CARDIOVASCULAR SYSTEM Juliet Ver-Bareng, M.D., FPSP.

CARDIOVASCULAR SYSTEM

Juliet Ver-Bareng, M.D., FPSP

Outline• Physiologic properties of the heart Electrical properties

< Excitability< Automaticity and Rhythmicity< ConductivityMechanical properties< Contractility< Distensibility

• Regulation of cardiac activity Neural controlHumoral control

Circulation• Role of the blood vessels

• Hemodynamics

• Blood Pressure determination

• Microcirculation – fluid exchange

• Factors affecting venous return

• Regulation of blood flow

• Regulation of blood pressure

Functions of the heart1. Generating blood pressure

- contraction of heart is responsible for movement of blood through the blood vessels

2. Routing blood to two circulation

- pulmonary and systemic circulation

3. Ensuring one way blood flow - presence of valves (AV and semilunar valves)

4. Regulating blood flow

- change in heart rate and force of contraction to match blood delivery to the changing metabolic needs of the tissues

Physiologic Properties of the heart

• Electrical Properties

- Excitability = bathmotropy

- Automaticity and Rhythmicity = chronotropy

- Conductivity = dromotropy

• Mechanical Properties

- Contractility = inotropy

- Distensibility = lucidotropy

Types of ion channels in the heartType Heart tissue

Na+ fast channels Atrial and ventricular myocardial cells, Purkinje fibers, AV nodal

Ca++ slow channels Atrial and ventricular myocardial cells, Purkinje,fibers SA nodal cells, AV nodal cells

K+ channels: Inwardly rectifying Delayed Transient outward

Atrial and ventricular myocardial cells, Purkinje fibersAtrial and ventricular myocardial cells, Purkinje,fibers SA nodal cells, AV nodal cellsAtrial myocardial cells, Purkinje,fibers

Pacemaker channels: “Funny” currents Hyperpolarizing currents

Purkinje fibersSA nodal cells and AV nodal cells

Ligand- operated channels: Ca++ activated nonspecific ATP sensitive K+ current Ach sensitive K+

current

Ventricular myocardial cells, Purkinje fibers

Atrial and ventricular myocardial cells

Atrial myocardial cells, Purkinje,fibers SA nodal cells, AV nodal cells

Resting membrane potential- the difference in ionic charge across the membrane of the cell = -70 to -9o mV- resting membrane potential is permeable to K+, and is relatively impermeable to other ions- maintenance of this electrical gradient is due to the: Na+- K+ pump and the Na+- Ca++ exchange mechanism

Electrical Properties A. Excitability – bathmotropy

SA node, AV node Myocardia, