Physiology (Cardio 1) Flashcards
Affects of cardiovacsular issues
1/3 of the world is affected by hypertension
Heart failure is the leading cause of death
Corony heart disease is very common
Shows that we need to find new mechanisms for treatments
What does the circulatry system include
Blood - contains Oxygen carying vehnicles (blood cells) –> blood cells are tramted through tubes
- Tubes = create a conserved cellular envirnment
- Blod = acts as a transmission system for sonignaling between organs + carres cellular waste
Role of Circulation
- Provide nuterients to all the cells (each cell gets the specific nutrients it needs)
- Provide oxygen to cells
- remove wast products of cell metabolsim + put waste in a place to be disposed
- Maintain constancy of the internal envirnment of cells (homeostasis)
How do organs get provided the same nuterint supply
To porvide organs will all the essential nuterints the ciruclatory systen has a paraelle circuit - each of the organs receives its own blood supply where the perfusion rate is locally controlled
- Allows organs to inctease the bloood requiemnet without compromising other organs
Excpetion - lung
Movment of blood (overall)
All lood passes form the right ventricle through the pulminary circulate (oxygenated in the pulminary circut) –> goes to the left ventricle –> goes to the body
What does the circulatory system contain (How do you get the circulatory to do its job)
- Carrier to ship out things and take away bad things
- Tranportation force (pump) to trasnport things t other places in the body
- Forece = flow –> pump to move things through the blood vessels
- Need a route system you can follow to transport things = have blood vessels
- You need to be able to control how much stuff you deliver to your end users (aka organs and cells) - chaneg where flow is needed or not needed
- Need some way to kow that the end users need more stuff when they need it and make chnages when they get it (need feedback)
- Inform when something is needed by the organ –> tell brain or local system (neurons or chemical)
- If some of te end users need more things you need to be able to deliver this to them without cimpormising the supply of stuff to other users
- Make sure the other organs don’t suffer
Solution of the circulatory system
A parrael circut systems carrying blood with vacular tone to vary regional flow with local and strategic snesors to know how much flow is needed and hwere it is needed and input systems to privde the good things and remove the bad things with elimination systems
- Parrellel circut = can chnage the resistnce in one of of teh ciructs and that increase in flow to that circut does not chnage the pumps force for other organs
- Can have different resistnce for each organ = each get what they need
Solution = makes sure that all of the good get delivered to the organs so they get them when they need it
Affect of the parrallel system
Allows every organ to get the same base things but can adjust teh flow to each organ
- Flow can be lower in some and higher in otehrs
How much of blood does each organ use
Brain using 14% of Cardiac Output
Kidney = gets a lot of the cardiac output
Lungs = get 100% of the cardiac output –> only serios part of the circulation - everything goes to the lungs
Reulst of circulatory system
- All orans revice blood with the same composition
- Relative flow to onw organ can be adjusted as required without neccasrily comprosing the flow of another
- Some organds can withsand having the flow lowered more than others as they serve blood condiiong functions well in excess of their metabolic needs
Changing the pump function of the heart
Can change the pump function of the heart to make sure the brain gets what it needs
Uses a sensor –> push on the coroted snus (contains barroreceptors - mediate distention) –> barrorepctor smeasure pulastion of the circulation + pressure (chnages in distenction) –> triggers the brain to chnage pressure –> heart pumps flow
- Vessels will constrict or not conrtict at the base of the brain (where coroted is)
Giraffes
Girafes are tall but their hearts are tall (far form their head) –> have to pump blood agaisnt gravity –> herat generates more pressure to get to brain = keep base of brain intact
***Have barrorecpetor at the base of the brain
Receptors for local blood flow
- When excerisze (using legs) –> skeltal muscle is working = increase demand for O2 –> creates an anerobic envirnment –> increase lactic Acid –> decrease pH –>pH is a local vasodilator
