CARDIOVASCULAR

PHYSIOLOGY

INTRODUCTION AND OVERVIEW

CARDIOVASCULAR PHYSIOLOGY
LECTURES

STUDENT LECTURE NOTEBOOK

Guido E. Santacana Ph.D.
DEPT. of PHYSIOLOGY
 MAIN FUNCTIONS OF THE
CIRCULATORY SYSTEM
 Transport and distribute essential
substances to the tissues.
 Remove metabolic byproducts.
 Adjustment of oxygen and nutrient supply
in different physiologic states.
 Regulation of body temperature.
 Humoral communication.
 THE MAIN CIRCUIT

COLLECTING
PUMP TUBULES

DISTRIBUTING THIN
TUBULES VESSELS
 Pressure Drop in the Vascular
System
ELASTIC TISSUE
LARGE ARTERIES
MUSCLE

SMALL ARTERIES
MEAN PRESSURE

ARTERIOLES

CAPILLARIES
VENULES &VEINS

LARGE SMALL LARGE

INSIDE DIAMETER
 Distribution of Blood in the
Circulatory System
 67% IN THE SYST. VEINS/VENULES
 5% IN THE SYSTEMIC CAPILLARIES
 11% IN THE SYSTEMIC ARTERIES
 5% IN PULMONARY VEINS
 3% IN PULMONARY ARTERIES
 4% IN PULMONARY CAPILLARIES
 5% IN HEART ATRIA/VENTRICLES
 Organization in the
Circulatory System

SERIES AND

PARALLEL CIRCUITS
 CARDIAC
ELECTROPHYSIOLOGY

LECTURE NOTEBOOK
Guido E. Santacana Ph.D.
 GENESIS OF THE MEMBRANE
POTENTIAL AND EQUATIONS TO
REMEMBER!!

? EK = -60 LOG ([Ki]/[Ko])

= -94mv
:>(

ENa = -60 LOG ([Nai]/[Nao])

= +70mv
PK (K+)o + PNa(Na+)o + PCl(Cl-)i
Em = RT/F ln
PK (K+)I + PNa(Na+)i + PCl(Cl-)o
 THE RESTING MEMBRANE
POTENTIAL OF THE CARDIAC CELL

IN OUT

K+ K+
145mEq 5mEq

Em= -60LogKi/Ko
-90mv
 EXTRA INTRA-
CELL. CELL.
Em

Na+ 145Mm 15Mm 70mv

Ca++ 3Mm 10-7 M 132mv

K+ 5Mm 145Mm -100mv

WHY NOT Na+ 0R Ca++ FOR THE CARDIAC CELL

MEMBRANE POTENTIAL ?
 ACTION POTENTIALS FROM
DIFFERENT AREAS OF THE HEART

ATRIUM VENTRICLE
0 0
mv

mv
-80mv
-80mv

0
mv

SA NODE
-80mv
time
ELECTROPHYSIOLOGY OF THE FAST
RESPONSE FIBER

o pe AMP
+20 1 lo sc
i l
2 o sc
0 To

0 3
mv

Cardiac Cell
4
-80

0 300
t (msec)
 PHASE 0 OF THE FAST FIBER ACTION
POTENTIAL

Na+ Na+

A m B m
m
h h
-90mv -65mv

Na+ Na+
C m D m
h h
0mv +20mv

Chemical Na+
Gradient m
E h
Electrical +30mv
Gradient
K+ CURRENTS AND REPOLARIZATION

 PHASE 1-TRANSIENT OUTWARD

CURRENT (TOC) Ito
 PHASE 1-3-DELAYED RECTIFIER
CURRENT IK
 PHASE 1-4-INWARDLY RECTIFIED
CURRENT IKl
 THE PLATEAU PHASE AND
CALCIUM IONS

OPEN CLINICAL VALUE

L Ca++ Ca++
+10MV
CHANNELS BLOCKERS

T Ca++
CHANNELS -20MV NO (physiological)
 Ca++ CHANNEL BLOCKERS AND THE
CARDIAC CELL ACTION POTENTIAL
ACTION POTENTIAL

CONTROL DILTIAZEM
10 uMol/L
10 30 uMol/L
30

CONTROL
FORCE

10
30
TIME
OVERVIEW OF SPECIFIC EVENTS IN
THE VENTRICULAR ACTION
POTENTIAL
 ELECTROPHYSIOLOGY OF THE
SLOW RESPONSE FIBER

0
2
0
mvs -40 3
4

-80 ERP RRP

time (msec)

