Download increase

The Cardiovascular System
Physiology
Dr. Yasir M. Khaleel, M.Sc., PhD
The College of Medicine, University of
Mosul
Components of the CVS
•
•
•
•
Blood,
Vessels,
Heart,
Associated control systems
Circulatory System Overview
Heart – "four chambered"
- Right atrium & ventricle
Pulmonary circuit
- Left atrium & ventricle
Systemic circuit
- Blood Vessels – "closed circulation"
Arteries –from heart
Capillaries– cell exchange
Veins – to heart
Functions of the heart
1- Generating Blood Pressure
Strength of contraction
2- Routing Blood
Separate the pulmonary and systemic circulations
3- Ensuring one-way blood flow
Valves prevent backflow of blood.
4- Regulating Blood supply
Increase demand (e.g. exercise) results in increase
heart rate and strength of contraction
Hemodynamics
1- Velocity of Blood Flow:
v = Q/A
Where v: Velocity of blood flow (cm/sec), Q: Flow (mL/sec), A:
Cross-sectional area (cm2)
The smallest vessel represents the aorta, the medium-sized vessel represents all of
the arteries, and the largest vessel represents all of the capillaries.
The total blood flow at each level of blood vessels is the same and is equal to the
cardiac output (constant)
2- Relationships between Blood flow, Pressure, and Resistance
Q= ΔP/R
Where,
Q: Flow (mL/min),
ΔP: Pressure difference or pressure gradient (mm Hg),
R: Resistance (mm Hg/mL/min)
The major mechanism for changing blood flow in the cardiovascular system is
by changing the resistance of blood vessels, particularly the arterioles.
R = ΔP/Q
So, TPR= Pressure gradient (aorta – vena cava) / C.O
3- Resistance to Blood Flow
R: Resistance;
η: Viscosity of blood;
L: Length of blood vessel;
r4: Radius of blood vessel raised to the fourth power.
When the radius of a blood vessel decreases, its resistance increases, not
in a linear fashion but magnified by the fourth power relationship. For
example, if the radius of a blood vessel decreases by one half, resistance
does not simply increase twofold, it increases by 16-fold (24).
4- Series and Parallel Resistances
Series resistance
Arrangement of blood
vessels within a given
organ
The total resistance of the system arranged
in series is equal to the sum of the
individual resistances
Parallel resistance is illustrated by the
distribution of blood flow among the
various major arteries branching off the
aorta
The total resistance in a parallel
arrangement is less than any of the
individual resistances.
Advantages of parallel resistances
- The flow through each organ is a fraction of the total blood
flow, and there is no loss of pressure in the major arteries and
that mean pressure in each major artery will be approximately
the same as mean pressure in the aorta.
-Adding a resistance to the circuit causes total resistance to
decrease, not to increase.
-If the resistance of one of the individual vessels in a parallel
arrangement increases, then total resistance increases.
- Increase resistance in one individual vessel will reduce blood
flow in that vessel and increase blood flow in other vessels in
parallel
5- Laminar and Turbulent Blood Flow
Laminar : the velocity of flow at the vessel
wall is zero, and the velocity at the center of
the stream is maximal
Turbulent: the streams mix radially and
axially. Because energy is wasted in
propelling blood radially and axially, more
energy (pressure) is required to drive
turbulent blood flow than laminar blood
flow. Turbulent flow is often accompanied
by audible vibrations called murmurs.
6- Compliance of Blood vessels
The volume of blood the vessel can hold at a given pressure
C=V/P
C: Compliance (ml/mmHg),
V: Volume (ml),
P: Pressure (mmHg)
The higher the compliance of a vessel, the more volume it can hold at a given
pressure.
Veins: highly compliant = hold large volume under low pressure
(unstressed blood volume)
Arteries: much less compliant = hold low volume under high pressure
( stressed blood volume)
7- Pressure in the CVS
Blood flow requires a driving force or
pressure difference. The pressure
differences that exist between the heart
and blood vessels are the driving force for
blood flow.
Systemic arterial pressure
Systolic pressure is the highest
pressure measured during systole.
Diastolic pressure is the lowest
pressure measured during diastole.