- If need O2 = get acidic envirnment = dialted the vessels
- Lung - If you have a part if the ling with no O2 in aveoli –> sending blood to that area would be bad because the blood would not get oygenated –> instead the pulminary vessels constrict in areas with no O2–> only get profusion to areas with O2
- Opposite of what happens in the leg (when acidc = constricts)
How can we consider the hemodynamics of circulation
The hemodynamics of circulation can be considered as a simple electrical circute (have a volatge that dirves current past a resister)
Ohms law
V = I * R –> Pressure = Flow X resistnce
End - dP = F * R OR R = dP/F
What is dP
dP (pressure driving systemics blood flow) = the mean artery pressure you could meaure in the promixal aorta - pressure you would measure as the veins enter the heart
Creates the tran-circulatpry pressure gradients
- mean flow = cardiac output
Normal cardiac output
Normal cardiac output is 4-6 liters/minute
- cardiac output can rise to 5X
Cardiac output scales to body size (including obesity)
How do arteries and vein affect the disrbution of blood _ pressure + resistnce + flow rates
Image - shows the distribution of different parameters in different vessles
Example - Blood volume - have little volume in the arteries ; most vilume is in the veins ; almost no blood in the capilaries
- Vein = storage (mostly in the gut/spleen = blood resivoirs)
Increasing volume in the veins
Increase volume in the veins = constrict the veins
Veins = low pressure = can put a lot of volume of blood in them
- If had same volume in arteries = then BP would get too high
Blood presure in ateries vs. capilaries
Smaller arteries = have resistnce = BP decrease and flow decreases
Capilaries = force decrease = pressure decreases
- BUT the BP does NOT go to zero becase then you have have to force to put the blood in the veins (need a pressure gradient = need driving force)
- Pressure is lowest when you get to the heart then increases again
Basic Principle of macro hemodynamics
You have a pump generating flow - cardiac output is flow
You have large artries to transports the blood to orangds (no resistnce)
- Have compliance - makes sure the pressure doesn’t drop to 0
You have smaller local artieres in the organs that get small enough to cause resistnce to flow
You have tiny capillaries and by the time blood gets there flow is no longer pulsatile and goes much slower
You regroup at the other end into large veins (have minimal resisnce) to get back to the pump
Scenrio where flow is 0
Based on P = F X R
If flow is 0 when the heart is flling then P would go to zero
BUT the BP stays 120/80 because because the large arteries stretch as the heart beats (pulse is bffered by the aorta) –> aorta expands
When there is no flpw have expansion and contactons = gives volume back = maintains pressure
- BP increases as you age becaise the aorta gets stiff
- BP is able to go higher while have refilling and no flow
Cardiac output equation
CO = Mean blood pressure/vacsular resistnce
What determines resistnce in small arterioles
restince = 8/pi X viscosity (n) X legnth (L)/radius^4
As the radius gets smaller resistnce gets higher (because diving a small number to the poweer of the fourth)
- Very sensitive especially in small vessels (radius decreased by 1/2 the resisce increase by X16)
Why isn’t blood pressure insanley high
Because you are putting 4 liters per minute of blood flow into yiou arteiers AND at some point the radits is small so you would think you would have 1000 mHg to get through the resistnce
THIS isn’t the case because you have many parallel vesslves
- Becuase all of the vessels are a paraeled branches = net is resistnce is not so high
1Rtotal = Sum of 1/Ri
Viscosity
Things in blood make it more viscous
1. Serum - more protein = more viscous = increase resistnce
- Example Fibulin or glbulin
- RBCs
- Example - smoking or chronic hypoxia –> lungs don’t work for oxygen delivery = increase RBCs = increase viscosity
Blood flowing through teh aorta vs. smalleer vessls
resistnce imporsed by large arteiries (like aorta) is minimal - blood flows through these tubes with neglible loss of pressure
As artieres get smaller there is increaseing resistnce (higher receistnce when arteries are in the micron range)
Smaller vessles - resistnce is difined by restince = 8/pi X viscosity X legnth/radius^4
