Physiology of Cardiovascular

Introduction

Cardio-vascular system
Transports nutrients & oxygen to cells in body while
carbon dioxide and waste products of cells’ metabolism
are removed.
Pump that circulates the transport medium (blood) is the
heart.
System Overview
Components include heart, blood,
and network of blood vessels.
Arteries carry blood away from
heart, branch into smaller vessels
called arterioles, which become
capillaries, where nutrients are
exchanged; capillaries become
venules, that enlarge and become
veins.
 System Overview con’t

Veins differ from arteries because they carry blood toward

heart, have valves, and have thinner walls.
 The Heart
Size of your fist: located slightly left of center of chest.
Base is proximal to your head while apex is distal.
One single organ but with two pumps working together.
Right side collects blood from body and sends it to lungs;
left side collects blood from lungs and sends it to rest of
body.
 Four Chambers in Heart
Septum: seperates heart in right & left half
Interatrial Septum: seperates right Atrium from left
Atrium.
Interventricular Septum: seperates right & left
ventricles.
 Chambers of the Heart con’t

Right Atrium: collecting chamber where blood is returned

to heart after trip around body.
Superior & Inferior Vena Cavae: large veins return blood
to right atrium.
Tricuspid Valve (atrioventricular): directs blood from rt.
Atrium to rt. Ventricle.
Chambers of the Heart con’t

Heart contraction occurs: when rt. Ventricle is full of

blood.
Tricuspid valve prevents backflow of blood into rt.
Atrium.
Blood flows through pulmonary semilunar valve to
“pulmonary arteries.”
Chambers of the Heart con’t

Rt. & Lt. “pulmonary arteries” goes to lungs where

vessels get smaller and smaller, ending in capillaries
around each air sac (alveolus)
Blood returns to Lt. Atrium via “pulmonary veins.”
Chambers of the Heart con’t
Mitral Valve (Bicuspid Valve): allows blood flow from Lt.
Atrium to Lt. Ventricle.
Left ventricular pressure increases as it fills
Heart contracts forcing mitral valve (Bicuspid Valve)
closed.
Blood is ejected through aortic semilunar valve to
ascending aorta, and then out to rest of body.
The Route of an RBC

Superior/Inferior vena cava

Right Atrium
Tricuspid valve
Right Ventricle
Pulmonary Valve
Pulmonary Artery
Lungs
Pulmonary Veins
Left Atrium
Bicuspid Valve
Left Ventricle
Aortic Valve
Aorta
Chambers of the Heart con’t

Systole: contraction phase when blood is ejected from

the ventricles.
Contraction: begins at apex and travels upward
Diastole: resting period when chambers refill with
blood.
 Chambers of the Heart con’t

Atrial walls: thinner than ventricular walls

Ventricular walls:
Lt. ventricle pumps blood to body thus thick walls
Rt. Ventricle pumps blood to lungs thus thinner walls.
Coronary Arteries
Right coronary artery: provides
blood for right ventricle, posterior
portion of interventricular
septum, and inferior parts of
heart.
Left coronary artery: provides
blood to left lateral and anterior
walls of left ventricle, and
portions of right ventricle and
interventricular septum.
CARDIAC CYCLE
EVENTS DURING CARDIAC CYCLE
 INTRODUCTION

 The heart as a pump.

 2 separate pump in series.
 Systole – contraction
 Diastole – relaxation.
 Cardiac cycle – both
electrical & mechanical
events from beginning of
one heart beat to beginning
of next.
DURATION OF CARDIAC CYCLE

 IF Normal Heart rate

is 75 beats /min
 Duration of one (1)
beat = 60/75
= 0.8 sec.
 PHASES OF CARDIAC CYCLE

 Atrial cycle (0.8)

 Atrial systole (0.1)
 Atrial diastole (0.7)
 Ventricular cycle (0.8)
 Ventricular systole (0.3)
 Ventricular diastole.
(0.5)
 ATRIAL CYCLE

 Atrial systole (0.1)

 Coincide with last rapid
filling phase of
ventricles.
 Before this valves are
open, ventricles relaxed
with already 75%
blood
 Contraction add only
remaining 25% blood.
 EFFECTS OF ATRIAL SYSTOLE.