Pulse pressure is the difference
between systolic pressure and
diastolic pressure.
Mean arterial pressure is the average pressure in a complete cardiac
cycle and is calculated as follows:
MAP= Diastolic Pressure + 1/3 Pulse Pressure
Blood Pressure Measurement
Cardiac Electrophysiology
The function of the heart as a pump needs to be well
synchronized in a very precise sequence
Conducting cells :
1- Rapidly spread action
potentials over the entire
myocardium
2- Generate action
potentials spontaneously
Cardiac conduction system
Normal Sinus Rhythm
It means:
1- The action potential must originate in the SA node
2- The SA nodal impulses must occur regularly at a rate of
60 to 100 impulses per minute
> 100 + from sinus node= sinus tachycardia
< 60 + from sinus node= sinus bradycardia
3- The activation of the myocardium must occur in the
correct sequence and with the correct timing and delays.
Action Potentials of Ventricles, Atria, and the Purkinje
System
1- Long duration
250 msec Ventricles
150 msec Atria
300 msec Purkinje fibers
Long AP = Long RP
2- Stable resting
membrane potential
3- Plateau
Sustained period
of depolarization
Phase 0: Upstroke. phase
of rapid depolarization
Phase 1: Initial repolarization
Phase 2: Plateau. a long
period (150 to 200 msec) of
relatively stable,
depolarized membrane
potential
Phase 3: Repolarization
Phase 4: Resting
membrane potential
Inward and outward currents
are equal
Ventricular action potential
Action Potentials in the SA Node
Phase 0: Upstroke
T-type Calcium channel
Phase 3: Repolarization
Phase 4: Spontaneous
depolarization or pacemaker
potential
Funny or leaky Na channels =
inward Na+ current called If
If is turned on by
repolarization from the
preceding AP, thus ensuring
that each AP in the SA node
will be followed by another
AP
(1) The SA node exhibits automaticity;
that is, it can spontaneously generate
action potentials without neural input.
(2) It has an unstable resting membrane
potential
(3) It has no sustained plateau.
Sympathetic NS
Activation of β1 receptors in the
SA node produces an increase in
If, which increases the rate of
phase 4 depolarization
(Positive chronotropic effects )
Parasympathetic NS
activate muscarinic (M2)
receptors in the SA node.
Has two effects
- Decrease in If decreases
the rate of phase 4
- Increases the conductance
of K+ resulting in outward
K+ current that hyperpolarize
the maximum diastolic
potential so that more inward
current is required to reach
threshold potential
The pacemaker with the fastest rate of phase 4 depolarization controls the
heart rate. Normally, the SA node has the fastest rate of phase 4
depolarization, and therefore, it sets the heart rate
When the SA node drives the heart rate, the latent pacemakers are
suppressed, a phenomenon called overdrive suppression. That is,
latent pacemakers as long as their firing rate is driven by the SA
node, their own capacities to spontaneously depolarize are
suppressed.
Mechanism of Propagation of Cardiac Action Potential
The cardiac muscle work as syncytium
- Atrial syncytium
- Ventricular syncytium
This achieved by Intercalated discs which connects cardiac muscle cells
together to work as one unit (syncytium)
Intercalated discs
- Desmosomes make strong mechanical attachments between the cells and
transmit the force of contraction.
- Gap junctions cause every cell in the heart to be electrically coupled to its
neighboring cells and that is what causes the heart to behave like a single
motor unit.
CONDUCTION VELOCITY
Differences in
conduction velocity
among the cardiac
tissues have
implications for
their physiologic
functions
ELECTROCARDIOGRAM (ECG)
The entire myocardium is not depolarized at once:
- The atria depolarize before the ventricles;
-The ventricles depolarize in a specific sequence;
-The atria repolarize while the ventricles are depolarizing;
- The ventricles repolarize in a specific sequence.
As a result of the sequence and the timing of the spread of
depolarization and repolarization in the myocardium, potential
differences are established between different portions of the heart,
which can be detected by electrodes placed on the body surface.
The electrocardiogram (ECG or EKG) is a measurement of
tiny potential differences on the surface of the body that
reflect the electrical activity of the heart.
P wave duration is (80-110 msec)
PR interval (120-200 msec)
It reflects delay in the AV
node.
