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The Pulmonary and Systemic Circuits

Heart is transport system; two �side-by-side pumps

Right side receives oxygen-poor blood from tissues

Pumps to lungs to get rid of CO₂, pick up O₂, via pulmonary circuit

Left side receives oxygenated blood from lungs

Pumps to body tissues via systemic circuit

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The Pulmonary and Systemic Circuits

Receiving chambers of heart:

Right atrium

Receives blood returning from systemic circuit

Left atrium

Receives blood returning from pulmonary circuit

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The Pulmonary and Systemic Circuits

Pumping chambers of heart:

Right ventricle

Pumps blood through pulmonary circuit

Left ventricle

Pumps blood through systemic circuit

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Heart Anatomy

Approximately size of fist
Location:

In mediastinum between second rib and fifth intercostal space
On superior surface of diaphragm
Two-thirds of heart to left of midsternal line
Anterior to vertebral column, posterior to sternum

Animation: Rotatable heart

PLAY

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Heart Anatomy

Base (posterior surface) leans toward right shoulder
Apex points toward left hip
Apical impulse palpated between fifth and sixth ribs, just below left nipple

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Figure 18.2b Location of the heart in the mediastinum.

Mediastinum

Heart

Left lung

Body of T₇

vertebra

Posterior

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Figure 18.2c Location of the heart in the mediastinum.

Superior

vena cava

Pulmonary

trunk

Diaphragm

Aorta

Parietal pleura

(cut)

Left lung

Pericardium (cut)

Apex of heart

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Chambers

Four chambers:

Two superior atria
Two inferior ventricles

Interatrial septum – separates atria

Fossa ovalis – remnant of foramen ovale of fetal heart

Interventricular septum – separates ventricles

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Figure 18.5b Gross anatomy of the heart.

Brachiocephalic trunk

Superior vena cava

Right pulmonary artery

Ascending aorta

Pulmonary trunk

Right pulmonary veins

Right atrium

Right coronary artery

(in coronary sulcus)

Anterior cardiac vein

Right ventricle

Right marginal artery

Small cardiac vein

Inferior vena cava

Left common carotid artery

Left subclavian artery

Aortic arch

Ligamentum arteriosum

Left pulmonary artery

Left pulmonary veins

Auricle of

left atrium

Circumflex artery

Left coronary artery

(in coronary sulcus)

Left ventricle

Great cardiac vein

Anterior interventricular

artery (in anterior

interventricular sulcus)

Apex

Anterior view

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Heart Valves

Ensure unidirectional blood flow through heart
Open and close in response to pressure changes
Two atrioventricular (AV) valves

Prevent backflow into atria when ventricles contract
Tricuspid valve (right AV valve)
Mitral valve (left AV valve, bicuspid valve)
Chordae tendineae anchor cusps to papillary muscles

Hold valve flaps in closed position

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Figure 18.7 The atrioventricular (AV) valves.

1

2

3

Blood returning to the heart fills

atria, pressing against the AV valves.

The increased pressure forces AV

valves open.

As ventricles fill, AV valve flaps

hang limply into ventricles.

1

2

3

Atria contract, forcing additional

blood into ventricles.

Ventricles contract, forcing

blood against AV valve cusps.

AV valves close.

Papillary muscles contract and

chordae tendineae tighten,

preventing valve flaps from everting

into atria.

AV valves open; atrial pressure greater than ventricular pressure

AV valves closed; atrial pressure less than ventricular pressure

Direction of

blood flow

Cusp of

atrioventricular

valve (open)

Atrium

Chordae

tendineae

Papillary

muscle

Atrium

Cusps of

atrioventricular

valve (closed)

Blood in

ventricle

Ventricle

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Heart Valves

Two semilunar (SL) valves

Prevent backflow into ventricles when ventricles relax
Open and close in response to pressure changes
Aortic semilunar valve
Pulmonary semilunar valve

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Figure 18.8 The semilunar (SL) valves.

As ventricles contract and intraventricular pressure rises, blood is pushed up against semilunar valves, forcing them open.

