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Chapter 14
Cardiac Output, Blood Flow, and
Blood Pressure
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Objectives




Explain the intrinsic regulation of SV (FrankStarling Law of the Heart).
List the factors that affect the venous return
of blood to the heart.
Explain how ADH helps to regulate blood
volume, plasma osmolality, and blood
pressure.
Describe the renin-angiotensin-aldosterone
system and discuss its significance in CV
regulation.
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Objectives





(continued(
Define TPR and explain how vascular resistance is
regulated by extrinsic control mechanisms.
Explain the mechanisms by which blood flow to the
heart and skeletal muscles is regulated.
Describe the changes that occur in the CO and
distribution of blood flow during exercise.
List the factors that regulate the arterial blood
pressure.
Describe the baroreceptor reflex and explain its
significance in blood pressure regulation.
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Cardiac Output (CO)

Volume of blood
pumped/min. by each
ventricle.


CO = SV x HR


Pumping ability of
the heart is a
function of the beats/
min. and the volume
of blood ejected per
beat.
Total blood volume
averages about 5.5
liters.
Each ventricle pumps
the equivalent of the
total blood volume
each min. (resting
conditions).
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Regulation of Cardiac Rate



Without neuronal influences, the
heart beats according to the
rhythm set by SA node.
Regulation of HR (chronotropic
effect):

May be + or – effect.
Autonomic control:


Sympathetic and parasympathetic
nerve fibers to the heart modify
the rate of spontaneous
depolarization.
Innervate the SA node.



NE and Epi stimulate opening of
Na+/Ca2+ channel.
ACH promotes opening of K+
channel.

Major means by which
cardiac rate is regulated.
Cardiac control center (medulla):

Coordinates activity of
autonomic innervation.
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Regulation of SV

Stroke volume is regulated by 3
variables:

EDV:


Total peripheral resistance (TPR):


Volume of blood in the ventricles at the end of
diastole.
Frictional resistance or impedance to blood flow
in the arteries.
Contractility:

Strength of ventricular contraction.
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EDV

Workload on the heart prior to contraction
(preload).


Increase in EDV results in an increase in SV.



SV directly proportional to preload.
SV directly proportional to contractility.
Strength of contraction varies directly with
EDV.
Ejection fraction:

SV/ EDV.

Normally is 60%.

Clinical diagnostic tool.
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TPR

Total Peripheral Resistance:


Impedance to the ejection of blood from ventricle.
Afterload.



In order to eject blood, pressure generated in the
ventricle must be greater than pressure in the arteries.
Pressure in arteries before ventricle contracts is a
function of TPR.
SV inversely proportional to TPR.

Greater the TPR, the lower the SV.
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Frank-Starling Law of the Heart


Relationship between
EDV, contraction
strength, and SV.
Intrinsic mechanism:
 Varying degree of
stretching of
myocardium by EDV.
 As EDV increases:
 Myocardium is
increasingly
stretched.

Contracts
more
forcefully.
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Frank-Starling Law of the Heart
(continued)



As the ventricles
fill, the
myocardium
stretches; This
increases the
number of
interaction
between actin
and myosin.
Allows more
force to develop.
Explains how the
heart can adjust
to rise in TPR.
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Extrinsic Control of Contractility

Contractility:


Strength of contraction
at any given fiber
length.
Depends upon
sympathoadrenal
system:

NE and Epi produce an
increase in contractile
strength.

+ inotropic effect:

More Ca2+ available
to sarcomeres.
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Extrinsic Control of Contractility
(continued)

Parasympathetic
stimulation:

- chronotropic
effect.


Does not
directly
influence
contraction
strength.
CO affected 2
ways:


+ inotropic effect
on contractility.
+ chronotropic
effect on HR.
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Venous Return



Return of blood to the
heart via veins.
Venous pressure is
driving force for return
of blood to the heart.
Veins have thinner
walls, thus higher
compliance.


