physio lecture 7 – introduction to cardiovascular physiology prof. dr. Željko dujić

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