physio lecture 7 – introduction to cardiovascular physiology prof. dr. Željko dujić
TRANSCRIPT
Physio Lecture 7 – Physio Lecture 7 – Introduction to Cardiovascular Introduction to Cardiovascular
PhysiologyPhysiology
Prof. dr. Željko Dujić
MAIN FUNCTIONS OF THE CIRCULATORY SYSTEMMAIN FUNCTIONS OF THE CIRCULATORY SYSTEM
-Transport and distribute essential substances Transport and distribute essential substances to the tissuesto the tissues (most important to the vital (most important to the vital organs – brain and heart)organs – brain and heart)..
-Remove metabolic byproducts.Remove metabolic byproducts.
-Adjustment of oxygen and nutrient supply in Adjustment of oxygen and nutrient supply in different physiologic states.different physiologic states.
-Regulation of body temperature.Regulation of body temperature.
- - Humoral communicationHumoral communication by maintaining by maintaining tissue perfusiontissue perfusion..
Pressure Profile of the Circulatory System
ELASTIC TISSUE
MUSCLE
THE SYSTEMIC CIRCULATION
CAPACITY VESSELS
Distribution of Blood in the Circulatory System
PULMONARYCIRCULATION
1. LOW RESISTANCE2. LOW PRESSURE
(25/10 mmHg)
SYSTEMICCIRCULATION
1. HIGH RESISTANCE2. HIGH PRESSURE
(120/80 mmHg)
PARALLELSUBCIRCUITS
UNIDIRECTIONALFLOW
VEINS
CAPACITYVESSELS
HEART
80 mmHg 120 mmHg
SYSTOLE
DIASTOLE
ARTERIES (LOW COMPLIANCE)
CAPILLARIES
Membrane potential and critical equations
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
CARDIAC ELECTROPHYSIOLOGY UPDATE
Na+
EXTRACELL.
INTRA-CELL. Em
145Mm 15Mm 70mV
Ca++ 3Mm 10-7 M 132mV
K+ 5Mm 145Mm -100mV
Action potentials from different heart areas
mv
0
-80mv
mv
0
-80mv
mv
0
-80mv
ATRIUM VENTRICLE
SA NODE
time
ME
MB
RA
NE
PO
TE
NT
IAL
(m
V)
-90
0
0
12
3
4
TIME
PHASE0 = Rapid Depolarization (inward Na+ current) 1 = Overshoot2 = Plateau (inward Ca++ current)
3 = Repolarization (outward K+ current)4 = Resting Potential
Mechanical Response
K+ CURRENTS AND REPOLARIZATION
• Phase 1- transient outward current (TOC) Ito
• Phase 1-3 - delayed rectifier current IK
• Phase 1-4 – inwardly rectifier current IKl
THE PLATEAU PHASE AND CALCIUM IONS
L Ca++ CHANNELS
L Ca++ CHANNELS
T Ca++ CHANNELS
T Ca++ CHANNELS
OPEN
+10mV
-20mV
CLINICAL VALUE
Ca++ BLOCKERS
NO (physiological)
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
Cont’ed with 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
RECALL: INWARD Ca++ CURRENT CAUSES DEPOLARIZATION
0
-80
-400
2
34
ARP RRP
time (msec)
mV
CONDUCTION OF THE ACTION POTENTIAL IN CARDIAC FIBERS
- ------- - -
---- --+ ++ + + + + + +
+ + + ++ +
FIBER A FIBER B
DEPOLARIZEDZONE
POLARIZED ZONE
LOCAL CURRENTS
CONDUCTION OF THE ACTION POTENTIAL
• FAST RESPONSE: Depends on AP Amplitude, Rate of Potential Change,level of Em.
• SLOW RESPONSE: Slower conduction. More apt to conduction blocks.
• WHAT ABOUT MYOCARDIAL INFARCTS AND CONDUCTION?
AFTER THE EFFECTIVE OR ABSOLUTE REFRACTORY
PERIOD (FAST FIBER)
TIME
MV
-80
0
RRP
ARP
POST-REPOLARIZATION REFRACTORINESS (SLOW FIBER)
A
B
C
mV
TIME
-60
0
200 MSEC
POSTREPO
CHARACTERISTICS OF THE PACEMAKER POTENTIAL
PHASE 4-PACEMAKER POTENTIAL(PP).FREQUENCY DEPENDS ON: THRESHOLD, RESTING POTENTIALSAND SLOPE OF THE PP
THE CONDUCTION SYSTEM OF THE HEART
PACEMAKERS (in order of their inherent rhythm)
• Sino-atrial (SA) node (HR 60-70)
• Atrio-ventricular (AV) node (HR 40)
• Bundle of His (HR 15-40)
• Bundle branches
• Purkinje fibers
CARDIAC MECHANICS
MAIN THEMES
THE HEART AS A PUMP
THE CARDIAC CYCLE
CARDIAC OUTPUT
THE HEART AS A PUMP• REGULATION OF CARDIAC OUTPUT
– Heart Rate via sympathetic & parasympathetic nerves– Stroke Volume
• Frank-Starling “Law of the Heart”
• Changes in Contractility
• MYOCARDIAL CELLS (FIBERS)– Regulation of Contractility– Length-Tension and Volume-Pressure Curves– The Cardiac Function Curve
LENGHT/ TENSION AND THE FRANK-STARLING RELATION
LE
FT
VE
NT
RIC
UL
AR
PR
ES
SU
RE
INITIAL MYOCARDIAL FIBER LENGHTLEFT VENTRICULAR END-DIASTOLIC VOLUME
Diastole
Systole
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)
CONTRACTILITY:THE VENTRICULAR FUNCTION CURVE
CHANGES INCONTRACTILITY
EFFECT?