Capacitance vessels.
 2/3 blood volume
is in veins.
EDV, SV, and CO are
controlled by factors
which affect venous
return.
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Blood Volume


Distribution of H20 within the body:
Intracellular compartment:


2/3 of total body H20 within the cells.
Extracellular compartment:

1/3 total body H20.



80% interstitial fluid.
20% blood plasma.
Maintained by constant balance between H20
loss and gain.
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Blood Volume
(continued)
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Exchange of Fluid between
Capillaries and Tissues



Distribution of ECF between plasma and interstitial
compartments is in state of dynamic equilibrium.
 Balance between tissue fluid and blood plasma.
Hydrostatic pressure:
 Exerted against the inner capillary wall.
 Promotes formation of tissue fluid.
 Net filtration pressure.
Colloid osmotic pressure:
 Exerted by plasma proteins.
 Promotes fluid reabsorption into circulatory system.
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Net Filtration Pressure

Hydrostatic pressure of blood capillaries
minus the hydrostatic pressure in the
interstitial fluid.



Blood hydrostatic pressure (arteriolar
pressure) = 37 mm Hg.
Blood hydrostatic pressure (venular end) =
17 mm Hg.
Interstitial hydrostatic pressure = 1 mm Hg.
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Colloid Osmotic Pressure


Pressure exerted by plasma proteins or
interstitial proteins.
Difference between plasma osmotic
pressure and interstitial osmotic pressure
is called oncotic pressure.


Plasma osmotic pressure = 25 mm Hg.
Interstitial osmotic pressure = 0 mm Hg.
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Fluid Movement


Starling force=(Pc + Pi) - (Pi + Pp)
Pc =


Pi =


Colloid osmotic pressure of the interstitial fluid.
Pi =


Hydrostatic pressure in the capillary.
Hydrostatic pressure in the the interstitial fluid.
Pp =

Colloid osmotic pressure of the blood plasma.
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Fluid Movement
(continued)
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Causes of Edema


Excessive accumulation of tissue fluid.
Edema may result from:






High arterial blood pressure.
Venous obstruction.
Leakage of plasma proteins into interstitial fluid.
Myexedema.
Decreased plasma [protein].
Obstruction of lymphatic drainage.
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Regulation of Blood Volume by
the Kidney


Formation of urine begins by filtration
of plasma through glomerular capillary
pores.
Volume of urine excreted can be varied
by changes in reabsorption of filtrate.

Adjusted according to needs of body by
action of hormones.
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Regulation by ADH


Released by posterior
pituitary when
osmoreceptors
detect an increase in
plasma osmolality.
Dehydration or
excess salt intake:


Produces sensation of
thirst.
Stimulates H20
reabsorption from
urine.
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Regulation by Aldosterone


Steroid hormone secreted by adrenal cortex.
Mechanism to maintain blood volume and
pressure through absorption and retention of
Na+ and Cl-.




Stimulates reabsorption of NaCl.
Indirectly increases H20 reabsorption.
Does not dilute osmolality.
Release stimulated:


During salt deprivation.
Reduced blood volume and pressure.
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Renin-Angiotension-Aldosterone
System




When blood pressure and flow are reduced in
renal artery, juxtaglomerular apparatus secretes
renin.
Renin converts angiotensinogen to angiotensin I.
Angiotensin I is converted to angiotensin II by
ACE.
Angiotensin II:



Powerful vasoconstrictor.
Stimulates production of aldosterone.
Stimulates thirst.
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Juxtaglumerular Apparatus
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Renin-Angiotension-Aldosterone
System
(continued)
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Atrial Natriuretic Peptide (ANP)


Produced by the atria of the heart.
Stretch of atria stimulates production of
ANP.



Antagonistic to aldosterone and
angiotensin II.
Promotes Na+ and H20 excretion in the
urine by the kidney.
Promotes vasodilation.
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Vascular Resistance to Blood
Flow

Physical laws describing blood flow:


The flow of blood through the vascular
system is due to the difference in pressure
at the two ends (DP).
Flow = DP/R

R = TPR (sum of all vascular resistance
within the systemic circulation).


Blood flow directly proportional to pressure
differences.
Inversely proportional to resistance.
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Resistance




Opposition to blood
flow.
Resistance is directly
proportional to length of
vessel and to the
viscosity of the blood.
Inversely proportional
to 4th power of the
radius of the vessel.
R = _L  _
r4

L = length of the vessel

 = viscosity of blood

r = radius of the vessel
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Poiseuille’s Law

Blood flow = DPr4(p)
L(8)


Vessel length and blood viscosity do not
vary significantly.
Major regulators of blood flow through
an organ are:


Mean arterial pressure.
Vascular resistance to flow.
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Resistance and Blood Flow
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Extrinsic Regulation of Blood
Flow


Controlled by autonomic nervous system
and endocrine system.
Sympathoadrenal:


Increase CO.
Increase TPR:

Alpha-adrenergic stimulation:


Vasoconstriction of arteries in skin and viscera.
Cholinergic sympathetic fibers:

Vasodilate to skeletal muscles.
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Extrinsic Regulation of Blood
Flow
(continued)

Parasympathetic nervous system:

Parasympathetic innervation limited.


Promotes vasodilation to the digestive tract,
external genitalia, and salivary glands.
Less important than sympathetic nervous
system in control of TPR.

Parasympathetic endings in arterioles promote
vasodilation.
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Paracrine Regulation of Blood
Flow

Endothelium produces several paracrine
regulators:
 Endothelium of arterioles contains eNOS, which
produces NO:

NO diffuses into smooth muscle:

Activates guanylate cyclase:



Production of NO can be increased by Ach:

Stimulates opening of Ca2+ channels.




Converts GTP to cGMP (2nd messenger).
Lowers cytoplasmic [Ca2+].
Ca2+ binds to calmodulin.
Calmodulin activates an enzyme to produce NO.
Bradykinin, prostacyclin: Vasodilate.
Endothelin-1: Vasoconstrict
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Intrinsic Regulation of Blood
Flow (Autoregulation)

Myogenic control mechanism:

Occurs because of the stretch of the
vascular smooth muscle.

A decrease in systemic arterial pressure causes
cerebral vessels to dilate.


Maintains adequate flow.
A increase in systemic arterial pressure causes
cerebral vessels to contract

Maintains adequate flow.
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Intrinsic Regulation of Blood
Flow (Autoregulation)
(continued)

Metabolic control mechanism:


Intrinsic receptors sense chemical changes
in environment.
Vasodilation:

Decreased 02:


Increased C02:


Decreased ventilation.
Decreased pH:


Increased metabolic rate.
Lactic acid.
Increased adenosine or increased K+:

From tissue cells.
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Aerobic Requirements of the
Heart

Survival requires that the heart and brain receive
adequate blood supply at all times.

Coronary arteries supply an enormous # of capillaries.




Each myocardial cell is within 10 mm of a capillary.
Systole contracts the coronary blood vessels.
Diastole increases blood flow to the heart muscle.
Myocardium contains large amounts of
myoglobin.

Myoglobin stores 02 during diastole to release during
systole.

Heart muscle contains increased number of mitochondria and
aerobic respiratory enzymes.
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Regulation of Coronary Blood
Flow


Sympathetic nervous system:
a receptors:


b receptors:


Vasoconstriction at rest.
Vasodilation.
Intrinsic:


Metabolism of the myocardium increases causing
accumulations of C02, K+, and adenosine;
decreased 02.
Acts directly on vascular smooth muscle to cause
relaxation.
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Regulation of Blood Flow
Through Skeletal Muscles


Decreased blood flow when muscles contract
and constrict arterioles.
Sympathetic:

a-adrenergic receptors:


Sypothetic cholinergic and b-adrenergic
receptors:


Vasoconstrict at rest.
Vasodilate.
Intrinsic control primary mechanisms as
exercise progresses:

Increased accumulations of C02, K+, and
adenosine; decreased 02.

