Transcript Cardiac muscle structure

Hematocrit, plasma & serum
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
fig 12-1
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Systemic, pulmonary circulations
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
fig 12-2
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Pressure, flow & resistance
flow = Δ pressure / resistance
It is Δ pressure that
drives flow
Later you will see that:
blood pressure = cardiac output (flow) x peripheral resistance
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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
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Heart structure
fig 12-6
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Heart valve structure
fig 12-7
atrioventricular valves: like parachutes
aortic & pulmonary valves: like pockets
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Heart muscle structure
fig 12-9
striated, branched cells, 1 nucleus/cell, connected by intercalated discs
spontaneous contraction, regulated by autonomic NS, hormones
coronary blood flow regulated by active hyperemia (see later)
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Conducting system
consists of modified cardiac muscle cells
Sequence:
sinoatrial node
atrial pathways
atrioventricular node
Bundle of His
only path to ventricles
R & L bundle branches
Purkinje fibers
fig 12-10
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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)
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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
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Cardiac action potential (conducting tissue)
RMP drifts to threshold (pacemaker potential)
K+ channels closing
funny Na+ channels open/close
T-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
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Excitation contraction coupling
fig 12-18
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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
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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
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Electrocardiogram
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)
fig 12-14
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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)
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1. Ventricular filling
AV valves
A&P valves
atrial P > ventricular P AV valves open
aortic P > ventricular P A&P valves closed
atrial contraction adds ~15% more blood
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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
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3. Ventricular ejection
AV valves
A&P valves
ventricular P > atrial P  AV valves closed
ventricular P > aortic P  A&P valves open
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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
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Right heart mechanics
fig 12-21
Notes:
Volumes, valves, sounds, & times are the same as left heart
Pressures are lower because peripheral resistance of lung is lower
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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%
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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)
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Regulation of heart rate: autonomics & epinephrine
fig 12-24
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Regulation of heart rate: autonomics & epinephrine
fig 12-23
Curve b:
sympathetic nerves end on sinoatrial node
 funny Na+ channels  rate of depolarization (cAMP 2nd messenger)
Curve c:
parasympathetic nerves end on sinoatrial node
AcCh open K+ channels (hyperpolarization),  funny Na+ channels
 rate of depolarization
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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)
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Regulation of stroke volume: Frank-Starling effect
Mechanism:
 end diastolic volume  stretch of ventricle  better alignment of Xbridges and binding sites on actin
Important for balancing output of left & right heart
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Regulation of stroke volume: sympathetic NS & epinephrine
Contractility
 contraction at a given end diastolic volume
i.e. same EDV,  ESV,  stroke volume
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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
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Sympathetic effects on contraction
 rate & force of contraction
 rate of relaxation
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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
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Regulation of cardiac output
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Arteries
Functions:
low resistance conduit
pressure reservoir
Structure:
large diameter  resistance
 elastic tissue in walls
fig 12-29
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Arteries as pressure reservoirs
fig 12-30
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Mean arterial pressure
Mean arterial pressure = diastolic pressure + 1/3 pulse pressure
fig 12-31a
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Arterial compliance
Compliance = ease of distension,
i.e. larger volume change for given pressure change
Mathematically: compliance = Δvolume / Δpressure
fig 12-31b
Aging & hypertension  arterial compliance (arteriosclerosis)
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Arterioles
Functions:
regulate blood flow to organs
main component of peripheral
resistance
Structure:
 smooth muscle in walls
rich autonomic supply,
especially sympathetic NS
fig 12-33a
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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
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Regulation of arteriolar tone: active hyperemia
fig 12-34a
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
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Regulation of arteriolar tone: flow autoregulation
Mechanism 1: metabolite accumulation
fig 12-34b
Mechanism 2: myogenic response
Especially important in brain & kidney
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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
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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
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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
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Microcirculation structure
fig 12-38
precapillary sphincters: regulated by metabolite levels
metarterioles: potential short circuits between arterioles & venules
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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
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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
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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)
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Starling forces: the numbers
fig 12-42b
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
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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
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Regulation of venous return (VR) to heart
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
fig 12-45
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Regulation of venous return
fig 12-46
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Lymph
Composition:
like interstitial fluid of tissue of origin
Lymphatics:
valves & smooth muscle
nodes (infection & metastasis)
Flow: 3-4 L/day (in health)
fig 12-47
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Blood pressure = Cardiac output X Peripheral resistance
fig 12-51
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Baroreceptor location
fig 12-53
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Baroreceptor response
fig 12-54
fig 12-55
 blood pressure  firing rate
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Response to hemorrhage
hemorrhage  blood pressure
 b.p.  baroreceptor response
fig 12-52
fig 12-56
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Response to standing up (from lying position)
standing

blood pools in legs

 venous return

 cardiac ouput

 arterial pressure
after a few seconds, little
change in blood pressure
fig 12-56 modified
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Response to standing up (from lying position)
standing

blood pools in legs

 venous return

 cardiac ouput

 arterial pressure
after a few seconds, little
change in blood pressure
fig 12-56 modified
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Exercise (blood flow)
Summary:
 heart, skeletal muscle, skin (late)
 brain
 kidney, GI, spleen, liver
fig 12-61 modified
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Exercise (cardiovascular changes)
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