Download Cardiovascular Physiology 2016

Cardiovascular Physiology
2016
Alan R. Burns, PhD
University of Houston
College of Optometry
Room 2168
[email protected]
1
Organization of the Cardiovascular System
1. Heart composed of two pumps
•
Right ventricle sends blood to the lungs
(pulmonary) while left ventricle sends blood
to the body (systemic)
2. Organs perfused in parallel
•
allows organ-specific control of flow by
regulating the diameter of arteries
supplying a particular organ
3. Chambers of the heart perfused in series
•
•
Rt Ventricle → Lft Ventricle → Rt
Ventricle
Output of the right and left ventricles must
be matched or equal
4. CV system designed to maintain constant
blood flow to brain and heart
Blood Flow Through the Heart
Function of the Ventricles
• Ventricles generate pressure gradient, which
produces blood flow
• Cardiac output is the amount of blood
pumped by a ventricle in a period of time
• Cardiac output of right and left ventricles must
be equal since the pulmonary and systemic
circulations are in series
• Two factors controlling cardiac output: CO =
HR X SV
Purpose of the Cardiovascular System
Purpose of CV system is to maintain adequate
blood pressure (BP) to achieve perfusion of the
organs
•
Pumping action of the heart maintains flow
or cardiac output (CO)
•
Diameter of arterial vasculature maintains
resistance (R)
•
Heart and vasculature work together to
control blood pressure, BP ~ CO x R
Remember: LAB RAT
Left AV Bicuspid
Right AV Tricuspid
Atrioventricular Valve Function
Figure 18.9
Semilunar Valve Function
Figure 18.10
Pericardial Layers of the Heart
Things to remember about the
Pericardium
• Parietal layer - lines the internal surface
of the fibrous pericardium
• Visceral layer (epicardium) - lines the
external surface of the heart
• Double-walled sac - pericardial space is
a fluid-filled cavity
What else should you
remember?
• The pericardium:
– Protects and anchors the heart
– Prevents overfilling of the heart with blood
– Allows the heart to work in a relatively
friction-free environment
Mechanical Events in Cardiac Cycle
4 Phases of the Cardiac Cycle
1. Inflow Phase: inlet valve open & outlet
valve closed
2. Isovolumetric Contraction: both valves
closed, no blood flow
3. Outflow Phase: Outlet valve open &
inlet valve closed
4. Isovolumetric Relaxation: both valves
closed, no flow
Blood Pressure (mm Hg)
Milliliters of Blood
Event: Opening of AV
Valves
Phase: 1 Diastole
• Rapid ventricular filling
• Decreased ventricular
filling (Diastasis)
• Atrial contraction
(atrial kick)
Event: Closing of AV
Valves
Phase: 2 Systole
• Isovolumetric
ventricular contraction
Event: Opening of
Semilunar Valve
Phase: 3 Systole
• Rapid ventricular
ejection
• Decreased
ventricular ejection
Event: Closing of
Semilunar Valve
Phase: 4 Diastole
• Isovolumetric
ventricular relaxation
Heart Sounds-Cardiac Cycle
First Heart Sound (S1)
•
•
•
•
“lub”
closure of AV valves
separated by ~ 10 msec
M1 and T1 components
Second Heart Sound (S2)
• “dup”
• closure of semilunar (aortic and
pulmonary) valves
• A2 and P2 components
• “normal” S2 splitting occurs
during inspiration (changes
pleural pressure and blood
flow)… P2 remains open longer
S3 and S4 audible in children and
young adults, but in the elderly:
•S3 - congestive heart failure (vibration of
ventricle walls and valves, resulting from early
Phase 1 rapid ventricular filling)
Systole
•S4 - hypertrophic ventricle (vibration of
ventricle walls and valves, resulting from late
fromPhase
Figure 121-2
slow ventricular filling)
M1
T1
A2
P2
The Pressure-Volume Relationship
The Pressure-Volume Loop
Systole
Diastole
Starling’s Law of the Heart
“…the mechanical energy set free in
the passage from the resting to active
state is a function of the length of the
fiber.”
In other words:
The initial length of the myocardial
fibers (end-diastolic volume)
determines the amount of tension
(pressure) generated during activation.