As ventricles relax and intraventricular pressure falls, blood flows back from arteries, filling the cusps of semilunar valves and forcing them to close.

Aorta

Pulmonary

trunk

Semilunar valves open

Semilunar valves closed

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Figure 18.6a Heart valves.

Pulmonary valve

Aortic valve

Area of cutaway

Mitral valve

Tricuspid valve

Myocardium

Mitral

(left atrioventricular)

valve

Tricuspid

(right atrioventricular)

valve

Aortic valve

Pulmonary valve

skeleton

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Figure 18.6b Heart valves.

Pulmonary valve

Aortic valve

Area of cutaway

Mitral valve

Tricuspid valve

Myocardium

Mitral

(left atrioventricular)

valve

Tricuspid

(right atrioventricular)

valve

Aortic valve

Pulmonary valve

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Microscopic Anatomy of Cardiac Muscle

Cardiac muscle cells striated, short, branched, fat, interconnected, �1 (perhaps 2) central nuclei
Connective tissue matrix (endomysium) connects to cardiac skeleton

Contains numerous capillaries

T tubules wide, less numerous; SR simpler than in skeletal muscle
Numerous large mitochondria (25–35% of cell volume)

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Figure 18.12a Microscopic anatomy of cardiac muscle.

Nucleus

Intercalated

discs

Cardiac

muscle cell

Gap junctions

Desmosomes

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Microscopic Anatomy of Cardiac Muscle

Intercalated discs - junctions between cells - anchor cardiac cells

Desmosomes prevent cells from separating during contraction
Gap junctions allow ions to pass from cell to cell; electrically couple adjacent cells

Allows heart to be functional syncytium

Behaves as single coordinated unit

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Cardiac Muscle Contraction

Three differences from skeletal muscle:

~1% of cells have automaticity (autorhythmicity)

Do not need nervous system stimulation
Can depolarize entire heart

All cardiomyocytes contract as unit, or none do
Long absolute refractory period (250 ms)

Prevents tetanic contractions

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Cardiac Muscle Contraction

Three similarities with skeletal muscle:

Depolarization opens few voltage-gated fast Na⁺ channels in sarcolemma, which lead to 🡪

The reversal of membrane potential from –90 mV to +30 mV
Brief; Na channels close rapidly

The depolarization wave travels down T tubules and eventually leads to the 🡪 SR to release Ca²⁺ 🡪 Excitation-contraction coupling occurs

Ca²⁺ binds troponin 🡪 filaments slide

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Cardiac Muscle Contraction

More differences

The depolarization wave also opens slow Ca²⁺ channels in the sarcolemma this allows about 10%-20% of the total Ca2+ needed for contraction in 🡪 once inside this Ca2+ cause the SR to release its Ca²⁺ which accounts for the remaining 80-90% required for contraction.
Ca²⁺ surge prolongs the depolarization phase (plateau)

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Cardiac Muscle Contraction

More differences

Action potential and contractile phase last much longer

Allow blood ejection from heart

Repolarization result of inactivation of Ca²⁺ channels and opening of voltage-gated K⁺ channels

Ca²⁺ pumped back to SR and extracellularly

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Figure 18.13 The action potential of contractile cardiac muscle cells.

Slide 2

Membrane potential (mV)

20

0

–20

–40

–60

–80

Absolute

refractory

period

Action

potential

Plateau

Tension

development

(contraction)

0

150

300

Time (ms)

Tension (g)

1

Depolarization is due to Na⁺ influx through fast voltage-gated Na⁺channels. A positive feedback cycle rapidly opens many Na⁺ channels, reversing the membrane potential. Channel inactivation ends this phase.

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Figure 18.13 The action potential of contractile cardiac muscle cells.

Slide 3

Membrane potential (mV)

20

0

–20

–40

–60

–80

Absolute

refractory

period

Action

potential

Plateau

Tension

development

(contraction)

0

150

300

Time (ms)

Tension (g)

1

2

1

2

Depolarization is due to Na⁺ influx through fast voltage-gated Na⁺channels. A positive feedback cycle rapidly opens many Na⁺ channels, reversing the membrane potential. Channel inactivation ends this phase.