QRS duration (60-100 msec).
QT interval duration (330-450 msec)
It represents the whole ventricular
depolarization and ventricular
repolarization.
T wave represents repolarization of the
ventricles
ECG Lab
CONTRACTILITY Inotropism
The intrinsic ability of myocardial cells to develop
force at a given muscle cell length
Agents that produce an increase in contractility are said
to have positive inotropic effects.
Positive inotropic agents increase both the rate of tension
development and the peak tension.
Agents that produce a decrease in contractility are said to
have negative inotropic effects.
Negative inotropic agents decrease both the rate of
tension development and the peak tension
Excitation Contraction
Coupling
Mechanisms for Changing Contractility
1- Intracellular Ca2+ concentration
- Action P. , inward Ca2+ current during plateau,
- Trigger more calcium release from SR (Ca2+-induced Ca2+ release)
-Ca2+ enhance the interaction of actin and myosin
-Contraction
The magnitude of the tension developed by myocardial cells is
proportional to the intracellular Ca2+ concentration.
The amount of Ca2+ released from the SR depends on two factors:
1- Size of the inward Ca2+ current during the plateau
2-Amount of Ca2+ previously stored in the SR for release.
Therefore, the larger the inward Ca2+ current and the larger the
intracellular stores, the greater the increase in intracellular Ca2+
concentration and the greater the contractility.
2- Autonomic Nervous System
Sympathetic nervous system: Stimulation of the
sympathetic NS has a positive inotropic effect mediated via
activation of β1 receptors.
This positive inotropic effect has three important features:
1-increased peak tension,
2- increased rate of tension development, and
3- faster rate of relaxation.
Faster relaxation means that the contraction is shorter,
allowing more time for refilling
Parasympathetic NS: Stimulation of the parasympathetic nervous
system has a negative inotropic effect on the atria.
This effect is mediated via the action of Ach on muscarinic
receptors;
3- Effect of Heart Rate
When the heart rate increases, contractility increases; when the heart
rate decreases, contractility decreases.
(1) When heart rate increases, there are more action potentials per unit
time and an increase in the total amount of trigger Ca2+ that
enters the cell during the plateau phases.
(2) Because there is greater influx of Ca2+ into the cell during the action
potentials, the sarcoplasmic reticulum accumulates more Ca2+ for
subsequent release (i.e., increased stored Ca2+).
Tension rises stepwise, like a staircase ; With each beat, more Ca2+ is
accumulated by the sarcoplasmic reticulum, until a maximum storage
level is achieved (Positive staircase effect)
Positive staircase effect
4- Cardiac muscle fiber length (Length-Tension Relationship )
a- (Lmax). At this length, there is maximal overlap of thick and thin
filaments; at either shorter or longer cell lengths, the tension developed
will be less than maximal (2.2 μm)
b- Increasing muscle length increases the Ca2+-sensitivity of troponin C
c- Increasing muscle length increases Ca2+ release from the sarcoplasmic
reticulum.
Frank-Starling relationship
Under normal physiological conditions, the volume of blood
ejected by the ventricle (strength of ventricular myocardial
contraction )during systole, depends on the volume of blood
present in the ventricle at the end of diastole.
Ventricular end-diastolic volume, or end-diastolic fiber length;
(Preload)
That is, preload is the resting length from which the muscle
contracts.
End diastolic pressure-volume relationship (EDPVR)
Number 3 and 4
are the best to
develop
contraction
The upper curve is the relationship
between ventricular pressure
developed during systole and enddiastolic volume (or end-diastolic
fiber length). This pressure
development is an active mechanism.
On the ascending limb of the curve,
pressure increases steeply as fiber
length increases, reflecting greater
degrees of overlap of actin and
myosin. The curve eventually levels
off when overlap is maximal. If enddiastolic volume were to increase
further and the fibers were stretched
to even longer lengths, overlap would
decrease and the pressure would
decrease (descending limb of the
curve).
The afterload is the force against which the ventricles eject blood.
The mechanical "load" on the ventricle during ejection.
For the left ventricle is aortic pressure.
The velocity of shortening of cardiac muscle is maximal when
afterload is zero, and velocity of shortening decreases as afterload
increases.