Ernest Starling
1866-1927
Matching Cardiac Inflow and Outflow
1. Starling’s Law of the Heart is based on the LengthForce relationship
2. Increased blood return → increased EDV →
increased sarcomere length
3. Increased sarcomere length → increased force by
mechanisms that may include greater Ca2+ release
from the SR and increased Ca2+-sensitivity of the
contractile proteins
Optimal
A Term to be Familiar With
Preload
in the cardiac myocyte -- the initial sarcomere
stretch before active tension development
in the whole heart -- end-diastolic volume (EDV)
correlates with the sarcomere length just prior to
contraction
Examples of Increased venous return
(preload):
• Exercise (increased skeletal muscle contraction
squeezes veins)
• Sympathetic activity constricts veins
(capacitance vessels) and thereby decreases
venous compliance
• Increased rate and depth of respiration. During
inspiration, lung expansion increases pulmonary
blood volume; during expiration, lung deflation
increases blood flow to left atrium
Cardiac Contractility is a Measure of the
Heart’s Intrinsic Contractile Performance
Cardiac contractility is a measure the
heart’s intrinsic ability to generate force
(pressure) for a given fiber length (preload)
Contractility is determined by a number
of variables
Contractility is approximated by several
means such as dP/dt, ejection velocity,
and ESPVR (End Systolic Pressure
Volume Relationship)
* Norepinephrine is an
inotrope that increases
contractility
The Pressure-Volume Loop response to changes in contractility,
preload, and after-load
Cardiac Output
The volume of blood ejected by the ventricle with each beat is called the
Stroke Volume (SV)
SV equals the difference between the End Diastolic Volume &
the End Systolic Volume
Cardiac output is SV multiplied by the Heart Rate (HR)
CO = SV X HR
CO = (EDV - ESV) X HR
CO = (70 mL/ beat) X (70 beats/min)
CO = 4,900 mL/min
Factors Controlling Cardiac Output
CO = HR x SV
BP ~ CO x R
1. Heart rate:
• Increasing HR → increased CO → increased BP
2. Stroke volume:
• Increasing SV → increased CO → increased BP
Cardiovascular Function at the
Cellular Level
Electrical conduction in the heart
action potential is a transient alteration of the transmembrane voltage
(membrane potential) across an excitable membrane in an excitable
cell (e.g., myocyte) generated by the activity of voltage-gated ion
channels embedded in the membrane
action potential originates in “pacemaker” cells - autorhythmic
action potential propagated through the heart via rapid and slow
conduction pathways
Excitation-contraction (EC) coupling
mechanism by which the action potential promotes contraction in
cardiac myocytes
Modulation: sympathetic and parasympathetic
Electrical conduction in the heart
Conduction of Action Potentials in the Heart
0.5 m/s
0.05 m/s
2 m/s
4 m/s
Electrical Conduction in the Heart
Diversity of Action Potentials
Membrane Potential (mV)
1 sec
SA nodal cell
myocardial contractile myocyte
skeletal muscle myocyte
0
V
cell
-60
Ionic Basis of Resting Membrane
Potential and Action Potential
Pacemaker cell (i.e. SA nodal cell)
close,
Figure 14-16
Note: If current is carried by cyclic nucleotide-gated ion
channels. These channels conduct Na+ and K+ and are
thus described as non-selective cation channels.
SA action potential – Ca++ and
K+
Spontaneous depolarization –
Na+ If currents and changes in K+
and Ca++
Ionic Basis of Resting Membrane
Potential and Action Potential
Contractile myocyte
K+ - brake
Na+ - gas
Ca++ - slow gas (modulates)
Figure 14-14
• No action potential
– Outside of cells positively charged relative to inside
– Outside of heart is positively charged
• As AP passes over the heart, outside becomes
negatively charged while inside becomes more
positive (depolarization)
• As repolarization passes over, outside becomes
positively charged again
• Electrodes placed on the skin can detect these
changes in charge on the heart
• Because body conducts the charges to the skin
• Transmembrane potential is the difference in
voltage between the interior and exterior of a cell
