarring depend on?
The severity/depth of the wound.
Does scar tissue or normal tissue have more collagen fibers?
Scar tissue
Does scar tissue or normal tissue have reduced elasticity/stretchiness?
Scar tissue
Why are scars sometimes a lighter colour than normal tissue?
The way blood vessels arrange themselves
What is an incised wound?
Caused by a clean cut from a sharp edged object.
What treatment is required for an incised wound?
If the wound is deep, stitches may be required.
They may be healed by primary intention as there is usually little or no tissue loss
What is a laceration?
These wounds occur when there is a blunt/ripping force
They may bleed less but there is likely to be more tissue damage
It is also more susceptible to infection due to the increased surface area
What treatment is required for an laceration?
These wounds require a lot of cleaning.
Even if they are repaired very neatly by primary intention they often leave a lot of scarring
What is an abrasion (graze)?
A superficial wound in which the topmost layers of skin are scraped off. They can often contain lots of foreign particles meaning a high risk of infection
What is a contusion (bruise)?
A blunt blow can cause the rupture of capillaries below the skin
What is a puncture wound?
A deep wound with a small entry site
How should a puncture wound be treated?
It’s often best to leave this type of wound open so that if there is any infection the wound can drain.
What is healing by primary intention?
- A clean, uninfected wound
- not much loss of tissue/cells
-The edges of the wound are approximated by sutures
What is healing by secondary intention?
- a wound with large tissue defects
- potentially infected
- the wound would not be approximated but is left open
At what age is a young person presumed to have capacity?
16
What are the laws in Scotland for 16/17 year olds who do not have capacity?
They are treated as an adult who doesn’t have capacity and treatment may be given where required.
What is the law in Scotland to do with parents overriding consent?
In Scotland parents cannot override the competent consent of a young person to treatment that the doctor believes is in the patients best interests
What is the law in Scotland to do with parents authorising treatment a young person has refused?
Parents cannot authorise treatment that a competent young person has refused
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
