Cardiac Output, Blood Flow, and

Blood Pressure
• Chapter 14 Outline

• Cardiac Output
• Blood & Body Fluid Volumes
• Factors Affecting Blood Flow
• Blood Pressure
• Hypertension
• Circulatory Shock
Cardiac Output
Cardiac Output (CO)

Is volume of blood pumped/min by each

ventricle
Heart Rate (HR) = 70 beats/min
Stroke volume (SV) = blood pumped/beat by
each ventricle
◦ Average is 70-80 ml/beat
CO = SV x HR
Total blood volume is about 5.5L

14-4
Regulation of Cardiac Rate
• Without neuronal influences, SA node will
drive heart at rate of its spontaneous activity
• Normally Symp & Parasymp activity
influence HR (chronotropic effect)
▫ Mechanisms that affect HR: chronotropic
effect
 Positive increases; negative decreases
• Autonomic innervation of SA node is main
controller of HR
▫ Symp & Parasymp nerve fibers modify rate of
spontaneous depolarization
14-5
Regulation of Cardiac Rate continued
Fig 14.1
• NE & Epi stimulate
opening of
pacemaker HCN
channels
▫ This depolarizes SA
faster, increasing
HR
• ACh promotes
opening of K+
channels
▫ The resultant K+
outflow counters
Na+ influx, slows
depolarization &
decreasing HR
14-6
 Regulation of Cardiac Rate continued

• Vagus nerve:
▫ Decrease activity: increases heart rate
▫ Increased activity: slows heart
• Cardiac control center of medulla coordinates activity
of autonomic innervation
• Sympathetic endings in atria & ventricles can
stimulate increased strength of contraction

14-7
14-8
Stroke Volume
• Is determined by 3 variables:
▫ End diastolic volume (EDV) = volume of blood in
ventricles at end of diastole
▫ Total peripheral resistance (TPR) = impedance to blood
flow in arteries
▫ Contractility = strength of ventricular contraction

14-9
 Regulation of Stroke Volume

• EDV is workload (preload) on heart prior to

contraction
▫ SV is directly proportional to preload & contractility
• Strength of contraction varies directly with EDV
• Total peripheral resistance = afterload which impedes
ejection from ventricle
▫ SV is inversely proportional to TPR
• Ejection fraction is SV/ EDV (~80ml/130ml=62%)
▫ Normally is 60%; useful clinical diagnostic tool

14-10
Frank-Starling Law of the Heart

• States that
strength of Fig 14.2
ventricular
contraction varies
directly with EDV
▫ Is an intrinsic
property of
myocardium
▫ As EDV increases,
myocardium is
stretched more,
causing greater
contraction & SV
14-11
 Frank-Starling Law of the Heart continued

• (a) is state of myocardial

sarcomeres just before
filling
▫ Actins overlap, actin-
myosin interactions are
reduced & contraction
would be weak
• In (b, c & d) there is
increasing interaction of
actin & myosin allowing
more force to be
developed

Fig 14.3
14-12
• At any given EDV,
contraction
depends upon level
of
sympathoadrenal
activity
▫ NE & Epi produce
an increase in HR &
contraction (positive
inotropic effect)
 Due to increased Ca2+
in sarcomeres
Fig 14.4
14-13
Extrinsic Control of Contractility
• Parasympathetic stimulation
▫ Negative chronotropic effect
 Through innervation of the SA node and myocardial
cell
▫ Slower heart rate means increased EDV
 Increases SV through Frank-Starling law
Fig 14.5
14-14
 Venous Return

• Is return of blood to
heart via veins
• Controls EDV & thus
SV & CO
• Dependent on:
▫ Blood volume & venous
pressure
▫ Vasoconstriction caused
by Symp
▫ Skeletal muscle pumps
▫ Pressure drop during
inhalation

Fig 14.7 14-15

Venous Return continued

• Veins hold most of

blood in body (70%)
& are thus called
capacitance vessels
▫ Have thin walls &
stretch easily to
accommodate more
blood without
increased pressure
(=higher
compliance)
 Have only 0-
10 mm Hg pressure Fig 14.6
14-16
Blood Volume
• Constitutes small
fraction of total body
fluid
• 2/3 of body H20 is
inside cells
(intracellular
compartment)
• 1/3 total body H20 is
in extracellular
compartment
▫ 80% of this is
interstitial fluid; 20% is Fig 14.8
blood plasma 14-18
 Exchange of Fluid between
Capillaries & Tissues

• Distribution of ECF between blood & interstitial

compartments is in state of dynamic equilibrium
• Movement out of capillaries is driven by hydrostatic
pressure exerted against capillary wall
▫ Promotes formation of tissue fluid
▫ Net filtration pressure= hydrostatic pressure in
capillary (17-37 mm Hg) - hydrostatic pressure of ECF
(1 mm Hg)