(Vint – Vext)
Depolarization wave front towards recording electrode
0
-1
+1
+2
-2
mV
-3
(-)
-
+3
-
-
-
-
-
(+)
Electrode facing an approaching wave of depolarization
records a positive potential
Electrical current is greatest when the ratio of polarized to
non-polarized tissue is 1:1; current decreases when <1:1
Depolarization wave front away from recording electrode
0
-1
+1
+2
-2
mV
-3
(-)
-
+3
-
-
-
-
-
(+)
Electrode facing a receding wave of depolarization records a
negative potential
0
-1
Depolarization
towards
electrode
+1
Depolarization
away from
electrode
+2
-2
mV
-3
-
+3
-
-
-
-
+3
+2
Away from
electrode
+1
mV
0
-1
-2
Towards
electrode
-3
Time
-
-1
0
+1
+2
-2
mV
-3
+3
Tangential vectors
+3
+2
+1
mV
0
-1
-2
Y component
-3
Time
X component
-1
0
+1
+2
-2
mV
-3
+3
Perpendicular vectors
+3
+2
+1
mV
0
-1
-2
Y component
-3
Time
X component
Willum Einthoven 18601927
Nobel Prize 1924
Einthoven’s Triangle
Einthoven’s Triangle
ST-segment = plateau phase
of ventricular action potential
QT-interval
= duration of systole
* Atrial repolarization is
masked by QRS wave
Atrial
depolarization
begins (P)
Travel time
from SA node
through AV
node (PQ)
Right & left
ventricular
depolarization
begins (Q)
Ventricular
depolarization
continues (R)
Rapid
ventricular
depolarization
ends (S)
Ventricles
remain
depolarized
(ST)
Ventricles
begin to
repolarize (T)
Ventricle
repolariztion
(recovery)
complete
• The shape of the ECG trace depends upon the
location of the skin (recording) electrode relative to
the conduction path of the cardiac AP
• The orientation of the heart and the conduction
path of the AP are fixed
• Electrodes placed at different locations will
generate different ECG patterns
• The potentials recorded depend
on the angle between the cardiac
dipole and the leads on the body
surface
Precordial Leads
(precordium = portion of body over the heart and lower chest (thorax))
*12 leads used in a standard electrocardiogram: the standard bipolar
limb leads I–III, 3 augmented unipolar limb leads, and 6 precordial leads
Determination of
Cardiac Vector
6mm
Lead 1
11mm
Lead 2
4mm
Lead 3
L
(e.g., left ventricular
hypertrophy)
Cardiac Vector
Axis Deviation
Left Axis
Deviation
<0°
-90°
180°
0°
+90°
Right Axis
Deviation
>+90°
(e.g., right
ventricular
hypertrophy)
L
Normal Range
0° to +90°
Causes of Arrhythmias
SA node sets the rhythm
• if SA node becomes damaged, AV node will take over but at a
slower pace
• if AV node becomes damaged, Bundle of His will take over but
pace is too slow (28 bpm) and is not really compatible with life
Ectopic Foci
• abnormal conducting or contractile cells that generate AP’s and
override the impulse rhythm of the SA or AV node
No P wave
- not stimulated by
SA node
Tachycardia example
Abnormal Impulse
Conduction
• block of conduction leading to
re-entry
• block can occur as a result of
myocarditis, cardiomyopathy,
congentital defect, rheumatic
fever, myocardial infarction, etc.
Most commonly, atrial fibrillation occurs as a result of some other cardiac
condition (secondary atrial fibrillation……hypertension, MI, myocarditis).
Pacemaker – provides electrical stimulation for slow ventricular contraction
Defibrillator - fires a preset number of rapid pulses in succession in an attempt to
terminate ventricular tachycardia
Electrical conduction in the heart
Efficient Distribution of the Action Potential Throughout
Cardiac Myocytes via “T-System”
Transverse tubules (t-system)
• invaginations of the
sarcolemma
• open to the extracellular
space
• carry propagated action
potentials deep within
myocardial cell
Mechanism of Cardiac Myocyte Contraction
Excitation-contraction coupling
Ca
Ca
Ca
Ca
+ + + + + + + + + + + +
VOC
- - - - - - - - - - - -
Ca
Ca
Ca
Ca
Ca
Ca
SERCA
ATP
Ca
Ca
+
+
phospholamban
+ + +
Ca
- - - - -
Ca
Ca
Ca
Ca
Ca
-
-
Relaxed state
- - -
- - - - - - - - - - - - - -
Ca
RyR
Ca
Ca
Ca
+ + +
+ + + + + + + +
Ca
+ + + + +
- - - - -
Ca
Ca
Ca
Ca
Ca
+ +
Fully
hyperpolarized
Ca
Ca
T-tubule
Ca
Ca
Ca
Mechanism of Cardiac Myocyte Contraction
Excitation-contraction coupling
Ca
Ca
Ca
Ca
- - - - - - + + + + + +
+ + + + + +
- - - - - -
Ca
Ca
Ca
Ca
SERCA
ATP
Ca
Ca
+
+
phospholamban
+ + +
Ca
-
-
Action potential
- - -
- - - - - - - - - - - - - -
Ca
Ca
- - - - -
Ca
+ + +
Ca
Ca
Ca
Ca
Ca
+ + + + + + + +
Ca
Ca
RyR
Ca
Ca
+ + + + +
Ca
Ca
- - - - -
Ca
Ca
Ca
VOC
+ +
Propagation of
action potential
Ca
Ca
T-tubule
Ca
Ca
Ca
Mechanism of Cardiac Myocyte Contraction
Excitation-contraction coupling
Ca
Ca
Ca
Ca
Ca
Ca
- - - - - - - - - - - -
VOC
+ + + + + + + + + + + +
Ca
Ca
Ca
Ca
Ca
Ca
SERCA
+
Ca
-
phospholamban
Ca
-
ATP
Ca
- - -
Ca
+ + + +
Ca
Ca
Ca
Ca
Ca
- - - - - - - - - - - - - + +
Ca
Ca
RyR
Ca
Ca
Ca
+ + +
+ + + + + + +
Ca
Ca
- - - - -
+ + + + +
Ca
Ca
Ca
Ca
+ +
Propagation of
action potential
Ca
Ca
T-tubule
Ca
Ca
Ca
+
+
+
Depolarization
activates VOCs
permitting influx of
extracellular Ca2+
Mechanism of Cardiac Myocyte Contraction
Excitation-contraction coupling
Ca
Ca
Ca
Ca
- - - - - - - - - - - -
VOC
+ + + + + + + + + + + +
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
Ca
SERCA Ca
ATP
+
Ca
Ca
-
phospholamban
- - -
Ca
Ca
Ca
+ + + +
Ca
Ca RyR
Ca
Ca
+ + +
+ + + + + + + + + + + + +
Ca
Ca
Ca
Ca
Ca
- - -
- - - - - - - -
Ca
Ca
- - - - -
+ + + + +
Ca
Ca
Ca
Ca
- -
Fully
depolarized
Ca
Ca
T-tubule
Ca
Ca
Ca
+
+
+
Release of
intracellular stores
Ca2+ via CICR
Excitation-contraction coupling in
contractile Cardiac Myocytes
1. Level of intracellular Ca2+ determines magnitude of
contraction:
• more Ca → bigger contraction → greater cardiac
output → greater blood pressure
2. Ca2+ stored intracellularly in sarcoplasmic reticulum
(SR)
3. When Ca2+ is released from SR it binds Troponin C
which forces Tropomyosin off the myosin binding
region of actin – promotes contraction
4. Reuptake of Ca2+ by SR required for cardiac muscle
relaxation between beats
5. Ca2+ release and reuptake happens ~70 times/min
at resting heart rate
Modulation of Contractility by
Cardiac Glycosides
Cardiac glycosides inhibit Na+/K+-ATPase
activity.
X X
Na+
Na+
Ca2+
Na+
Ca2+
Na+
Na+
Na+
Ca2+
Ca2+
cardiac glycosides
(digitalis)
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
How does inhibition of Na+/K+ATPase activity eventually affect
cardiac contractility?
Digitalis purpurea (Purple Foxglove)
Modulation: Sympathetic and
Parasympathetic Pathways
Sympathetic Stimulation
Parasympathetic Stimulation
Catecholamines (epinephrine and Acetylcholine (ACh) acts via
norepinephrine) act via β1muscarinic receptors
adrenergic receptors
Leads primarily to decreased
Leads to 1) more forceful
heart rate
contractions and 2) increased
heart rate
Sympathetic stimulation leads to more forceful contraction
P
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
P
Ca2+
Ca2+
Ca2+
Ca2+
P
P
P
Sympathetic stimulation leads to increased heart rate
 Na+ (through non-selective cation channels)
and Ca2+ (through VOCs) influx leads to a
more positive start point (depolarization point)
and more rapid depolarization ( rate of SA
node firing)
Figure 14-17
 Na+ entry (If)
nodal cells
*Norepinephrine & epinephrine
have chronotropic and inotropic
effects on heart rate and
contractility, respectively
more rapid depolarization
from more positive
startpoint
nodal cells
 Heart Rate
Parasympathetic stimulation leads to
decreased heart rate
(little effect on force of contraction)
Muscarinic receptor (M2) activation by ACh
inhibits Adenylate Cyclase (AC), resulting in a
fall in cAMP levels
ACh
M2 receptor promotes activation of Kchannels
Lower cAMP levels decrease the activity of
non-selective cation channels responsible for
If current
(-)
P
ATP
PKA
Lower cAMP levels decrease the activity of
VOCs (T-type)
PKA
 K+ efflux and  Na+ and Ca2+ influx leads to
hyperpolarized pacemaker potentials and
slower depolarization
The slower depolarization rate results in a
longer time between action potentials and
thus a lower HR
*ACh is a chronotrope
cAMP
Figure 14-17
Special Role of Large Outflow Arteries
The large outflow arteries of the heart are designed
to absorb the energy from the ejected blood and
release it more evenly over time in order to maintain
a more constant blood pressure.
1. Contain many layers of smooth muscle
•
Necessary for vessel wall to withstand the
high pressures
2. Contain multiple layers of elastic elements
•
Necessary to absorb and redistribute the
force over time
Vasculature
• Arterioles, the smallest arterial subdivision,
are the site of resistance control
Control of Resistance Vessel Diameter
Agent
Source
Site of Action
Result
NE
sympathetic neurons
VSM α1 adrenergic receptors
vasoconstriction
Epi
adrenal medulla
VSM β2 adrenergic receptors
vasodilation
nitric oxide (NO)
endothelium, perivasc. nerves
VSM guanylate cyclase
vasodilation
endothelin (ET)
endothelium
VSM ET receptors
vasoconstriction
prostacyclin (PGI2)
endothelium
VSM PGI2 receptors
vasodilation
adenosine
surrounding tissue metabolite
VSM purinergic receptors
vasodilation
Note: very abbreviated list of vasoactive agents and mechanisms
Jean Louis Marie Poiseuille 1799-1869
Determinants of Mean Arterial Blood Pressure
1. Arteriolar Resistance
•
Resistance (R) ~ Lη/r4
•
Vessel diameter is the primary determinant of
vascular resistance
•
Vascular diameter controlled by local factors as
well as the endothelium and sympathetic nerves
slight constriction
r = 0.8 mm
slight dilation
r = 1.0 mm
r = 1.2 mm
CSA = 2.01 mm2 CSA = 3.14 mm2
CSA = 4.52 mm2
R ~ 2.44
R ~ 0.48
R ~ 1.00
Determinants of Mean Arterial Blood Pressure
1. Arteriolar Resistance
•
Resistance (R) ~ Lη/r4
•
Vessel diameter is the primary determinant of
vascular resistance
•
Vascular diameter controlled by local factors and
sympathetic nerves
2. Cardiac Output
•
•
Blood Pressure (BP) ~ CO x R
Increased CO → Increased BP
3. Total Blood Volume
•
Increased blood volume → BP
4. Distribution of blood
•
•
Most blood is normally in “venous reserve”
Contraction of veins makes more blood volume
available
Components of the Homeostatic System
1. Aortic and Carotid Baroreceptors
•
•
Sense arterial blood pressure
Send signals to the medullary cardiovascular control
center
2. Medullary Cardiovascular Control Center
•
Responds to baroreceptors by modulating
sympathetic and parasympathetic nerve activity
3. Sympathetic and Parasympathetic Nerve Activity
•
•
Affect vascular resistance
Affect CO
Tonic
stimulation
SA node
Medulla
Baroreceptor reflex
nerve pathways:
Response to elevated
blood pressure
Dorsal motor
nucleus of the
vagus
Nucleus
tractus soltarius
Baroreceptor
afferents
-
vasomotor area
Nucleus ambiguus
interneuron
Thoracic
spinal cord
Carotid
sinus
parasym
postgang
parasympathetic
preganglionic
sympathetic
preganglionic
Thoracic
ganglion
sympathetic
postganglionic
Peripheral blood vessels
(dilation due to loss of sympathetic constriction)
Heart
(decreased HR)
Adrenal medulla
Sweat gland
(decreased secretion)
Medulla
Baroreceptor reflex
nerve pathways:
Response to decreased
blood pressure
Dorsal motor
nucleus of the
vagus
Nuclues tractus
solitarius
Baroreceptor
afferents
-
vasomotor area
Nucleus ambiguus
interneuron
Carotid
sinus
parasympathetic
preganglionic
Thoracic
spinal cord
parasym
postgang
Heart
(increased HR and contractility)
Thoracic
ganglion
sympathetic
preganglionic
sympathetic
postganglionic
Peripheral blood vessels
(constriction)
Adrenal medulla
(epinephrine release)
Sweat gland
(secretion)