Cardiac Output and its

regulation

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Objectives

– Describe cardiac output

– Discuss regulation of cardiac output
– Discuss functional classification of blood
vessels with their functions

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 Cardiac Output

The volume of blood each ventricle pumps as a

function of time expressed in L/min, is (CO).
In the steady state, the cardiac output flowing
through the systemic and the pulmonary circuits is
the same.
The cardiac output can be calculated by multiplying
the heart rate (HR), and the stroke volume (SV) :

Cardiac Out put = Stroke Volume x Heart Rate

Normally: CO (ml/min) = HR (75 beats/min) x SV(70

ml/beat)=5250 ml/min (5.25 L/min)
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 Cardiac Output cont’d…,

o Ventricular end diastolic volume (VEDV):

o The volume of blood in the ventricle at the end of
ventricular diastole (relaxation phase)
VEDV = 120-140 ml
o Ventricular end systolic volume (VESV):
o The volume of blood that remains in the ventricle at the end
of ventricular systole (contraction phase).
VESV = 50-60 ml

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 Cardiac Output cont’d…,
Cardiac reserve:
 It is the difference between maximal exercise and resting
CO
o CO = 5-6 liters per minute at rest
o CO = 20-40 liters per minute at maximum exercise
E.g. 35 L-5 L =30 L
 Permits cardiac output to increase dramatically during periods of
physical activity.
Cardiac Index:
It is the ratio of amount of blood pumped of the left
ventricle each minute to body surface area.
CI = Cardiac output÷ Body surface area
E.g. 5.5 L/min ÷1.7 =3.23 L/min/m2

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 Cardiac Output cont’d…,
• EDV: 110 to 130 milliliters
• Stroke volume output: 70 ml
• ESV=120-70ml =50 ml
• Ejection fraction
 Measures cardiac performance
 ~2/3 of blood contained
 i.e. ejection fraction=SV/EDV=70/120, EF=58%
• It is normally: 53-70%
• Related to contractility

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 Regulation of CO
I. General Factors Affecting C.O
II. Intrinsic (primary) Regulation of C.O
III. Extrinsic Regulation of C.O.

General Factors Affecting C.O

 Venous return (VR)

 Force of ventricular contraction
 Frequency of ventricular contraction
 Mean aortic pressure (MAP):MAP impedes LV output

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 General factors affecting CO

1. Venous Return (VR):

 Volume of blood flowing into RA/min
 Increased VR increases C.O.
 5.5L/min at rest; about 35L/min in well trained
athletes during strenuous exercise

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 Factors Affecting VR

1. Mean Systemic Filling Pressure (MSFP)

• Pressure measured every where in systemic
circulation 1 min after BF has been stopped by
clamping large blood vessels near heart
• Normal value: 7 mmHg
• Indicates degree of filling of systemic circulation
• The driving force for VR

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 Factors Affecting VR…

2. Right Atrial Pressure (RAP)

• Mean pressure in right atrium =2 mmHg
• Pressure gradient=MSFP-RAP (7-2)
• RAPVR
3. Resistance to venous return (RVR=TPR)
 Resistance blood meets (1mmHg/L/min) during
its flow from arterial side to RA occurs mainly at
venous

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 Factors Affecting VR…

4. Sympathetic stimulationVR by inducing

vasoconstriction, improved cardiac pumping
power and arteriolar dilatation
5. Blood volume
• BVVR by MSFP
6. Respiratory movements
• VR increases with inspiration and
decreases with expiration
7. Arteriolar dilatation RVRVR

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 Factors Affecting VR…

8. Capillary dilatation vascular capacity , MSFP VR

9. Skeletal muscle contraction
 Squeezes veins b/n musclesMSFPVR
10. Gravity:
• Standing motionless for sometime  pooling of blood in
lower extremitiesVR C.O hypotension brain
ischemia syncope

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 Intrinsic regulation of CO

• Things that can affect HR & SV will thus affect CO.

