PHYSIOLOGY
STUDENT MANUAL
Dr. Guido E. Santacana
CARDIOVASCULAR
PHYSIOLOGY
LECTURES
Humoral communication.
THE MAIN CIRCUIT
COLLECTING
PUMP TUBULES
DISTRIBUTING THIN
TUBULES VESSELS
Pressure Profile of the Circulatory
System
ELASTIC TISSUE
MUSCLE
Distribution of Blood in the
Circulatory System
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!!
If membrane
permeable
only to K+
If membrane
permeable
To both Na+ and
K+
If membrane permeable
To Na+, K+ plus with
A Na+/K+ Pump
WHY NOT Na+ 0R Ca++ FOR THE CARDIAC CELL
MEMBRANE POTENTIAL ?
EXTRA INTRA-
CELL. CELL.
Em
ATRIUM VENTRICLE
0 0
mv
mv
-80mv
-80mv
0
mv
SA NODE
-80mv
time
ELECTROPHYSIOLOGY OF THE FAST
RESPONSE FIBER
PHASE 0 OF THE FAST FIBER ACTION
POTENTIAL
Na+
Na+
A m B m
m
h h
-90mv -65mv
Na+ Na+
C m m
h
D h
0mv +20mv
Chemical Na+
Gradient m
E h
Electrical +30mv
Gradient
K+ CURRENTS AND REPOLARIZATION
L Ca++ Ca++
+10MV
CHANNELS BLOCKERS
T Ca++
CHANNELS -20MV NO (physiological)
EFFECTS OF Ca++ CHANNEL BLOCKERS
AND THE CARDIAC CELL ACTION
POTENTIAL
CONTROL DILTIAZEM
10 uMol/L
10 30 uMol/L
30
FORCE
CONTROL
10
30
TIME
Clinical Correlation
Early After-Depolarizations
Torsades de Pointes
0mV
-60mV
-90mV
Early After-Depolarization
OVERVIEW OF SPECIFIC EVENTS IN THE
VENTRICULAR CELL ACTION POTENTIAL
Overview of Important Channels in Cardiac
Electrophysiology
Sodium
Channels
Fast Na+ Phase 0 depolarization of non-pacemaker cardiac action potentials
Slow Na+ "Funny" pacemaker current (If) in cardiac nodal tissue
Potassium
Channels
Inward
rectifier (Iir Maintains phase 4 negative potential in cardiac cells
or IK1)
Transient
Contributes to phase 1 of non-pacemaker cardiac action potentials
outward (Ito)
Delayed
Phase 3 repolarization of cardiac action potentials
rectifier (IKr)
More Channels!
Calcium
Channels
0
2
0
mvs -40 3
4
time (msec)
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
AP-AMP
0MV
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)
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
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
NIFEDIPINE
CONTROL
(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.
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
REGION OF LONGER PATH
FAST CONDUCTION
DELAY
N REGION SLOW CONDUCTION SHORTER PATH
NH REGION
FAST CONDUCTION
B
A
ANTEGRADE
NORMAL
BLOCK
C D
REENTRY
UNIDIRECTIONAL
BI
BLOCK
Clinical Correlation
Re-entry Tachycardias
Paroxysmal Supraventricular Tachycardia
Ischemic Tissue
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
The main reason why the AV node filters out high stimulation
frequencies from the SA node is:
A. The long pathway that the stimulus must traverse in the AV node.
B. Post Repolarization Refractoriness of AV nodal cells.
C. The AV nodal cell is always hyperpolarized
D. Ca++ is the main ion in Phase 0 of the AV nodal cell.
E. I need to review this section very fast.
CARDIAC
MECHANICS
MAIN THEMES
THE HEART AS A PUMP
THE CARDIAC CYCLE
CHAPTER 3 B&L
CARDIAC OUTPUT
LENGHT/ TENSION AND THE FRANK-
STARLING RELATION
LEFT VENTRICULAR
PRESSURE
INCREASE IN FILLING
PRESSURE=INCREASED PRELOAD
PRELOAD REFERS TO END
DIASTOLIC VOLUME.
AFTERLOAD IS THE AORTIC
PRESSURE DURING THE EJECTION
PERIOD/AORTIC VALVE OPENING.