 Intraatrial pressure
 Right – 4-6mm Hg.
 Left – 7-8 mm Hg.
 Intraventricular
pressure.
 Narrowing of origin of
great veins-
Decreasing Venous
Return.
 ATRIAL DIASTOLE (0.7)

 Coincide with
Ventricular Systole &
most of the ventricular
diastole.
 Atria Relax – gradual
filling of atria –
pressure slowly
increases.
 VENTRICULAR CYCLE

 Ventricular systole
(0.3) – phases
 Phase of Iso-Volumic
(Iso-metric)
Contraction
 Phase of ventricular
ejection.
 Rapid phase
 Slow phase.
 VENTRICULAR CYCLE (cont….)

 Phase of Iso-Volumic (Iso-metric)

Contraction (0.05)
 When intra-ventricular pressure
rises – closes AV valves –
semilunar valves not yet open –
so contracts as closed chamber.
 No change in volume so called –
Iso-Volumic contraction.
 Sharp rise in Intraventricular
pressure
 VENTRICULAR CYCLE (cont….)

 Phase of ventricular
ejection (0.25) – begins
with opening of semilunar
valves.
 Rapid phase (0.1) – 2/3rd of
stroke volume ejected.
 Rt ventricles velocity is less
than left but duration is more.
 Slow phase.(0.15) – 1/3rd of
stroke volume ejected.
 VENTRICULAR CYCLE

 Venntricular Diastole
(0.5) – phases
 Protodiastole
 Isovolumic or Isometric
Relaxation phase.
 Rapid passive filling
phase.
 Reduced filling &
Diastosis
 Last rapid filling
phase.
 PROTODIASTOLE

0.04 sec.
 Ventricular systole ends
– ventricles relax –
Intraventricular
pressure falls – blood
comes back from vessels
to ventricles –
semilunar valves closes
– 2ndheart sound
 Causes Diacrotic Notch
in pulse.
 ISOVOLUMIC OR ISOMETRIC

 Lasts for 0.06 sec

 Begins with closure of
semilunar valves.
 A-V valves not yet open –
relax as closed chamber –
as volume remains same
– Iso-Volumic relaxation.
 Ends with opening of A-V
valves
 RAPID PASSIVE FILLING PHASE.

 As A-V valves open

atria till now in
diastole filled with
venous return with
increased pressure
causes – rapid passive
filling of ventricles ( 3rd
heart sound)
 REDUCED FILLING &
DIASTOSIS

 As ventricles filling
continues pressure
differences reduces –
so filling rate
decreases – Diastasis.
 Total blood
transferred with rapid
& slow filling is 75%
of total atrial blood.
 LAST RAPID FILLING PHASE.

 As said earlier – it
coincide with atrial
systole – add
remaining 25 % of
blood to ventricles.
 With this ventricular
cycle completes.
EVENTS DURING CARDIAC CYCLE
 VALVULAR EVENTS (HEART
SOUNDS)

 First heart sound

 Second heart sound
 Third heart
sound
 Fourth heart
sound
 FIRST HEART SOUND

 Cause – closure of A-V

valves.
 Characteristics – ‘LUBB’,
duration -0.15 sec, freq –
25-45 Hz.
 Site for auscultation –
Mitral & Tricuspid area.
 Correlation with ECG –
coincide with peak of R
wave.
 SECOND HEART SOUND

 Cause – closure of
semilunar valves.
 Characteristics – ‘DUBB’,
duration – 0.12 sec, freq –
50Hz.
 Site for auscultation –
Aortic & Pulmonary area.
 Correlation with ECG –
coincide with T wave.
 THIRD HEART SOUND

 Cause – Inrush of blood

during rapid filling
phase.
 Characteristics –
Duration – 0.1 sec.
 Correlation with ECG –
appears between T & P
wave.
 FOURTH HEART SOUND

 Cause – last rapid filling

phase.
 Characteristics –
Duration 0.03 sec, freq-
3 Hz.
 Correlation with ECG –
appears between P
wave 7 onset of Q wave.
CARDIAC ACTION
POTENTIAL
CELL MEMBRANE

