Physiology Quiz #1 Flashcards
Distrubutions of Ions Across Cell membrane
Distribution of Ions across cell membrane are not equal (unequal concentrations in the inside of cell vs. outside of cel)
Na - more Na outside the cell
K - more inside the cell
Ca - More calcium outside the cell (less than micromolar inside)
- Reason for amount of calcium outside the cell = because calcium is a signaling molecule
Mg - Similar inside and outside (more inside)
Cl - more outside
What is magnesium bound to
Magnesium is always bound to ATP
Main anions outside the cell
Cl- and Bicorbinate (More outside the cell)
- Bi corbinate - because we breath out CO2
***Also have phospahte and sulfate (less sulfate) - more inside the cell
Anion Gap
Measured difference between overall positive and negative charges in the cells
- Often is not calculated as zero BUT this is often due to the fact that there are anions that we do not measure
- In reality this value is escially zero - no differences in overall positive vs. negative charge
Anion Gap in clinic
Clinicians know the anion gap –> this value can provide insight into boldily disfunctions
Transporters in membrane
Have transporters in the hydrophobic lipid membrane because lipdi memebrane won’t let ions cross
- Diffusion - Passive (High to low)
- Chanel - Passive
- Uniporter - Passive
- Symporter - Active
- Antiporter - Active
- Pump - Active
Diffusion
Ions go down gradient (High to low)
- Goes slowly
Chanel and Uniporter
Facilitate movemnt of ions High to Low (Passive movement - no energy required)
- Regulated pore in the membrane
Chanel vs. Uniporter
Uniporter = never open on both sides of the membrane at once (Opens on one side and then the other side)
- Slower + more regulated than chanel
- Moves glucose and water (less ions)
Chanel = both sides open at once = ions can move
Symporter + Antiporter + pump
Building gradients - Uses Active Transport
Build the gradients so that there is energy for a different ion to move against the gradient
FOT SYMPORTER AND ANTIPORTER - How it works - one ion moves down the gradients = releases energy = transproters campture the energy = can move a different ion across the gradient
Symporter vs. Antiporter
Symporter - the two ions wil move in the same direction (one is still high to low and otehr is low to high but both will move inside to out or out to inside)
Pump
Still active transport to move ion against gradient (low to high) - BUT it is coupled with a direct source of energy (redox poential in mitrocondria or ATP o light)
Example - Na /K pump –> generates Na and K pump
Secondary vs. Primary Active
Secondary Active = Symporter + Antiporter - because need gradient to exist
Primary Active = Pump because doesn’t need anything else (Already has ATP)
What affects the expression of transproters
How many transproters have depends on how fast the work
Genes encoding transporters
Pumps - few genes coding for it BUT high expression
- Don’t have many types = few genes BUT have many of them = high expression (Ex. 50% of protein in ER = Calcium ion pump)
- Work slowly = need many of them
Chanels - more genes coding for it in multicellular (especially for bigger organisms because use for many things) BUT few genes in unicellular
- LOW expression because veery active = don’t need a lot
Secondary transproters - There are many genes that code for them because need a different one for every class of chemical
- Secondary transport dominates membrane function
Carriers - Many genes coding + moderate exppression
- Have different carriers for everything = many genes
- Moderatley fast because don;t need to break moleculars = moderate expression
Example Transporter
Pump - hydrolyases ATO and moves something –> this movement creates a gradient –> that gradient can be used to do other things
- Example - can move something down gradient and use the energy created by the gradient to move glucose
Chanels = do the same as pump - things go down gradient and can change the charge across the memebrane
Chemiosmotic circuts
Circuts = occur at every membrane
- The transport is organized in space
Example - pumps in lysosome to make acidic envirnmnt to then capture things to ultimatley digest
What are gradients
Gradients are ENERGY - take the energy from ATP and convert to different form to do work on membrane
Example of work - ATP synthesis + nutrient uptake + drug efflux + homeostasis of ions + moving metabiolites
What are the consequences of moving ions?