Frequency of ventricular contraction(HR)

• No of cardiac cycles (frequency) per minute
• Heart rate is initiated by Autorhythmic cells in the SA
node, but it is modulated by neural and hormonal input
.
• Normal HR of adult: 60-100 bpm
 < 60 bpm, bradycardia but normal in athletes
 > 100 bpm, tachycardia

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 Factors Affecting Heart Rate

Increased heart rate can be caused by:

1. ↑ Output of the cardioacceleratory center.
~ greater activity of sympathetic nerves running to the
heart & greater release of norepinephrine on the heart.
2. ↓ Output of the cardioinhibitory center.
~ less vagus nerve activity & a decrease in the release of
acetylcholine on the heart.

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 Factor affecting heart rate

• Factor affecting heart rate stimuation are;

• Sympathetic stimulation,
• increase body tempreture,
• Hypercalcemia ,
• Hypokalemia,
• increase periperial chemoreceptor,
• T3/T4
• Hypocalcemia,hyperkalemia,
parasympathetic stimulation inhabit heart
rate.
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 Heart rate…,

• The sympathetic and parasympathetic branches of

ANS influence heart rate.

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 Regulation of HR

• Age: higher in new born infants (120 bpm)

• Sex: higher in females
• Body temperature /Time of day: ↓morning,
↑evening
• Resting and sleep: slightly decreased
• Physical fitness/Physical training: low in athletes
(45-60 bpm)
• Body position: ↑standing, ↓supine positions
• Neural( SNS, PNS)
• Chemicals:
 Hormones, electrolytes( Na+, K+, Ca2+)
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 Regulation of stroke volume

1. Intrinsic:
 Preload, Contractility and After load
2. Extrinsic: involves neural and hormonal control
Stroke volume is determined by:
I. End diastolic volume(EDV): volume of blood
in the ventricles at end of diastole
II. Total peripheral resistance(TPR): impedance
to blood flow through arteries.
III.Contractility: strength of ventricular
contraction
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 Factors Affecting Stroke Volume

1. Preload
• The amount of tension in the ventricular myocardium
just prior to contraction.
• The blood returns to the heart (↑ venous return): the
more the heart muscle stretches, the greater the force of
contraction & the extra blood gets pumped out.
• This direct relationship between preload & stroke
volume is called the Frank-Starling Law of the Heart.
• The preload applies tension to the muscle and stretches it
passively to a new length.

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 Preload…,
Frank- starling’s law of Heart
 The greater VR, the greater cardiac output
 Increase in EDV cause an increase in ventricular fiber length,
which produces an increase in developed tension (myocardial
force of contraction)

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 Factors affecting preload:

• Total blood Stroke volume

volume
• Venous return
Strength of cardiac contraction
 An increase VR,
increase EDV, so
that increase SV.
End-diastolic volume

Venous return
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 Factors Affecting SV…
2. Contractility
• Refers to the contraction force
• Governed by neural, hormonal & chemical factors.

+ve inotropic agents ‒ve inotropic agents

-Sympathetic stimulation -Parasympathetic stimulation
-Hypercalcemia -Hyperkalemia
-Glucagon, T3/T4 -Hypocalcemia
-Digitalis, Xanthenes -Acidosis
-Cathecolamines -Toxins
-Heart diseases
hypoxia

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Contractility…,

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 3. Afterload:

• It is the load against which the ventricles pump

• For the left ventricle the load is aortic pressure
– Increase in aortic pressure cause an increase in
afterload on the left ventricle
• For the right ventricle the load is pulmonary artery
pressure
– Increase in pulmonary artery pressure causes an
increase in afterload on the right ventricle.
 SL valves to be pushed open, the pressure within the
ventricles must exceed the pressure within the aorta and
pulmonary trunk 24
 Remember
• Preload is the degree to which the myocardium is stretched
before it contracts
• Myocardial length
• Afterload is the resistance against which blood is expelled
 Vascular resistance

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26
 2. Extrinsic factors affecting CO

 Sympathetic NS & Parasympathetic NS

 Hormones
 Cathecholamines & glucagon (increases cAMP)
 Caffeine (inhibits cAMP breakdown)
 Electrolytes( K+ , Ca2+ )
 Body temperature
 Acid-base status
 Hypercapnia, hypoxia and acidosis decreases cardiac
contractility
 Digitalis via inhibiting Na+-K+ ATPase

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Extrinsic factors…

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29
 Control of Cardiovascular system

 The heart rate is under neural control.

