Cardiovascular Physiology-- Electrical Activity Of The Heart

Front 1

Time relationship between muscle twitch and action potential

Back 1

- rapid depolarization precedes force development
- repolarization coincides with maximum force
- duration of contraction parallels duration of action potential
- as the frequency of cardiac contractions increase, the duration of action potentials and mechanical contractions decrease

Front 2

Fast response action potentials

Back 2

- occur in normal atrial and ventricular myocytes and in Purkinje fibers
- resting membrane potential much more negative than in slow response
- slope of upstroke, amplitude of action potential, extent of overshoot, greater than in slow response
-

Front 3

Slow response action potentials

Back 3

- occur in SA node and AV node (conducts cardiac impulse from atria to ventricles)
- resting membrane potential less negative than in fast response
- slope of upstroke, extent of overshoot, amplitude of action potential, less than fast response
- amplitude of action potential and steepness of upstroke determine propogation velocity --> slow response = slower, more easily blocked

Front 4

Pathalogic conversion of fast response to slow response

Back 4

coronary artery disease: region of cardiac muscle deprived of blood supply --> K+ concentration in interstitial fluid rises bc K+ is lost from inadequately perfused (ischemic) cells --> action potentials in some of these cells may change from fast response to slow response

Front 5

Intracellular and Extracellular ion concentrations and equilibrium potentials in cardiac muscle cells

Back 5

Ion EC IC Eq Pot
(mM) (mM) (mV)
Na+ 145 10 70
K+ 4 135 -94
Ca++ 2 10^-4 132

Front 6

Resting cell membrane ion permeabilty

Back 6

much more permeable to K+ than Ca++ or Na+, K+ tends to diffuse out of the cell down its concentration gradient

Front 7

inwardly rectifying K+ current

Back 7

many of the anions cannot freely diffuse out of the cell, during the repolarization phase, K+ diffuses out of the cell, leaving behind the anions, and returning the cell to its negative resting potential

Front 8

opposing forces involved in K+ movement

Back 8

more K+ inside the cell --> concentration gradient --> wants to diffuse out (chemical)
anions inside the cell --> attract K+ --> doesn't want to leave cell (electrostatic)
- electrostatic force is lightly weaker than the chemical force, K+ tends to leave the cell

Front 9

digitalis

Back 9

inhibits Na+/K+ pump --> resting membrane potential becomes less negative

Front 10

tetrodotoxin

Back 10

block fast Na+ channels --> inhibit action potential

Front 11

effect of extracellular sodium concentration

Back 11

- has little effect on resting membrane potential (because of low conductance)
- determines amplitude of action potential

Front 12

fast sodium channel gates

Back 12

m gate (activation gate): opens the channel as Vm gets less negative, opening of m gates responsible for large and abrupt increase in Na+ conductance in action potential, m gates open very rapidly
h gate (inactivation gate): closes channel as Vm gets less negative, close slowly, closure of h gate inactivates channel, stay closed until the cell has partially repolarized
- when the cell is at rest (-90mV) m gates are closed and h gates are open

Front 13

what changes during an action potential, the chemical force or electrostatic force of Na+?

Back 13

- electrostatic, amount of Na+ that enters the cell during an action potential is too small to change the intracellular sodium concentration , chemical force is constant
Na+ neutralizes negative charges as it rushes into cell --> Vm becomes less negative

Front 14

Phase 1 notch

Back 14

- in cells with prominent plateau, brief repolarization in phase 1 caused by transient outward current by K+
- size of notch varies: big in myocytes in epicardial and midmyocardial regions of the left ventricular wall and in ventricular purkinje fibers
- notch is negligible in myocytes from the endocardial region of the left ventricle because the density of the transient outward current channels is less
- notch is less prominent in presence f 4-aminopyridine, blocks K+ channels that carry transient outward current

Front 15

L type Ca++ channels

Back 15

- "long lasting", close slowly, predominant Ca++ channel in heart
- activated in during action potential upstroke when Vm = -20mV
- blocked by Ca++ channel antagonists such as: verapamil, amlodipine, dilitiazem
- opening of channels --> increase Ca++ conductance and current (after the upstroke) --> influx of Ca++ down concentration gradient

Front 16

T type Ca++ channels

Back 16

- less abundant than L type
- "transient", inactivate quickly
- activated at more negative potentials (-70mV)

Front 17

inward rectification K+ channels

Back 17

- during plateau, Vm is positive and the concentration gradient for K+ is the same --> K+ wants to leave the cell
- if gK were the same in the plateau as phase 4, K+ efflux would exceed Ca++ influx and you couldn't get a plateau --> inwardly rectifying K+ channels have high conductance at negative Vm but at 0 or positive Vm (action potential) they have little conductance --> diminished conductance of K+ during plateau

Front 18

delayed rectifier K+ channels (ik)

Back 18

- closed during phase 4, activated very slowly by potentials at end of phase 0
- increases gk gradually in phase 2
- contribute to final repolarization
- two types: iks = slow activating; ikr = fast activating --> distribution of of iks and ikr helps determine duration of action potential (action potential persists as long as K+ efflux is balanced by Ca++ influx)

Front 19

effect of diltiazem

Back 19

- Ca++ channel agonist
- more diltiazem --> less positive plateau voltage, shorter plateau

Front 20

What does addition of K+ channel agonists do to the plateau?