RECALL: INWARD Ca++ CURRENT CAUSES DEPOLARIZATION

 CONDUCTION OF THE ACTION
POTENTIAL IN CARDIAC FIBERS

LOCAL CURRENTS
- ------- +++++++
++++++++ --------

FIBER A FIBER B

DEPOLARIZED POLARIZED
ZONE ZONE
 CONDUCTION OF THE ACTION
POTENTIAL

 FAST RESPONSE: Depends on

Amplitude,Rate of Change,level of Em.
 SLOW RESPONSE: Slower
conduction.More apt to conduction blocks.
 WHAT ABOUT MYOCARDIAL INFARCTS
AND CONDUCTION?
 EFFECTS OF HIGH K+ ON CONDUCTION
AND AP OF FAST FIBERS

0MV
AP-AMP

Em K+=3mM K+=7mM K+=14mM

0MV

K+=16mM
K+=3mM
WHAT HAS VARIED? LOOK AT: Em,AP SLOPE-AMPLITUDE
 HIGH K+ AND m/h Na+ GATES

LOWER
HIGH K+ Em

CLOSED h GATES
(SOME)

LOWER AP LOWER Na+ ENTRY

AMPLITUDE
 EXCITABILITY OF FAST AND SLOW
FIBERS

FAST m/h GATES COMPLETE RESET AFTER

PHASE 3
CONSTANT AND COMPLETE
RESPONSE IN PHASE 4

SLOW LONG RELATIVE REFRACTORY

PERIOD.
POST-REPOLARIZATION
REFRACTORINESS
AFTER THE EFFECTIVE OR
ABSOLUTE REFRACTORY
PERIOD (FAST FIBER)

MV

ARP

-80 RRP
TIME
 POST-REPOLARIZATION
REFRACTORINESS (SLOW FIBER)

200 MSEC C
0
B

MV A
-60

POSTREPO

TIME
AUTOMATICITY RHYTMICITY

SA NODE

AV NODE
IDIOVENTRICULAR- ectopic
PACEMAKERS foci
THE SA NODE PACEMAKER
POTENTIAL
 CHARACTERISTICS OF THE
PACEMAKER POTENTIAL

RECALL: PHASE 4-PACEMAKER POTENTIAL(PP) OBSERVED HERE.

FREQUENCY DEPENDS ON: THRESHOLD,RESTING POTENTIALS
AND SLOPE OF THE PP
CAUSES OF THE PACEMAKER
POTENTIAL

K+
if iCa OUT

IN
iK

Na+ Ca++
 THE PACEMAKER POTENTIAL
CURRENTS AFTER
DEPOLARIZATION

if iCa

iK
WHICH CURRENT WILL BE MORE AFFECTED BY
ADRENERGIC STIMULATION? WHICH BY CHOLINERGIC
STIMULATION?
LOOKING AT THE PACEMAKER
CURRENTS

voltage

iK

if
ionic currents
iCa
 EFFECTS OF Ca++ CHANNEL
BLOCKERS ON THE PACEMAKER
POTENTIAL

CONTROL NIFEDIPINE
(5.6 X 10-7 M)
0

MV

-60

TIME
 OVERDRIVE SUPRESSION AND
AUTOMATICITY OF PACEMAKER
CELLS
 Na+/K+ ATPase ENHANCEMENT BY
HIGH FREQUENCY.
 CONSEQUENT HYPERPOLARIZATION.
 SUPRESSION OF AUTOMATICITY.
 RECOVERY TIME REQUIRED.
 ECTOPIC FOCI/SICK SINUS
SYNDROME.
THE CONDUCTION SYSTEM OF THE
HEART
 ATRIAL AND ATRIOVENTRICULAR
CONDUCTION