Semi permeable - How

moleceules move in & out
of cell ?
CHANNELS PORES CARRIERS & PUMPS
• Aqueous channel • Continuously open to • Not open
• Conformational change both environment simultaneously to both
• Action usually • No conformational environments
regulated changes • Energy dependent
• Open to both • Movement both ways • Limited number of
environment according to molecules diffuse
• Large number of concentration gradient. across
molecules diffuse • Maintain the
across concentration
gradients
- Movement can be
against concentration
gradient
ION MOVEMENT

Steady state is reached when the magnitude of the chemical and electric
gradients are equal
CONCENTRATION OF MAJOR IONS

Ion Extracellular Intracellular Ex (mV

Conc Conc
Na+ 145 20 +52
K+ 4 135 -92
Ca2+ 2 10-4 +129
CL- 120 10 -64
ION CHANNELS
 Electrical signaling in heart  passage of ions
through ionic channels.
 Na+, K+, Ca2+ , and Cl− are the major ions
 Opening of ion channels  selected ions flow
passively down the electrochemical gradient
 Pumps  responsible for mainataining the
electrochemical gradient by active (energy
required) movement of ions
 This flow of current generates excitation and
signals in cardiac myocytes.
BASIC TERMS

 Inward current & Outward current

 Rectifying
 Rectifier or diodes allow current only in one direction
 Delayed (s) vs fast/ rapid (r)
 Gating & Inactivation Ion channels may be induced to open
or close (gated) by
 Extracellular and intracellular ligands (ligand gated)
 Changes in transmembrane voltage (Voltage gated)
 Mechanical stress
 The permeability ratio index of a channel’s ionic selectivity
 Ratio of the permeability of one ion type to that of the main
permeant ion type.
GATING & INACTIVATION

 Closing and opening of channels

 Voltage, Metabolic, Stretch
3 STATES
EXCITABLE TISSUES

Skeleta
Neuron
l
Muscle
Smooth Cardiac

Muscle Muscle
ACTION POTENTIAL
 Sudden rise & fall in membrane voltage
in a characteristic pattern
 Depolarization followed by
repolarization
 Passive movement of ions across electro
chemical gradient established by active
ion pumps
 Net current of all open channels
[amplitude & direction]
 Depends on 2 factors
 Electromechanical gradient across
 Open Channels
 Fixed time & voltage relationship
according to the specific cell type
 Neurons few milliseconds , Cardiac fibers
- several 100 milliseconds
ACTION POTENTIAL
Independent of size of depolarizing stimulus.

Pattern dependent on individual cell type

Threshold stimulus

“All-or-none” response

Refractory period

But hyperpolarizing pulses in contrast - elicit a response

proportional to the strength of the stimulus.
SITES OF ACTION POTENTIAL
GENESIS

Nodal tissue – AV node and SA node

His - Purkinje fibres

Atrial muscle

Ventricular muscle
SITES OF ACTION POTENTIAL
GENESIS
 Nodal tissue – AV node and SA node
 His - Purkinje fibres
 Atrial muscle
 Ventricular muscle
CARDIAC ACTION POTENTIAL

2 types : Myocyte & Pacemaker potential

Typical 5 Phases  myocyte potential
Phase 0 • Upstroke or rapid depolarization

Phase 1 • Early rapid repolarization

Phase 2 • Plateau

Phase 3 • Final rapid repolarization

Phase 4 • Resting membrane potential and diastolic depolarization

FAST & SLOW RESPONSE IN
ACTION POTENTIAL
 Atrial and ventricular muscle , His-Purkinje fibres
 action potentials with very rapid
amplitude
large- upstrokes called fast responses.
 SA & AV nodes , many diseased tissue 
reduced-amplitude
slow, upstrokes and are
called slow responses
 Fast response  Voltage gated Na Channel (INa)
 Slow responses  slow inward, predominantly
L-type voltage-gated Ca2+ current (ICaL) rather
than by the fast inward INa
 Phase 0 • INa –Voltage gated Na Channel

Phase 1 • ITo –Transcient Outward K channel

• ICaL –L type Ca channel

Phase 2
• IKs –Delayed Rectifier slow K channel
• IKr –Delayed Rectifier rapid K channel
Phase 3
• IKs IK1
RMP • IK1–Inwardly Rectifying K channel