14-19
 Exchange of Fluid between
Capillaries & Tissues

• Movement also affected by colloid osmotic

pressure
▫ = osmotic pressure exerted by proteins in fluid
▫ Difference between osmotic pressures in & outside
of capillaries (oncotic pressure) affects fluid
movement
 Plasma osmotic pressure = 25 mm Hg; interstitial
osmotic pressure = 0 mm Hg

14-20
 Overall Fluid Movement

• Is determined by net filtration pressure & forces

opposing it (Starling forces)

▫ Pc + i (fluid out) - Pi + p (fluid in)

• Pc = Hydrostatic pressure in capillary

• i = Colloid osmotic pressure of interstitial fluid
• Pi = Hydrostatic pressure in interstitial fluid
• p = Colloid osmotic pressure of blood plasma

14-21
Fig 14.9

14-22
Edema

• Normally filtration, osmotic reuptake, &

lymphatic drainage maintain proper ECF levels
• Edema is excessive accumulation of ECF
resulting from:
▫ High blood pressure
▫ Venous obstruction
▫ Leakage of plasma proteins into ECF
▫ Myxedema (excess production of glycoproteins in
extracellular matrix) from hypothyroidism
▫ Low plasma protein levels resulting from liver disease
▫ Obstruction of lymphatic drainage
14-23
Regulation of Blood Volume by Kidney

• Urine formation begins with filtration of plasma in

glomerulus
• Filtrate passes through & is modified by nephron
• Volume of urine excreted can be varied by changes in
reabsorption of filtrate
▫ Adjusted according to needs of body by action of
hormones

14-24
ADH (vasopressin)

• ADH released by Post

Pit when osmoreceptors
detect high osmolality
▫ From excess salt
intake or dehydration
▫ Causes thirst
▫ Stimulates H20
reabsorption from
urine
• ADH release inhibited
by low osmolality
Fig 14.11
14-25
Aldosterone

• Is steroid hormone secreted by adrenal cortex

• Helps maintain blood volume & pressure
through reabsorption & retention of salt & water
• Release stimulated by salt deprivation, low
blood volume, & pressure

14-26
Renin-Angiotension-Aldosterone System

• Decreased BP and flow (low blood volume)

• Kidney secreted Renin (enzyme)
▫ Juxaglomerular apparatus
• Angiotensin I to AngiotensinII
▫ By angiotensin-converting enzyme (ACE)
• Angio II causes a number of effects all aimed
at increasing blood pressure:
 Vasoconstriction, aldosterone secretion, thirst

14-27
Angiotensin II

• Fig 14.12
shows when
& how Angio
II is
produced, &
its effects

14-28
Atrial Natriuretic Peptide (ANP)

• Expanded blood volume is detected by

stretch receptors in left atrium & causes
release of ANP
▫ Inhibits aldosterone, promoting salt & water
excretion to lower blood volume
▫ Promotes vasodilation

14-29
Vascular Resistance to Blood Flow

• Determines how much blood flows through a tissue

or organ
▫ Vasodilation decreases resistance, increases blood
flow
▫ Vasoconstriction does opposite

14-31
14-32
Physical Laws Describing Blood Flow

• Blood flows
through vascular
system when there
is pressure
difference (P) at
its two ends
▫ Flow rate is directly
proportional to
difference
▫ (P = P1 - P2)
Fig 14.13
14-33
Physical Laws Describing Blood Flow

• Flow rate is inversely proportional to

resistance
▫ Flow =P/R
▫ Resistance is directly proportional to length of vessel
(L) & viscosity of blood ()
 Inversely proportional to 4th power of radius
 So diameter of vessel is very important for resistance
• Poiseuille's Law describes factors affecting
blood flow

▫ Blood flow = Pr4()

L(8)

14-34
Fig 14.14. Relationship
between blood flow,
radius & resistance

14-35
Extrinsic Regulation of Blood Flow
• Sympathoadrenal activation causes increased
CO & resistance in periphery & viscera
▫ Blood flow to skeletal muscles is increased
 Because their arterioles dilate in response to Epi &
their Symp fibers release ACh which also dilates
their arterioles
 Thus blood is shunted away from visceral & skin to
muscles

14-36
Extrinsic Regulation of Blood Flow
continued

• Parasympathetic effects are vasodilative

▫ However, Parasymp only innervates digestive
tract, genitalia, & salivary glands
▫ Thus Parasymp is not as important as Symp
• Angiotensin II & ADH (at high levels) cause
general vasoconstriction of vascular smooth
muscle
▫ Which increases resistance & BP