BACHMANS PATH
RA SAN
LA
INTERNODAL PATHS AN REGION

AV NODE
N REGION
NH REGION

BH
LV
RV
RIGHT BUNDLE LEFT BUNDLE
BRANCH BRANCH
 NODAL DELAY

AV NODE
NA REGION LONGER PATH
REGION OF
FAST CONDUCTION
DELAY
N REGION SLOW CONDUCTION SHORTER PATH

NH REGION
FAST CONDUCTION

REFLECTED IN THE P-QRS INTERVAL

OF THE ECG
 UNI AND BIDIRECTIONAL BLOCK
CLINICAL IMPLICATIONS

B
A
NORMAL
BI

C D

UNI REENTRY
 AV NODE AND AV BLOCKS
FOCUS ON N REGION
NORMA ECG
L

1ST DEGREE
PROLONGUED AV
CONDUCTION TIME

2ND DEGREE
1/2 ATRIAL IMPULSES
CONDUCTED TO VENTRICLES

3RD DEGREE

VAGAL MEDIATION
IN N REGION/COMPLETE
BLOCK
 CONDUCTION IN THE VENTRICLES

 PURKINJE FIBERS WITH LONG

REFRACTORY PERIODS.
 PROTECTION AGAINST PREMATURE
ATRIAL DEPOLARIZATIONS AT SLOW
HEART RATES.
 AV NODE PROTECS AT HIGH HEART
RATES.
CARDIAC MECHANICS

MAIN THEMES
THE HEART AS A PUMP
THE CARDIAC CYCLE
CARDIAC OUTPUT
CHAPTER 23 B&L
 LENGHT/ TENSION AND THE FRANK-
STARLING RELATION
VENTRICULAR
PRESSURE

INITIAL MYOCARDIAL FIBER LENGHT

VENTRICULAR END-DIASTOLIC VOLUME
 PRELOAD AND AFTERLOAD IN THE
HEART

 INCREASE IN FILLING
PRESSURE=INCREASED PRELOAD
 PRELOAD REFERS TO END
DIASTOLIC VOLUME.
 AFTERLOAD IS THE AORTIC
PRESSURE DURING THE EJECTION
PERIOD/AORTIC VALVE OPENING.
 LEFT VENTRICULAR PRESSURE AND
AFTERLOAD
LEFT VENTRICULAR
PRESSURE

AFTERLOAD (aortic pressure)

NOTE: WHAT HAPPENS IN THE NORMAL HEART VS ONE IN THE LAST
PHASES OF CARDIAC FAILURE?
CONTRACTILITY:THE VENTRICULAR
FUNCTION CURVE

EFFECT?

CHANGES IN
CONTRACTILITY
 dP/dt AS A VALUABLE INDEX OF
CONTRACTILITY
MAX dP/dt

B
LEFT VENTRICULAR

120 A
PRESSURE (mmHg)

40

.2 TIME (s) .6
 :>O

opens

Mitral
Aortic

Closes

CARDIAC CYCLE
Atrial
Isovolumic
Systole contract.

S1
Rapid Ejection

Reduced Ejection

S2
Isovolumic Relax.
Rapid Ventricular
Filling

Reduced Ventricular
Filling

Atrial
Systole
opens
closes
Mitral
Aortic

:>D
LEFT VENTRICULAR PRESSURE (mmHg) LEFT VENTRICULAR
PRESSURE/VOLUME P/V LOOP

120 F
E

80 D

40

A B
C
0
50 100 150
LEFT VENTRICULAR VOLUME (ml)
PRESSURE/VOLUME RELATIONSHIPS
UNDER DIFFERENT CONDITIONS

PRELOAD AFTERLOAD CONTRACTILITY

 CARDIAC OUTPUT AND THE FICK
PRINCIPLE
BODY O2 CONSUMPTION

Lungs
250mlO2/min
PULMONARY PULMONARY
ARTERY VEIN

PaO2 PvO2
0.15mlO2/ml blood 0.20mlO2/ml blood
Pulmonary capillaries

O2 CONSUMPTION (ml/min)
CARDIAC OUTPUT=
PvO2 - PaO2
 HEMODYNAMICS

 VELOCITY,FLOW,PRESSURE
 LAMINAR FLOW
 POISEUILLE’S LAW
 RESISTANCE(SERIES-PARALLEL)
 TURBULENT FLOW AND
REYNOLD’S NUMBER
CHAPTER 25 B&L
 HYDROSTATIC PRESSURE

136cm 100
0 200
100
0 200
P=pxgxh
0
100mmHg
136cm 100
0 200
P = Pressure mmHg
100
p = density 0 200

g = gravity
h = height 0
 REQUIRED CONCEPTS

VELOCITY = DISTANCE / TIME

V = D / T

FLOW = VOLUME / TIME

Q = VL / T

VELOCITY -FLOW- AREA

V = Q / A
ENERGY OF A STATIC VS A DYNAMIC
FLUID

TOTAL ENERGY= POTENTIAL E. + KINETIC E.