 Cardiac sympathetic efferent activity increases the
heart rate, whereas parasympathetic (vagal) efferent
impulses decreases heart rate.
Cardiovascular Center ,
• Group of neurons in the medulla that regulates heart
rate, contractility, and blood vessel diameter.

• Even though the heart has its own pacemaker, CNS can
alter / influence its rhythm, contractility,and rate.

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 Control of Cardiovascular s…,

• Input to the Cardiovascular Center/medulla

• Higher brain centers such as cerebral cortex, limbic
system & hypothalamus
– anticipation of competition
– increase in body temperature
• Proprioceptors
– input during physical activity
• Baroreceptors
– changes in pressure within blood vessels
• Chemoreceptors
– monitor concentration of chemicals in the blood

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32
 Factors affecting cardiac activity

1. ANS:
SyNS: Innervates SA-node, AV-node,
conductive and contractile muscles
 ↑Rhythmicity, +ve chronotropic effect
 Mechanism: increases the slope of
pacemaker potential of SA-node by
decreasing K+ permeability
PaNS: Innervates SA-node, AV-node, atrial
muscles
 Inhibits autorhythmicity, -ve
chronotropic effect
 Strong vagal stimulation leads to
cardiac arrest
Mechanism: decreases the slope of pacemaker
potential by increasing K+ conductance in
the SA-node
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Effect of autonomic nervous system on the
heart and structures that influence the heart

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 Factors affecting cardiac
activity …
2. Body temperature:
• ↑BT by 1oC, ↑HR by 20 beats/min
• ↑BT increases SA- nodal discharge
• Rise (e.g. Fever) : weak myocardial contraction (exhaust metabolic
system)
3. PH:
• Acidosis: -ve inotropic effect, due to depression of affinity of troponin
C to Ca++ ; Severe acidosis stops heart in diastole
 Alkalosis: +inotropic; increase affinity of troponinin C to Ca++
• Severe alkalosis stops heart in systole
4. Inorganic ions:
a. Na+
 Hypernatremia (-ve inotropic effect
• Stimulate Na+-Ca++ exchanger to take Na+ in
• Drive Ca++ out of cardiac myocyte, cytosolic Ca++ level
decreases
 Hyponatremia: + inotropic effect
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 Factors affecting cardiac activity…
b. Ca++
 Hypercalcemia: Increase cytosolic Ca++ level, stronger systole &
incomplete diastole
 If level very high, heart stop in systole (Calcium Rigor)
• Hypocalcemia:
 Decrease myocardial contractility, but have no serious effect
C. K+
 Hyperkalemia: ( -ve inotropic effect)
• Low amplitude AP—weak contraction
• Marked hyperkalemia heart stop in diastole
 Hypokalemia: weak + inotropic effect
5. Drugs:
 AD, NAD, T3/T4 increase cardiac rhythmicity
• They have +ve chronotropic effect
 Cholinergic drugs: Ach, pilocarpin have -ve chronotropic effect
6. Mechanical factors:
 Atrial wall stretch by high blood volume, ↑HR 36
 Objectives
At the end of this session, the students will able to:
– Discuss functional classification of blood vessels with
their
functions
– Discuss about hemodynamics, blood flow and factors
affecting them

– Elaborate the regulations mechanisms ABR

» Local
» Neural
» Hormonal
– Explain
wastes, the exchange
& signaling mechanisms
molecules of nutrients,
in systemic gases,
capillaries 2
Atrial venous system

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 Blood Vessels
• Vascular is derived from Latin word vas (=vessel)
• Few structures (eg. cartilage & lens of eye) lack blood
vessels
• Vascular system has network of blood passageways
– Artery, Capillary, Vein
• Vascular smooth muscle

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 Function of blood vessels
1. Distribution of materials: Arteries;

– Carry blood away from the heart

– Transports blood through the tissues

2. Exchange of substances: Capillaries

– B/n the blood and body tissues through the capillaries

3. Return blood to the heart: Veins

– Waste products like CO2 diffuse from tissue through

interstitial fluid into blood

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 Functional
1. Elastic Classification
(Windkessel) of Bloodvessels
vessels 3. Exchange Vessels
– Aorta, big arteries – Capillaries
– Pressure storing
– Thin enough for exchange
components
– High ability of stretching 4. Capacitance vessels
and recoiling – Big to small veins
2. Resistance (Stopcock – Very high capacity of
vessels)
distension
– Small arteries and
arterioles – Can accommodate

– High muscular component 65% of blood

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Types and walls of Blood
Vessels

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 The walls of arteries & veins have 3
layers that surround the lumen:
1. Tunica externa:

• Outermost layer.

