Transcript CARDIOVASCULAR PHYSIOLOGY

CARDIOVASCULAR
PHYSIOLOGY
STUDENT MANUAL
Dr. Guido E. Santacana
CARDIOVASCULAR
PHYSIOLOGY
LECTURES
STUDENT LECTURE NOTEBOOK
Guido E. Santacana Ph.D.
DEPT. of PHYSIOLOGY
INTRODUCTION TO
CARDIOVASCULAR
PHYSIOLOGY
GENERAL ASPECTS OF
THE CARDIOVASCULAR
SYSTEM
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
VESSELS
TUBULES
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!!
EK = -60 LOG ([Ki]/[Ko])
= -94mv
ENa = -60 LOG ([Nai]/[Nao])
= +70mv
Em = RT/F ln
PK (K+)o + PNa(Na+)o + PCl(Cl-)i
PK (K+)I + PNa(Na+)i + PCl(Cl-)o
THE RESTING MEMBRANE POTENTIAL
OF THE CARDIAC CELL
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
CELL.
INTRACELL.
Em
Na+
145Mm
15Mm
70mv
Ca++
3Mm
10-7 M
132mv
K+
5Mm
145Mm
-100mv
ACTION POTENTIALS FROM DIFFERENT
AREAS OF THE HEART
ATRIUM
VENTRICLE
0
mv
mv
0
-80mv
-80mv
SA NODE
mv
0
-80mv
time
ELECTROPHYSIOLOGY OF THE FAST
RESPONSE FIBER
PHASE 0 OF THE FAST FIBER ACTION
POTENTIAL
Na+
Na+
m
A
-90mv
B
h
-65mv
m
m
h
Na+
Na+
m
C
0mv
Chemical
Gradient
Electrical
Gradient
m
D
h
+20mv
Na+
m
E
+30mv
h
h
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++
CHANNELS
+10MV
Ca++
BLOCKERS
T Ca++
CHANNELS
-20MV
NO (physiological)
EFFECTS OF Ca++ CHANNEL BLOCKERS
AND THE CARDIAC CELL ACTION
POTENTIAL
CONTROL
FORCE
30
10
10
CONTROL
30
TIME
DILTIAZEM
10 uMol/L
30 uMol/L
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
or IK1)
Maintains phase 4 negative potential in cardiac cells
Transient
outward (Ito)
Contributes to phase 1 of non-pacemaker cardiac action potentials
Delayed
rectifier (IKr)
Phase 3 repolarization of cardiac action potentials
More Channels!
Calcium
Channels
L-type (ICa-L)
Slow inward, long-lasting current; phase 2 non-pacemaker cardiac action
potentials and phases 4 and 0 of SA and AV nodal cells; important in
vascular smooth muscle contraction
T-type (ICa-T)
Transient current that contributes to phase 4 pacemaker currents in SA and AV
nodal cells
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
ZONE
POLARIZED
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?
AP-AMP
EFFECTS OF HIGH K+ ON CONDUCTION
AND AP OF FAST FIBERS
Em
0MV
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
HIGH K+
LOWER
Em
CLOSED h GATES
(SOME)
LOWER AP
AMPLITUDE
LOWER Na+ ENTRY
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)
0
MV
ARP
-80
RRP
TIME
POST-REPOLARIZATION
REFRACTORINESS (SLOW FIBER)
200 MSEC
0
MV
B
A
-60
POSTREPO
TIME
C
RHYTMICITY
AUTOMATICITY
SA NODE
AV NODE
IDIOVENTRICULARPACEMAKERS
ectopic
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
if
iCa
K+
iK
Na+
Ca++
OUT
IN
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.
 RECOVERY TIME REQUIRED.
 ECTOPIC FOCI/SICK SINUS
SYNDROME.
THE CONDUCTION SYSTEM OF THE
HEART
ATRIAL AND ATRIOVENTRICULAR
CONDUCTION
RA
BACHMANS PATH
SAN
LA
AN REGION
INTERNODAL PATHS
AV NODE
N REGION
NH REGION
BH
RV
RIGHT BUNDLE
BRANCH
LV
LEFT BUNDLE
BRANCH
NODAL DELAY
AV NODE
REGION OF
DELAY
NA REGION
FAST CONDUCTION
N REGION SLOW CONDUCTION
LONGER PATH
SHORTER PATH
NH REGION
FAST CONDUCTION
REFLECTED IN THE P-QRS INTERVAL
OF THE ECG
UNI AND BIDIRECTIONAL BLOCK
CLINICAL IMPLICATIONS
A
NORMAL
C
BI
B
ANTEGRADE
BLOCK
REENTRY
UNIDIRECTIONAL
BLOCK
D
Clinical Correlation
Re-entry Tachycardias
Paroxysmal Supraventricular Tachycardia
Ischemic Tissue
Slow
Pathway
Fast
Pathway
Normal Conduction
Slow
Pathway
Fast
Pathway
Re-Entry Circuit
AV NODE AND AV BLOCKS
FOCUS ON N REGION
NORMA
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
ECG
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.
