1

Hematocrit, plasma & serum

fig 12-1

Hematocrit = volume of red cells (~45%)

Plasma = fluid in fresh blood

Serum = fluid after blood has clotted

Plasma = serum + fibrinogen (& other clotting factors)

Normal volumes:blood ~5.5L, plasma ~3L, rbc’s ~2.5L

2

Systemic, pulmonary circulations

fig 12-2

2 hearts, each with 2 chambers

Left heart to all body except lungs (systemic)

Right heart to lungs (pulmonary)

Systemic arteries: oxygenated blood

Pulmonary arteries: deoxygenated blood

Systemic veins: deoxygenated blood

Pulmonary veins: oxygenated blood

Atria: receive blood from veins

Ventricles: pump blood to arteries

3

Pressure, flow & resistance

flow = Δ pressure / resistance

Later you will see that:

blood pressure = cardiac output (flow) x peripheral resistance

It is Δ pressure that drives flow

4

Resistance

resistance = 8 x x L

x r4

where:

= viscosity (“eta” mostly depends on hematocrit)

L = length of vessel

r = radius of vessel

conclusion:

the body regulates blood flow by altering vessel radius

halving the radius 16x resistance

5

Heart structure

fig 12-6

6

Heart valve structure

fig 12-7

atrioventricular valves: like parachutesaortic & pulmonary valves: like pockets

7

Heart muscle structure

fig 12-9

striated, branched cells, 1 nucleus/cell, connected by intercalated discsspontaneous contraction, regulated by autonomic NS, hormonescoronary blood flow regulated by active hyperemia (see later)

8

Conducting system

consists of modified cardiac muscle cells

fig 12-10

Sequence:

sinoatrial node

atrial pathways

atrioventricular node

Bundle of Hisonly path to ventricles

R & L bundle branches

Purkinje fibers

9

Conducting system properties

Spontaneous depolarization

all conducting system shows spontaneous depolarization

intrinsic rates:SA node (70/min), AV node (40/min), Purkinje fibers (20/min)

therefore SA node sets heart rate

Conduction rates

slowest: AV node, ~ 100 msec

delay between atrial & ventricular contraction

fastest: Purkinje fibers

all ventricular muscle contracts together (apex slightly ahead)

10

Cardiac action potential (ventricular muscle)

RMP close to K+ equilibrium potential

depolarization: Na+ channels open/inactivate

plateau phase:

Ca++ channels open, K+ channels close

repolarization:

Ca++ channels close, K+ channels open

refractory period ~250 milliseconds

value of plateau & refractory period:heart must relax before contracting again

fig 12-12

11

Cardiac action potential (conducting tissue)

RMP drifts to threshold (pacemaker potential)K+ channels closingfunny Na+ channels open/closeT-type Ca++ channels open

depolarization: L-type Ca++ channels open

repolarization:Ca++ channels close, K+ channels open

plateau phase:

Ca++ channels open, K+ channels close

repolarization:

Ca++ channels close, K+ channels open

refractory period ~250 milliseconds

fig 12-13

12

Excitation contraction coupling

fig 12-18

13

Excitation contraction coupling

L-type channel Ca++ channel acts as voltage gated channel

Ca++ enters cytosol from T tubules

Ca++ from T tubules stimulates opening of ryanodine receptor Ca++ channel

Ca++ enters cytosol from sarcoplasmic reticulum contraction

fig 12-17

14

Excitation contraction: cardiac vs. skeletal muscle

Ca++ channels

1. L-type Ca++ channels (DHP receptor) in T tubule membrane 2. Ryanodine receptor Ca++ channels in wall of sarcoplasmic reticulum

Skeletal muscle:

L-type (DHP) Ca++ channel acts as voltage sensor (not as channel) L-type (DHP) mechanically opens ryanodine receptor channel Ca++ enters cytosol from sarcoplasmic reticulum contraction

Cardiac muscle

L-type channel Ca++ channel acts as voltage gated channel Ca++ enters cytosol from T tubules Ca++ from T tubules stimulates opening of ryanodine receptor Ca++ channel Ca++ enters cytosol from sarcoplasmic reticulum contraction

Why is this important?