• Made primarily of loose connective tissue.

• Anchors the blood vessel to the surrounding

tissue.

2. Tunica Media :

• Usually the thickest layer in arteries.

• Consists primarily of smooth muscle.

• Responsible for vasoconstriction & vasodilation.

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 The walls of…
3. Tunica Interna :

• Endothelium overlying sparse connective tissue.

• Acts as a selectively permeable barrier to blood solutes.

• Secretes vasoconstrictors & vasodilators.

• Provides a smooth surface that repels blood cells &

platelets.

Note that capillaries contain only a tunica intima.

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 Arteries
• Constructed to withstand surges of blood pressure associated
with ventricular systole.

• More muscular than veins & appear relatively round in tissue

sections.

• There are 3 basic categories of arteries:

1. Conducting arteries [Elastic arteries].

2. Distributing arteries [Muscular arteries].

3. The smallest arteries [Arterioles].

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 Capillaries
• Area where exchange occurs, contain only an endothelium & a
basement membrane.

• Approximately 1billion in the human body.

• Thin wall and high surface area of capillaries facilitate

exchange of gases, nutrients, wastes, etc.

• Organized into groups of 10-100 in capillary beds.

• Of 3 types:
1. Continuous
2. Fenestrated
3. Sinusoidal 46
Types of capillaries

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 Capillaries…
1. Continuous Capillaries: most common, abundant in skin and
muscle.
2. Fenestrated Capillaries: Found in sites of :
– active absorption (small intestine),
– secretion (endocrine organs) and
– capillary filtration (kidneys).
3. Sinusoidal Capillaries: Highly modified, extremely leaky and
found in areas such as:
 bone marrow (passage of nascent blood cells).
 lymphoid organs (for easy entry/exit by WBCs).
 liver (for large plasma proteins, e.g., albumin). 12
 Venous System
• Blood flows from the capillaries into venules and venules join

to form veins.

• Veins have 3 tunics, but the walls are thinner & the lumens

larger compared to arteries.

• Pressure in the veins is typically quite low (10mmHg) and

does not fluctuate with the heartbeat.

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 Venous System…
• Veins are quite distensible
• Their thin walls allow them to act as
• Reservoirs of blood (~65% of the body's
blood)

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 Venous return
• Considering the relatively low pressure in the veins,

– how blood is forced through them to get back to the heart ?

• Since there is a minimal pressure gradient,

– combination of 3 different factors provide the driving force.

– These are:

• Respiratory & skeletal muscle pump, valves.

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 Venous return …
1. Respiratory Pump

– As we inhale, our thoracic cavity expands while our

abdominal cavity compresses.

– This increase pressure in the abdominal veins resulting in an

increased blood flow towards the heart.

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 Venous return …
2. Venous Valves
- One way valves made of flaps of endothelium are found in
medium veins (mostly in the legs & the arms) where they help
prevent backflow.

3. Skeletal Muscle Pump

– The contraction or relaxation
cycles of skeletal muscles
squeeze the veins forcing the
contained blood towards the
heart. 54
 Venous return …
• In people who stand for long periods of time,

– blood tends to pool in the lower limbs and stretch the

veins.

– It is because of the lack of movement

• i.e. lack of skeletal muscle pump activity

• Stretching can pull the cusps of the venous valves farther and

farther apart until the valves are unable to prevent backflow.

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 Venous return …
• The veins can then become even further distended & twisted
and then they are known as varicose veins.

• In obese & pregnant individuals,

– the pelvic veins are compressed

• This retards the return of blood from the legs.

– With more blood remaining within the leg veins,

• the likelihood of varicose veins in individuals increases.

• Varicose veins of the anal canal are known as hemorrhoids.

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Venous return …

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