Moving ions establishes electrical and chemical gradients
Uncompensated movement
Only one ion goes in (positive goes in) and no ion comes out to balance - the movment of ions reults mostly in elictrical gradient
Electronueutral transport
Charge is not an issue (positive goes in and negative comes out) = no electrical gradient established only a chemical gradient
Example - stomach pump makes pH gradient –> proton/potasium pump moves a proton out for each ATP AND moves Potasium into the cell = net is nuetral change (positive charge into lumen and posutive charge leaving cell) = makes only a chemical gradient
What type of gradient has more energy
Electrical gradient has more energy because the memebrane cam’t handle a large charge difference –> means that every ion that moves across the memebrane has a large effect
- When move ions you quickly build an electrical gradient (gradient will make it harder to move additional ions)
Development of membrane potential (Start have a cell with more KCl inside than outside)
If only have KCl diffference = only uncharged molecules = only establish a chemical gradient
IF add a K+ chanel then the chanel will open and move K+ out of teh cell (because there is less KCl outside the cell and ions move high to low) BUT at the same time a small amount of K goes into the cell because here is a positive charge building outside the cell (Positive charge will then go inside the cell to balance positive charge outside the cell) –> Over time less K+ goes out because it is repealed by the positive charge that built outside the cell AND K+ increases inside because there is a negaitive charge inside (birng K+ in to reduce negative charge) –> over time chemical gradient will be equal and opposite to the electrical gradeint = creates an equilibirum (turns conecentration gradients to electruc –> then reac equillibrium)
Charge in cell chart based on this diagram
Voltage across the memebrane will decrease (become more negative) - over time the decrease become sless steep and eventually reaches equilibirum
Equilirbium = Ek = Nernst potential
Nernst potential
Voltage value at which the cell is at equiliubrium
***Nothing happens to concetration gradient once it is reached
- Setting up concentration takes work (uses ATP) - very efficient
Nernst equation
log[ki] = log of the concetation inside - in example [Ki] =150
log[ko] = log of the cencentraion outside - in example [Ko] = 1.5
z = charge of the ion
NOTE log 10 = 1 ; log 100 = 2
Shunting the membrane potential - Lysosome example
Need the lysosome to to be acidic = it has a proton pump
Proton pump in lysasome = moves uncompinsated charge across the membrane meaning there will be no chemical gradient-> creates an electrical gradients (negative in cytoplasm; positive outside)
- BUT there is no pH chnafe because there is no chemical gradient chnage –> MEANS in order to become acidic = pump only makes a charge gradient –> the has a chnage to move a different positive charge (move K+ out or birng negative charge in using the electrical gradient) –> NOW dirving K+ out means proton can come in to build the pH = keeping pumping protons in = make acidic
Issue in osteoplast cells
Osteoplast cells = degrade bone
Have a disease that affects VADPase - if have a mutaion in this enzyme then you can’t get an acidic envirnment = get osteopetrosis
OR can get osteopetrosis if have a mutation in chlorine transproter gene (No cl out = no pH gradient)
Example nernst equations
Gradient = affects if value is positive or negative
Resting membrane potential
-60 and -80 v
Example - Ek change if have multiple chanels/ions
Start - have concentration gradient of K+ –> over time voltage will go to Ek –> then K+ chaels close and open Na chnales –> Na will go into the cell and bring in a positive charge SO Ek will become positive –> THEN Cl goes into cell and Ecl is negative so voltage will become negative –> THEN ca chanels open and Ca goes in (Ca will have 2+ charge = divide by 2 in nernst equation) = goes to postive Eca
- SHOWS - chnage the memebrane charge by having different chanels
Overall - opening difefrent chanels = charge of membrane can change easily –> THIS IS HOW NERVES FIRE
Why is Eca not X2 Ecl
because Ca has a 2+ charge so in nerst equation you duvide by 2 = goes to positive Eca but NOT 2X Ena
How do nerves fire
Fire because opening different chnaels changes the charge of the memebrane
Opening multiple chanels at once
Harder to chnage the charge of membrane
Example - Both K+ and Cl- open –> ions cancel each other out = do’t get to nernst potential INSTEAD charge goes to zero
- The chanels can disipate the gradient if they are not regulated
IF multiple chanels open THEN the final potential will be the weighted average of the 2 pump’s nernst equations
- The membrane potential will be between Ek and ENa
What affects the charge if multiple chanels are open
The exact end value of the charge will depend on the relative number of Na and K values and the conductance of the chanels