Back 20

- prolongs it

Front 21

Genesis of final repolarization

Back 21

- K+ exodus (ito, ik, ik1) begins to exceed Ca++ influx
- ito and ikr/iks help initiate repolarization -- determine plateau length
-

Front 22

magnitude of ik and duration of action potential and different kinds of myocytes

Back 22

endocardial: smallest duration of action potentials, greatest ik
midmyocardial: longest duration of action potential, smallest ik
epicardial: in the middle

Front 23

Does the inwardly rectifiying K+ channel (ik1) help initate repolarization?

Back 23

no --> conductance is small over Vm values present in plateau
- substantially contribute to rate of repolarization once phase 3 is initiated --> Vm becomes more negative --> ik1 conductance increases --> accelerated repolarization

Front 24

Restoration of ionic concentrations (phase 4)

Back 24

- steady inward Na+ leak --> Na+/K+ ATPase
- excess Ca++ from phase 2 --> 3Na+/1Ca++ antiporter, or ATP driven Ca++ pump

Front 25

What is one way to get a slow response in a fast acting fiber?

Back 25

- blocking fast Na+ channels with tetrodotoxin

Front 26

slow response action potentials

Back 26

- cells in SA and AV nodes
- depolarization is achieved by influx of Ca++ through L-type Ca++ channels instead of Na+ through fast Na+ channels
- repolarization by inactivations of Ca++ channels and increase K+ conductance through ik1 and ik channels

Front 27

conduction of current in cardiac fibers

Back 27

- gap junctions
- impulses along length of cell -- isotropic -- pass more easily than impulses laterally from cell to cell -- anisotropic, because gap junctions at ends of cells
- channels are non-selective, low electrical resistance

Front 28

conduction velocity of fast response

Back 28

greater action potential amplitude (potential difference between polarized and depolarized regions) --> faster conduction
faster rate of change of potential in phase 0 --> faster conductance
depolarization of resting membrane potential --> inactivation fast Na+ channels --> decreased amplitude of action potential and slope of upstroke --> slower conductance

Front 29

How does the Na+/Ca++ exchanger work?

Back 29

• Uses the energy that is stored in the electrochemical gradient of sodium (Na+) by allowing Na+ to flow down its gradient across the plasma membrane in exchange for the countertransport of calcium ions (Ca2+)
• A single calcium ion goes out for every 3 sodium ions that go in

Front 30

correlation between action potential duration and cycle length

Back 30

direct: decrease in cycle length --> decrease in action potential
ik (important in repolarization) activated at Vm near zero, activates and inactivates slowly --> as cycle length decreases action potentials occur earlier in the ik inactivation period (from previous action potential) --> greater outward K+ current during stage 2 --> shorter action potential duration

Front 31

How does the ito current effect the relationship between action potential duration and cycle length?

Back 31

- activated at near zero Vm
- magnitude varies inversely with cardiac cycle length
i.e shorter cycle length --> bigger ito K+ current --> shorter plateau

Front 32

Excitation of the heart

Back 32

SA node initiates action potentials --> spreads through atria --> AV node - conduction is slowed so atria can contract and ventricles can be filled --> excitation spreads through ventricles via purkinjie fibers

Front 33

SA node anatomy

Back 33

- main cardiac pacemaker
- 2-3 sites of automaticity, 1-2 cm from SA node with SA node = atrial pacemaker complex, sometimes all sites initiate impulses simultaneously, site of earliest excitation shifts from locus to locus
- posteriorly in groove at junction between superior vena cava and right atrium, runs lengthwise through center of node

Front 34

two types of cells in SA node

Back 34

1) small round cells, few organelles and myofibrils, pacemaker cells
2) slender, elongated cells, intermediate in appearance between round and ordinary atrial myocardial cells, conduct impulses with node and nodal margins

Front 35

SA node action potential

Back 35

when compared to a ventricular myocardial cell:
- resting potential is less negative
- upstroke of action potential (phase 0) is less steep
- plateau is not sustained
- repolarization is more gradual
--> characteristic of slow response
- tetrodotoxin (inhibits fast Na+ current) has no effect
- transmembrane potential during phase 4 is much less negative because lack ik1 (responsible for K+ efflux during phase 4) --> ratio of gK/gNa+ much less than in myocytes --> in phase 4 Vm deviates much more from K+ potential than in myocytes
- in nonautomatic cells potential in phase 4 stays the same, in pacemaker cells gets steadily depolarized until threshold

Front 36

What changes pacemaker cell frequency?