QUICK QUIZ
Which of the following is not true about the effect of
acetylcholine (Ach) in the electrophysiology of the cardiac pacemaker
cell:
A. Ach lowers the magnitude of the minimum repolarization potential.
B. Ach lowers the slope of the pacemaker potential.
C. Ach decreases the SA node frequency.
D.Ach increases the ik current of the pacemaker cell.
E. Ach decreases the iCa++ current of the pacemaker cell.
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
LEFT VENTRICULAR
PRESSURE
LENGHT/ TENSION AND THE FRANKSTARLING RELATION
INITIAL MYOCARDIAL FIBER LENGHT
LEFT 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.
 LAPLACES’S LAW & WALL STRESS,
WS = P X R / 2(wall thickness)
LEFT VENTRICULAR
PRESSURE
LEFT VENTRICULAR PRESSURE AND
AFTERLOAD AT CONSTANT PRELOADS
EFFECT OF INCREASED
PRELOAD
PEAK
ISOMETRIC
FORCE
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
LEFT VENTRICULAR
PRESSURE (mmHg)
dP/dt AS A VALUABLE INDEX OF
CONTRACTILITY
MAX dP/dt
B
120
A
C
40
.2
TIME (s)
.6
CARDIAC CYCLE
Atrial Systole
Mitral
Closes
S1
S2
Atrial Systole
Reduced Ventricular
Filling
Rapid Ventricular
Filling
Isovolumic Relax.
Reduced Ejection
Rapid Ejection
Isovolumic contract.
Aortic
opens
Aortic
closes
Mitral
opens
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
Aortic Stenosis
Normal
Aorta
Aorta
Ventricle
Ventricle
LEFT VENTRICULAR PRESSURE (mmHg)
LEFT VENTRICULAR
PRESSURE/VOLUME P/V LOOP
END OF SYSTOLE
120
F
E
D
80
40
A
0
50
B
C
100
END OF DIASTOLE
150
LEFT VENTRICULAR VOLUME (ml)
LEFT
VENTRICULAR
PRESSURE (mmHg)
EFFECT OF PRELOAD ON
THE VENTRICULAR P/V
LOOP
ESV
1
2
3
EDVs
VOLUME (ml)
EFFECT OF AFTERLOAD IN
THE LEFT VENTRICULAR
P/V LOOP
ESV
LEFT
VENTRICULAR
PRESSURE (mmHg)
ESV
3
ESV
2
1
EDV
VOLUME (ml)
LEFT
VENTRICULAR
PRESSURE (mmHg)
EFFECT OF CONTRACTILITY
ON THE LV P/V LOOP
2
1
VOLUME (ml)
QUICK QUIZ
PRELOAD
AFTERLOAD
CONTRACTILITY
CARDIAC OUTPUT AND THE FICK
PRINCIPLE
BODY O2 CONSUMPTION
Lungs
250mlO2/min
PULMONARY
ARTERY
PULMONARY
VEIN
PaO2
0.15mlO2/ml blood
PvO2
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 5 B&L
REQUIRED CONCEPTS
VELOCITY = DISTANCE / TIME
V
=
D
/ T
FLOW = VOLUME / TIME
Q =
VL
/ T
VELOCITY -FLOW- AREA
V
=
Q
/ A
CROSS SECTIONAL AREA AND
VELOCITY
A= 2cm2
Q=10ml/s
a
V= 5cm/s
10cm2
b
1cm/s
V=Q/A
1cm2
c
10cm/s
HYDROSTATIC PRESSURE
136cm
0
100
200
0
100
200
P=pxgxh
0
100mmHg
P = Pressure mmHg
p = density
g = gravity
h = height
136cm
0
100
200
0
0
100
200
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
0
0
100
200
POISEUILLE’S LAW GOVERNING FLUID
FLOW(Q) THROUGH CYLINDRIC TUBES
(FLOW)Q =
DIFFERENCE
IN PRESSURE
(Pi - Po) r
8nL
VISCOSITY
4
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.
PARALLEL
SERIES
R1
R2
R3
R1
R2
R3
WHAT REALLY HAPPENS IN THE CVS?
LOWER R
HIGHER R
LOWER R
CAPILLARIES
ARTERY
ARTERIOLES
LAMINAR VS TURBULENT FLOW
THE REYNOLD’S NUMBER
LAMINAR
FLOW
TURBULENT
FLOW
Nr = pDv / n
laminar = 2000 or less
p = density
D = diameter
v = velocity
n = viscosity
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
3. After a bout with hemorrhagic Dengue you would expect
to find a heart murmur at a lower level than before the
disease.
A. True B. False
PV Loop Refresher
B
A
B
A
What happens from A to B?