Calculating the charge when multple chanels
Use the Goldman-Hodgkin-Katz equation gives you the steady state value of membrane potential
- Takes the gradients
- The weighted average of nernst + taking into accound conductance
P in equation = conductance (Ex. if there are 10X K chanels than Na)
Why do gradients decay when ahve multiple chanels
Because the mebrane potential is neither Ek or Ena the gradients will continue to decay
- Gradients won’t reach equilibirum = they will keep going until they run down the gradient
IN REALITY - the chanel will shut so they do not ruin the gradient
Properties of ion chanels
Ion chanels open and shut at a milisecond scale (time will depend on movement of protein domains)
Ion chanels change the membrane potential by +/- 100 mv
Ion chanels mediate signaling events
Signaling events mediated by ion chanels
- Action potentials (Ex. signals along a muscle or nerve)
- Excitaon-contraction coupling (Ex. muscle contractions)
- message goes to effector
- Excitation sectration coupling (Ex. hormon release)
- Message is sent and cells release something
Purpose of ion chanels
Mediate signaling events
Ways that ion chanels open
- Ligand gating
- Voltage gating
Ligand gating
Ligand binds to chanel –> have conformation change –> chanel opens
Example - ATP, IP3, Ca2+, nuerotramsmitters binds and opens chanel
Voltage gating
Chanels can develope a charge differetial –> change in charge differential can chnage the conformation and therefore can regulate opening and closiing of chanel
- Open and shut as a result of charge
Example - membrane potential opens chanel
Activation and inactivation gates
There are activation and inactivation gates –> BOTH must be open for ion conductions
Shape of Ligand gated ion chanels
Pentameric symetry
Types of ligand gated ion chanels
- cation selective (Example - Selective for Na)
- includes nAchR, 5HT3
- Anion selectve (Ex. let cl- in)
- Includes GABA, Gly
Name for ligand chanels
Ligand chanels = called receptors (because they are the receptor for a ligand)
Example - Acylcholine recptor chanel (acytl choline binds to the chanel)
Shape fo voltage gated chanels
Tetrameric sturcture (4 Subunits)
Often made up of repeating units
Contain a voltage sensor
Chanel is charged = opens/closes based on charge of membranes
- Ex sensors. S4 helix + repeating Arg/Lysine residues
Poor forming loop in voltage centers
Poor forming loop = creates selctivity filter
- See part of sensor that dips inside cell –> has Amino acid residues that determines what is let through
How do you measure the charge across the membrane
Overall - Use electrode
How its done: Caplary tube is put into a flame so it becomes narrow at the bottom –> tube is poked so it has a small opening so elecrode ca go through the tube —> put the tube through the membrame –> put wire and elctrode inside + have a voltmeter + referebce electrode
When put the elctrode in = voltmeter reads -60 - -90 = cell is polarized
Why can a capilary tube go into the hydrphobic membrane
Tube can go through the memerane because the hydrophibic lipids stick to the glass to form a tight seal
Polarized cell
Cell that is negative inside (Ex. -60 - -90 mv)
Video - charged inside relative to outside
Depolarization
When the inside of a cell becomes less negative (goes to a more positive value)
Hyperpolarized
When inside of a cell becomes more plarized
What happens if you add an elctrode to the reading or if add positive charge
The cell will become depolarized –> if you add enough positive charge then the cell will reach a threshold and go t positive –> when does so there is a spike and you have an action potential
What is potential relative to
Potential is always relative to the inside of a cell
Action potential
Wave form of depolorization (Spikes of depolorizatin)
Action potential wave forms in different cells
Different cells = have different wave forms
- Shape + duration + frequencey - depends on the cell type
Labled wave form
Start at resting potential –> becomes less negative (depolarized) –> have spike and get positive value inside –> quickl lose the positive
ALL together = forms an acion potential
What channels are needed for action potentials
Three voltage gated chanels contribute to action potentials:
1. Leak K+ chanels
2. Na channels
3. Delayed Rectified K+ chanels
Leak K+ chanels in action potentials
Chanels are open at rest + low conductance (let little K+ out)
Keeps the memebranes near Ek Value
Closes upon depolorizations (closes as because positive value)
Na chanels in action potentials
Closed at rest
Opens upon depolorization (opens when inside becomes positive)
Has an inactivation gate = closes quickly (will shut within 1-2 milliseconds and will take time to open again)
Delayed Rectified K+ chanels in action potentials
Closed at rest
Opens slowly upon depolorization BUT slow to open (10 fold slower to open than Na channels)
Mechanism of Action potential
1.Leak chanels are open –> cell becomes more positive because of outside(K+ going into the cell???)
- Na chanel opens and Na goes in becaise becomeing more positive = depolorizing
- Na comes in = increase the positive charge more = all the Na chanels open
- Eventuallly hits a threshold = opens all Na chnagels
- All Na chanels are open = HUGE spike in Positive value
- Na chanels close very fast and the delayed rectidfied K+ chanels open
- At the peak of chart - Na shuts and Dealyed K+ is open = cell gets more negative (K+ leaves the cell)
- End - Cell is no longer depolarized = delayed K+ chanels close and leak K+ chanels open –> cell goes to rest = cell goes back to Ek value
Where in chart are all of the Na chanels open
Middle of the spike
Extra AP image
Direction of Action potential
Will only go towards cells on axon or muscle that have not expreinced action potential yet
How does AP only go in one direction
Only goes foward to part of membrane that has not fired an AP because the Na chanels are slower = they need time = AP only goes where it has not fired befire
Because the Na chanels are inacted on cells that already had an AP - those Na chanels take time to open = memebranes that aleady had AP are not excitabl until Na can open back up BUT since slow to open up = can’t excite past memebranes = only goes in one direction
***Called Refractory period
Mylin sheeth + Action potentials
Vertabretes = have a mylin sheet that insulates most of nueron - have gaps in that sheeth
ONLY have AP in those gaps - AP jumps from gap to gap
- THIS speeds things up - makes vertabrets faster compared to invertabres
What hapens at the end of an axon
At end of an axon the nerve needs to tell the effector a message (Ex. tell muscle to contract) + at the end this message turns into a chemical signal
- At synapse - message gets across using chemicals
What happens at synapse
At synapse the the a chemicl signal is created to tell efector to do something
Chanels that are used at end of axon
- Volatage gated calcium chanel (on presynatptic memrane)
- Ligand gated cation chanel (On post synaptic)
- Example nAChR
Volatage gated calcium chanel at end of axon
Opens during depolorization to let calcium ions in
Calcium ions triggers synaptic vessicles exocytosis
Nuerotransmitters are realsed
How does Volatage gated calcium chanel at end of axon work?
When AP arrives the Ca chanel opens = lets in Ca2+ ; synapse has vesciles that contain things such as nuerotransmitters –> Ca will make the vesices frim will membrane to be realsed via exocyosis –> realses nuerotransmitters into cleft –> Neurotrasmitters go to post synaptic embrae which has the Liagnd gated cation chanel
Ligand gated cation chanel (On post synaptic)
Opens upon ligand binding (ex. Acytlcholine binding)
Non sleective cation chanel - lets positive ions across
Depolarizes post-synaptic membrane
Action potential triggered
How does Ligand gated cation chanel (On post synaptic) work
Neurotransmitters (released from Volatged gated calcium chanel) = binds and chanel opens
Chanel then opens and allows positive ions across = depolorizes mebrane = triggers NEW action potential
- Have depolorization at post synaptic = triggers Action potential = transfer the Action potential from one cell to another
Excitation-contraction coupling
Example - nerve getting muscle to contract on surface of muscle = triggers AP
Excitation-contraction coupling Chanels
- Dihydropyridine Recetor
- Ryanodine receptor
Dihydropyridine Recetor
Voltage Gate Calcium chanel on the plasma membrane
Opens upon depolorizations to let Ca into cell
Interacts with RyR and SR memebrane
Can make muscles contract – Ca goes into muscles –> allows actin to bind to mysoin –> muscle contracts –> THEN muscle relaxes
Why is there Ca pumps in ER of muscles
Because need Ca to contract muscles = have lots of Ca pumps in ER in muscle cells
Issue with AP in fiberous muscles
Muscles (Ex. skelotal muscles) = have lots of fibers = need to get AP deep in tissue to contract
Solution for issue with AP in fiberous muscles
Plasma memebrane goes to the depth of the muscle and comes into contact with ER of muscle (Called SR)
SR = has all teh calcium – NOW instead of getting calcium from outside the cell to the ER to open the Ryno chanel = the chanels can inetract with each other = hold the ER and the plasma membarnes together –> THEN the volatge on the plasma membarne causes the Dihydropyridein to interact with Ryanodine receptore = opens Ryanodine receptor = dumps Ca of ER into the cytoplasm of teh cell = have muscle contraction
Ryanodine receptor
Calcium channel on SR membrane
Activated by Ca2+
Conformational coupling with Dihydropyridine Recetor
What intercats in muscle cells
Dihydropyridine Recetor and Ryanodine receptor interact to hold plasma mebrane and SR together
Why are the plasma membrane and ER in contact in msucle cels
Because the receptores interact to hold the two together
What is calcium
Calcium = second messenger BUT it is not syntehsized or degraded = it needs to be moved in and out of cells
Example of calium functions
Calcium chanels (opens by volatge or ligans) - Includes voltage gated + receptor operated + second messenger operated + TRP type + Store operated
Calcium transproters - Na/Ca exchangers + Ca2+-ATPases
Calcium activated kinases - Calmodulin + CAM kinases + Calcineurin (When Ca comes in = activates these kinases)
Calcium activated Transcription Factors - NFAT + NFkB + CREB (Ca can turn on TF)
Store operated Channels
Are able to see when the ER is empty = signals out of ER to plasma membrane to fill store
What processes are controled by calcium
- Exocytosis
- Contraction
- Metabolism
- Transcripton
- Fertalization + proliferation
Ca = regulated events and can be slow or fast
Functions of the skin
- Regulate Temperture (Protect against cold ad heat)
- Prevenrs mechanical impact
- Protect tissues against chemical and phycial damage
- Prevents microorganisms from penetrating
- Destruction of inauculated microorganisms
- Resorption of substrates
- Prevents dehydration BUT allows some water evaporation (using sebbacous glands + hydrolipids)
- Sense envirnment (pressure + vibration + tacticle sensation)
Overall - Protects from outside conditions (keep outsdie out) + keep water in (stay hydrated)
Architecture of the skin
Very complex
Includes:
1. Hair follicles
2. Glands
3. Nerves
4. Vascularization
5. Immune cells
Layers of the skin
- Epidermis (Thinner layer)
- Dermis
- Hypodermis (Fat layer)
Layers of the Epidermis
- Statum basale
- Statum Spinosum
- Stratum granulosum
- Stratum Lucidum
- Stratym corneum
Statum basale
Cells dividing by mitosis and some of the newly formed cells become cells of the more superficial strata + Keratonocytes differentiate
Statum Spinosum
Keratin fibers and lamellar bodies accumalate
Stratum Granulosum
Keritohaylin and hard protein envelope form + lamellar bodies release lipids + cells begin to die
Stratum lucidum
Dead cells containing dispersed keratohaylin
Stratum Corneum
Dead cells with a hard protein envelope
- Cells contain keratin and are surrounded by lipids
Layer of dead cells
Purpose of keratin fibers
Provide rigidity
Desmosomes
Bind keratinocytes
Attatch to the dermis through the basement membrane
Karatinocytes shape and function
Shape: Robe like fiberous structure
Function: Protect from mechanical stress + provide structure
Keratin gene family
Large gene family
Have two families - Type 1 and Type 2
Keratin expression in the epidermis
Keratin have different expression depending on where they are in the cycle
Basal layer = high expression of K5-K14 –> THEN as go up in layers have high expression of K1-K10 –> then highere have expression of K2e
***Can be seen in histology of basal layer (see K14 expression) vs. other layers (K10 Expression)
Fraction of keratin in cells
Fraction of keratin icreases in cells as it differentiates (goes up to 80% of protein content in cells)
Examle - Basal cells keratin content is >10% BUT in late differentiating cells it is >80%
Mutation in K14
Mutation in K14 causes EB simplex
- Leads to blistering of skin
SHOW importance of keratins (Keratins provide structure)
Cornified envelope
Top layer of skin protection
Have high expression of Fallagrin
Falagrin
Prodiced in long strings