Back 36

1) rate of depolarization in phase 4; if rate of depolarization is increased --> threshold attained earlier --> faster heart rate
2) maximal negativity in phase 4; if it becomes more negative --> takes longer to reach threshold --> slower heart rate
3) threshold potential; rise in threshold potential --> delays phase 0 --> slower heart rate

Front 37

effect of autonomic nervous system on frequency of firing of pacemaker cells

Back 37

increases sympathetic activity (i.e release of noroepinephrine) --> increases slope of depolarization --> rise in heart rate -- occurs during physical exertion, anxiety, certain infectious diseases
increased vagal activity (parasympathetic) via release acetylcholine --> hyperpolarizes cell membrane --> decreased slope depolarization --> slower heart rate

Front 38

currents that mediate diastolic depolarization in SA node -- automaticity

Back 38

- slow depolarization occurs in phase 4, mediated by 3 currents
1) inward current, if, induced by hyperpolarization, carried by Na+ (different from fast Na+ channels), activated during repolarization phase at -50mV, more negative --> greater activation --> greater influx of Na+
2) calcium current iCa: activated at end of phase 4, at -55mV --> increase in Ca+ influx --> upstroke of action potential
3) outward K+ current, ik: counteracts 2 inward currents, K+ efflux repolarizes cell after depolarization, continues well beyond time of maximal repolarization but decrease in phase 4
- slow diastolic depolarization principally mediated by imbalance between if and ik (basis of automaticity = the same in SA, AV and purkinje but purkinje do not involve Ca+ current)

Front 39

how do autonomic neurotransmitters effect automaticity?

Back 39

- alter ionic currents
adrenergenic transmitter: increase all 3 currents in SA (if, iCa, iK), however they cause an increase in the slope of depolarization --> enhancement of inward currents exceeds enhancement of iK
acetylcholine release from vagus (in heart): increase in gK, depression of if and iCa --> hyperpolarization (harder to get an action potential)

Front 40

overdrive suppression

Back 40

- automaticity of pacemaker cells gets depressed after period of excitation at high frequency
- SA node tends to suppress automaticity in other locations
more frequent depolarization --> more Na+ enters cell --> Na+/K+ pump becomes more active in extruding Na+ --> net loss of cations --> hyperpolarization of cell --> takes more time to reach threshold
- when overdrive ceases Na+ pump may not slow down immediately -- opposes depolarization, suppresses automaticity temporarily

Front 41

atrial action potential

Back 41

in comparison to ventricular action potential:
1) plateau phase (phase 2) is not as well developed
2) repolarization (phase 3) occurs more slowly
3) duration of the action potential is shorter

Front 42

AV node - anatomy

Back 42

- posteriorly on right side of interatrial septum near ostium of coronary sinus
- same 2 cell types as SA node but long cells predominate over round cells
3 functional regions:
1) AN region: transitional zone between atrium and remainder of node
2) N region: midportion
3) NH region: nodal fibers merge with bundle of His -- upper portion of conducting system for ventricles
(AV node and bundle of His = only pathway for atrial --> ventricular conduction)

Front 43

features of AV node

Back 43

- main delay in conduction from atria to ventricals occurs in AN and N regions
- conduction velocity greater in AN than N
- path length greater in AN than N

Front 44

characteristics of action potentials in different regions of the AV node

Back 44

N region:
- slow response action potentials prevail
- resting potential = -60 mV
- low upstroke velocity
- tetrodotoxin (blocks fast Na+ channels) has no effect,
- Ca+ antagonists decrease amplitude and duration of action potential, depress conduction
- relative refractory period extends well past repolarization -- post-repolarization refractoriness
AN: shapes of action potentials intermediate between those in the N region and atria
NH: action potentials transitional between N region and bundle of His

Front 45

first degree AV block

Back 45

- abnormal prolongation of AV conduction time
- relative refractory period extends well past repolarization -- post-repolarization refractoriness --> as repitition rate of depolarizations increases conduction through AV node slows

Front 46

second degree AV block

Back 46

- only a fraction of atrial impulses are conducted to the ventricles
- impulses tend to be blocked in AV node at repetition rates that are easily conducted in other regions
- may protect against excessive contraction frequencies --> allows enough time for ventricles to contract

Front 47

third degree (complete) AV block

Back 47

- none of the atrial impulses reach the ventricles for a substantial amount of time
- acetylcholine released from vagal nerve (autonomic)--> hyperpolarizes N region --> the more hyperpolarized at time atrial impulse arrives more impaired conduction
- weak vagal activity just prolongs AV conduction time

Front 48

what is the effect of cardiac sympathetic nerves on the AV node?