Plateau phase is due to Ca²⁺ influx through slow Ca²⁺ channels.

This keeps the cell depolarized because few K⁺ channels are open.

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Energy Requirements

Cardiac muscle

Has many mitochondria

Great dependence on aerobic respiration
Little anaerobic respiration ability

Readily switches fuel source for respiration

Even uses lactic acid from skeletal muscles

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Heart Physiology: Electrical Events

Heart depolarizes and contracts without nervous system stimulation

Rhythm can be altered by autonomic nervous system

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Heart Physiology: Setting the Basic Rhythm

Coordinated heartbeat is a function of

Presence of gap junctions
Intrinsic cardiac conduction system

Network of noncontractile (autorhythmic) cells
Initiate and distribute impulses 🡪 coordinated depolarization and contraction of heart

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Autorhythmic Cells

Have unstable resting membrane potentials (pacemaker potentials or prepotentials) due to opening of slow Na⁺ channels

Continuously depolarize

At threshold, Ca²⁺ channels open
Explosive Ca²⁺ influx produces the rising phase of the action potential
Repolarization results from inactivation of Ca²⁺ channels and opening of voltage-gated �K⁺ channels

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Action Potential Initiation by Pacemaker Cells

Three parts of action potential:

Pacemaker potential

Repolarization closes K⁺ channels and opens slow Na⁺ channels 🡪 ion imbalance 🡪

Depolarization

Ca²⁺ channels open 🡪 huge influx 🡪 rising phase of action potential

Repolarization

K⁺ channels open 🡪 efflux of K⁺

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Figure 18.14 Pacemaker and action potentials of pacemaker cells in the heart.

Slide 2

1

+10

0

–10

–20

–30

–40

–50

–60

–70

Time (ms)

Action

potential

Threshold

Pacemaker

potential

1

Pacemaker potential This slow depolarization is due to both opening of Na⁺ channels and closing of K⁺channels. Notice

that the membrane potential is never a flat line.

Membrane potential (mV)

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Figure 18.14 Pacemaker and action potentials of pacemaker cells in the heart.

Slide 3

1

2

1

+10

0

–10

–20

–30

–40

–50

–60

–70

Time (ms)

Action

potential

Threshold

Pacemaker

potential

1

2

Pacemaker potential This slow depolarization is due to both opening of Na⁺ channels and closing of K⁺channels. Notice

that the membrane potential is never a flat line.

Depolarization The action potential begins when the pacemaker potential reaches threshold. Depolarization is due

to Ca²⁺ influx through Ca²⁺channels.

Membrane potential (mV)

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Figure 18.14 Pacemaker and action potentials of pacemaker cells in the heart.

Slide 4

1

2

3

2

3

1

Membrane potential (mV)

+10

0

–10

–20

–30

–40

–50

–60

–70

Time (ms)

Action

potential

Threshold

Pacemaker

potential

1

2

3

Pacemaker potential This slow depolarization is due to both opening of Na⁺ channels and closing of K⁺channels. Notice

that the membrane potential is never a flat line.

Depolarization The action potential begins when the pacemaker potential reaches threshold. Depolarization is due

to Ca²⁺ influx through Ca²⁺channels.

Repolarization is due to Ca²⁺ channels inactivating and

K⁺ channels opening. This allows K⁺ efflux, which brings the membrane potential back to its most negative voltage.

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Sequence of Excitation

Cardiac pacemaker cells pass impulses, in order, across heart in ~220 ms

Sinoatrial node 🡪
Atrioventricular node 🡪
Atrioventricular bundle 🡪
Right and left bundle branches 🡪
Subendocardial conducting network (Purkinje fibers)

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Heart Physiology: Sequence of Excitation

Sinoatrial (SA) node

Pacemaker of heart in right atrial wall

Depolarizes faster than rest of myocardium

Generates impulses about 75X/minute (sinus rhythm)

Inherent rate of 100X/minute tempered by extrinsic factors

Impulse spreads across atria, and to AV node

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Heart Physiology: Sequence of Excitation