Faladrig = digested at keratinocytes differeentiate
Function - Acts as a barrier protein (Keeps water in)
Diseases faladrig
Image - see bottom layer has low faladrig expression or a mutation that prevents production of Faladrig –> Leads to Atopic dermatitus
Low faladrig = allergens can penetrate the skin + have loss of moisture
What is present in the cornefied envelope
In cornefied envelope = have proteins + lipids –> BOTH together help provide elasticity + stability + Mechanical resistance
Diseases associated with cornefied envelope
Have mutations or issues in enzymes or lipids —> leads to different diseases
Fish scale disease
Ichthyosis - have a down regulation of Flagrin or mutation in falarin –> leads to flaky dry scaly skin
Function of lipids in skin
Lipids = act as cement + oil barrier –> keep moisture in and othe rthings out
Ex. cermides = produced in skin to provide moisture
Desmosomes in Skin
Tight and structured
Act like velcro/glue providing seal of keranocytes
- Velcro interlocks to keep keranocytes together
Tight junctions
Overall - Keep things out (Larger antgens can’t penetrate but smaller things can)
BUT have things that can get through (Ex. Haptins)
Haptins
Bind to proteins and cause inflimation
Haptins = smaller than tiht junctions = can get in = get inflimation
How are the dermis and epidermis connected
Dermis and epidermis are conected by the Basal lamina
Bollus Pemphigoid
Disease that affects the basal lamina –> get seperation of the epidermis and the dermis –> leads to blistering
Immune cells in the epidermis
- Langerhand cells
- Gamma/delta T cells
- Rsident T Cells (Always there and can respond quickly if something comes in)
Langerhans Cells
Type of immune cell in Epidermis
Have long projectiles that go through the keratinocytes
Function: Important for sample envirnment
- Are able to respond when they should and make sure no response when it is not needed
Langerhans Cells Charachteristics
Start shaped
Have lobulated nuclei
Found in the stratum spinosum layer of the epidermis
Contains rod like granules (Grauals = called Birbeck’s granuals)
Function - Sense the envirnment + Antigen presentaions
Langerhans Cells Antigen presentations
When find something bad = cells take in the antigen and present it to adaptive immune cells
Melanoma - cancer of melanocytes
Melanocytes
Found in Epidermis + in Hair folicles
Function - gives skin and hair color
Melanocytes = have projectiles that produce melanin –> the melanin is taken up by the keratinocytes
- More melanin = more pigmentation
Vilitaigo
Autoimmune disease where the immune system attacks melanocytes = get low pigmentation in certain areas
Jack inhibitor drugs = work well for pateints with vitilaigo by supressing the immune system (Pigment often comes back)
Histology image = can see loss of pigmentations in A vs. E
Skin microbiome
Skin = has microbiome because the epidermis is exposed to the environment
- Have microbiome containing pathogens + fungi on skin
- Microbiome affscts health and disease
Ex. Propionbacterium spp. + Stapylococcus spp + Corynebacteriam Sp + Cutanous acne + malasezia Spp (fungi) + viruses
Skin microbiota sequences
Have done amplicon and whole genome sequencing to learn about the microbiome on skin (ound types of bacteria + fungi in microbiome)
- Found that there are parasites + mites
S. aerus in Atopic dermatitus
S. aerus affects atopic dermatias = need to know wha bacteria is normal = need to study what is there (Do so by doing whole genome or amplicon sequencing)
New feild = trying to apply bacteria to skin to normalize microbiome if the microbiome is off balance
Microbiome across body
Different parts of the body have bifferent compositions of microbiom (have different function and bacteria/amounts of types of fungi and bacteria in different parts of the body)
Skin across the body
Skin is not the same everywhere (Dfefrent envirnment = different microbiome - feet will have different microbiom that arms)
- Example face is oily but the forearm is dry
What do bacteria in skin produce
Bacteria in skin can produce peptides that can increase their own virulnce or to reduce the virlunce of something else