Cappilaries
Capilaries = where good things and bad things are exchnaged
Capilaries = a tube that is one cell thinck –> lies next to the cells that need what the capilary is carrying
Net Filtration rate
Net Filtration rate = K[(PC-Pi) - (Pic-Pii)
Pc = hydrostatic pressure in intercapicalry compartents
- Dirving pressire in the arterial side
Pi = hydrostatic pressure in intestinal compartment
- Pressure on the extrcellular side
PiC = intracapilary oncotic pressure
Pii = intestical oncotic pressures
K = constant expression of how readily fuild can move acoss capilaries
Image - cross section of capilary - shows oncotic pressure vs. hydrostatic presure
Pc vs Pi
Pc = pressure on the arterial side
Pi = pressure on the extraacellular tissue soace around teh cells
Two pressures appose each other
Pc - Pi –> driving pressure to move water and the solvents the water contains out form the capilary intertore to the fluo around the cell
Oncotic pressure
Protein pressure - oppsoposes the driving pressure from Pc-Pi
- Realtes to an increaseing concentraion of proetsin that remian in teh capilary as the fluid is dirving out into the tissue space
Albumin
Major protein contibuting to permability of fluids/solutes in capilaries
- Made in the liver
Concentration of protein in tissue space
PiC - Pii
Rising concetarion of protein (Albumin???) in teh blood passing throuh the capialry is countered by the concetrayon (of protein???) in the tissue soace
Provides a concetration gradient to brinh fluid back into the post cailary venule
Capilary permability at homestastos
At homoestais the amoint of that moves into the tissue space due to hydrostatic force is counters by protein force (osmotic force) –> tissues remian relativley dry
What happens during heart failure
During heart failure the equilirbium in the capilaries falls apart
- Get water in the tisue –> water can’t get back into the capilary
Pressure in the venous side increase –> there is a stringer hydrosttic force (keeps fluid in the tissues) –> the ncotic pressure can’t compensate
Result of heart failure
- Fluid builds up in the lungs (pulmanry edema - wet sponge lung) = hard to breath and oxygenate blood (shortness of breath)
- Space in the aveoli sac get filled with water = oygenation is poor
- Interstitial Edema/Pitting edema - Fluid builds up in peripheral tissues
- Ex. ankle and legs - gravity helps the fluid pool
- Occurs if have issue with oncotic pressire (decrease protein = decrease vicosity = water gets trapped)
- Can occur if have liver or renal disease –> decrease albumin = dcrease visocity = get edema
Renal disruption
Renal disruption can lead to pitting edema –> get rid of too much albumin (because disrput the membrane) = pee out the protain = decrease the protein = decrease viscoity = get edema
COVID 19
COVID 19 = destroys the capillary endothelium (especially in the lungs) –> get leaking vessles
- Leaking if the vessles is not because of hemodynamic pressures INSTEAD get leaks because of breakdown of membranes
- Can fix issue based on sterlings low –> lower the pressure by getting rid of fluid in pee or venodilators = removes fluid from the heart BUT won’t work here
- Heart to treat because the memebrane is permable = proteins and water can go out
results - Adult respitory Distress syndrome (aka lung white out)
Structures of the heart
Shows the chambers of the heart
Pulminary valve - 3 leaflets –> when pressure drops it makes sure the blood doesn’t floow back
Right atrium - get the blood from the periphery
Tricuspid valve - Right ventricle has high pressire and pulminary artery is low pressure = blood moves from high to low
Overall principle of blood movment in heart
Blood moves from high pressure to low pressure
Ex. High pressure in right atrium to low pressure in right ventricle
How do valves work
Papilary muscle pulls on the valvle = keeps it closed = keeps blood form flowing back
Basic Cardiac cycle
- Filling phase (Diastole) - ventrcile needs to fill with blood at a low pressure (doesn’t require much force)
- Starting of contraction - valves are still closed - muscle must stifen and contract to expel the blood
- Continuing contractions - valvles open and heart ejects into both lungs and arteries
- Heart muscle relaxes - valves remai shut - muscle needs to relax and pressure needs to fall so the ventricle can fill again
- Heart starts filling again