Atrioventricular (AV) node

In inferior interatrial septum
Delays impulses approximately 0.1 second

Because fibers are smaller diameter, have fewer gap junctions
Allows atrial contraction prior to ventricular contraction

Inherent rate of 50X/minute in absence of SA node input

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Heart Physiology: Sequence of Excitation

Atrioventricular (AV) bundle�(bundle of His)

In superior interventricular septum
Only electrical connection between atria and ventricles

Atria and ventricles not connected via gap junctions

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Heart Physiology: Sequence of Excitation

Right and left bundle branches

Two pathways in interventricular septum
Carry impulses toward apex of heart

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Heart Physiology: Sequence of Excitation

Subendocardial conducting network

Complete pathway through interventricular septum into apex and ventricular walls
More elaborate on left side of heart
AV bundle and subendocardial conducting network depolarize 30X/minute in absence of AV node input

Ventricular contraction immediately follows from apex toward atria

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Extrinsic Innervation of the Heart

Heartbeat modified by ANS via cardiac centers in medulla oblongata

Sympathetic 🡪 ↑ rate and force
Parasympathetic 🡪 ↓ rate
Cardioacceleratory center – sympathetic – affects SA, AV nodes, heart muscle, coronary arteries
Cardioinhibitory center – parasympathetic – inhibits SA and AV nodes via vagus nerves

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Electrocardiography

Electrocardiogram (ECG or EKG)

Composite of all action potentials generated by nodal and contractile cells at given time

Three waves:

P wave – depolarization SA node 🡪 atria
QRS complex - ventricular depolarization and atrial repolarization
T wave - ventricular repolarization

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Figure 18.18 The sequence of depolarization and repolarization of the heart related to the deflection�waves of an ECG tracing.

Slide 2

SA node

R

P

T

Q

S

Depolarization

Repolarization

Atrial depolarization, initiated by the SA node, causes the P wave.

1

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Figure 18.18 The sequence of depolarization and repolarization of the heart related to the deflection�waves of an ECG tracing.

Slide 3

AV node

R

P

T

Q

S

SA node

R

P

T

Q

S

Depolarization

Repolarization

With atrial depolarization complete, the impulse is delayed at the AV node.

2

Atrial depolarization, initiated by the SA node, causes the P wave.

1

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Figure 18.18 The sequence of depolarization and repolarization of the heart related to the deflection�waves of an ECG tracing.

Slide 4

R

P

T

Q

S

Ventricular depolarization begins at apex, causing the QRS complex. Atrial repolarization occurs.

3

AV node

R

P

T

Q

S

With atrial depolarization complete, the impulse is delayed at the AV node.

2

SA node

R

P

T

Q

S

Atrial depolarization, initiated by the SA node, causes the P wave.

1

Depolarization

Repolarization

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Figure 18.18 The sequence of depolarization and repolarization of the heart related to the deflection�waves of an ECG tracing.

Slide 5

R

P

T

Q

S

Ventricular depolarization is complete.

Depolarization

Repolarization

4

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Figure 18.18 The sequence of depolarization and repolarization of the heart related to the deflection�waves of an ECG tracing.

Slide 6

R

P

T

Q

S

Ventricular repolarization begins at apex, causing the T wave.

5

R

P

T

Q

S

Ventricular depolarization is complete.

4

Depolarization

Repolarization

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Figure 18.18 The sequence of depolarization and repolarization of the heart related to the deflection�waves of an ECG tracing.

Slide 7

S

Q

P

T

R

Ventricular repolarization is complete.

6

R

P

T

Q

S

Ventricular repolarization begins at apex, causing the T wave.

5

R

P

T

Q

S

Ventricular depolarization is complete.