Bacteria can also produce antibiotcs
Interaction of microbiome cells
Microbiome cells interacts with our cells
Example - cells can produce a anti microbiom peptide to control the popultioon
Host microbiome interactions
Langerhand cells = smaple the envirmment -> controls when have inflamatory response and makes sure you are not always have repsonse (can react when barrier is breached)
Karatonocytes = release inflamatory factors if need
Skin microbiome and atopic dermatitus
Image
Can see the baseline S. aerus values –> see at a flare have a lot of pink (S. aerus takes over skin) –> then whe have reduction in S. areus have a reduction in inflamation
Dermis
Loose connective tissue below the epidermis
Made mostly of collegen (mostly type 1) + then elastic fibers (90% elastin) + ground substance (includes protoglycans + glycosaminoglycans + PGs/GAGs that are hydroscopic)
Epidermis
Tighter tissue
Collgen
Accounts for 75% of dermis dry weight
> 80% is Type 1 collegen
10% is type 3 collegen
5% is type 5 collegen
Type 4 collegen = seen in basal lumina
Fibroblasts make collegen
Function: Gives dermis structure
Elastic fibers
Account for 4% of dermis dry weight
Allows for skin elasticity
90% of elastic fibers = elastin
Cellular composition of the dermis
- Fibroblasts (make collegen)
- Macrphages + lymphocytes
- Mast cells
Cutis Laxa
Due to elastin mutation (or pathway) –> lose elasticity because elastin gives skin elasticity
Dermal Immune Cells
Includes dendritic cells + Gamma/delta T-cells + Fibroblasts
- Fibroblasts = can recruit cells for the immune system
- Gamma/delta T cells = innate adaptive immunity = doesn’t need antigen presetation
ALSO Have skin vasculature
Cells in skin + immunity
Essentially ALL cells in the skin = have some immune effect
Skin vasulature
Have lymphastic and blood vessles (artery supply runs through he dermis to junction with epidermis and to the hair follicle)
- Vsacular suppliy = arterial supply + venous drainage –> fulflls two roles (immunity + ______)
Arterivenous anastomosis = important for thermal regulation
Also ave subpapillary plexus + Cutenous plexus
Vasculature + Immunity
Vasculature = important in immune function because the immune cells will cluster around the vasculature to intrecat + to receive nutrinets
- Around vasculature have imune cells (Ex. perivascular macrophages)
ALSO have antibodies in the blood - if there is no inflamation then the vasculature is tight and no Antibodies can go through BUT if there is inflamation then the vasculature is leaking = antibodies and immune cells can get through
Receptors in skin
- Free nerve endings (go to the epidermis) - feel pain, heat, cold
- Merkle disks (at epithelian/dermal junction) - feel touch
- Krasuse blubs - feel touch
- Root hair plecus - feel har movement
- Meissner Corscicules - feel touch
- Pacinian corpsucles - feel pressure
- Ruffini endings - feel pressure
Merkle cells
Projects into the epidermis –> in he epidermis it commicates through nerve fibers
Function - Perceives touch
Meissner’s corpsicle
Smaller receptive feild compared to pacinian corpsicle
Higher spatial resolution detected compared to pacinian corpsicle
Radpidly adapting receptor
Pacinian corpsicle
Sense touch but has larger surface area for receptive feild and lower resolution than meisner’s corpsicle
Radpidly adapting receptor
Slow vs. Rapid adapting
Slow adapting = fires through sustained stimulus
Rapidly Adapting = Fre only at the onset and offset of a stimulus
Nerves + Immune system
Nerves = part of immune system – immune system communicates with nerves
- Receptors on immune cells communicate with never cells
Nerves project to epidermis and open into the epidermis = nerve is exposed to bacetria = get a regulated immune response (immune cells go to site and respond to inflamatry cytokines)
Example nerve and immune system
S. Aerues proteases = can activate nerve fivers in skin to induce an itch = scratch the itch = get inflamation
Anticipator Immunity
Nerve = can detect infections = sends warning to other neveres in other parts of the body - prevents pread of infection