Skeletal muscle will contract even if there is no extracellular Ca++

Ca++ channel blocking drugs (DHP derivatives):cardiac contractility, but do not skeletal muscle strength

15

Electrocardiogram

fig 12-14

P wave: atrial depolarization

QRS complex: ventricular depolarization

T wave: ventricular repolarization

Atrial repolarization wave obscured by QRS complex

note voltage (compare with ic electrode)

16

Cardiac cycle

Systole = contraction (~ *0.3 sec)

Diastole = relaxation (~ *0.5 sec) *resting rate

4 phases:

1. ventricular filling (diastole)

2. isovolumetric ventricular contraction (systole)

3. ventricular ejection (systole)

4. isovolumetric ventricular relaxation (diastole)

17

1. Ventricular filling

AV valvesA&P valves

atrial P > ventricular P AV valves openaortic P > ventricular P A&P valves closed

atrial contraction adds ~15% more blood

18

2. Isovolumetric ventricular contraction

ventricular P > atrial P AV valves closed

aortic P > ventricular P A&P valves closed

1st heart sound: closing of AV valves

19

3. Ventricular ejection

ventricular P > atrial P AV valves closed

ventricular P > aortic P A&P valves open

AV valves

A&P valves

20

3. Isovolumetric ventricular relaxation

ventricular P > atrial P AV valves closed

aortic P > ventricular P A&P valves close

2nd heart sound: closing of A&P valves

21

Right heart mechanics

fig 12-21

Notes:Volumes, valves, sounds, & times are the same as left heartPressures are lower because peripheral resistance of lung is lower

22

Cardiac output & ejection fraction

Cardiac output = stroke volume x heart rate

Stroke volume = end diastolic volume (EDV) – end systolic volume (ESV)

Hence:

cardiac output = (EDV – ESV) x heart rate

at rest: EDV = ~130 ml, ESV = 60 ml, heart rate = 70/min

so: resting cardiac output = (130 – 60) x 70 = 4900 ml/min = ~5L/min

Ejection fraction = percentage of blood ejected with each beat

= stroke volume/EDV = 70/130 = 54%

23

Regulation of cardiac output

Heart rate:

sympathetic nervous activity

epinephrine

parasympathetic nervous activity

Stroke volume:

end diastolic volume (Frank-Starling effect)

sympathetic nervous activity (contractility

epinephrine (contractility)

24

Regulation of heart rate: autonomics & epinephrine

fig 12-24

25

Regulation of heart rate: autonomics & epinephrine

Curve b:sympathetic nerves end on sinoatrial node funny Na+ channels rate of depolarization (cAMP 2nd messenger)

Curve c:parasympathetic nerves end on sinoatrial nodeAcCh open K+ channels (hyperpolarization), funny Na+ channels

rate of depolarization

fig 12-23

26

Regulation of cardiac output

Heart rate:

sympathetic nervous activity

epinephrine

parasympathetic nervous activity

Stroke volume:

end diastolic volume (Frank-Starling effect)

sympathetic nervous activity (contractility

epinephrine (contractility)

27

Regulation of stroke volume: Frank-Starling effect

Mechanism:

end diastolic volume stretch of ventricle better alignment of X-bridges and binding sites on actin

Important for balancing output of left & right heart

28

Regulation of stroke volume: sympathetic NS & epinephrine

Contractility

contraction at a given end diastolic volume

i.e. same EDV, ESV, stroke volume

29

Frank Starling vs. sympathetic/epinephrine

These numbers are just examples

Condition EDV ESV Stroke volume

Ejection fraction

resting cardiac output 120 ml 48 ml 72 ml 60%

Frank Starling effect 150 ml 60 ml 90 ml 60%

sympathetic-epinephrine 120 ml 30 ml 90 ml 75%

Frank Starling: end diastolic volume stroke volume

Sympathetic NS-epinephrine: stroke volume at given end diastolic volume

30

Sympathetic effects on contraction

rate & force of contraction

rate of relaxation

31

Autonomic nerves on heart

Sympathetic nervous system & epinephrine

(all via 1 receptors, cAMP, protein kinase A, phosphorylation)

heart rate ( funny Na+ channels, Ca++ channels)

contractility ( Ca++ channels)

relaxation rate ( Ca++ ATPase activity, faster Ca++ release from troponin)

Parasympathetic nervous system

heart rate

minimal effects on contractility

32

Regulation of cardiac output

33

Arteries

Functions: Structure:low resistance conduit large diameter resistancepressure reservoir elastic tissue in walls

fig 12-29

34

Arteries as pressure reservoirs

fig 12-30

35

Mean arterial pressure

Mean arterial pressure = diastolic pressure + 1/3 pulse pressure

fig 12-31a

36

Arterial complianceCompliance = ease of distension,

i.e. larger volume change for given pressure change

Mathematically: compliance = Δvolume / Δpressure

fig 12-31b

Aging & hypertension arterial compliance (arteriosclerosis)

37

Arterioles

Functions:

regulate blood flow to organs

main component of peripheral resistance

Structure:

smooth muscle in wallsrich autonomic supply, especially sympathetic NS

fig 12-33a

38

Regulation of arteriolar tone

1. active & reactive hyperemia

2. flow autoregulation

3. sympathetic, parasympathetic nerves

4. hormones (epinephrine, angiotensin II, ADH/vasopressin, NO)