TE = PE + KE

FLUID AT REST (HYDROSTATIC )

FLUID IN MOTION (HYDROSTATIC

+ HYDRODYNAMIC)
 VELOCITY AND PRESSURE

100
0 200

0
 CROSS SECTIONAL AREA AND
VELOCITY

A= 2cm2 10cm2 1cm2

Q=10ml/s a b c

V= 5cm/s 1cm/s 10cm/s

V=Q/A
 POISEUILLE’S LAW GOVERNING FLUID
FLOW(Q) THROUGH CYLINDRIC TUBES

4
(Pi - Po) r
(FLOW)Q =
8nL

DIFFERENCE
IN PRESSURE VISCOSITY LENGHT RADIUS
 RESISTANCE TO FLOW IN THE
CARDIOVASCULAR SYSTEM
BASIC CONCEPTS
Rt = R1 + R2 + R3…. SERIES RESISTANCE

1/Rt = 1/R1 + 1/R2 + 1/R3… PARALLEL RES.

R1
SERIES PARALLEL R2
R1 R2 R3 R3
WHAT REALLY HAPPENS IN THE CVS?

LOWER R HIGHER R LOWER R

ARTERY CAPILLARIES

ARTERIOLES
 LAMINAR VS TURBULENT FLOW
THE REYNOLD’S NUMBER

LAMINAR
TURBULENT
FLOW
FLOW

p = density
D = diameter
Nr = pDv / n v = velocity
n = viscosity
laminar = 2000 or less
 ARTERIAL SYSTEM

 COMPLIANCE
 MEAN ARTERIAL PRESSURE
 PULSE PRESSURE
 PRESSURE MEASUREMENT

CHAPTER 26 B&L
 THE CONCEPT OF THE HYDRAULIC
FILTER
SYSTOLE DIASTOLE

COMPLIANT

RIGID
 EFFECTS OF PUMPING THROUGH A
RIGID VS A COMPLIANT DUCT
O2 CONSUMPTION (mlO2/100g/beat)

0.1

PLASTIC TUBING

NATIVE AORTA

0
5 STROKE VOLUME (ml) 15
STATIC P-V RELATIONSHIP
IN THE AORTA
% INCREASE IN VOLUME

PRESSURE (mmHg)
 ELASTIC MODULUS OR
ELASTANCE

Ep= ELASTIC MODULUS

D= MAX. CHANGE IN
Ep = P / D/D AORTIC DIAMETER.
D= MEAN AORTIC DIAM.

ELASTANCE COMPLIANCE
P V V P
EP IS INVERSELY PROPORTIONAL TO C
 MEAN ARTERIAL PRESSURE (MAP)

REMEMBER OHMS LAW?

CARDIAC OUTPUT PERIPHERAL RESISTANCE

INSTANTANEOUS
INCREASE

STEADY STATE
INCREASE
 EFFECT OF COMPLIANCE ON MAP
Qh- inflow (CO)
Qr- outflow
Ca- Compliance
Pa = Qh - Qr / Ca
ARTERIAL PRESSURE (mmHg)

Pa- MAP

SMALL Ca

LARGE Ca

INCREASE CARDIAC OUTPUT

TIME
 PULSE PRESSURE

STROKE VOLUME COMPLIANCE

V4
VB
VOLUME V3

V2
VA
V1
P1 PA P2 P3 PB P4 PRESSURE
 PULSE PRESSURE
EFFECTS OF:

COMPLIANCE TOTAL PERIPHERAL RESISTANCE

TPR
 CHAPTER 29 B&L
COUPLING OF THE HEART AND BLOOD VESSELS

VASCULAR FUNCTION CURVE

HOW CARDIAC OUTPUT REGULATES

CENTRAL VENOUS PRESSURE

CARDIAC FUNCTION CURVE

HOW CENTRAL VENOUS PRESSURE (PRELOAD)

REGULATES CARDIAC OUTPUT
 VASCULAR FUNCTION CURVE
HOW CHANGES IN CARDIAC OUTPUT INDUCE
CHANGES IN CENTRAL VENOUS PRESSURE?