Back 48

- facilitate conduction -- decrease conduction time
- neuroepinephrine --> increases amplitude and slope of upstroke, principally in AN and N regions

Front 49

ventricular conduction -- anatomy

Back 49

- bundle of His passes subendocardially down right side of intraventricular septum --> divides into right and left
right branch: direct continuation of bundle of His, goes down right side of intraventricular septum
left bundle: much thicker than right, arises perpendicular to His, perforates interventricular septum, subendocardial surface of left side of interventricular septum -- splits into thin anterior division and thick posterior division
- both branches and divisions then subdivide into purkinje fibers

Front 50

Purkinje fibers

Back 50

- broadest cells in heart, large diameter --> greater conduction velocity
- abundant sarcomeres
- no T-tubule system
- fastest conduction of action potential --> rapid activation of entire endocardial surface of ventricles
- action potentials similar to other ventricular cells but phase 1 more prominent and plateau longer

Front 51

what protects the ventricles from premature contraction? at low heart rates? at high heart rates?

Back 51

purkinje fibers have relatively long refractive periods --> many premature activations of atria conducted by AV node blocked by purkinje, premature contraction of ventricles doesn't happen
- especially pronounced at slow heart rates bc, slow heart rate = longer effective refractory period (fast heart rate, shorter refractory period)
In contrast: in AV node, effective refractory period does not change significantly with change in heart rate, but gets longer with increase in heart rate --> in AV node, at high heart rates AV node protects ventricles from impulses arriving at excessive rates

Front 52

Circuitry

Back 52

1. oxygenated blood fills left ventricle (from lungs --> pulmonary vein --> left atrium --> left ventricle)
2. blood ejected from left ventricle into aorta --> aortic valve (semilunar)
3. cardiac output distributed among different organs: parallel arrangement, total systemic blood flow = cardiac output
4. blood flow from organs collected in veins
5. vena cava (higher) --> right atrium (lower)
6. mixed venous blood fills right ventricle via AV valve (tricuspid)
7. blood ejected from right ventricle into pulmonary artery (via pulmonic/semilunar valve) --> lungs
8. blood from lungs returned via pulmonary vein
- 2 sides of heart operate in series: cardiac output from left ventricle equals cardiac output of right ventricle, return to left heart equals return to right heart ...

Front 53

How can the distribution of cardiac output among organs be changed during strenuous exersize?

Back 53

1. cardiac output = constant, blood flow redistributed via arteriole resistance change
2. cardiac output increases or decreases but percent distribution among organs stays the same
3. both cardiac output and percent distribution are changes

Front 54

arteries

Back 54

- thick walled
- lots of elastic tissue
- also smooth muscle, connective tissue
- "stressed volume" , high pressure

Front 55

arterioles

Back 55

- lots of smooth muscle: tonically active = always contracted
- highest resistance to blood flow
- sympathetic innervation:
i. alpha adrenergic --> constriction --> decrease in diameter --> increase in resistance
ii. beta 2 adrenergic (skeletal muscle) --> relaxation etc...

Front 56

capillaries

Back 56

- lining = single layer endothelial cells surrounded by basal lamina (thin walled)
- lipid soluble solutes (O2, CO2) --> dissolve and diffuse
- water soluble solutes (ions) --> enter via water filled clefts or large pores (fenestrated capillaries)
- selective perfusion dependent on metabolic needs: sympathetic signals --> dilation/perfusion arterioles/precapillary sphincters --> degree of capillary perfusion

Front 57

venules and veins

Back 57

- thin walled (endothelial cell layer, elastic tissue, connective tissue, smooth muscle) --> largest volume of blood in body = unstressed volume (low pressure)
- sympathetic innervation: increase in sympathetic activity --> contraction --> decrease capacitance --> decrease in unstressed volume

Front 58

P wave

Back 58

- depolarization of the atria
- duration = conduction time through atria
- atrial repolarization not seen on an ECG because "buried" in QRS complex

Front 59

PR Interval

Back 59

- time from initial depolarization of atria to initial depolarization of ventricles, usually 160ms
- includes P wave and PR segment
PR segment: isoelectric (flat), corresponds to AV node conduction,