Sebaccous Gland
Location in skin - comes off hair folicle
Function - produces oil + lipids = hydrates + has antimicrobial function
Cycle - the glands mature and develope –> THEN fill with lipids –> THEN cells die –> THEN release the lipids and the lipid goes up the hair shaft
Types of glands in skin
- Sebacous glands
- Sweat Glands
Sebbacous glands + Sex hormones
Sebacous glands = relay station for sex hormones
- Sebacous glands = produce and respond to sex hromones
- During pubity sebecous glands enlarge –> They produce lipids + get inflamed = blocks the hair shaft (because right next to hair shaft) = get acne
S. aerues + sebbecous glands
S. Aeurs blocks maturation of Sebecious glands –> this could help S. aerus colinize the skin
Apocrine Glands
Type of Sweat gland
Connected to the hair shaft = in places with hair (Arm pits)
- Produces the odor in armpits
Types of Sweat Glands
- Apocrine Glands
- Eccrine Gland
Eccrine Glands
Throughout whole body
Function - regulates temperture –> produces sweat
- makes lipids and fat+ makes ear wax + fat droplets in breast milk (Have gland near breasts)
Myoepithelial cells
Contracts and pushes sweat out - contraction causes the secretory ells to release sweat unto the lumen (Center of the gland)
Hair follicle parts
- Arrector Pilli muscle - Makes hair stand when scared
- Bulg - Where stem cells come form in wound repair
- Hair bulb - germination and proliferation of hair
K17 Null Mice
Have alopecia
K17 = keratin in hair shaft –> when remove the keratin = mice develop alopecia = can’t regrow hair
Basal Cell carcinoma
Skin or UV damage
Hypohidrotic ectodermal dysplasia
Due to issue in EDAR gene
EDAR gene = important for development of epidermal cells
Patients = have no hair + irregular teeth + no sweat + no sebbacous gland
- hard to regulate temperture + get no oil (lacks hydration)
Can we create a new hair follicle from epidermal single cell sluries
What did they do - Took cell slury of keratinocytes –> put on mice that would take a skin graft
Results:
1. When only add keratinocytes = no hair
2. When add keratinocytes + fibroblasts = get hair follicles
Fibroblast cells
Dermal cell - can be reticular or pailary fibroblast
Maintains skin integrity –> Makes elastin + collegen + structrual proteins
Important for communication –> Secretes signaling molecules (growth factors + cytokins + metabolites)
Types of Skin
- Non-volar - In places where there is less pressure on teh skin
- Volar - Has stratum corneum (on palms of hand + feet - more pressure)
- Friction + irritant + pressure resistant
Reserach with volar and non-volar skin
Trying to turn non-volar to volar skin
How - by adding fibroblasts
Ex use - for protestscs to turn place that had non volar skin to be volar because now there will be more pressure
Reserach with volar and non-volar skin results
Found an increase in area (in thickness) iff you add fibroblasts (get non-volar to volar transition)
When add volar fibroblasts to non volar = get volar identity
Add non-volar to volar karatinicytes = get thicker?
KRT9
ONLY found in volar skin
When looking at KRT9 - when add volar fibroblasts to non volar = get volar idetity
Atopic March
Overall - Atopic Dermatitus = leads to more allergic disorders
Start - have babies with atopic dermatitus = increases allergen presentation –> kid then developes food allergies –> develop more allergies (envirnmental) –> eventually leads to asthma
SHOWS - skin has systemic consequences
Studying Atopic march
Model = add Sareus on skin + Add cockroach allergen –> get inflamation + asthma model
Add S. aerus and cochreach = get downstream affects on other epithelial tissues
- Found production of IL-36 –> that can go to lungs and cause issues
- When add S. aerus get repsonse in lungs –> leads to 2 types of asthma (Including non-T2 ashtma)
Question - how are epithelial tissues commincating + how to we prevent snowball effect + hoes does it affect brain/nerves
Conclusions
- Skin is a prototype epithelial organ
- Diverse cell types and phenomon
- Perfect Model system for many questions