Stroke volume is the volume of blood ejected by the ventricle on each
beat.
SV= End diastolic volume – End systolic volume (about 70 mL)
Ejection fraction is the fraction of the end-diastolic volume ejected in
each stroke volume, which is a measure of ventricular efficiency.
Cardiac output is the total volume ejected by the ventricle per unit time.
Cardiac output = Stroke volume x Heart rate
SAMPLE PROBLEM: A man has an end-diastolic volume of
140 mL, an end-systolic volume of 70 mL, and a heart rate of 75
beats/min. What are his stroke volume, his cardiac output, and his
ejection fraction?
Stroke volume= 140 mL – 70 mL = 70 mL
Cardiac output= 70 mL x 75 bpm = 5250 mL/min
Ejection fraction= SV/EDV = 70 mL/140 mL = 0.50 = 50%
Positive inotropic agents like
digoxin produce increases in
stroke volume and cardiac output
for a given end-diastolic volume.
The result is that a larger fraction
of the end-diastolic volume is
ejected per beat and there is an
increase in ejection fraction.
Negative inotropic agents produce
decreases in stroke volume and
cardiac output for a given enddiastolic volume. The result is that
a smaller fraction of the enddiastolic volume is ejected per
beat and there is a decrease in
ejection fraction.
Ventricular Pressure-Volume Loop
Isovolumetric contraction (1 → 2)
(all valves are closed)
Ventricular ejection (2 → 3)
Isovolumetric relaxation (3 → 4)
(all valves are closed)
Ventricular filling (4 → 1)
Width of the loop is the difference between EDV and ESV = SV
A- Increase preload (EDV) …..Increased SV
B- Increase afterload …………Decreased SV
C- Increase contractility……….Increased SV
SV= End diastolic volume – End systolic volume (about 70 mL)
So, SV determined by (Preload, Afterload, Contractility)
Cardiac Cycle
The mechanical and electrical events
that occur during a single cardiac cycle;
A-ATRIAL SYSTOLE atrial systole is atrial
contraction. It is preceded by the P wave on the
ECG
B-ISOVOLUMETRIC VENTRICULAR
CONTRACTION
-It begins during the QRS complex
- Mitral & Tricuspid valve close (S1)
C-RAPID VENTRICULAR EJECTION
- Begins by opening of aortic and pul valves
D-REDUCED VENTRICULAR EJECTION
E-ISOVOLUMETRIC VENTRICULAR
RELAXATION
-After full repolarization , ventricles start to relax
(diastole)
- Aortic and pul valves close (S2)
F-RAPID VENTRICULAR FILLING
-Mitral and tricuspid valves open (lowest LVP)
- Blood flows from atria to ventricles passively
Rapid ventricular filling may cause S3
G-REDUCED VENTRICULAR FILLING
Reduced ventricular filling or diastasis is the
longest phase of the cardiac cycle and includes
the final portion of ventricular filling
A-ATRIAL SYSTOLE
Active ventricular filling (S4) may be heard if
ventricular compliance is decreased
Relationships between Cardiac Output and Venous Return
It should be clear now that one of the most important
factors determining cardiac output is
left ventricular end-diastolic volume (Preload).
In turn, left ventricular end-diastolic volume depends on
venous return,
Venous return determines right atrial pressure.
So, there is no only a relationship between cardiac output
and end-diastolic volume but also a relationship between
cardiac output and right atrial pressure
Cardiac Function
curve
As venous return increases, RAP increases, and end-diastolic
volume and end-diastolic fiber length increase. Increase in enddiastolic fiber length produce increases in cardiac output. Thus, in
the steady state, the volume of blood the left ventricle ejects as
cardiac output equals or matches the volume it receives in venous
return.
When right atrial pressure reaches a value of approximately 4 mm Hg,
cardiac output can no longer keep up with venous return, and the cardiac
function curve levels off.
This maximum level of cardiac output is approximately 9 L/min.
Vascular
Function Curve
The relationship between venous
return and right atrial pressure.
There is inverse relationship
between venous return and right
atrial pressure.