Front 60

QRS complex

Back 60

- waves Q,R,S -- represent depolarization of ventricles
- ventricles depolarize just as quickly as atria, even though much bigger, because His-Perkinje fibers much faster conducters

Front 61

T wave

Back 61

repolarization of ventricles

Front 62

QT interval

Back 62

- includes QRS complex, ST segment and T wave
- first ventricular depolarization --> last ventricular repolarization
ST segment: isoelectric, correlates with plateau of ventricular action potential

Front 63

Heart rate

Back 63

- number of QRS complexes per minute
- cycle length = R-R interval
heart rate = 1/cycle length

Front 64

myocardial cell structure

Back 64

- sarcomeres run from z line to z line
- thick filaments: composed of myosin, globular heads have actin binding sites and ATPase
- thin filaments: actin, tropomyosin, troponin
Ca++ --> troponin C --> removal of tropomyosin inhibition of actin-myosin interaction
- transverse T tubules invaginate at Z lines, continuous with cell membrane, carry action potentials to cell interior, form dyads with SR (site of storage and release of Ca++)

Front 65

effect of sympathetic nervous system on contractility

Back 65

- positive ionotropic effect on myocardium, i.e increased contractility
1. increased peak tension
2. increased rate of tension development
3. faster rate of relaxation -- faster relaxation means shorter contraction and more time to refill
- mediated by beta 1 receptors coupled via Gs protein to adenylyl cyclase --> cAMP production --> protein kinase activation --> phosphorylation of proteins that enhance contractility
a. phosphorylation of sarcolemma Ca++ channels --> increased inward Ca++ current --> triggers more Ca++ release
b. phosphorylation of phospholamban --> when phosphorylated stimulates Ca++ ATPase --> greater uptake and storage of Ca++ by SR --> faster relaxation and increases amount of stored Ca++ for subsequent release

Front 66

effect of parasympathetic nervous system on contractility

Back 66

- negative inotropic effect on atria via muscarinic receptors coupled via Gi protein (Gk) to adenylyl cyclase
- inhibitory g protein --> decreased contractility
a. ACh decreases inward Ca++ current during plateau of action potential
b. ACh increases Ik-ach (outward K+ current) --> shortening duration of action potential , indirectly decreasing inward Ca++ current (by shortening plateau)
- decreased amount of Ca++ entering atrial cells in action potential --> decreased amount of Ca++ triggered --> decreased Ca++ released from SR

Front 67

positive staircase effect
(bowditch staircase)

Back 67

- when heart rate increases, tension increases in a stepwise fashion until it reaches a maximum
- more action potentials per unit time, more total trigger Ca++ entering cell during plateau phase, more Ca++ accumulating in SR
- very first beat after increased HR shows no increase in contractility because Ca++ has not accumulated yet

Front 68

postextrasystolic potentiation

Back 68

- extrasystole (extra beat by latent pacemaker), tension on following beat is greater than normal
- tension on extrasystole beat itself if less than normal
- extra Ca++ entered cell on extrasystole, accumulated by SR

Front 69

effect of cardiac glycosides on contractility

Back 69

- positive inotropic agents
- derived from foxglove, digitalis, ex. digoxin, digitoxin, ouabain
- inhibition of Na+/K+ ATPase
1. cardiac glycosides inhibit Na+/K+ ATPase in myocardial membrane at EC K+ binding site
2. less Na+ pumped out --> increase IC Na+
3. altered Na+ gradient --> Ca++/Na+ exchanger activity decreased (usually uses downhill Na+ gradient to pump Ca++ out)
4. less Ca++ pumped out --> increase IC Ca++
5. tension = directly proportional to IC Ca++ --> increase in tension = positive inotropic effect

Front 70

therapeutic use of cardiac glycosides

Back 70

- congestive heart failure characterized by decreased contractility of ventricular muscle
- ventricle can't develop enough tension --> can't eject normal stroke volume (to aorta (L) or pulmonary artery (R))
- increased IC Ca++ in ventricular cells --> positive inotropic action

Front 71

length tension relationship in cardiac muscle cells

Back 71

- max tension depends on resting length
- physiologic basis for length-tension relationship: degree of overlap of thick and thin filaments and number of possible sites for crossbridging (Ca++ concentration determines what fraction cross bridges cycle)
- max tension (Lmax) = 2.2 micoM --> max overlap thick and thin filaments (shorter/longer <max)
- increasing muscle length --> increases Ca++ sensitivity of troponin C and Ca++ release from SR

Front 72

length tension relationship for ventricles during systole

Back 72

ventricular pressure during systole is a function of end-diastolic volume:
fiber length increases --> pressure increases (active) --> greater overlap thick and thin filaments, greater cross bridge formation and cycling, greater tension developed
- curve levels off when tension is max
- if lengthened beyond max tension would decrease, decreased overlap etc.. --> this doesn't happen because cardiac muscle = stiff -- high resting tension --> small length increase --> large increase resting tension --> difficult to lengthen beyond Lmax

