4 The Cardiovascular System
Vascular Function Curves
Flow versus driving force
Venous return
This curve is pretty easy to understand –
more driving force gives more flow.
The slope of the
curve is 1/TPR
MAP
Thought question: Why doesn’t the arterial pressure
fall to zero when flow falls to zero?
Changes in the VR/MAP curve with change in TPR
and blood volume
Arteriolar dilation (decreased TPR)
normal
VR
Arteriolar constriction (increased TPR)
MAP
Blood volume changes would move VR along the
normal curve – they would also change the stop-flow
pressure, but the magnitude of the changes would
be small relative to the scale of MAP
Flow versus venous pressure
Pressure that
would exist if
there were no
flow
This one is harder to grasp….
Understanding the vascular function curve with
respect to RAP
It helps to do a thought experiment.
Imagine bringing the heart to a stop.
Cardiac output will fall to zero. Aortic
pressure will plummet – venous
pressure will rise slightly – capillary
pressure will remain almost constant.
The 3 pressures will converge on the
stop-flow pressure. Now, restart the
heart. Imagine the pressure values
tracking back along the curves to their
normal values.
This is the
stop-flow
pressure
Now look back at the curve of VR versus RAP, and
remember that CO=VR
Normal range
Stop flow
pressure
When the heart is restarted, the RAP curve will follow the red curve
from right to left, ending up somewhere in the normal range indicated
by the arrows. If the heart is stimulated and becomes hypereffective,
the RAP value will move further to the left. Ultimately, as the heart
starts to apply suction to the venous supply, RAP enters the negative
range (i.e. is less than atmospheric pressure), and the great veins
leading to the heart start to collapse – this is why the curve flattens out.
Changes in the VR/RAP curve with change in TPR
Venous Return
Arteriolar dilation
Arteriolar constriction
RAP
These curves
say: Arteriolar
dilation improves
venous return –
arteriolar
constriction
impedes it.
Blood-volume changes move the VR/RAP curve
right or left
BV changes change
the stop-flow pressure,
but not the slope of the
curve
Venous Return
Increased BV
Decreased BV
RAP
Integration of the cardiac and
vascular function curves
Some definitions for the CV system model
• System Properties
– TPR
– Blood volume/Venous
capacitance
– Cardiac functionality
(inotropic state, HR)
• System Variables
– RAP
– MAP
– CO
VR=CO
The RAP curves
System
operating
point
RAP
When we overlay the two
curves that relate to the RAP,
we are allowing the two parts of
the CV system to interact. The
intersection of the two curves
describing potential values
determines the real system
variables of CO and RAP for a
system with a specific set of
system properties. Any change
in a system property would shift
one or the other of the curves
and thus change the operating
point.
The MAP curves
When the MAP curves are overlain, the
two parts of the system interact to
determine the real values of CO and
MAP. If the system properties are the
same as for the RAP curves in the
previous slide, the CO value will be the
same for both slides.
CO
Operating
point
MAP
Using the model
• The model can be used to predict the effects on system variables of
any change or set of changes in system properties. These would
include changes imposed from outside (disease, therapeutic drugs,
toxins), changes in physical activity levels, and reflexive responses
to homeostatic challenge. For example, the following situations can
be modeled:
–
–
–
–
–
The onset of hemorrhagic shock and the reflexive response to it
chronic heart disease
Effects of epinephrine and other cardiotonic drugs
Effects of vasoconstrictor or vasodilator drugs
exercise
• Some of these situations will be modeled in class (be there or be
square!) – some will be assigned for you to model.
System Responses to Stress
and Disease
Hemodynamic
changes in response
to hemorrhage
A drop in systemic arterial pressure
initiates the baroreceptor reflex and
greatly increases sympathetic outflow.
This accounts for the increases in
heart rate and TPR. Remember that
the regulated variable here is mean
arterial pressure. In this example, the
blood loss is mild (no more than about
1 liter for a 60-70 Kg person) and the
reflexive compensation is able to
protect MAP while slower responses
can restore the lost fluid, electrolytes
and blood cells. Note that cardiac
output is not a regulated variable and
cannot return to normal until volume
restoration occurs.