Increase right atrial pressure will
lead to decrease venous return
Because increased RAP will lead to
reduction in pressure gradient
between the veins and the RA, so
reduce blood flow to the RA
(decrease venous return).
Vascular
Function Curve
Continue……..
If RAP becomes negative
What will happen?
knee (flat portion) of the vascular function curve occurs at negative values
of RAP.
At such negative values, the veins collapse, impeding blood flow back to
the heart. Although the pressure gradient has increased venous return levels
off because the veins have collapsed
Slope of the Vascular Function Curve
Decreased resistance of the arterioles
(decreased TPR) makes it easier for blood
to flow from the arterial to the venous side of
the circulation and back to the heart.
So , for a given RAP, venous return is
increased and there will be clockwise
rotation of the vascular function curve.
The reverse is true,
Increase TPR for a given RAP….decrease
venous return and there will be counter
clockwise rotation of the vascular function
curve.
So, the slope of the vascular function curve
is determined by total peripheral resistance
Mean circulatory pressure (Mean Systemic Pressure)
Is the pressure that would be measured throughout the cardiovascular system
if the heart is stopped,
Under these conditions, pressure would be the same throughout the vasculature
and, by definition, would be equal to the mean systemic pressure.
When pressures are equal throughout the vasculature, there is no blood flow,
and therefore, venous return is zero (since there is no pressure gradient or
driving force).
In other word it is the value for RAP at which
venous return is zero and it is the point at which
the vascular function curve intersects the X-axis
(i.e., where venous return is zero and right atrial
pressure is at its highest value)
Factors determine the mean systemic pressure
(1) The blood volume,
(2) The distribution of blood between
the unstressed volume and the stressed
volume.
The unstressed volume (the volume of blood in the veins) is the volume of blood in the
vasculature that produces no pressure.
The stressed volume (the volume of blood in the arteries) is the volume that produces
pressure by stretching the elastic fibers in the blood vessel walls.
1-Effect of changing blood volume on MSP: When the blood volume ranges from
0 to 4 L, all of the blood will be in the unstressed volume, producing no pressure,
and the MSP will be zero.
While, if the total blood volume is 5 L, 4 L is in the unstressed volume, producing
no pressure, and 1 L is in the stressed volume, producing a pressure of
approximately 7 mm Hg.
So, when blood volume increases (>4 L) unstressed volume will be unaffected (it
is already full), but stressed volume will increase. When stressed volume
increases, MSP increases, and the vascular function curve and its intersection point
with the X-axis shift to the right.
When blood volume decreases then stressed volume decreases, MSP decreases
and the vascular function curve and its intersection point with the X-axis shift to
the left.
2-Redistribution of blood between the unstressed volume and the stressed
volume also produces changes in MSP.
For example, if the compliance of the veins decreases, then veins can hold
less blood and blood shifts from the unstressed volume to the stressed volume.
Although total blood volume is unchanged, the shift of blood increases the
MSP and shifts the vascular function curve to the right.
(Similar changes of increased blood volume)
Conversely, if the compliance of the veins increases, the veins can hold more
blood. Hence, the unstressed volume will increase, the stressed volume and
mean systemic pressure will decrease, and the vascular function curve shifts to
the left
(Similar changes of decreased blood volume)
Changes in the cardiac output
Changes in cardiac output can be produced by any of the following
mechanisms:
(1) Positive or negative inotropic effects that alter the cardiac function curve
(i.e. Contractility)
(2) Changes in blood volume or venous compliance that alter the vascular
function curve by changing mean systemic pressure
(3) Changes in TPR that alter both the cardiac and vascular function curves.
(1) Inotropic Effects
A-Positive inotropic agents (e.g. adrenalin, digoxin), produce an increase in
contractility, an increase in SV, and an increase in cardiac output for any level of
right atrial pressure. Thus, the cardiac function curve shifts upward, but the vascular
function curve is unaffected.
Also note that increased contractility will result in decrease RAP
B- Negative inotropic agents……The reverse effect.
(2) Effects of Changes in Blood Volume
A- Increased blood volume , results in increase MSP, vascular function curve
shift to right. Cardiac output increased, RAP increased.
Decreases in venous compliance , produce similar changes.