4

Depolarization

Repolarization

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Electrocardiography

P-R interval

Beginning of atrial excitation to beginning of ventricular excitation

S-T segment

Entire ventricular myocardium depolarized

Q-T interval

Beginning of ventricular depolarization through ventricular repolarization

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Heart Sounds

Two sounds (lub-dup) associated with closing of heart valves

First as AV valves close; beginning of systole
Second as SL valves close; beginning of ventricular diastole
Pause indicates heart relaxation

Heart murmurs - abnormal heart sounds; usually indicate incompetent or stenotic valves

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Mechanical Events: The Cardiac Cycle

Cardiac cycle

Blood flow through heart during one complete heartbeat: atrial systole and diastole followed by ventricular systole and diastole
Systole—contraction
Diastole—relaxation
Series of pressure and blood volume changes

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Phases of the Cardiac Cycle

1. Ventricular filling—takes place in mid-to-late diastole

AV valves are open; pressure low
80% of blood passively flows into ventricles
Atrial systole occurs, delivering remaining 20%
End diastolic volume (EDV): volume of blood in each ventricle at end of ventricular diastole

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Phases of the Cardiac Cycle

2. Ventricular systole

Atria relax; ventricles begin to contract
Rising ventricular pressure 🡪 closing of AV valves
Isovolumetric contraction phase (all valves are closed)
In ejection phase, ventricular pressure exceeds pressure in large arteries, forcing SL valves open
End systolic volume (ESV): volume of blood remaining in each ventricle after systole

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Phases of the Cardiac Cycle

3. Isovolumetric relaxation - early diastole

Ventricles relax; atria relaxed and filling
Backflow of blood in aorta and pulmonary trunk closes SL valves

Causes dicrotic notch (brief rise in aortic pressure as blood rebounds off closed valve)
Ventricles totally closed chambers

When atrial pressure exceeds that in ventricles 🡪 AV valves open; cycle begins again at step 1

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Cardiac Output (CO)

Volume of blood pumped by each ventricle in one minute
CO = heart rate (HR) × stroke volume (SV)

HR = number of beats per minute
SV = volume of blood pumped out by one ventricle with each beat

Normal – 5.25 L/min

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Cardiac Output (CO)

At rest

CO (ml/min) = HR (75 beats/min) × SV (70 ml/beat)

= 5.25 L/min

CO increases if either/both SV or HR increased
Maximal CO is 4–5 times resting CO in nonathletic people
Maximal CO may reach 35 L/min in trained athletes
Cardiac reserve - difference between resting and maximal CO

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Figure 18.22 Factors involved in determining cardiac output.

Exercise (by

sympathetic activity, skeletal muscle and

respiratory pumps;

see Chapter 19)

Heart rate (allows more time for

ventricular filling)

Bloodborne

epinephrine, thyroxine,

excess Ca2+

Exercise, fright, anxiety

Venous

return

Contractility

Sympathetic

activity

Parasympathetic

activity

EDV

(preload)

ESV

Stroke

volume

Cardiac

output

Heart

rate

Initial stimulus

Physiological response

Result

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Regulation of Stroke Volume

SV = EDV – ESV

EDV affected by length of ventricular diastole and venous pressure
ESV affected by arterial BP and force of ventricular contraction

Three main factors affect SV:

Preload
Contractility
Afterload

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CO = HR X SV

75 beats /min X 70ml / beat

= 5250 ml / min

= 5.25 L / min

SV= EDV – ESV

= 120 ml / beat – 50 ml / beat

= 70 ml / beat

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Regulation of Stroke Volume

Preload: degree of stretch of cardiac muscle cells before they contract (Frank-Starling law of heart)

Cardiac muscle exhibits a length-tension relationship
At rest, cardiac muscle cells shorter than optimal length
Most important factor stretching cardiac muscle is venous return – amount of blood returning to heart

Slow heartbeat and exercise increase venous return
Increased venous return distends (stretches) ventricles and increases contraction force

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Regulation of Stroke Volume

Contractility—contractile strength at given muscle length, independent of muscle stretch and EDV
Increased by

Sympathetic stimulation 🡪 increased Ca²⁺ influx 🡪 more cross bridges
Positive inotropic agents

Thyroxine, glucagon, epinephrine, digitalis, high extracellular Ca²⁺

Decreased by negative inotropic agents

Acidosis, increased extracellular K⁺, calcium channel blockers

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Figure 18.23 Norepinephrine increases heart contractility via a cyclic AMP secondmessenger system.

