Physiology 501 #3

Front 1

Blood flow cardiac output

Back 1

Q = (Pa – Pv)/R

Pa ~ constant

Pv = 0 (ie atm P)

Front 2

Poiseuille's resistance equation

Back 2

Front 3

Reynold's number

Back 3

■   When Reynolds’ number is increased, there is a greater tendency for turbulence, which causes audible vibrations called bruits.

Reynolds’ number (and therefore turbulence) is increased by the following factors:

a. ↓ blood viscosity (e.g., ↓ hematocrit, anemia)

b. ↑ blood velocity (e.g., narrowing of a vessel)

•NR = ρ*d*v/η

NR > 2000, turbulence can develop

Front 4

Cardiac output

Back 4

CO = SV x HR

1 ml/kg

Front 5

Cardiac Index

Back 5

CI = CO / body surface area

CI = 2.2-4.0 L/min/m2

Front 6

Law of laplace

Back 6

T = P*r / w

P = 2HT / r

H, w = wall thickness

T= circumferential wall tension

P = transmural pressure

Front 7

EDV / ESV / Ejection fraction

Back 7

End diastolic volume: volume of blood in ventricle the instant before systole begins (140ml)

End systolic volume: volume of blood in ventricle at the completion of systole (60-70ml)

EDV»140 ml Timing:Atclosure of AV valve ESV»60-70ml Timing:At closure of aortic/pulmonic valve

SV = 70-80ml

Ejection fraction: SV / EDV ≥ 0.55

Front 8

Newtonian fluid

Back 8

•Formostfluids (e.g., blood plasma) viscosity is independent of fluid velocity; thesefluids are called "Newtonian" fluids.

•Wholeblood,however, is a suspension of red cells in plasma and the viscosity of blood does depend on fluid velocity. Thisbehavior is termed "non-Newtonian."

Front 9

polycythemia

Back 9

an abnormally increased concentration of hemoglobin in the blood, through either reduction of plasma volume or increase in red cell numbers.

Hct > normal

Front 10

shear rate

Back 10

•Shear rate is the relative velocity of onelayer of fluid with respect to that of adjacent layers

•RBCs tend to aggregate and the existence of a relative velocitytends to break up aggregates as shear rate increases

•It is expressed as γ =-dv/dr

Front 11

Nitric oxide

Back 11

•Vasodilator nitric oxide (NO) is continuously released from endothelial cells lining all blood vessels

Front 12

vascular runoff

Back 12

•There are two determinants of blood volume in large arteries (and hence pressure in large arteries)

•1: Rate at which blood enters large arteries from left ventricle (i.e., cardiac output)

•2: Rate at which blood leaves large arteries by flowing through organs of body (i.e., blood flow through TPR or SVR, sometimes called ‘vascular runoff’)

Front 13

components of arterial pressure

Back 13

•Diastolic pressure:Pd (min Pa)

•Systolic pressure:Ps(max Pa)

•Mean arterial press:Pa ≈ Pd + (Ps - Pd)/3

Pulse pressure:Pp = Ps - Pd

•Pp ≈ stroke volume/Ca

Front 14

mean circulatory pressure

Back 14

•Increment in blood volume that produces a recoil pressure within the CV system

•Recoil pressure called “mean circulatory pressure” or Pmc

Pmc = Vs/Cs, where Cs is capacitance of stressed volume

Two ways to change Pmc:

1. Changes in BV (BV->Vs[stressed])

2. Changes in Venus contraction (decreased Vu -> increased Vs -> increase in Pmc)

Front 15

phospholamban

Back 15

inhibits SERCA; after phosphorylation, it stops inhibiting the SERCA; hence, activating the pump

Front 16

TnI

Back 16

phosphorylation stimulates Ca2+ unbinding from TnC and permits faster Ca2+ reaccumulation

Front 17

Ca2+ influx / efflux methods

Back 17

ALL TAKEN PLACE IN SARCOLEMMA

influx: Ca2+ channels

efflux: Na/Ca exchanger (3:1) high capacity low affinity; Sarcolemmal Ca-ATPase low cap/ high aff

Front 18

modulation of contractile force

Back 18

X-bridgecycle & ATP split => A-M complexes x fraction TnC-Ca

Developedforce & shortening => length x contractility

Front 19

SR Ca release

Back 19

Trigger (Ica): Ca channel modulated by sym/para

SR Ca stores: depends on [Ca]i

Front 20

What is responsible for stretching cardiac muscle?