B- Decreased blood volume , results in decreased MSP, vascular function curve
shift to left. Cardiac output decrease, RAP decrease.
Increase venous compliance, produce similar changes
(3) Effects of Changes in TPR
A- Increase in TPR,
-By restricting the flow of blood out of the
arteries, produces an increase in arterial blood
pressure (Increase afterload , so decrease
C.O)
- At the same time it decreases the venous
return
- The curves intersect at a new steady
state point at which both cardiac output
and venous return are decreased
In the figure, right atrial pressure is shown as
unchanged.
Actually, the effect of increased TPR on right
atrial pressure is not easily predicted because
TPR has different effects via the cardiac and
vascular function curves.
-An increase in TPR decreases cardiac output,
which increases right atrial pressure (less blood
is pumped out of the heart).
-An increase in TPR decreases venous return,
which decreases right atrial pressure (less flow
back to the heart).
Depending on the relative magnitude of effects
on the cardiac and vascular function curves,
right atrial pressure can be
-slightly increased,
-slightly decreased,
-or unchanged.
B- Decrease in TPR
-Decrease arterial BP, decrease
afterload, so C.O will be increased
and cardiac function curve shifts
upward.
- Decrease in TPR produces a
clockwise rotation of the vascular
function curve, which means that
more venous return for a given right
atrial pressure.
-The curves intersect at a new
steady state point at which both
cardiac output and venous return are
increased
The effect of decreased TPR on
RAP is not easily predicted because
a change in TPR has different effects
via the cardiac and vascular function
curves.
-A decrease in TPR increases cardiac
output, which decreases RAP (more
blood is pumped out of the heart).
-A decrease in TPR increases venous
return, which increases RAP
(increased flow back to the heart).
- Depending
on
the
relative
magnitude of the effects, right atrial
pressure can be slightly increased,
slightly decreased, or unchanged.
Regulation of Arterial Pressure
Mean arterial pressure (Pa) is the driving force for blood flow, and it must be
maintained at a high, constant level of approximately 100 mm Hg.
Because of the parallel arrangement of arteries out of the aorta, the pressure in
the major artery serving each organ is equal to Pa.
(The blood flow to each organ is then independently regulated by changing the
resistance of its arterioles through local control mechanisms.)
Pa = CO X TPR
Pa can be changed by
•Altering the cardiac output (or any of its parameters),
•Altering the TPR (or any of its parameters), or
• Altering both cardiac output and TPR.
Cardiac output and TPR are not independent variables.
In other words, changes in TPR can alter cardiac output, and
changes in cardiac output can alter TPR.
Therefore, it cannot be stated that if TPR doubles, Pa also doubles.
(In fact, when TPR doubles, cardiac output simultaneously is
almost halved, and Pa will increase only modestly.)
Likewise, it cannot be stated that if cardiac output is halved, Pa
also will be halved. (Rather, if cardiac output is halved, there is a
compensatory increase in TPR, and Pa will decrease but it will not
be halved.)
There are mechanisms closely monitor Pa and compare it with the set-point
value of approximately 100 mm Hg.
If Pa increases above the set point or decreases below the set point, the
cardiovascular system makes adjustments in cardiac output, in TPR, or in both,
attempting to return Pa to the set-point value.
1- The baroreceptor reflex (neurally mediated)
attempts to restore Pa to its set-point value in a matter of seconds.
2- Renin-angiotensin-aldosterone system, which regulates Pa more slowly,
primarily by its effect on blood volume.
The baroreceptor reflex mechanisms are fast, neurally mediated
reflexes that attempt to keep arterial pressure constant via changes in
the output of the sympathetic and parasympathetic nervous systems to
the heart and blood vessels
Reflex arc
-Sensors for blood pressure;
-Afferent neurons, (IX, X )
-Brain stem centers, which process the information and coordinate an
appropriate response NTS (medulla)
cardiovascular centers (which
are tonically active)
-Efferent neurons, (sympathetic and parasympathetic)
The parasympathetic outflow is the effect of the vagus nerve on the SA node to decrease
the heart rate.
The sympathetic outflow has four components: effect on the SA node to increase heart
rate, an effect on cardiac muscle to increase contractility and stroke volume, an effect on
the arterioles to produce vasoconstriction and increase TPR, and an effect on veins to
produce venoconstriction and decrease unstressed volume.