Vasodilate arterioles.
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Circulatory Changes During
Exercise

Vascular resistance decreases to skeletal muscles. Blood
flow to skeletal muscles increases.

SV and CO increase.




Metabolic vasodilation.
Diversion of blood away from vicera and skin.
HR increases to maximum of 190 beats/min.


Blood flow to brain stays same.
Ejection fraction increases due to increased contractility.
Vascular resistance:
 Decreases to skeletal muscle.
 Increases to GI tract and skin.
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Circulatory Changes During
Exercise
(continued)
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Circulatory Changes During
Exercise
(continued)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Cerebral Circulation


Cerebral blood flow is not normally influenced
by sympathetic nerve activity.
Normal range of arterial pressures:

Cerebral blood flow regulated almost exclusively
by intrinsic mechanisms:

Myogenic:



Dilate in response to decreased pressure.
Cerebral arteries also sensitive to [C02].
 Dilate due to decreased pH of crebrospinal fluid.
Metabolic:

Sensitive to changes in metabolic activity.
 Areas of brain with high metabolic activity receive
most blood.
+
 May be caused by [K ].
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Cutaneous Blood Flow

Thermoregulation:


Blood flow through the skin is adjusted to maintain
deep-body temperatures at about 37o C.
Occurs due to:


Bradykinin:


Vasoconstriction/vasodilation ordinary arteries and
arteriovenous anastomosis.
Sweat glands secrete bradykinin which increases blood
flow to skin and sweat glands.
Changes in cutaneous blood flow, occur as a
result to changes in sympathetic nerve activity;
which is controlled by the brain.
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Arteriovenous Anastomosis



Controlled by
sypothetic nervous
system
Divert blood from
arterioles to depp
venules
 In hands, toes, ear,
nose and lips.
Ambient temperature
is low

Arteriovenous
anastomosis constrict
and divert blood in to
superfical capillary
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Blood Pressure (BP)

Pressure of arterial blood is regulated by blood
volume, TPR, and cardiac rate.


Arteriole resistance is greatest because they have
the smallest diameter.


Capillary BP is reduced because of the total crosssectional area.
3 most important variables are HR, SV, and TPR.


MAP=CO  TPR
Increase in each of these will result in an increase in
BP.
BP can be regulated by:

Kidney and sympathoadrenal system.
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MAP
TPR
CO
HR
SV
ANS
Hormones
Chemicals
Viscosity
Blood vessel length
Blood vessel diameter
Local factors
EDV
ANS
Hormones
Venous Return
Lytes
Body temp
Kidney
Brain
Respiratory pump
Angiotensin Skeletal muscle pump
Aldosterone
ADH
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Blood Pressure (BP)
(continued)
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Baroreceptor Reflex





Stretch receptors located in the aortic arch and
carotid sinuses.
An increase in pressure causes the walls of these
regions to stretch, increasing frequency of APs.
Baroreceptors send APs to vasomotor control and
cardiac control centers in the medulla.
Baroreceptor reflex activated with changes in BP.
More sensitive to decrease in pressure and
sudden changes in pressure.
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Baroreceptor Reflex
(continued)
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Baroreceptor Reflex
(continued)
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Atrial Stretch Reflexes


Located in the atria of the heart.
Receptors activated by increased
venous return.



Stimulate reflex tachycardia.
Inhibit ADH release.
Promote secretion of ANP.
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Measurement of Blood Pressure

Auscultation:


Art of listening.
Laminar flow:


Normal blood flow.
Blood in the central axial stream moves faster
than blood flowing closer to the artery wall.