Note: “injury” is in the objectives, but will not be on the test

39

Regulation of arteriolar tone: active hyperemia

Metabolites ( relaxation of smooth muscle blood flow to organ)

decreased: O2

increased:CO2, adenosine, K+, H+ (from CO2 & lactate), osmolality

Important in regulating blood flow to heart (coronaries) & skeletal muscle

Reactive hyperemia

block blood flow, metabolites accumulate, arterioles dilate

release block, high blood flow until metabolites washed out

fig 12-34a

40

Regulation of arteriolar tone: flow autoregulation

Mechanism 1: metabolite accumulation

fig 12-34b

Mechanism 2: myogenic response

Especially important in brain & kidney

41

Regulation of arteriolar tone: autonomics

Sympathetics:

Generally vasoconstrictor ( receptors)

Intrinsic tone (basal discharge) constriction or relaxation possible

Important in constricting GI, kidney, skin arterioles

Parasympathetics:

Not important

Nonadrenergic, noncholinergic (NANC) neurons:

NO is neurotransmitter; important in genitals, GI tract

42

Regulation of arteriolar tone: hormones

Epinephrine:

Generally vasoconstrictor ( receptors)

Vasodilator in skeletal muscle ( receptors)

Angiotensin II

Powerful vasoconstrictor

Additional action to aldosterone release

ADH (aka vasopressin)

Powerful vasoconstrictor

Additional role to cause water retention by kidneys (antidiuresis)

Nitric oxide NO

Acts as neurotransmitter & paracrine: vasodilator

43

Capillaries: anatomy

fig 12-37

permeability: permeable to all molecules except proteins, transport by diffusion via intercellular clefts & transcellular

vesicles & fused vesicle channels: uncertain function

44

Microcirculation structure

fig 12-38

precapillary sphincters: regulated by metabolite levels

metarterioles: potential short circuits between arterioles & venules

45

Capillary flow velocity

fig 12-39

Distinguish between:

flow volume of blood (ml/min) & flow velocity of single red cell (cm/min)

flow velocity in capillaries is slowest because total XS area is greatest

Consequence: blood lingers in capillaries for nutrient & waste exchange

46

Fluid exchange across capillary wall

Permeability of capillary endothelium:

freely permeable to molecules < ~ 5000 MWt (gases, ions, glucose, amino acids, hormones)

relatively impermeable to protein

Therefore, interstitial fluid = plasma without the protein & red cells

Transport of solutes:

mostly by simple diffusion via intercellular clefts & some transcellular

some “bulk flow” ( fluid flow carries solutes across endothelium)

Edema:

excessive accumulation of fluid in interstitial fluid space

47

Fluid exchange across capillary wall (Starling forces)

fig 12-42a

Balance of fluid between plasma & interstitium controlled by 4 forces

Outward forces: plasma interstitial fluid (“filtration”), given +ve sign

capillary hydrostatic pressure (PC)

interstitial fluid protein osmotic pressure (IF)

Inward forces: interstitial fluid plasma (“reabsorption”), given –ve sign

plasma protein protein osmotic pressure (P)

interstitial fluid hydrostatic pressure (PIF)

48

Starling forces: the numbers

The most important forces are capillary hydrostatic pressure (PC) & plasma protein protein osmotic pressure (P)

3-4 L/day more fluid is filtered than is absorbed

That 3-4 L re-enters blood via the lymph

(lymph composition = interstitial fluid composition)

Edema develops if net filtration > lymph flow

fig 12-42b

49

Veins

Function:

capacitance vessels

contain ~60% of blood

regulate venous flow to heart

Structure:

thin walls, smooth muscle

valves

large diameter, low resistance

fig 12-44

50

Regulation of venous return (VR) to heart

fig 12-45

1. sympathetic activity

SNS vein compression VR

2. muscle pump

muscle activity vein compression VR

3. ventilation

inspiration atrial pressure VR

4. blood volume

blood volume (kidney) VR

51

Regulation of venous return

fig 12-46

52

Lymph

fig 12-47

Composition:

like interstitial fluid of tissue of origin

Lymphatics:

valves & smooth muscle

nodes (infection & metastasis)

Flow: 3-4 L/day (in health)

53

Blood pressure = Cardiac output X Peripheral resistance

fig 12-51

54

Baroreceptor location

fig 12-53

55

Baroreceptor response

fig 12-54

blood pressure firing rate

fig 12-55

56

Response to hemorrhage

fig 12-56

hemorrhage blood pressure b.p. baroreceptor response

fig 12-52

57

Response to standing up (from lying position)

fig 12-56 modified

standing

blood pools in legs

venous return

cardiac ouput

arterial pressure

after a few seconds, little change in blood pressure

58

Response to standing up (from lying position)

fig 12-56 modified

standing

blood pools in legs

venous return

cardiac ouput

arterial pressure

after a few seconds, little change in blood pressure

59

Exercise (blood flow)

fig 12-61 modified

Summary:

heart, skeletal muscle, skin (late)

brain

kidney, GI, spleen, liver

60

Exercise (cardiovascular changes)