Top row - big peak -> aortic valvle closes –> ventricle pressure falls to below the pressure in the atrium (blood can flow high to low)
- Left artrium and left ventrcile have a small pressure difference BUT because there is low resitnce you can have a small pressure difference and still have plenty of flow
Blue peak on top row = Pressure in the right ventrcile but the aorta is close –> when the mitral valve closes the pressure increase higher than the atrial = heart ejects = aortic valce opens and the mitral vlave closes (mitral valve closes becuase the hearts pressures higher than atrrum - once the pressure is lower thna the atrium the aorta valve will close again
Green line
1. First blip is a P wave
2. Spike - ventricles are activated
3. Third blip = T wave –> hert relaxes (repolarization
Boster pumpes = the little blips in EKG
What happens if the two chambers have the same pressure
If the 2 chambers have the same pressire then the atrium constricties = gives a boost pump (booster pump wull fill 15% and the rest will fill due to passive flow)
Atrial fibulation
Common arthyia (chaotic herat beat)
- Often fine (vs. ventril fiberlation people die)
What happens - instead of coordiating contraction the atria is constaly quivering
A fib = big problem if have 60% of the atrium boost BUT since the boost is only 15% A-fib is survivable
- If you have heart disease (high BP + stiffer heart = can;t fil = atrium contracts more = if they have A-fib it is worse)
Pressure volume loop in the cardiac cycle
Shows the pahses and teh correpsonsindg wave forms for arterial, ventricle, atrial pressures + shows the cardiac ventriculaar volume + shows the elctrical activation waveform – plots the volume in the heart chmaber (X-axis) and pressure in chabe (Y-axis)
A - mitral valve closes
A -> B ventrcile pressure rises
B –> Aortic valve opens
C –> Aortic valve closes
D -> mitral valvle opens
During filling = have stertching = volume increases but the pressure does not increase
Distaly vs. Sistaly
Sustaly = Actvation
Diastly = Deactivation = low pressure = filling
Ventrcile Cardiac Cycle
Viewed as a spring with time varying stiffness
Left - Slope = stiffness –> goes from bottom where it os not stiff ; top red line is the stiffest
If have more stiff = it is able to contract t generate pressure = get forve to put to arteries with enough flow to get all of the blood profused THEN will relax in diastily
Ventrcile Cardiac Cycle (image 2)
Top = peak - heart is stiff even if pressire doesn;t chnage = move the activation of the muscle
Middle - peak = shows the muscle is stiff until teh aortic valve is closed
Bottom = relaxation
Stroke volume
The volume that is ejected with eat heart beat
Stroke volume X number of heartbeats per minute = Cardiac output
What affects stroke volume
- Heart contraction strength (contractility)
- Arterial load (resistnce) against which the heart beats
- Dilate the arteries = decrease resisnce = increase CO
- How much blood volume is in th heart before it contracts
- Heart is designed to start with more volume = ejects more colume = stroke volume increase = cardiac output increases
- Cardiac output as a linear relationship with endiastolic volume (higher CO = Higher volume)
Cardiac Output
CO = mean flow rate form the herat = heart rate X volume ejected per beat
- Volume ejected per beat = Stroke volume
Effect of excersizing
- Decrease the amount of resistnce during excersie
- Increase contraction strenhth
- Preload is higher = incerease cardiac output
- Preload is higher becasie body adpated to have a lowere HR = higher stroke volume
INcreasing Cardiac output
- Increase the HR - Cardiac output can increase with a higher heart rate as long as the stroke volume dosn’t fall BUT at really fast heart rates the stroke volume does fall because the heart does not have enough time to fill between hartbeats
- In a range from 60-100 beats per minute you can increase cradiac output with heart rate
- Cardiac output increases if you increase the stroke volume
A. Heart cintraction strength - Stroke volume can increase if the instrincic contractility of the heart muscle increases(increase contractility)
B. Arterial resistence against which the heart beats - if you lower the arterial resistrnece to amke it easier for the heart to eject (lower reistnce)
C. How much blood volume is in the heart before it starts to contract - if you fill the heart with more blood OR f you streatch the herat muscle
What does intrinsic contractality do?