Back 20

venous return / arterial contraction

Front 21

Muscle shortening is regulated by

Back 21

Length (preload)

contractility

HR

Front 22

Frank-StarlingCompensation

Back 22

Increased afterload & decreased contractility are compensated by increased preload (ie RAP)

Front 23

Cardiac function curve

Back 23

Primaryeffect: ­RAP®­SV& ­CO

Secondaryeffects: limit ­CO

(1) + ­RAP -> + SV -> + ­afterload -> - SV

(2)­+RAP -> +­length -> +­ejectionvel -> +afterload -> -SV

(3)Aortic: -Caas +­Pa(afterload) -> -SV

(4)Diastolic limits on filling: 1.pericardium 2. steep diastolic P-V curve

Front 24

CFC vs VFC

Back 24

•Parameters which affect pump function are:•Heartrate•Contractility•Afterload

•Parameters which affect blood transport function are:•Bloodvolume•Capacitancesof the arteries and veins•Totalperipheral resistance (TPR or SVR)

Front 25

Venus return

Back 25

blood returning from veins into right atrium

This represents the normal state ofaffairs in terms of CO(called Qh here) and venous return (called Qr here)

Qh = Qr = (Pa – Pv)/R

Front 26

Starling’sHypothesis

Back 26

inthe steady state,thereis a balance between hydraulic and osmotic pressures which leads to little or no netflow of water.

•F = K {(Pc - PISF) - (Πpl -ΠISF)}

K = capillary filtration coefficient(=permeability towater x perfused capillary surface area)

Front 27

How much is filtered and reabsorbed?

Back 27

20L / day filtered and 16L / day reabsorbed which leaves 4L / day to lymphatic system

•Control of ISF protein concentration is one of the most importantfunctions of the lymphatic system

Front 28

Determinantsof Lymph Flow

Back 28

•Interstitial fluid pressure

•Thelymphatic"pump" (movesfluid from extremitiesto central circulation) Note that lymphatic “circulation” is a passive system with no real pump

•One-way flap valves (produce unidirectional flow)

•Skeletalmusclecontraction (periodicallysqueezes fluid in lymphatics)

•Tissue compression (squeezes fluid in lymphatics)

Front 29

Edema formation

Back 29

•Increase in net fluid filtration (see Starling equation)

•Most common factors would be:

•­ +Pc• -Πpl•­ +capillary filtration coefficient •Decrease in lymph flow due to obstruction of lymphatics or removal of lymph nodes

Front 30

Baroreceptor Reflex

Back 30

•Location of sensor: Bifurcation of common carotid into internal and external carotids

•Mechanism: Stretch receptors in wall of carotid sinus

•Passive stretch increases firing rate of carotid sinus nerve (Hering's nerve)

Front 31

Global vs local control of the blood flow

Back 31

•Global or overall regulation of flow is accomplished by (1) autonomic innervation of blood vessels and (2) circulating vasoactive hormones (“neurohumoral” regulation)•Typically involves all organssimultaneously•“Extrinsic” in the sense that source of vasoactive stimulus arises fromoutside organ•Often vasoconstrictor in nature (e.g., norepinephrine,angiotensin II)

•Local regulation of flow is accomplished by production and release of vasoactivemolecules from(1) nearby parenchymal cells and/or (2) endothelial cells•Typically involves only singleorgan•“Intrinsic” in the sense that source ofvasoactive stimulus arises from inside organ. •Isolated •No sympathetic nerves•No circulating hormones •Often vasodilator in nature (e.g., adenosine, nitricoxide)

Front 32

Decreased arterial pressure induces

Back 32

+ HR

+ contractility

+ Pmc

+ TPR

Front 33

Ohm's law equivalent

Back 33

•Flow through a single organ is givenby

•Q = (Pa – Pv)/R

For the entire parallel network oforgans in the systemic circulation, we have

•CO = (Pa – Pv)/TPR

•Thus, Q = (TPR/R) x CO, where (TPR/R) is the fraction ofCO passing through the organ

hence, CO & Q are equivalent to current

Front 34

Examples of local blood flow

Back 34

•Autoregulation: Tendency for organ blood flow to remainconstant inthe faceoflocal changes in arterial pressure

•Reactive hyperemia: Elevated blood flow observed in an organfollowing a period of circulatory arrest

•Active (or functional) hyperemia: Increase in blood flow which accompanies anincrease in metabolicactivityof an organ

Front 35

Theories of Local Blood Flow Regulation

Back 35

•Myogenic mechanism – vascular smooth muscle contractsin response to stretch. •Appearsthat myogenic response tries to keep wall tension of ‘resistance’vessels constant•Law of Laplace: T = P r/w; hence, decreasing r in response to increased P.

•Metabolic mechanism – link between blood flow andcellular metabolism (eg. adenosine, H+, lactate, [K]isf, CO2, increased ISF osmolarity)

Front 36

Diffusion consideration of excercise

Back 36

•1. Surface area for exchange (proportional tonumber of perfused capillaries)••2. Maximum diffusion distance of oxygen (proportional to intercapillary distance)••3. Residence time of blood in capillary (inversely proportionalto velocity of red blood cells)

Front 37

Temporal phases of excercise

Back 37

•Phase 1 (mechanical response): •During this phase muscles, particularly of the abdomen, are tensed. Effect of mechanical phase is to decrease unstressed volume and, hence, to increase stressedvolume. This leads to increase in Pmc and cardiac output.

•Phase 2 (neural response): •Allpartsof sympatheticresponseare activated:

•a. Vagal stimulation of SA node is depressed; •b. Sympathetic stimulation of SA node is increased andsympathetic stimulation of ventricular muscle is increased;

•c. Sympatheticstimulation of arteries and arterioles is increased;

•d. Sympatheticstimulation of venules and veins isincreased. •Therefore, heart rate, TPR, Pmc and the VFC and CFC areshifted. Consequenceofchangesisincrease in cardiac output.