Response of baroreceptor reflex to increased
arterial pressure
Response of the Baroreceptor Reflex to Hemorrhage
Renin-angiotensin -aldosterone system
The renin-angiotensin -aldosterone system regulates Pa primarily by
regulating blood volume.
This system is much slower than the baroreceptor reflex because it is
hormonally, rather than neurally, mediated.
This system is activated in response to a decrease in the Pa, which in turn,
produces a series of responses that attempt to restore arterial pressure to
normal.
Angiotensin II is an octapeptide with biologic actions in the:
1- Adrenal cortex : stimulates synthesis and secretion of aldosterone which acts on the
principal cells of the renal distal tubule and collecting duct to increase Na+ reabsorption
and, thereby, to increase ECF volume and blood volume.
Actions of aldosterone require gene transcription and new protein synthesis in the kidney.
These processes require hours to days to occur and account for the slow response time of
the renin-angiotensin II-aldosterone system.
2- Vascular smooth muscle, direct action on the arterioles to cause vasoconstriction
which increase TPR
3- Kidneys, direct action, stimulates Na+-H+ exchange in the renal proximal tubule and
increases the reabsorption of Na+ and HCO3
4- Brain acts on the hypothalamus to increase thirst and water intake. It also stimulates
secretion of ADH, which increases water reabsorption in collecting ducts. By increasing
total body water, these effects complement the increases in Na+ reabsorption (caused by
aldosterone and Na+-H+ exchange), thereby increasing ECF volume, blood volume, and
blood pressure.
Other regulatory mechanisms for blood pressure
1- Peripheral chemoreceptors for O2 are located in the carotid bodies
near the bifurcation of the common carotid arteries and in the aortic
bodies along the aortic arch.
They respond to decreased arterial Po2 especially when the PCO2 is
increased or the pH is decreased.
When stimulated-----------activate sympathetic vasoconstrictor centers
2- Central (cerebral) Chemoreceptors: the brain is intolerant of
decreases in blood flow, chemoreceptors are located in the medulla
and they are most sensitive to CO2 and pH and less sensitive to O2.
Changes in PCO2 or pH stimulate the medullary chemoreceptors,
which then direct changes in outflow of the medullary cardiovascular
centers.
Cushing reaction
3- Antidiuretic hormone (ADH)
Its secretion from the posterior pituitary is increased by two types of
stimuli: by increases in serum osmolarity and by decreases in blood
pressure.
There are two types of receptors for ADH:
-V1 receptors, which are present in vascular smooth muscle, and
- V2 receptors, which are present in principal cells of the renal
collecting ducts.
When activated, the V1 receptors cause vasoconstriction of arterioles
and increased TPR. The V2 receptors are involved in water reabsorption
in the collecting ducts and the maintenance of body fluid osmolarity.
4- Cardiopulmonary (Low-Pressure) Baroreceptors
They are located in the veins, atria, and pulmonary arteries. They sense
changes in blood volume, or the "fullness" of the vascular system. They
are located on the venous side of the circulation where most of the blood
volume is present.
When there is an increase in blood volume, the resulting increase in venous and
atrial pressure is detected by the cardiopulmonary baroreceptors.
The function of the cardiopulmonary baroreceptors is then coordinated to return
blood volume to normal, primarily by increasing the excretion of Na+ and water.
The responses to an increase in blood volume include the following:
1- Increased secretion of ANP which is secreted by atrial cells in response to
increase atrial pressure.
Results in vasodilation and decreased TPR. In the kidneys, this vasodilation
leads to increased Na+ and water excretion
2- Decreased secretion of ADH.
Pressure receptors in the atria also project to the hypothalamus, where the cell
bodies of neurons that secrete ADH are located. In response to increased atrial
pressure, ADH secretion is inhibited and, as a consequence, there is decreased
water reabsorption in collecting ducts, resulting in increased water excretion
3- Renal vasodilation.
There is inhibition of sympathetic vasoconstriction in renal arterioles,
leading to renal vasodilation and increased Na+ and water excretion,
complementing the action of ANP on the kidneys.