Smooth and silent.
Turbulent flow and vibrations produced in the
artery when cuff pressure is greater than
diastolic pressure and lower than systolic
pressure.
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Measurement of Blood Pressure
(continued)



Blood pressure cuff is
inflated above systolic
pressure, occluding the
artery.
As cuff pressure is lowered,
the blood will flow only when
systolic pressure is above
cuff pressure, producing the
sounds of Korotkoff.
Korotkoff sounds will be
heard until cuff pressure
equals diastolic pressure,
causing the sounds to
disappear.
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Measurement of Blood Pressure
(continued)



Different phases in
measurement of blood
pressure are identified
on the basis of the
quality of the Korotkoff
sounds.
Average arterial BP is
120/80 mm Hg.
Average pulmonary BP
is 22/8 mm Hg.
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Pulse Pressure



The expansion of the artery in response to the
volume of blood ejected by the left ventricle.
Pulse pressure = systolic pressure –
diastolic pressure
Mean arterial pressure (MAP):

Represents the average arterial pressure during
the cardiac cycle.


Is closer to diastolic pressure, as the period of diastole is
longer than the period of systole.
MAP = diastolic pressure + 1/3 pulse
pressure
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Hypertension (HTN)

Blood pressure in excess of normal
range for age and gender.


Primary or essential hypertension:


> 140/90 mm Hg.
Is the result of a complex or poorly
understood process.
Secondary hypertension:

Is a result of a known disease process.
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Essential Hypertension

Majority of the population with hypertension.






Increase in TPR is a universal characteristic.
CO and HR elevated in many.
Secretion of renin, angiotensin II, and aldosterone
is variable.
Sustained high stress (via sympathetic nervous
system) and high Na+ intake act synergistically in
development of hypertension.
Adaptive response is thickening of arterial wall,
resulting in atherosclerosis.
Kidneys may not be able to properly excrete Na+
and H20.

A shared characteristic of all cases of essential HTN.
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Dangers of Hypertension


Silent killer:
Patients are asymptomatic until substantial
vascular damage occurs.


Increases afterload.



Atherosclerosis.
Increases workload of the heart.
Congestive heart failure.
Damage cerebral blood vessels.

Cerebral vascular accident (stroke).
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Treatment of Hypertension

Modification of lifestyle:






Cessation of smoking.
Moderation in alcohol intake.
Weight reduction.
Programmed exercise.
Reduction in Na+ intake.
Diet high in K+.
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Treatment of Hypertension

Medications:

Diuretics:


Beta-blockers:


Block Ca2+ channels.
ACE inhibitors:


Decrease HR.
Calcium antagonists:


Increase urine volume.
Inhibit conversion to angiotensin II.
Angiotension II-receptor antagonists:

Block receptors.
(continued)
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Circulatory Shock

Hypovolemic shock:


Circulatory shock that is due to low blood volume.
Decreased CO and blood pressure.


Bleeding, dehydration, and burns.
Compensations:

Baroreceptor reflex:



Kidneys stimulate production of renin-angiotensinaldosterone system.


Tachycardia.
Vasoconstriction to GI, skin, kidneys, and muscles.
Vasoconstriction.
Increase in ADH.
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Circulatory Shock

Septic shock:


Dangerously low blood pressure as a result
of sepsis.
Occurs through the action of endotoxin.



(continued)
Endotoxin activates nitric oxide synthetase,
producing NO.
NO causes vasodilation.
Treat with drugs that inhibit the
production of NO.
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Other Causes of Circulatory
Shock

Anaphylactic shock:




Severe allergic reaction.
Widespread release of histamine.
Vasodilation.
Neurogenic shock:

Rapid fall in BP.


Sympathetic tone is decreased.
Cardiogenic shock:

Cardiac failure.

CO inadequate to maintain perfusion.
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Congestive Heart Failure

CO is insufficient to maintain the blood flow required
by the body.




Increased venous volume and pressure.
Caused by:
 MI (most common cause).
 Congenital defects.
 Hypertension.
 Aortic valve stenosis.
 Disturbances in electrolyte concentrations.
+ and Ca++.
 K
Compensations similar to those of hypovolemic shock.
Treated with medications:
 Digitalis, vasodilators, and diuretics.
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Xuesong Chen
[email protected]
Department of Pharmacology,
Physiology and Therapeutic.
Room 5730