ARTERIAL SYSTEM
 COMPLIANCE
 MEAN
ARTERIAL PRESSURE
 PULSE PRESSURE
 PRESSURE MEASUREMENT
CHAPTER 26 B&L
THE CONCEPT OF THE HYDRAULIC
FILTER
SYSTOLE
DIASTOLE
COMPLIANT
RIGID
O2 CONSUMPTION (mlO2/100g/beat)
EFFECTS OF PUMPING THROUGH A
RIGID VS A COMPLIANT DUCT
0.1
PLASTIC TUBING
NATIVE AORTA
0
5
STROKE VOLUME (ml)
15
% INCREASE IN VOLUME
STATIC P-V RELATIONSHIP IN
THE AORTA
PRESSURE (mmHg)
ELASTIC MODULUS OR
ELASTANCE
Ep = P / Da/Db
ELASTANCE
P
V
Ep= ELASTIC MODULUS
Da= MAX. CHANGE IN
AORTIC DIAMETER.
Db= MEAN AORTIC DIAM.
COMPLIANCE
V
P
EP IS INVERSELY PROPORTIONAL TO C
MEAN ARTERIAL PRESSURE (MAP)
REMEMBER OHMS LAW?
CARDIAC OUTPUT
PERIPHERAL RESISTANCE
INSTANTANEOUS
INCREASE
STEADY STATE
INCREASE
ARTERIAL PRESSURE (mmHg)
EFFECT OF COMPLIANCE ON
MAP
Pa = Qh - Qr / Ca
SMALL Ca
LARGE Ca
INCREASE CARDIAC OUTPUT
TIME
Qh- inflow (CO)
Qr- outflow
Ca- Compliance
Pa- MAP
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
A
B
CHAPTER 9 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
CENTRAL VENOUR PRESSURE (mmHg)
HOW CHANGES IN CARDIAC OUTPUT INDUCE
CHANGES IN CENTRAL VENOUS PRESSURE?
8
Pmc
B
VASCULAR FUNCTION
CURVE
A
-1
0
8
CARDIAC OUTPUT (L/min)
CENTRAL VENOUR PRESSURE (mmHg)
HOW BLOOD VOLUME AND VENOMOTOR
TONE CHANGE THE VASCULAR FUNCTION
CURVE?
VASCULAR FUNCTION
CURVE
8
-1
0
8
CARDIAC OUTPUT (L/min)
CENTRAL VENOUR PRESSURE (mmHg)
TOTAL PERIPHERAL RESISTANCE
AND THE VASCULAR FUNCTION
CURVE.
8
VASCULAR FUNCTION
CURVE
-1
0
8
CARDIAC OUTPUT (L/min)
CARDIAC OUTPUT (L/min)
THE CARDIAC FUNCTION CURVE
CENTRAL VENOUS PRESSURE (mmHg)
CARDIAC OUTPUT (L/min)
EFFECTS OF SYMPATHETIC STIMULATION
ON THE CARDIAC FUNCTION CURVE
CENTRAL VENOUS PRESSURE (mmHg)
HOW BLOOD VOLUME AND PERIPHERAL
RESISTANCE CHANGE THE CARDIAC
FUNCTION CURVE?
CARDIAC OUTPUT (L/min)
VOLUME
CENTRAL VENOUS PRESSURE (mmHg)
RESISTANCE
CARDIAC OUTPUT (L/min)
THE CARDIAC FUNCTION CURVE IN
HEART FAILURE
CENTRAL VENOUS PRESSURE (mmHg)
HEART - BLOOD VESSELS
COUPLING
MORMAL FUNCTION
PUMP
VEINS
ARTERIES
Qh
5L/min
Pa
CPV=2mmHg=Pv
5L/min
COMPLIANCES
Cv = 19Ca
Cv>>>>Ca
Qr
PERIPHERAL R= Pa - Pv / Qr
R = 20mmHg/L/min
MPA=102mmHg
CARDIAC ARREST!
INMEDIATE EFFECT
FLOW STOPS HERE
PUMP
VEINS
ARTERIES
Qh
0L/min
Pa
CPV=2mmHg=Pv
5L/min
FLOW CONTINUES HRE
TRANSFER ART-->VEINS
Qr
R = 20mmHg/L/min
Qr= Pa - Pv/20
Qr CONTINUES AS LONG AS
A PRESSURE GRADIENT
IS SUSTAINED
CARDIAC ARREST
STEADY STATE
FLOW STOPPED
PUMP
VEINS
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
FLOW STARTS
SOME VENOUS BLOOD
PUMP
VEINS
ARTERIES
Qh
1L/min
Pa = 7mmHg
Pv = 7mmHg
NO FLOW HERE YET
0L/min
Qr
FLOW RETURNS AT Qr AT
THE NEW Qh
PUMP
VEINS
ARTERIES
Qh
1L/min
Pa = 26mmHg
Pv = 6mmHg
FLOW STARTS
1L/min
Qr
R = 20mmHg
Qr = Pa - Pv / 20 = 1L/min
THE END