14-37
Paracrine Regulation of Blood Flow

• Endothelium produces several paracrine

regulators that promote relaxation:
▫ Nitric oxide (NO), bradykinin, prostacyclin
 NO is involved in setting resting “tone” of vessels
 Levels are increased by Parasymp activity
 Vasodilator drugs such as nitroglycerin or Viagra act
thru NO
• Endothelin 1 is vasoconstrictor produced by
endothelium

14-38
Intrinsic Regulation of Blood Flow
(Autoregulation)
• Maintains fairly constant blood flow despite BP
variation
• Myogenic control mechanisms occur in some tissues
because vascular smooth muscle contracts when
stretched & relaxes when not stretched
▫ E.g. decreased arterial pressure causes cerebral vessels
to dilate & vice versa

14-39
Intrinsic Regulation of Blood Flow (Autoregulation)
continued

• Metabolic control mechanism matches blood

flow to local tissue needs
• Low O2 or pH or high CO2, adenosine, or K+ from
high metabolism cause vasodilation which
increases blood flow (= active hyperemia)

14-40
Aerobic Requirements of the Heart
• Heart (& brain) must receive adequate blood
supply at all times
• Heart is most aerobic tissue--each myocardial
cell is within 10 m of capillary
▫ Contains lots of mitochondria & aerobic enzymes
• During systole coronary vessels are occluded
▫ Heart gets around this by having lots of myoglobin
 Myoglobin is an 02 storage molecule that releases 02 to heart
during systole

14-41
Regulation of Coronary Blood Flow

• Blood flow to heart is affected by Symp activity

▫ NE causes vasoconstriction; Epi causes
vasodilation
• Dilation accompanying exercise is due mostly to
intrinsic regulation

14-42
Regulation of Blood Flow Through Skeletal
Muscles

• At rest, flow through skeletal muscles is low

because of tonic sympathetic activity
• Flow through muscles is decreased during
contraction because vessels are constricted

14-43
Circulatory Changes During Exercise
• At beginning of exercise, Symp activity causes
vasodilation via Epi & local ACh release
▫ Blood flow is shunted from periphery & visceral to active
skeletal muscles
▫ Blood flow to brain stays same
• As exercise continues, intrinsic regulation is major
vasodilator
• Symp effects cause SV & CO to increase
▫ HR & ejection fraction increases vascular resistance

14-44
Fig 14.19

14-45
Fig 14.20

14-46
Cerebral Circulation

• Gets about 15% of total resting CO

• Held constant (750ml/min) over varying
conditions
▫ Because loss of consciousness occurs after
few secs of interrupted flow
• Is not normally influenced by sympathetic
activity

14-47
Cerebral Circulation
• Is regulated almost exclusively by intrinsic
mechanisms
▫ When BP increases, cerebral arterioles constrict;
when BP decreases, arterioles dilate (=myogenic
regulation)
▫ Arterioles dilate & constrict in response to
changes in C02 levels
▫ Arterioles are very sensitive to increases in local
neural activity (=metabolic regulation)
 Areas of brain with high metabolic activity receive
most blood

14-48
Fig 14.21
14-49
Cutaneous Blood Flow
• Skin serves as a heat
exchanger for
thermoregulation
• Skin blood flow is
adjusted to keep deep-
body at 37oC
▫ By arterial dilation or
constriction & activity of
arteriovenous anastomoses
which control blood flow
through surface capillaries
 Symp activity closes surface
beds during cold & fight-or-
flight, & opens them in heat &
exercise
Fig 14.22
14-50
Blood Pressure (BP)
• Arterioles play role in blood distribution &
control of BP
• Blood flow to capillaries & BP is controlled by
aperture of arterioles
• Capillary BP is decreased because they are
downstream of high resistance arterioles

Fig 14.23

14-52
Blood Pressure (BP)

• Capillary BP
is also low
because of
large total
cross-
sectional area

Fig 14.24
14-53
Blood Pressure (BP)

• Is controlled mainly by HR, SV, & peripheral

resistance
▫ An increase in any of these can result in increased BP
• Sympathoadrenal activity raises BP via arteriole
vasoconstriction & by increased CO
• Kidney plays role in BP by regulating blood volume &
thus stroke volume

14-54
Baroreceptor Reflex

• Is activated by changes in BP
▫ Which is detected by baroreceptors (stretch receptors)
located in aortic arch & carotid sinuses
 Increase in BP causes walls of these regions to stretch,
increasing frequency of APs
 Baroreceptors send APs to vasomotor & cardiac control
centers in medulla
• Is most sensitive to decrease & sudden changes in BP

