Download CV 4 Cardiac Output

Cardiac Output
Cardiac Output = Heart Rate X Stroke Volume
CV 4
Stroke Volume = EDV – ESV
= 135 ml – 65 ml = 70 ml
i.e about ½ the volume remains in the left ventricle
At rest:
CO = 72 beats / min X 0.07 L/beat =5.0 L/min
Blood volume in most people = ~5L
CO in trained athletes can = 35 L/min
Control of Heart Rate by Autonomic
Nervous system
To Understand cardiac output (CO)
1. What controls HR?
2. What controls SV?
• SNS ↑ HR via β adrenergic receptors
• PNS ↓ HR via muscarinic Ach receptors
• Normal rhythm of the SA node is 100
beats/min
• But, resting heart rate ~70 beats/min
¾PNS activity dominant at rest
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Effect of epinephrine on pacemaker
potential
Epi
Effect of Ach on Pacemaker
potential
Control
250 ms
Ach 0.01 μm
0
cont
-50
Evidence for involvement of cAMP
How do Epi and Ach regulate pacemaker
potential?
Probability of
funny Na+
channel being
open
recall β adrenergic receptor and
muscarinic Ach receptor linked to cAMP
pathway
open probability
Increase this much with
cAMP
Membrane voltage
At this voltage
2
SA node cell
• Conclusion
– “funny” Na+ channel opening is regulated by
the level of cAMP (in addition to
hyperpolarization)
Na+
β
mAch
Adeylate
cyclase
Gs
Gi
“funny” Na+ channel
ATP
cAMP
↑cAMP ↑ channel opening
↓cAMP ↓ channel opening
• Therefore, HR controlled by SNS and PNS
regulation of “funny” Na+ channel
• As channel opening ↑, slope of pacemaker
potential ↑
Other factors that can influence HR
1. Arterial pressure receptors
(Baroreceptors)
2. Atrial pressure receptors
We’ll come back to these later in blood pressure regulation
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EDV & SV:
Frank-Starling Mechansim
• SV = End Diastolic Volume – End Systolic Volume
EDV
Blood flowing back to heart
(venous return)
ESV
Effectiveness of heart pump
(contractility)
Stroke Volume (ml)
• What controls Stroke Volume?
200
100
0
100
200
300
400
Ventricular end diastolic volume (ml)
• Thus, any factor that ↑ venous return will
increase cardiac output
• Ventricle contracts more forcefully when it
is filled to a larger volume
• Why?
More about venous return later
– Length-tension relationship of cardiac muscle
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Length-tension relationship of muscle
1
2
4
Relative tension
3
1.0
• At rest, cardiac muscle sarcomere length
is less than optimal (about position 4 on
previous graph)
2
3
4
0.5
• Therefore, filling ventricles with more
blood stretches the sarcomeres
1
5
1.25
5
1.65
2
2.25
– They produce more force
3.65
Sarcomere length (μm)
• How does SNS affect muscle contractility?
Contractility
Stroke Volume (ml)
• ↑ SNS activity or Epi from adrenal gland →↑ force
production at any EDV
↑SNS activity or
↑ Epi
200
L-type Ca++
Channel
(dihdryopyride receptor)
β
Adeylate
cyclase
Gs
Protein kinase A
rest
ATP
100
cAMP
Ca++
0
100
200
300
400
Ventricular end diastolic volume (ml)
Ca++ pump
SR
Ryanodine receptor
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In cardiac myocytes cAMP/Protein kinase A:
1. Increase L-type Ca++ channel opening
2. Increase RyR opening
Both serve to increase cytoplasmic Ca++ and
increase contraction
Therefore factors affecting Stroke Volume:
1. EDV
¾ venous return & Frank-Starling mechanism
2. ESV
¾ Contractility, SNS and Epi
3. Increase Ca++ pump activity
Serves to increase Ca++ clearance and
increase relaxation
baroreceptors
End Diastolic Volume
(Frank-Starling Mech)
Sympathetic activity
Blood Epinephrine
Parasympathetic activity
Heart Rate
Stroke volume
Relative Contributions of SNS and
PNS to Heart Function
PNS primarily to SA node, AV
node and Atria
→ Mainly effect HR, small
effect on atrial contractility
SNS to all areas of heart
→ effects HR and contractility
Cardiac Output
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capillaries
Vascular System
arterioles
venules
arteries
veins
aorta
vena cava
Blood flow
Diameter
Wall Thickness
25 mm
2mm
aorta
30 mm
1.5 mm
4 mm
1 mm
vena
cava
artery
30 μm
5 mm
0.5 mm 6 μm
vein
8 μm
0.5μm
20 μm
1 μm
Flow (Q) = Δ pressure / resistance
arteriole capillary venule
Generated by the heart
Function of volume & compliance
Endothelium
Elastic tissue
Smooth muscle
Fibrous tissue
Blood vessels
Blood flow must = cardiac output
Q= CO = ΔP/R
Proportion of vessel wall
Major site of regulation
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Aortic blood pressure
for the whole CV system:
P1 = mean arterial pressure (MAP)
P2 = right aterial pressure ≈ 0
MAP = DP + 1/3 (SP – DP)
= 75 + 1/3 (125 – 75)
= 92 mmHg
In response to the pulsatile contraction of the heart:
pulses of pressure move throughout the vasculature,
decreasing in amplitude with distance
Compliance, Volume, Pressure
Compliance = Δ volume / Δ pressure
How stretchy is it?