a

b

c

Norepinephrine

β₁-Adrenergic

receptor

G protein (G_s)

Adenylate cyclase

GDP

ATP is converted

to cAMP

Ca²⁺

Extracellular fluid

Ca²⁺

channel

Cytoplasm

Phosphorylates plasma

membrane Ca²⁺

channels, increasing

extracellular Ca²⁺ entry

Phosphorylates SR Ca²⁺ pumps, speeding

Ca²⁺ removal and relaxation, making more

Ca²⁺ available for release on the next beat

Active protein

kinase

Ca²⁺

Ca²⁺ uptake pump

Sarcoplasmic

reticulum (SR)

Inactive protein

kinase

Phosphorylates SR Ca²⁺ channels, increasing

intracellular Ca²⁺ release

Ca²⁺

binds

to

Troponin

Enhanced

actin-myosin

interaction

SR Ca²⁺

channel

Cardiac muscle

force and velocity

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Regulation of Stroke Volume

Afterload - pressure ventricles must overcome to eject blood
Hypertension increases afterload, resulting in increased ESV and reduced SV

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Regulation of Heart Rate

Positive chronotropic factors increase heart rate
Negative chronotropic factors decrease heart rate

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Autonomic Nervous System Regulation

Sympathetic nervous system activated by emotional or physical stressors

Norepinephrine causes pacemaker to fire more rapidly (and increases contractility)

Binds to β₁-adrenergic receptors 🡪 ↑ HR
↑ contractility; faster relaxation

Offsets lower EDV due to decreased fill time

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Autonomic Nervous System Regulation

Parasympathetic nervous system opposes sympathetic effects

Acetylcholine hyperpolarizes pacemaker cells by opening K⁺ channels 🡪 slower HR
Little to no effect on contractility

Heart at rest exhibits vagal tone

Parasympathetic dominant influence

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Figure 18.22 Factors involved in determining cardiac output.

Exercise (by

sympathetic activity, skeletal muscle and

respiratory pumps;

see Chapter 19)

Heart rate (allows more time for

ventricular filling)

Bloodborne

epinephrine, thyroxine,

excess Ca2+

Exercise, fright, anxiety

Venous

return

Contractility

Sympathetic

activity

Parasympathetic

activity

EDV

(preload)

ESV

Stroke

volume

Cardiac

output

Heart

rate

Initial stimulus

Physiological response

Result

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Chemical Regulation of Heart Rate

Hormones

Epinephrine from adrenal medulla increases heart rate and contractility
Thyroxine increases heart rate; enhances effects of norepinephrine and epinephrine

Intra- and extracellular ion concentrations (e.g., Ca²⁺ and K⁺) must be maintained for normal heart function

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Erythrocytes

Biconcave discs, anucleate, essentially no organelles
Diameters larger than some capillaries
Filled with hemoglobin (Hb) for gas transport
Contain plasma membrane protein spectrin and other proteins

Spectrin provides flexibility to change shape

Major factor contributing to blood viscosity

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Erythrocytes

Structural characteristics contribute to gas transport

Biconcave shape—huge surface area relative to volume
>97% hemoglobin (not counting water)
No mitochondria; ATP production anaerobic; do not consume O₂ they transport

Superb example of complementarity of structure and function

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Erythrocyte Function

RBCs dedicated to respiratory gas transport
Hemoglobin binds reversibly with oxygen
Normal values

Males - 13–18g/100ml; Females - 12–16 g/100ml

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Hemoglobin Structure

Globin composed of 4 polypeptide chains

Two alpha and two beta chains

Heme pigment bonded to each globin chain

Gives blood red color

Heme's central iron atom binds one O₂
Each Hb molecule can transport four O₂
Each RBC contains 250 million Hb molecules

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Hemoglobin (Hb)

O₂ loading in lungs

Produces oxyhemoglobin (ruby red)

O₂ unloading in tissues

Produces deoxyhemoglobin or reduced hemoglobin (dark red)

CO₂ loading in tissues

20% of CO₂ in blood binds to Hb 🡪 carbaminohemoglobin