CARDIAC FUNCTION CURVE
CA
RD
IAC
OU
TP
UT
(L
/min
)
RAP mmHg
15-
10-
5-
-4 0 +4 +8
Volume
Pre
ssur
e
THE FRANK- STARLING “LAW OF THE HEART”
CARDIAC FUNCTION CURVE
CA
RD
IAC
OU
TP
UT
(L
/min
)
RAP mmHg
15-
10-
5-
-4 0 +4 +8
THE FRANK- STARLING “LAW OF THE HEART”
IncreasedContractility
CARDIAC FUNCTION CURVE
CA
RD
IAC
OU
TP
UT
(L
/min
)
RAP mmHg
15-
10-
5-
-4 0 +4 +8
THE FRANK- STARLING “LAW OF THE HEART”
DecreasedContractility
ISOVOLUMETRIC RELAXATIONRAPID INFLOW
DIASTASISATRIAL SYSTOLE
EJECTION
ISOVOLUMETRICCONTRACTION
SYSTOLE DIASTOLE SYSTOLE
AORTICPRESSURE
ATRIALPRESSURE
VENTRICLEPRESSURE
ECG
PHONO-CARDIOGAM
VO
LU
ME
(m
l)P
RE
SS
UR
E (
mm
Hg)
HEART - BLOOD VESSELSCOUPLING AT REST
PUMP ARTERIESVEINS
Qh 5L/min
Qr5L/min
PERIPHERAL R= Pa - Pv / Qr
R = 20mmHg/L/min
MPA=102mmHgCPV=2mmHg=Pv
COMPLIANCESCv = 19CaCv>>>>Ca
Pa
CARDIAC ARREST!INMEDIATE EFFECT
PUMP ARTERIESVEINS
Qh 0L/min
Qr5L/min
CPV=2mmHg=Pv
Pa
FLOW STOPS HERE
FLOW CONTINUES HERETRANSFER ART-->VEINS
R = 20mmHg/L/minQr= Pa - Pv/20
Qr CONTINUES AS LONG ASA PRESSURE GRADIENT IS SUSTAINED
CARDIAC ARRESTSTEADY STATE
PUMP ARTERIESVEINS
Qh 0L/min
Qr0L/min
Pv = 7mmHg = MEAN CIRCULATORY PRESSURE OR Pmc
Pa = 7mmHg
FLOW STOPPED
FLOW STOPPED
Qr = 0 ( NO Pa - Pv DIFFERENCE)
95mmHg
5mmHg
WE START PUMPING!INMEDIATE EFFECT
PUMP ARTERIESVEINS
Qh 1L/min
Qr0L/min
Pv = 7mmHg
Pa = 7mmHg
FLOW STARTS
NO FLOW HERE YET
SOME VENOUS BLOOD
FLOW RETURNS AT Qr AT THE NEW Qh
PUMP ARTERIESVEINS
Qh 1L/min
Qr1L/min
Pv = 6mmHg
Pa = 26mmHg
FLOW STARTS
R = 20mmHg
Qr = Pa - Pv / 20 = 1L/min
HEMODYNAMICS
• VELOCITY, FLOW, PRESSURE
• LAMINAR FLOW
• POISEUILLE’S LAW
• RESISTANCE (SERIES-PARALLEL)
• TURBULENT FLOW AND REYNOLD’S NUMBER
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
Q=10ml/s
A= 2cm2 10cm2 1cm2
V= 5cm/s 1cm/s 10cm/s
V = Q / A
a b c
POISEUILLE’S LAW GOVERNING FLUID FLOW(Q) THROUGH CYLINDRIC
TUBES
(FLOW)Q(FLOW)Q = (Pi - Po) r
DIFFERENCEIN PRESSURE RADIUS
8nL
VISCOSITY
4
LENGHT
LAMINAR VS TURBULENT FLOWTHE REYNOLD’S NUMBER
LAMINARFLOW
TURBULENTFLOW
Nr = pDv / n
p = densityD = diameterv = velocityn = viscosity
laminar = 2000 or less
Right coronary blood flow
Left coronary blood flow
* The peak left coronary flow occurs at the end of isovolumetric relaxation
*
Cessation of Myocardial Blood Flow
Cessation of Myocardial Blood Flow
mitochondria
cellular pO2 < 5mmHg within seconds
oxidative phosphorylation stops
cytosol
anaerobic glycolysis
glycogen
glucose-6-phosphate
pyruvate
lactate
cellular acidosis
depletion of ATP
Blood Vessel
• Intima primarily the endothelial lining
• Mediavascular smooth muscle, collagen, elastin
• Adventitiaconnective tissue
Vascular Endothelium
Vasodilators Vasoconstrictors
Nitric OxideProstacyclinEndothelium-derived hyperpolarizing factorBradykinin
Endothelin-1 Angiotensin II
Wilson SH, Lerman A.Heart Physiology and Pathophysiology, Academic Press(edited by Sperelakis N.) 473-480
L-Arginine is converted to NO by the enzyme nitric oxide synthase (NOS)
Nitric Oxide (NO)Function
• Vasodilator• Inhibitor of vascular smooth muscle cell
proliferation• Inhibitor of platelet adherence/aggregation• Inhibitor of leukocyte/endothelial interactions
Endothelin-1(ET-1)
• Peptide first sequenced in 1988• Most potent vasoconstrictor in humans
• Maintenance of basal arterial vasomotor tone
• Strong chemoattractant for circulating monocytes and macrophage activation “proatherogenic”
Endothelial Dysfunction
• Imbalance of endothelium-derived relaxing and contracting factors
Atherosclerotic risk factors
Decreased NO bioavailabilityIncreased levels of ET-1