Diastolic • ICaT –T type Ca channel

Depolarisation • If –Funny (slow) Na channel
RESTING MEMBRANE
POTENTIAL
 Membrane potential when the
cell is not stimulated.
 Horizontal line in most cardiac
tissues
 Cells with automaticity no static
RMP
 Corresponds to equilibrium
potential of K+
 -50 to -90 according to type
of cell
 Ventricular myocardium is about -
85 to -95 mV
IONS - RMP
 Outward K+ current – Inwardly rectifying K+
channels(IK1 ) -contributes to RMP atrial and
ventricular myocytes, as well as in Purkinje cells.
 Low [K] Voltage leads to less IK1 activity  RMP
less negative more excitability
 Ca- No direct effect but intra cellular Ca can
influence other ions ex: Cl- & Na+/Ca++ exchanger
 Na+ K+ ATPase – 3 Na+ outward and 2 K+ inward
against their gradient.

K+
PHASE 0
0

 Rapid depolarisation phase

 Opening of the fast Na+ channels causing a
rapid increase in membrane conductance to Na+
(INa)
 Membrane potential goes upto the Na+ equilibrium
 potential
Rate of
of +60 mV
depolarization dV/dt max  rate
magnitude
and of Na+ entry into the cell : corresponds
to conduction velocity V Max
 Action potential = Na+ current (INa) is regenerative
 SA node & AV node - Ica
RMP AND Na CHANNELS
 RMP at baseline (-85 mV) all
fast Na+ channels are closed and
excitation will open all of them 
maximum conduction velocity
 Na conduction  time dependent
 Any decrease in RMP (less neg)
some of the fast Na+ channels will
be in an inactivated state insensitive
to opening  conduction velocity
decreases . Ex: Ischemia
FAST & SLOW CHANNELS
 In fast response tissues also ICaL is normally activated
in phase 0 by the depolarization caused by the fast
INa. especially in latter part ofupstroke
 However ICa.L << INa  contributes little to the AP
 Significance after the fast INa is inactivated (after
completion of phase 0)  plateau phase
 ICa.L  release of Ca2+ from SR stores  cardiac
excitation contraction coupling
 Recovery of voltage & time dependent a
I
phenomenon CaL termed post repolarization

 refractorines
SA and AV nodal cells remain refractory even after
sfull voltage repolarization
CLINICAL ASPECTS
 Acute MI  depressed form of fast conduction
in centre & slow reponse in border area
 Increase cAMP – Increased Ica L
 CCB – Decreases Ica L
 Class I antiarrhythmics – affects fast channel &
not slow channel
PHASE 1

Shortest phase

Inactivation of the fast Na+ channels

Outward current Mainly K+ and Cl- ions

Na+/Ca2+ Exchanger
PHASE 1 OUTWARD K+
 Termed Ito current
 Turned on rapidly by depolarization and then rapidly inactivates
 4-aminopyridine–sensitive transient outward K+ current
 Density and the Recovery exhibit transmural gradients in the left
and right ventricular free wall From epicardium to endocardium
Density decreases
Reactivation progressively prolonged
 Failing Heart - Downregulation of Ito  phase 1 repolarization
slows
OTHER CURRENTS
 4-aminopyridine–resistant Ca2+
-activated chloride current ICl.Ca (or Ito2)
 Outward Na+ movement through the Na+/Ca2+
exchanger operating in reverse mode.
PHASE 2 - PLATEAU

 Characteristic feature of cardiac myocyte & conducting

system
 Not present in other tissues including cardiac pacemaker
cell
 All ion channels – in a state of resistance ie. slow
ion movement
Outward movement of K+ through the slow
delayed rectifier potassium channels (IKs)