14-55
Fig 14.26
14-56
Fig 14.27

14-57
Atrial Stretch Receptors
• Are activated by increased venous return & act to
reduce BP
• Stimulate reflex tachycardia (slow HR)
• Inhibit ADH release & promote secretion of ANP

14-58
Measurement of Blood Pressure
• Is via auscultation (to examine by listening)
• No sound is heard during laminar flow (normal, quiet,
smooth blood flow)
• Korotkoff sounds can be heard when
sphygmomanometer cuff pressure is greater than
diastolic but lower than systolic pressure
▫ Cuff constricts artery creating turbulent flow & noise as blood
passes constriction during systole & is blocked during
diastole
▫ 1st Korotkoff sound is heard at pressure that blood is 1st able
to pass thru cuff; last occurs when can no long hear systole
because cuff pressure = diastolic pressure

14-59
Measurement of Blood Pressure continued

• Blood pressure cuff

is inflated above
systolic pressure,
occluding artery
• As cuff pressure is
lowered, blood flows
only when systolic
pressure is above
cuff pressure,
producing Korotkoff
sounds
• Sounds are heard
until cuff pressure
equals diastolic
pressure, causing
sounds to disappear Fig 14.29
14-60
Fig 14.30
14-61
Pulse Pressure

• Pulse pressure = (systolic pressure) –

(diastolic pressure)
• Mean arterial pressure (MAP) represents
average arterial pressure during cardiac cycle
▫ Has to be approximated because period of
diastole is longer than period of systole
▫ MAP = diastolic pressure + 1/3 pulse pressure

14-62
Hypertension

14-63
Hypertension

• Is blood pressure in excess of normal range for age &

gender (> 140/90 mmHg)
• Afflicts about 20 % of adults
• Primary or essential hypertension is caused by
complex & poorly understood processes
• Secondary hypertension is caused by known disease
processes

14-64
Essential Hypertension
• Constitutes most of hypertensives
• Increase in peripheral resistance is universal
• CO & HR are elevated in many
• Secretion of renin, Angio II, & aldosterone is
variable
• Sustained high stress (which increases Symp
activity) & high salt intake act synergistically in
development of hypertension
• Prolonged high BP causes thickening of arterial
walls, resulting in atherosclerosis
• Kidneys appear to be unable to properly excrete
Na+ and H20

14-65
Dangers of Hypertension

• Patients are often asymptomatic until substantial

vascular damage occurs
▫ Contributes to atherosclerosis
▫ Increases workload of the heart leading to ventricular
hypertrophy & congestive heart failure
▫ Often damages cerebral blood vessels leading to stroke
▫ These are why it is called the "silent killer"

14-66
Treatment of Hypertension
• Often includes lifestyle changes such as cessation of
smoking, moderation in alcohol intake, weight
reduction, exercise, reduced Na+ intake, increased K+
intake
• Drug treatments include diuretics to reduce fluid
volume, beta-blockers to decrease HR, calcium
blockers, ACE inhibitors to inhibit formation of Angio
II, & Angio II-receptor blockers

14-67
Circulatory Shock
• Occurs when there is inadequate blood flow to, &/or
O2 usage by, tissues
▫ Cardiovascular system undergoes compensatory changes
▫ Sometimes shock becomes irreversible & death ensues

14-69
Hypovolemic Shock
• Is circulatory shock caused by low blood volume
▫ E.g. from hemorrhage, dehydration, or burns
▫ Characterized by decreased CO & BP
• Compensatory responses include sympathoadrenal
activation via baroreceptor reflex
▫ Results in low BP, rapid pulse, cold clammy skin, low
urine output

14-70
Septic Shock
• Refers to dangerously low blood pressure resulting
from sepsis (infection)
• Mortality rate is high (50-70%)
• Often occurs as a result of endotoxin release from
bacteria
▫ Endotoxin induces NO production causing vasodilation
& resultant low BP
▫ Effective treatment includes drugs that inhibit
production of NO

14-71
Other Causes of Circulatory Shock
• Severe allergic reaction can cause a rapid fall in BP
called anaphylactic shock
▫ Due to generalized release of histamine causing
vasodilation
• Rapid fall in BP called neurogenic shock can result
from decrease in Symp tone following spinal cord
damage or anesthesia
• Cardiogenic shock is common following cardiac failure
resulting from infarction that causes significant
myocardial loss

14-72
Congestive Heart Failure
• Occurs when CO is insufficient to maintain blood flow
required by body
• Caused by MI (most common), congenital defects,
hypertension, aortic valve stenosis, disturbances in
electrolyte levels
• Compensatory responses are similar to those of
hypovolemic shock
• Treated with digitalis, vasodilators, & diuretics

14-73