Front 73

length tension relationship for ventricles during diastole

Back 73

- end diastolic volume increases --> ventricular pressure increases (passive) (muscles being stretched -- longer)
preload: left ventricular end diastolic volume/fiber length, i/e resting length from which muscle contracts
afterload: aortic pressure, velocity of shortening of cardiac muscle is max when afterload is zero, velocity of shortening decreases as afterload increases

Front 74

stroke volume

Back 74

- volume of blood ejected on one ventricular contraction
- 70mL
stroke volume = end-diastolic volume - end-systolic volume

Front 75

ejection fraction

Back 75

- fraction of end-diastolic volume ejected in each stroke volume --> measure of effectiveness of ventricles
- 55% = normal
- indicates contractility, increase in ejection fraction = increase in contractility
ejection fraction = stroke volume/end-diastolic volume

Front 76

cardiac output

Back 76

- total volume ejected by the ventricle per unit time
- depends on volume ejected by a single beat and on beats per minute
- 5000 mL/min (70kg man, HR 72)
cardiac output = stroke volume x heart rate

Front 77

Frank-Starling relationship

Back 77

- volume of blood ejected by the ventricle depends on volume present in ventricle at end of diastole
- volume present at end of diastole depends on venous return --> makes sure volume heart ejects in systole equals volume received in venous return
- venous return increases --> end-diastole volume increases --> stroke volume increases
- at very high end-diastolic volume, ventricle can't keep up, curve flattens out, stroke volume stops increasing

Front 78

effects of positive and negative inotropic agents on frank-starling relationship

Back 78

positive inotropic agents: (ex. digoxin), increase in stroke volume and cardiac output for given end-diastole volume (cause increase in IC Ca++ --> increase in tension) --> increase in ejection fraction
negative inotropic agent: decrease contractility, decrease stroke volume and cardiac output for given end-diastolic volume --> decrease in ejection fraction

Front 79

ventricular pressure volume loop
(in left ventricle)

Back 79

- describes complete ventricular cycle (systole plus diastole)
isovolumetric contraction:
1. end of diastole, high volume, low pressure (ventricle relaxed)
2. ventricle activated --> contracts --> high pressure, aortic valve not open yet so volume is constant
ventricular ejection:
3. ventricular pressure reaches aortic pressure --> aortic valve opens --> ejection --> volume decreases dramatically as blood is ejected
isovolumetric relaxation:
4. ventricular pressure decreases below aorta --> aortic valve closes (volume is constant)
ventricular filling:
5. pressure is less than atrial pressure --> mitral valve opens --> L ventricle fills with blood --> volume increases (pressure = constant)

Front 80

changes in ventricular pressure volume loops

Back 80

increased preload: (i.e end diastolic volume), stroke volume increases (width of pressure volume loop increases), greater end diastolic volume --> greater stroke volume
increased afterload: increased aortic pressure --> ventricular pressure rises above normal during isovolumetric contraction and ventricular ejection --> decreased stroke volume --> increases end systolic volume
increased contractility: greater tension and pressure during systole --> stroke volume and ejection fraction increase --> end systolic volume decreases

Front 81

cardiac work

Back 81

work = force x distance
L ventricle: work = aortic pressure x stroke volume
power = work/unit time
cardiac minute work = cardiac output (volume work) x aortic pressure (pressure work)
--> increase in cardiac output (due to increase in stroke volume or increase in HR) or increase in aortic pressure

Front 82

myocardial O2 consumption

Back 82

- pressure work (aortic pressure) uses much more oxygen than volume work (cardiac output)
cardiac minute work = cardiac output x aortic pressure
--> left ventricle must work harder than right ventricle because mean aortic pressure higher than pressure in pulmonary artery (although cardiac output is the same on both sides) --> left ventricular wall thicker than right ventricular wall

Front 83

myocardial oxygen consumption and aortic stenosis

Back 83

- incomplete opening of aortic valve --> increased pressure work -- very oxygen costly (pressure work more costly than volume work)

Front 84

myocardial oxygen consumption and strenuous exersize

Back 84

- high cardiac output --> greater contribution of volume work --> oxygen consumption doesn't increase that much because volume work is not as costly as pressure work

Front 85

systemic hypertension and myocardial oxygen consumption

Back 85

left ventricle must perform more pressure work (requires a lot of oxygen) --> left ventricular wall hypertrophies