•Phase 3 (local response): loss of muscle K+ to interstitium; build up of adenosine; breakdown of glycogen producing H+; vasodilators enhance extraction of oxygen. Dilationof VSM of arterioles also decreases TPR significantly, leading to increase in CO. •Note that increase in vasodilator concentration in interstitial space overcomes sympathetic constrictor effect on arterioles, but not on venous vessels. There is vasodilation inarterioles of active tissues (contracting muscles and heart), while veins remain constricted and maintainelevated Pmc.

Front 38

Compensation for hemorrhage

Back 38

FAST:

-Pa -> -baroceptor firing rate

- activation of vasomotor inhibitory center

+ activation of vasomotor center

+ inhibition of vagal stimulation of SA node

+ sympathetic stimulation

Arteriolar constriction

- Pa & Pv -> - Pc -> absorption of ECF

INTERMEDIATE:

RAA system will be activated. Activationof this system will increase renal retention of sodium, and, indirectly water; thus, expand extracellular fluid volume, including blood volume. •This will increase Pmc and, thus, cardiac output and arterial bloodpressure. Blood pressure is generally returned close tonormal by this part of the control system.

SLOW:

•Expansion of blood volume by sodium and waterproduces dilutedblood whichis lowin red blood cells and plasma proteins •Deficiencies corrected by activation of hematopoietic system and plasma protein synthesis. •Combination of low renal blood flow and lowblood hematocrit causes release of erythropoietin;carriedby vascularsystemto bone marrow where it stimulates red blood cell (RBC)maturationand release of RBCs into blood •Perfusionof liver by blood containing subnormalconcentrations of plasma proteins activates protein synthesis by liver. Increased protein formation returns concentration of plasma proteins to normal

Front 39

Chronotropic / dromotropic / inotropic / lucitropic

Back 39

Chronotropic drugs may change the heart rate and rhythm by affecting the electrical conduction system of the heart and the nerves that influence it, such as by changing the rhythm produced by the sinoatrial node.

A dromotropic agent is one which affects the conduction speed in the AV node, and subsequently the rate of electrical impulses in the heart. Agents that are dromotropic are often (but not always) inotropic and chronotropic.

Inotropic - contractility; peak developed P; rate of P development

lucitropic - relaxation; rate of relaxation; contraction duration

Front 40

Factors that are affected by APD

Back 40

§Force of contraction

§Refractory periods

§ECG (Q-T interval)

§Arrhythmogenesis

Front 41

Cardiac innervation

Back 41

Parasympathetics

Vagusn. ®primarily supraventricular (SAN, atria, AVN) ® some fibers reach His-Purkinje and ventricle

ACh®muscarinicM2receptors; Gi-coupled(atropine:non-selective M receptor antagonist)

Sympathetics

Superior cervical ganglion ®Allregions

NE ® adrenergic b1receptors ; Gs-coupled(propranolol:non-selective breceptor antagonist)

Front 42

Role of main ionic currents

Back 42

INa(phase 0-1) -

Front 43

Recovery from inactivation modulates:

Back 43

§Refractoryperiods

§Excitability

§Conductionvelocity

Front 44

Blood reconditioner

Back 44

a. Lung - gas exchange (oxygen, carbon dioxide)b. Kidney - electrolyte composition, fluid balancec. Gut - nutrient absorptiond. Skin - temperature regulation

Front 45

Blood vessels are in a partially constricted state due to

Back 45

NE

Front 46

Mechanisms that alter contractility

Factors that alter contractility

Back 46

size of trigger

amount of SR [Ca2+]

nervous input

serum [Ca2+]

HR

Front 47

Resting stiffness in large part is due to

Back 47

titin (different isoforms found in cardiac and skeletal muscles)

Front 48

Initial shortening velocity is increased by

Back 48

increasing initial length, contractility, HR

Front 49

Oncotic pressure

Back 49

osmotic pressure set by protein; aka colloid osmotic pressure

Front 50

Increasing capillary hydraulic pressure

Back 50

increasing arterial / venous pressure

increasing venous resistance

decreasing arterial resistance

Front 51

Angiotensin II

Back 51

secretion of aldosterone from adrenal cortex

increased arterial pressure, Pmc, CO (constrictor of artery and vein)

Front 52

Normal sinus rhythm

Back 52

must occur from SAN

be at between 60-100 BPM

follow the correct sequence

Front 53

Equilibrium potential equation

Back 53

E = 61/z log (out/in)

Front 54

APD

Back 54

primarily the duration of phase 2:

defined by slow activation of IK / inactivation of ICa

Front 55

overdrive suppression

Back 55

suppression of ectopic pacemakers(latent pacemakers) from taking over the pacemaker activity of SAN

Front 56

rate of firing of pacemaker is depended on

Back 56

phase 4 depolarization

threshold potential

maximum diastolic potential

Front 57

determinants of conduction velocity

Back 57

excitability

passive properties (resistance, capacitance of cell membrane)

amplitude of inward current