If very stretchy - low pressure required for change
in volume
If not stretchy - high pressure required for change
in volume
Aorta
Recall: aorta and arteries high % elastic tissue
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Blood flow
Flow (Q) = Δ pressure / resistance
MAP-RAP
Generated by the heart
Function of volume & compliance
Blood vessels
Flow must = cardiac output
Q= CO = ΔP/R
length
Resistance =
viscosity
8 ⎛ Lη ⎞
π ⎜⎝ r 4 ⎟⎠
radius
• Length of blood vessels usually constant
• Viscosity usually constant over short term
Plasma includes
water, ions, proteins,
nutrients, hormones,
wastes, etc.
– Exceptions
• Dehydration ↓ blood volume ↑ blood cell concentration
• Change in Blood cell production
η
normal
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hematocrit
The hematocrit is the
percent of the
blood volume that is
composed of RBCs
(red blood cells).
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Importance of vessel radius:
Resistance ∝
1
radius 4
ra is 2 times rb;
Flow in A is 16 times flow in B
Factors affecting vessel radius
1. Transmural pressure
•
Pressure difference across wall of vessel
Poutside
Pinside
Eg during inspiration Po decrease therefore radius ↑
during valsalva maneuver Po increase therefore radius ↓
Resistance =
8 ⎛ Lη ⎞
π ⎜⎝ r 4 ⎟⎠
• Small change in radius → big change in
resistance
Factors affecting arteriole radius
2a Local Controls of radius
• Depends on metabolic state of tissue
– Active tissue
•
•
•
•
↓O2,↑ CO2
↓pH
↑ adenosine
↑ K+
– all can lead to dilation of vessel and ↑ flow
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Factors affecting arteriole radius
2b. Autoregulation
• without any neural or endocrine signals
vessels can control flow in response to
pressure change
Max Vessel Dilation
• Autoregulation is a myogenic response
– As flow increases, smooth muscle stretches
• Opens stretch activated calcium channels
• Smooth muscle contracts
Normal
Q
(ml/min)
Max Vessel Contraction
Autoregulatory range
70
150
Press (mm Hg)
Factors affecting arteriole radius
3. Sympathetic nervous system
•
most arterioles receive sympathetic
postganglionic nerves
vasoconstriction
norepinephrine
Smooth muscle contraction
α1 Adrenergic receptors
↑ Intracellular Ca++
Notes on SNS activity and vessel radius
a. Sympathetic tone
•
•
↑ SNS → vasoconstriction
↓ SNS → vasodilation
b. Recall arterioles don’t receive
parasympathetic
Activation of phospholipase C
Production of DAG & IP3
Enhance v-gated Ca++
channels
Activate Protein Kinase C
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Factors affecting arteriole radius
4a. Hormones
• Circulating epinephrine from adrenal medulla
– All blood vessels have α-adrenergic receptors to
which causes constriction
– most vessels also have β-adrenergic receptors
• These cause vasodilation
– But, for most vessels,
• Exception
– Blood vessels in skeletal muscle
– the number of β receptors >> α receptors
– Therefore if SNS or Epi is high, then these
vessels dilate, even when the rest of the
blood vessels constrict
• the number of α-receptors >> β-receptors
• Therefore, if SNS or Epi is high, constriction is dominant
Factors affecting arteriole radius
4b. Other Hormones
1.
2.
Angiotensin II released from kidney
Anti-diuretic hormone (vasopressin) from posterior
pituitary
•
3.
These two are vasoconstrictors
Atrial naturetic peptide from the atria
•
This is a vasodilator
We’ll come back to these 3 later renal physiology section
Factors affecting arteriole radius
Summary
Neural Controls
Sympathetic Nervous System
Hormonal Controls
Vasoconstrictors
Epinephrine
Angiotensin II
Vasopressin
Vasodilators
Epinephrine
Atrial Naturetic Peptide
Local metabolic
Controls:
Vasodilators
↓ oxygen
↓ pH
↑ K+
↑ CO2
↑ adenosine
Autoregulation
Arteriole smooth muscle
↓
Arteriole radius
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Venous Return
• Different vascular beds have different
importance of controls
– Coronary & cerebral – local (metabolic)
– Skin – neural
– Muscle – neural, metabolic, hormonal
• SNS can be used to regulate flow to different
tissues
•
Factors Affecting Venous pressure
1. Transmural pressure
1. Muscle pumps
2. Respiratory pumps
2. SNS activity
– ↑ SNS activity → venoconstriction →
↓ blood volume stored in veins → ↑ venous return
– i.e. increased SNS activity in one tissue and reduced
activity in another will redirect blood flow
Muscle pumps and venous return
Venous Return
↑ Sympathetic activity
respiratory pump
↑ blood volume
Skeletal muscle pumps
↑ venous pressure
↑ venous return
↑ EDV
↑ stroke volume
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Q
Blood flow
Flow (Q) = CO = Δ pressure / resistance
= MAP - RAP / TPR
Q RAP ≈ 0
Aortic pressure
MAP = HR x (EDV-ESV) x TPR
CO = MAP / TPR
MAP = CO x TPR
VR
Venous
pressure
SNS
radius
PNS
MAP = HR x SV x TPR
MAP = HR x (EDV-ESV) x TPR
viscosity
Blood volume
Muscle pumps
Respiration pump
Hormones
autoregulation
Metabolic / local
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