Front 86

law of Laplace

Back 86

- pressure correlates directly with tension and wall thickness
- pressure correlates inversely with radius
ex. left ventricular wall is thicker, can develop more pressure

Front 87

Fick Principle

Back 87

rate of O2 consumption by body = amount of O2 leaving lungs via pulmonary vein - amount of O2 returning to lungs via pulmonary artery
- O2 consumption typically 250 mL/min (70kg man)
- measures cardiac output:
cardiac output = O2 consumption/ [O2] pulmonary vein - [O2] pulmonary artery
(same formula can be used for organs as well as whole body O2 consumption)

Front 88

Atriole systole

Back 88

- atrial contraction
ECG: preceded by P wave - atrial depolarization
Heart sounds: fourth heart sound, not present in normal individuals, heard in ventricular hypertrophy (decreased compliance), coincides with atrial contraction, caused by atrium contracting against/trying to fill stiffened ventricle
venous pulse: a wave, increase in left atrial pressure reflected back to veins
left ventricle: blip in left ventricle pressure as blood ejected form L atrium enters ventricle

Front 89

Isovolumetric ventricular contraction

Back 89

- ventricular volume constant because all valves closed
ECG: begins in QRS complex, electrical activation of ventricles
Heart sounds: first heart sound, produced by closure of AV valves (mitral valve, tricuspid) as ventricular pressure exceeds aortal pressure, may be split because mitral valve closes slightly before tricuspid
L ventricle: L ventricle contracts --> increase in L ventricle pressure, once it exceeds aortal pressure --> mitral valve closes

Front 90

Rapid ventricular ejection

Back 90

ECG: end of ST segment (isoelectric portion of QT interval in between depolarization and repolarization of ventricles), beginning of T wave (repolarization of ventricles)
L ventricle: when ventricular pressure highest --> aortic valve opens, most of stroke volume ejected --> aortic pressure increases because of large volume entering aorta
atrial pressure: atrial filling begins, L atrial pressure slowly increases

Front 91

Reduced ventricular ejection

Back 91

ECG: beginning of T wave (repolarization)
ventricular pressure: falls because no longer contracting, aortic valve still open -- blood still ejecting but at reduced rate
aortic pressure: falls, blood is still being added to aorta but is leaving aorta at faster rate
L atrial pressure: increasing as fills with blood

Front 92

Isovolumetric ventricular relaxation

Back 92

ECG: end of T wave (ventricles repolarized)
L ventricular pressure: decreased because ventricle is relaxed and highly compliant
Heart sound: 3rd, rapid flow of blood from atria to ventricles, normal in children, not heart in adults, in older adults S3 indicates volume overload -- congestive heart failure, advanced mitral/tricuspid regurgitation
aortic pressure: decreases as blood leaves

Front 93

Reduced ventricular filling (diastasis)

Back 93

- longest phase of cardiac cycle
- final portion ventricular filling at slower rate
- changes in heart rate effect time for diastasis
- if diastasis is shortened too much --> ventricular filling compromised --> reduced stroke volume

Front 94

Heart sounds

Back 94

S1: mitral and tricuspid valves closing (can split)
S2: aortic and pulmonic valves closing
S3: mitral valve and tricuspid open (heard in children and adults with congestive heart failure)
S4: atrium contracting against stiffened ventricle, not normally heard

Front 95

baroreceptor reflex

Back 95

- baroreceptors keep arterial pressure constant via changes in output of sympathetic/parasympathetic nervous system
- baroreceptors (in walls of carotid sinus and aortic arch) --> relay information to cardiovascular vasomotor centers in brainstem via afferent neurons --> change in ouput autonomic nervous system via efferent neurons --> change in pressure

Front 96

Baroreceptors

Back 96

- located in walls of carotid sinus -- where common carotid artery bifurcates into internal and external carotid arteries, and in aortic arch
- carotid sinus receptors: respond to increases/decreases arterial pressure, carotid sinus nerve joins glossopharyngeal nerve (CN IX)
- aortic arch receptors: primarily respond to increases in arterial pressure, vagus nerve (CN X)
- mechanoreceptors: sensitive to pressure/stretch, stretch --> change in membrane potential = receptor potential, increases/decreases likelihood action potentials will be fired in afferent nerves to brainstem (depolarization - increased frequency and v.v)
- more sensitive to change in pressure than absolute level of pressure

Front 97

effect of chronic hypertension on baroreceptors

Back 97

- do not see elevated BP as abnormal --> hypertension maintained
- mechanism: either decreased sensitivity of receptors to increases in arterial pressure, or reset of BP point of brainstem

Front 98

colloidosmotic/oncotic pressure

Back 98

- effective osmotic pressure contributed by protein in capillary blood --> only protein contributes to effective osmotic pressure because it is the only solute than cannot cross the membrane