Irreversible Hemorrhagic Shock
If the immediate responses were inadequate, a rapid
positive-feedback cycle would cause hemorrhagic shock.
Cardiac depression: heart fails to pump enough blood to
meet the needs of itself and the CNS, leading to
Vasomotor Failure: depressed blood flow to brain is the
most potent of sympathetic stimulants, but after a few
minutes of depressed blood flow, sympathetic outflow
drops and those arterioles that had been constricted by
their adrenergic inputs then dilate, causing a collapse of
MAP.
Hemodynamic changes during exercise
Organ
Resting
Perfusion
Dominant effect
Perfusion during Exercise
(L/min)
(L/min)
Brain
1
1
autoregulation
Heart
0.5
1
autoregulation
Skeletal Muscle
1
12
autoregulation + beta
adrenergic effect
Skin
0.5
4
thermoregulation
Splanchnic
2
1
Alpha adrenergic effect
Kidney
2
1
Alpha adrenergic effect
TOTAL CO
7
20
How is a 3X increase in CO possible during exercise?
• Can it be the result of cardiac effects only? Use the
model to find out.
CO
RAP
Exercise responses are
multifactorial
The magnitudes of MAP, CO and
TPR changes in exercise are
affected by multiple factors,
including
Conditioning
Muscle mass
Exercise intensity level
Environmental temperature
In some highly muscular
individuals, MAP may
decrease significantly in
intense exercise, due to a
profound decrease in diastolic
pressure.
Capillary Filtration, Interstitial
Fluid and the Lymphatic System
Capillaries and Capillary Filtration
• Capillaries are the major sites of exchange of
materials between tissues and bloodstream
• Materials may move across capillary walls by
diffusion and bulk flow
• Ordinarily, capillary slits are not permeable to
molecules as large as plasma proteins, but in
order for protein hormones to enter the
bloodstream and to reach their targets, there is
extensive protein movement across capillary
endothelial cells by pinocytosis.
Capillary filtration
3
28
Osmotic pressure gradient is due to
plasma proteins and doesn’t change along
capillary length – little protein is filtered.
3
28
Arteriolar end
Venular end
Total
pressure
= 10
outward
35
~0
15
Capillary hydrostatic pressure
decreases along capillary length due
to friction
~0
Total
pressure =
10 inward
Edema is an excess of ISF that reflects an imbalance
between rates of formation and drainage of ISF
Hydrostatic factors that promote systemic edema:
–
–
–
–
–
–
Hypertension
Vasodilation
Increased venous pressure
Erect posture or compression of central veins
Lymphatic blockage
Right Heart failure
Osmotic factors that promote systemic edema:
Loss of serum proteins (protein undernutrition)
inflammation with increased capillary leakiness and release of
tissue proteins
Edema and congestive
heart failure
“Congestive” refers to the fact that
the disease-weakened heart must
operate in a larger range of EDV
and ESV to be able to generate
enough force to sustain MAP.
The edema results from increased
venous pressure that backs up to
increase capillary hydrostatic
pressure, favoring filtration over
absorption.
Patients with generalized congestive
heart failure typically experience
peripheral edema during the day
and pulmonary edema at night.
The Lymphatic System
• Lymphatic capillaries are
blind-ended tubes with flap
valves that permit entry of
ISF
• Lymphatic veins have 1way valves like blood
veins, so periodic
compression of lymphatics
improves lymph flow.
• Ultimately, lymph drains
back into the blood
vascular system through
two ducts – the thoracic
duct (to left subclavian
vein) and right lymphatic
duct (right subclavian
vein).
Lymph drainage
• opposes edema
• recovers proteins that escape across
capillary walls
• delivers information about presence of
infectious agents and non-self antigens to
lymph nodes for immune surveillance