Inward movement of Ca2+ (ICa) through L-type

calcium channels & Na+/Ca2+ exchanger
PHASE 2
 Even gradient of K+ is high after a
depolarization
though the movement is restricted.
 K1 current inwardly rectified
 Delayed rectifier K current  Rapid
(IKr)& slow(IKs)
 Rapid channels inactivated by the depolarization
current.
 This fast inactivation sensitive to
extracellular [K+]  Accentuated at low
extracellular K+
 Hypokalemia  Decreases IKr  Prolongs APD
PHASE 2
 Reduced intracellular ATP (e.g.
ischemia), K+ efflux through activated
hypoxia, KATP
channels is enhanced shortening the
plateau phase
 Inactivation of the L-type Ca2+ dependent on
intracellular free Ca2+
 Reduced efficiency in inactivation, such as
in myocytes from hypertrophic hearts 
delayed repolarization.
PHASE 3 –
FINAL RAPID
REPOLARIZA
TION

 Terminal repolarization – rapid because of two

currents
 Time-dependent inactivation of ICaL  decrease
in the intracellular movement of positive charges
 Activation of repolarizing K+ currents,
 Including IKs and IKr
 Inwardly rectifying K+ currents IK1 and IKACh
 Membrane potential moves to RMP
REFRACTORY PERIOD
ABSOLUTE RP
Second stimulus however
strong fails to evoke a
response.
RELATIVE RP
Second stimulus evokes a
response if it is
sufficiently high (supra
threashold stimulus)
EFFECTIVE RP
Suprathreashold stimulus
 action potential but
not propogated
MECHANISM
 ARP Na are in an inactivated
state -
 RRP  sufficient number of Na
channels back to their resting state
– a stronger stimulus can generate
AP
 Cardiac RP (250 ms) very long
compared to other exetitable
tissues (ex: Skeletal muscle – 3 ms)
 Prevents tetany
 Prevents Fatigue
 Diastole >>systole
 Responsible for compensatory
pause after a VPC
AFTER DEPOLARIZATIONS
Membrane voltage oscillations
induced by 1 or more preceeding
AP
Clinical conditions or interventions
causing increase in intracellular
positivity
Important role in Arrhythmias
Most of then will not reach
threshold potential. If
sufficiently strong – trigger
another AD & self perpetuates)
Delayed after depolarizations  Phase 4 after
repolarisation has completed but before next AP
PHASE 4 DIASTOLIC
DEPLARISATION
 Normal conditions  membrane
potential of atrial and ventricular
muscle cells remains steady
throughout diastole (RMP).
 IK1 responsible for maintaining
the RMP
 Pacemake cells- No constant
r RMP
 Unstable membrane potential that starts at – 60mv
and slowly depolarizes upwards towards threshold
 The property possessed by spontaneously discharging cells
is called phase 4 diastolic depolarization
 Leads to initiation of action potentials resulting
in automaticity.
 ACTION POTENTIAL IN PACEMAKER
CELL - AUTOMATICITY
•PHASE 4: PACEMAKER POTENTIAL:
•Opening of voltage-gated Na channels
called Funny channels (If or f channels ).
•Closure of voltage-gated K channels.
•Opening of Voltage-gated Transient-
type
Ca (T-type Ca2+ channels) channels .

• PHASE 0: THE RISING PHASE OR • PHASE 3: THE FALLING PHASE OR

DEPOLARIZATION: REPOLARIZATION:
•Opening of Long-lasting voltage-gated Ca • Opening of voltage-gated K channels
channels (L-type Ca2+ channels). • Closing of L-type Ca channels.
• Large influx of Ca. • K Efflux.
AUTOMATICITY
 Chronotropism depends on the slope of
pacemaker potential
 Modulation of HR by the ANS
 Discharge rate of the SA node normally exceeds
the other potentially automatic pacemaker sites
 Discharge rate of the SA node more sensitive
to the effects of ANS
 Normal or abnormal automaticity at other sites
in disease states  rates faster than the SA node
 control of the cardiac rhythm for one cycle or
more
ANTI ARRHYTHMIC DRUGS
↑ AP Duration
Ia ↑ ERP
↑ QT interval
↓ AP
↓ ERP
Ib
affects ischemic or
depolarized tissue
↑ ERP in AV node but
Ic not in ventricular
tissue
↓ SA & AV nodal
activity
↓ cAMP and
II
↓ Ca2+
currents
↓ slope of
phase 4
↑ PR interval

↑ AP Duration
III ↑ ERP
↑ QT interval
↑ ERP
IV ↑ PR interval
↓ Conduction velocity
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