Front 99

Starling equation

Back 99

- fluid movement across capillary wall driven by starling pressures (osmotic pressure and hydrostatic pressure)
- filtration: net fluid movement out of capillary into interstitial fluid
- absorption: net fluid movement into capillary out of interstitial fluid
- magnitude of fluid movement determined by hydraulic conductance, Kf (water permeability) of capillary wall

Front 100

Pc, capillary hydrostatic pressure

Back 100

- force favors filtration out of capillary
- Pc determined by both arterial and venous pressures -- closer to arterial pressure, but is effected more by changes in venous pressure than changes in arterial pressure
- Pc declines along length of capillary as filtration occurs, highest at arteriole end, lowest at venule end
(exception: Pc constant in glomerular capillaries)

Front 101

Pi, interstitial hydrostatic pressure

Back 101

- force opposes filtration
- normally near zero, may be negative

Front 102

Pi c, capillary oncotic pressure

Back 102

- force opposes filtration
- effective osmotic pressure of capillary due to plasma proteins (determined by protein concentration)
- increase in [protein] --> increase capillary oncotic pressure --> decrease in filtration

Front 103

Pi i, interstitial osmotic pressure

Back 103

- force favors filtration
- determined by interstitial protein concentration
- usually very little loss of protein from capillaries --> little protein in interstitial fluid --> low interstitial oncotic pressure

Front 104

Lymph

Back 104

- lymphatic system returns interstitial fluid and proteins to vascular compartment
- lymphatic capillaries in interstitial fluid near vascular capillaries, --> one way flap valves: allow fluid and protein to enter but not leave --> merge into larger lymphatic vessels --> thoracic duct (largest lymphatic vessel) --> empties into large veins
- have smooth muscle, contracts helps fluid flow back to thoracic duct, also compression of surrounding skeletal muscle helps fluid flow

Front 105

Edema

Back 105

- increase in interstitial fluid volume --> when volume of interstitial fluid exceeds ability of lymphatics to drain it --> forms when increased filtration or lymphatic drainage impaired
things that can cause increased filtration: increased capillary hydrostatic pressure, decreased capillary oncotic pressure, increased hydraulic conductance
- lymph drainage impaired when lymph nodes surgically removed/irradiated, parasite infection (filariasis), or lack of muscle activity

Front 106

Coronary circulation

Back 106

- controlled by local metabolites, sympathetic innervation has minor role
- hypoxia (local metabolic factor): increase in myocardial contractility --> increased O2 demand --> increased O2 consumption --> local hypoxia --> vasodilation of arterioles --> increase in coronary blood flow --> more O2 delivered
- mechanical compression of blood vessels during systole --> brief occlusion/reduction blood flow --> when occlusion is over -- hyperemia (increase of blood flow) -- repays O2 debt from compression

Front 107

Response of cardiovascular system to exercise

Back 107

- CNS response and local response
- CNS response: central command from cerebral motor cortex --> changes in autonomic nervous system
- local response: metabolites increase blood flow and O2 delivery to exercising skeletal muscle
- changes in arterial PO2, PCO2 are not significant, do not change significantly during exercise

Front 108

Central Command -- cardiovascular response to exercise

Back 108

- responses directed by cerebral motor cortex initiated by anticipation/initiation of exercise
- triggered by mechanoreceptors, maybe chemoreceptors
- efferent limb produces increased sympathetic outflow to heart and blood vessels and decreased parasympathetic outflow to the heart
- increase in cardiac output (cardiac output = HR x stroke volume):
1. increase in sympathetic (beta 1) receptors in heart, and decrease in parasympathetic activity --> increase in HR
2. increase in sympathetic activity (beta 1) receptors --> increase contractility --> increase in stroke volume
- increase in cardiac output insures O2 delivery to exercising skeletal muscle (if it did not increase, only other way to increase blood flow would be redistribution)
- venous return must increase because cardiac output increases: contraction skeletal muscle + activation sympathetic nervous system --> venoconstriction --> decrease unstressed volume --> increase venous return

Front 109

selective arteriolar vasoconstriction -- cardiovascular response to exercise

Back 109

- consequence of increased sympathetic outflow in central command
- vasoconstriction in some vascular beds so blood flow is redistributed to exercising skeletal muscle and heart, blood flow maintained to essential organs like brain

Front 110

Local response: cardiovascular response to exercise

Back 110

- active hyperemia: metabolic rate of skeletal muscle increases --> production of vasodilator metabolites (lactate, potassium, adenosine) --> local vasodilation -->increased blood flow meets metabolic demand
- vasodilation --> overall increase in TPR (even though selective vasoconstriction caused by sympathetic response)