Cardio Physiology

Question 1

role of circulation

Answer 1

-provide nutrients to all cells in an organism
-provide oxygen to all cells
-remove waster products of cell metabolism that are otherwise toxic
-maintain constancy of the internal environment of cells (homeostasis)

Question 2

what factors are involved in circulation?

Answer 2

-you need carriers to ship out the good stuff and take away the bad stuff
-you need transportation force (aka a pump) to transport this stuff everywhere in the body
-you need a route system you can follow to transport the stuff
-you need to be able to control how much stuff you deliver to your end-users (aka organs and cells)
-you need some way to know that your end users need more of the stuff when they need it and make changes so they get it
-if some of your end users suddenly need a lot of stuff, you need to be able to deliver this to them without compromising the supply of the stuff to others

Question 3

significance of parallel circuit

Answer 3

-all organs are receiving blood with the same composition
-relative flow to one organ can be adjusted as required without necessarily compromising flow to another
-some organs can withstand having flow lowered far more than others as they serve blood conditioning functions well in excess of their metabolic need
-only organs in series are the heart and lungs —> everything goes through the lungs

Question 4

carotid baroreceptors

Answer 4

-carotid baroreceptors sit at the base of the brain and they measure strain —> they will trigger the brain to change pressure
-solve cross species problems with this concept since scaling at level of capillaries is the same

Question 5

example of giraffe baroreceptors

Answer 5

giraffe has head close to the ceiling and heart close to the ground and the heart has to pump against gravity —> generates big pressure

Question 6

what causes vessels to dilate during exercise?

Answer 6

more CO2 buildup, which leads to acidosis and the pH drops —> a local vasodilator is activated when the chemoreceptors sense the change and trigger response from the brain

Question 7

what is the one organ that doesn’t dilate with less O2?

Answer 7

lung- block off blood flow to an airway of lung and you ventilate to send blood —> pulmonary vessels constrict to match profusion with ventilation

Question 8

distribution of blood volume, pressures, resistances and flow rates

Answer 8

-most blood is in veins and very little in arteries
-increase blood volume acutely, constrict veins
-very little blood in capillaries
-in large arteries, the BP is fairly constant
-as you get into smaller arterioles, the resistance increases and the pressure goes down —> speed of flow declines
-if the pressure went down completely, you would have a force to move the blood back up to the heart —> need pressure gradient otherwise blood will pool from gravity

Question 9

macro hemodynamics

Answer 9

-need a pump to generate flow —> cardiac output
-you have large arteries to transport the blood to the organs (no resistance here)
-you have smaller local arteries in the organs that get small enough to cause resistance to flow
-you have tiny capillaries and by the time the blood gets there, flow is no longer pulsatile and goes much more slowly
-you then regroup at the other end into large veins (minimal resistance) to get it back to the pump
-need compliance of 120/80 —> no flow then you don’t have pressure

Question 10

relationship between cardiac output, pressure, and vascular resistance

Answer 10

cardiac output = mean blood pressure/vascular resistance

Question 11

what determines resistance in small arterioles?

Answer 11

-resistance = 8/pi * viscosity * length/radius^4
-every time the radius decreases, the resistance increases
-very sensitive when you get to smaller organs

Question 12

what can increase the viscosity of blood?

Answer 12

proteins in the plasma can increase the viscosity

Question 13

multiple myeloma

Answer 13

cancer of the plasma cells that produce abnormal antibodies, or immunoglobulins, and make it harder to push blood through

Question 14

how can we increase red blood cells

Answer 14

smoking- body produces more red blood cells to compensate for the lack of oxygen and you end up getting big bubbles in the lungs

Question 15

what allows us to not need a very high blood pressure to get through the resistance?

Answer 15

parallel vessels —> 1/Rtotal = sum of 1/Ri

Question 16

heart failure

Answer 16

-imbalance of starling’s forces —> water gets trapped in tissues in between and can’t get back into the capillaries
-in radiography, lung should be dark on both sides but in dilated heart failure you see wispy white parts

Question 17

interstitial edema (pitting edema)

Answer 17

-fluid overload in peripheral tissues since gravity is pooling the fluid
-usually a problem with the ectotic pressure

Question 18

liver disease

Answer 18

-liver produces albumin, which can decrease the amount of proteins in the blood and water gets trapped
-often you see edema in the belly

Question 19

renal disease

Answer 19

kidney is a filter and pees out the proteins in your blood

Question 20

wet sponge lung

Answer 20

space for gas exchange in the capillaries is filled with water and makes it difficult to diffuse gases

Question 21

acute respiratory distress syndrome (ARDS) from covid-19

Answer 21

-total breakdown of membranes in the lung —> profusion of it leaks into the airways
-in heart failure, you can reduce pressures and move fluid out of lungs but in this the membrane is no longer impermeable and everything gets out
-ventilate a person and blow in O2 but when lungs transfer capacity doesn’t work
-extracorporeal oxygenation- often you have to take out the blood, put it in machine and put O2 in it then put it back in

Question 22

structure of the heart

Answer 22

-consists of four valves
-blood from the periphery —> goes to the right atrium through the superior and inferior vena cava
-tricupsid valve allows the blood to flow from the right atrium to the right ventricle then to the lungs through the pulmonary valve
-oxygenated blood from lungs goes to the left atrium then the left atrium
-mitral valve connects the left atrium to the left ventricle —> brings oxygenated blood through the aortic valve to the aorta