8 Pmc
CENTRAL VENOUR PRESSURE (mmHg)

VASCULAR FUNCTION
B CURVE

-1
0 8
CARDIAC OUTPUT (L/min)
HOW BLOOD VOLUME AND VENOMOTOR
TONE CHANGE THE VASCULAR FUNCTION
CURVE?
8
CENTRAL VENOUR PRESSURE (mmHg)

VASCULAR FUNCTION
CURVE

TR
A
N
SF
NO OR

U
H

RM RH

SI
EM

O
N
A L
A
G
E

-1
0 8
CARDIAC OUTPUT (L/min)
TOTAL PERIPHERAL RESISTANCE
AND THE VASCULAR FUNCTION
CURVE.
8
CENTRAL VENOUR PRESSURE (mmHg)

VASCULAR FUNCTION
CURVE

VA
VA

SO
S

DI
OC

LA
NO
ON

TI
R O
ST

M
AL
N
RI
CT
IO
N

-1
0 8
CARDIAC OUTPUT (L/min)
 THE CARDIAC FUNCTION CURVE
CARDIAC OUTPUT (L/min)

CENTRAL VENOUS PRESSURE (mmHg)

EFFECTS OF SYMPATHETIC STIMULATION
ON THE CARDIAC FUNCTION CURVE
CARDIAC OUTPUT (L/min)

CENTRAL VENOUS PRESSURE (mmHg)

 HOW BLOOD VOLUME AND PERIPHERAL
RESISTANCE CHANGE THE CARDIAC
FUNCTION CURVE?
VOLUME RESISTANCE
CARDIAC OUTPUT (L/min)

CENTRAL VENOUS PRESSURE (mmHg)

 THE CARDIAC FUNCTION CURVE IN
HEART FAILURE
CARDIAC OUTPUT (L/min)

CENTRAL VENOUS PRESSURE (mmHg)

HEART - BLOOD VESSELS
COUPLING
MORMAL FUNCTION
VEINS PUMP ARTERIES

Qh 5L/min

Pa

CPV=2mmHg=Pv
COMPLIANCES MPA=102mmHg
Cv = 19Ca
Cv>>>>Ca

5L/min Qr
PERIPHERAL R= Pa - Pv / Qr
R = 20mmHg/L/min
 CARDIAC ARREST!
INMEDIATE EFFECT
FLOW STOPS HERE

VEINS PUMP ARTERIES

Qh 0L/min

Pa
FLOW CONTINUES HRE
CPV=2mmHg=Pv
TRANSFER ART-->VEINS

5L/min Qr
Qr CONTINUES AS LONG AS
R = 20mmHg/L/min A PRESSURE GRADIENT
Qr= Pa - Pv/20 IS SUSTAINED
 CARDIAC ARREST
STEADY STATE
FLOW STOPPED

VEINS PUMP ARTERIES

Qh 0L/min

Pa = 7mmHg

Pv = 7mmHg = MEAN CIRCULATORY PRESSURE OR Pmc

95mmHg

5mmHg FLOW STOPPED

0L/min Qr
Qr = 0 ( NO Pa - Pv DIFFERENCE)
 WE START PUMPING!
INMEDIATE EFFECT
SOME VENOUS BLOOD FLOW STARTS

VEINS PUMP ARTERIES

Qh 1L/min

Pa = 7mmHg

Pv = 7mmHg

NO FLOW HERE YET

0L/min Qr
FLOW RETURNS AT Qr AT
THE NEW Qh
VEINS PUMP ARTERIES

Qh 1L/min

Pa = 26mmHg

Pv = 6mmHg

FLOW STARTS

1L/min Qr
R = 20mmHg
Qr = Pa - Pv / 20 = 1L/min
THE END