LAPLACES’S LAW & WALL STRESS,
WS = P X R / 2(wall thickness)
LEFT VENTRICULAR PRESSURE AND
AFTERLOAD AT CONSTANT PRELOADS
EFFECT OF INCREASED
LEFT VENTRICULAR
PRELOAD
PRESSURE
PEAK
ISOMETRIC
FORCE
EFFECT?
CHANGES IN
CONTRACTILITY
dP/dt AS A VALUABLE INDEX OF
CONTRACTILITY
MAX dP/dt
B
LEFT VENTRICULAR
120
PRESSURE (mmHg)
40
.2 TIME (s) .6
opens
Mitral
Aortic
Closes
CARDIAC CYCLE
Atrial Systole
Isovolumic contract.
S1
Rapid Ejection
Reduced Ejection
S2
Isovolumic Relax.
Rapid Ventricular
Filling
Reduced Ventricular
Filling
Atrial Systole
opens
closes
Mitral
Aortic
QUICK QUIZ
How to find out that you know
the Cardiac Cycle.
150
Atrial Mitral
systolecloses Aortic
opens
Aortic
Mitral
closes
opens
50
TIME (SEC)
Clinical Correlation
Diagnosis of Aortic Stenosis by Pressure
Graphs
Aorta Aorta
Ventricle Ventricle
LEFT VENTRICULAR PRESSURE (mmHg) LEFT VENTRICULAR
PRESSURE/VOLUME P/V LOOP
END OF SYSTOLE
120 F
E
80 D
40
A B END OF DIASTOLE
C
0
50 100 150
LEFT VENTRICULAR VOLUME (ml)
EFFECT OF PRELOAD ON
THE VENTRICULAR P/V
LOOP
ESV
PRESSURE (mmHg)
VENTRICULAR
2 3
1
LEFT
EDVs
VOLUME (ml)
EFFECT OF AFTERLOAD IN
THE LEFT VENTRICULAR
P/V LOOP
ESV
ESV
3
PRESSURE (mmHg)
ESV
2
VENTRICULAR
1
LEFT
EDV
VOLUME (ml)
EFFECT OF CONTRACTILITY
ON THE LV P/V LOOP
PRESSURE (mmHg)
VENTRICULAR
LEFT
1
2
VOLUME (ml)
QUICK QUIZ
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)
CHAPTER 5 B&L
REQUIRED CONCEPTS
V = Q / A
CROSS SECTIONAL AREA AND
VELOCITY
Q=10ml/s a b c
V=Q/A
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
ENERGY OF A STATIC VS A DYNAMIC
FLUID
100
0 200
0
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
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
QUICK QUIZZ
1. Which of the following vessels will produce a dramatic
decrease in blood flow through the tissues by a change in
radius?
A. Aorta
B. Venules
C. Arterioles
D. Capillaries
B A
B
A
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
ELASTANCE COMPLIANCE
P V V P
EP IS INVERSELY PROPORTIONAL TO C
MEAN ARTERIAL PRESSURE (MAP)
INSTANTANEOUS
INCREASE
STEADY STATE
INCREASE
EFFECT OF COMPLIANCE ON
MAP
Qh- inflow (CO)
Qr- outflow
Ca- Compliance
ARTERIAL PRESSURE (mmHg)
Pa = Qh - Qr / Ca Pa- MAP
SMALL Ca
LARGE Ca
TIME
PULSE PRESSURE
V4
VB
VOLUME V3
V2
VA
V1
P1 PA P2 P3 PB P4 PRESSURE
PULSE PRESSURE
EFFECTS OF:
A B
CHAPTER 9 B&L
COUPLING OF THE HEART AND BLOOD VESSELS
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?
CENTRAL VENOUR PRESSURE (mmHg)
VASCULAR FUNCTION
8 CURVE
-1
0 8
CARDIAC OUTPUT (L/min)
TOTAL PERIPHERAL RESISTANCE
AND THE VASCULAR FUNCTION
CURVE.
8
CENTRAL VENOUR PRESSURE (mmHg)
VASCULAR FUNCTION
CURVE
-1
0 8
CARDIAC OUTPUT (L/min)
THE CARDIAC FUNCTION CURVE
CARDIAC OUTPUT (L/min)
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
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
Qh 0L/min
Pa = 7mmHg
0L/min Qr
Qr = 0 ( NO Pa - Pv DIFFERENCE)
WE START PUMPING!
INMEDIATE EFFECT
SOME VENOUS BLOOD FLOW STARTS
Qh 1L/min
Pa = 7mmHg
Pv = 7mmHg
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