Question 23

basic cardiac cycle

Answer 23

1. filling phase (diastole)
2. start contraction and the valves are all closed still
3. continue contraction- valves open and heart ejects into both lungs and arteries
4. heart muscle relaxes, valves remain shut
5. heart starts filling again
   -once you have two chambers without a gradient —> atrium contracts

Question 24

atrial fibrillation

Answer 24

-chaotic heart rhythm activation pattern with no concerted beating
-atrium is always quivering and individual activation are not getting to the ventricle
-we all experience this, however, those with heart disease, heart failure, hypertension are less tolerable since the atrium has to continue to pump more

Question 25

pressure-volume loop

Answer 25

-beginning at A, the mitral valve closes and the amount of ventral pressure is at the highest
-at B, the aortic valve opens and the heart ejects
-at C, the aortic valve closes once the ventricular pressure falls below the aorta and the mitral valve is still closed since the pressure of the heart is higher than the atria
-at D, the mitral valve opens and the ventricle begins to fill

Question 26

ventricular cardiac cycle

Answer 26

-if you poke your arm with a little bit of pressure, you notice indentation but as it becomes stiffer, you do not see the indentation as much
-process of relaxing and contracting is what the heart is doing with each cardiac cycle —> compliant by filling at low pressures
-when contracting, you get stiffer to keep the pressure high for enough flow to profuse tissues
-slope of the graph is the stiffness of the spring
-time varying elastance (stiffness)- heart continues to stiffen more and more with activation of actin-myosin filaments until the aortic valve closes and it destiffens

Question 27

contractility

Answer 27

-measure of how strong the heart is when it contracts
-change contractility, change how much blood flows out

Question 28

cardiac output

Answer 28

heart rate * volume ejected/beat (stroke volume)

Question 29

how can the stroke volume vary?

Answer 29

-heart contraction strength (contractility)
-arterial load (resistance) against which the heart beats
-how much blood volume is in the heart before it contracts
Ex. someone exercising a lot —> arterial resistance to go down and need a lot of blood flow so the contraction strength goes up

Question 30

mechanisms to enhance cardiac output reserve

Answer 30

-increase the volume ejected with each beat- stroke volume —> fill the heart more (the more it is filled the greater the stroke volume), enhance its contractility, and make it easier to eject blood (lower the arterial resistance)
-increase the heart rate —> make sure it is not too fast or you will not have enough time for the heart to fill between beats, the volume it fills will go down, and then the stroke volume will decrease

Question 31

situations where a higher cardiac output is found

Answer 31

-exercise
-normal growth
-pregnancy
-lung disease (oxygen diffusion is reduced)
-obesity
-hormonal stimulation like hyperthyroidism

Question 32

from AP to getting a sarcomere to contract

Answer 32

-Ca driven
-Ca induced Ca release —> a certain amount of Ca comes in but a lot are in the T-tubule network
-every time the heart beats, Ca comes in from outside and had to find binding sites on the Troponin Cs in sarcomere
-massive parallel delivery that is local s the T tubule network has a storage of Ca that is released
-ryanodine receptor is activated by the Ca and causes the SR to release more Ca —> drives contraction
-some Ca goes through the mitochondrial Ca uniporter that tells us how much ATP is needed
-some Ca goes back through the SR in the SR-ATPase
-Na-Ca pump bringing Ca out and Na in —> helps maintain the electrochemical gradient

Question 33

tropomyosin

Answer 33

protein in a macro-helix structure that blocks binding sits on actin for myosin binding

Question 34

contraction

Answer 34

myosin head goes from disorganized inactivation state to activation state

Question 35

structure of sarcomere

Answer 35

-Ca binds to the Troponin protein complex, specifically Troponin C, and allows the rope to move off the groove for binding sites to be available
-when the Ca level falls again, the Troponin comes back and closes the binding sites
-regulates contractions

Question 36

isoproterenol

Answer 36

beta receptor agonist that activates heart muscle

Question 37

rise and fall of calcium with isoproterenol

Answer 37

-Ca increases very quickly and decreases very quickly —> sympathetic nervous system is activated
-heart beats and relaxes faster when in fight/flight or exercising

Question 38

beta-adrenergic receptor to PKA

Answer 38

-isoprotrenol interacts with the g-coupled protein receptor with a regulatory alpha subunit
-when the receptor is occupied, you break it up and the activated alpha subunit is bound to GTP —> activates adenylate cyclase and converts ATP to cAMP
-cAMP is a secondary messenger that acts on the regulatory domain of the PKA which phosphorylates

Question 39

what does the PKA phosphorylate?

Answer 39

-myofilament proteins like Titin that interacts with thick filaments and acts as a molecular spring that provides stiffness to the heart
-myosin binding protein C (myPBC), which acts as a jockey by keeping pace for coordinated action and acts as an intrinsic brake but also has moments where it is let up and allows more sarcomeres to form and faster
-troponin I- inhibitory and acts to reduce responsiveness of myofilaments to Ca and the more it’s phosphorylated, the less it does this
-phospholamban- makes it easier for ATP to bring Ca in

Question 40

hypertrophic cardiomyopathy

Answer 40

50% of patients with this have mutations of myPBC and you will contract more

Question 41

increase in Ca

Answer 41

-sarcomere phosphorylates the Ca channel to increase depolarization, more Ca and Ca release
-Ca gets to the troponin C and more Ca means more unfolding of tropomyosin —> more contractions

Question 42

what happens if you can’t phosphorylate the myPBC?

Answer 42

can’t increase contractility

Question 43

pulmonary edema

Answer 43

can lead to heart failure