Contractility = how strong is the heart when it contractions (measure of stiffness)
- Increase excersize = increase conractility + have drugs that increase contractility
At decreased contractility vs. increased
- Not chnaging the amount of volume being filled at reast but increase contractility = increase stroke volume = increase cardiac output
Why does stretatching heart muscle increase stroke volume
Stretching heart muscle incerases its contraction force and strole volume - based on Frank starling Law
Situations where higher CO is found
- Excersize
- Normal growth
- Pregnacy
- Lung disease (oxugen diffision is reduced_
- Obesity (most common)
- Hormonal stimulation (often hyperthyridsm)
How does the heart muscle contract
Deporlarization of the muscle cell causes the Ca2+ chanels to open –> ca goes into the cell AND the SR lets Ca2+ into the cell because Ca from th eoutside binds to the Rynosin receptor –> Ca2+ binds with the tropinin complex
How does heart muscle speed up the contrcaction
Ca neds to go from the outside of the cell to the Tropinin
To speed this up = have Ca2+ going from the outsisde of the cell AND have paralel local delivery so the Ca does not have to go all teh way in for each beat
- Helpful because the msucle = have a fast HR –> most Ca comes from SR
Instead - T tubule network has ca2+ = releases locally to the sacromeres
- Have rynoninde receptors = actiaved by teh Ca2+ from the outsde = ca leaves teh SR Ca binds to teh sacromere = get contraction
Ca2+ leaving the cell
SERCA2a - Takes up Ca2+ back to the SR
Ca/K chanel - take Ca out if the cell and brings in Na
- Maintains the elctricochemical balance
Actin and Myosin complex
Thick filaments = myosin
thin = Actin
At the ends = Have Z-disk –> have signing molecule –. force is sensed and trasnduced = corrdinates everything
Shortens when activated
Mitocondria in Muscle contraction
Mitocondira = fuel
Sacromere happening all happens around mitocondria because mitocnidra has ATP
Ca2+ goes through mitocindra uniporter = tells mitocindra how much ATP is needed
- Increase Ca2+ = increase actin/myosin = increase contraction = Increase ATP needed
Tropinin complex
Rope = troponin –> blocks the myosin binidng sites on actin
- Need Tropomysin to move –> Ca2+ binds to tropinin complex on tropomysin –> allows the rop to roll off
- When Ca2+ decreases = tropinin rolls back and blocks sites = stop contraction
Need the mysoin helix to go from relaxed to activate to string activated so it can bind to myosin –> get contraction
PKA activation
PKA activation increases both myocyte formation and calcium transients
Isoproterenol = activates heart muscles (increases and decreases calcium)
- Top right = peak have increase in Ca2+ - goes up and down quickly (fatser when activates sympathetic nervous) ; get higher force + faster force
Myofilament response to calcium
Regulation of scraromere
Beta receptor aginists binds to alpha subunit of the GPCR recetor –> breaks up the heterodiner –> activates the alpha subunit = actiaves adeylate cylcalse –> uses truns ATP into cAMP –> cAMP intercats with protein kinase A -> get phospherylation
- Phosphoylates the Ca2+ chanel
- Phosphorylate Rynein
- Phosphorylates myPBC and titan (mcrofilaments)
- Phosphorylates PLB
- Phosphorylates Tropinin 2
Phosphorylation of Ca2+ AND phosphorylation of reynein recpetor
Protein kinase A phospherylates the Ca2+ chanel = get increase of Ca2+ = get increase of Ca2+ from SR
ALSO phosphorylation of Runein receptpr = get increase in Ca2+
Ca2+ goes to troponin –> actin can bind to myson = increase contraction
Phosphorylation of myPBC and titan
Phosphorylate titan - titan acts like a molecular spring = causes stiffening BUT can chnage the stiffeing by phosphorylation
Phosphorylation - makes less stiff = easier to fill
ALSO phospherylation myPBC
- myPBC iteracts with Actin = keeps pace of the scaromere shortning (acts like a break) BUT when phosphorylated = decrease the break = increase movment of the sacromere
Phosphorylation of PLB
Makes it easier to bring calcium to the SR
Phosphorylation of Tropinin 2
Tropinin 2 = inhibitory = reduces the response of microfilamenrs to Ca2+
When phosphorylated = Trponin 2 is less inhibitory
- Phosphorylation allows the heart to release cross birdges as Ca2+ falls
Counter balance effct
Higher stiffness
Higher stiffess = pump more blood if everything else is connstant
- Contracts more = more blood out