4-Increased heart rate. Information from the low-pressure atrial receptors
travels in the vagus nerve to the nucleus tractus solitarius.
Increase in pressure at the venous low-pressure receptors produces an increase in
heart rate (Bainbridge reflex). The low-pressure atrial receptors, sensing that
blood volume is too high, direct an increase in heart rate and, thus, an increase in
cardiac output; the increase in cardiac output leads to increased renal perfusion
and increased Na+ and water excretion.
The Microcirculation
Capillaries are thin walled and are composed of a single layer of endothelial cells with
water-filled clefts between the cells.
The precapillary sphincters function like "switches": By opening or closing, these
switches determine blood flow to the capillary bed.
Exchange of substances across the capillary wall
The exchange of solutes and gases across the capillary wall
occurs by simple diffusion. Some solutes can diffuse through
the endothelial cells, and others must diffuse between the cells.
Generally, the route for diffusion depends on whether the solute
or gas is lipid soluble.
-Lipid soluble: through the endothelial cells (more surface area)
- Water soluble : aqueous clefts between endothelial cells (less
surface area)
- Proteins: large molecules, retained in the capillaries and
contribute to the colloidal osmotic pressure ( Oncotic Pressure)
Fluid Exchange across Capillaries
The Starling equation states that fluid movement (Jv) across a capillary
wall is determined by the net pressure across the wall, which is the sum
of hydrostatic pressure and oncotic pressures. The direction of fluid
movement can be either into or out of the capillary. When net fluid
movement is out of the capillary into the interstitial fluid, it is called
filtration; when net fluid movement is from the interstitium into the
capillary, it is called absorption. The magnitude of fluid movement is
determined by the hydraulic conductance, Kf (water permeability), of
the capillary wall. The hydraulic conductance determines how much
fluid movement will be produced for a given pressure difference.
A- Hydrostatic P= +30 -1 =+29
Oncotic = -26 +3= -23
Net pressure= +6 mmHg
B- Hydrostatic P= +25-1 =+24
Oncotic = -32 +3= -29
Net pressure= -5 mmHg
SAMPLE PROBLEM. In a skeletal muscle capillary, the following Starling
pressures were measured:
Pc= 30 mmHg, Pi = 1 mmHg, πc = 26 mmHg, πi = 3mmHg
Assuming that Kf is 0.5 mL/min.mm Hg, what is the direction and magnitude
of fluid movement across this capillary?
Net pressure = +30 - 1 -26 + 3 mm Hg = +6 mm Hg
Jv (fluid movement) = Net pressure * Kf
(+6mmHg * 0.5 ml/min.mmHg = 3ml/min)
So, the direction is filtration,
and the magnitude of fluid movement is 3 ml/min.
Lymph
Lymphatic capillaries lie in the interstitial fluid, close to the vascular
capillaries. Responsible for returning interstitial fluid and proteins to the vascular
compartment
1- One-way flap valves
2- Lymphatic vessels have a smooth muscle wall, which has intrinsic contractile
ability
3- Lymph flow back to the thoracic duct is promoted by contraction of
the smooth muscle in the lymph vessels and by compression of the
lymph vessels by activity of the surrounding skeletal muscle.
Edema (swelling or increase in the interstitial fluid volume) it occurs when the
volume of interstitial fluid (due to filtration out of the capillaries) exceeds the
ability of the lymphatics to return it to the circulation.
Thus, edema can form when there is increased filtration or when lymphatic
drainage is impaired.
Causes of Edema:
↑ Pc (capillary hydrostatic pressure)
Examples: Arteriolar dilation, venous constriction, increased venous pressure,
heart failure, extracellular fluid volume expansion.
↓ πc (capillary oncotic pressure)
Examples: Decreased plasma protein concentration, severe liver failure
(failure to synthesize protein), protein malnutrition, nephrotic syndrome (loss
of protein in urine).
↑ Kf (hydraulic conductance); increase capillary permeability.
Examples: Burns, inflammation (release of histamine; cytokines)
Impaired lymphatic drainage
Examples: Standing for long time (lack of skeletal muscle compression of
lymphatics), removal or irradiation of lymph nodes, parasitic infestation of the
lymphatics.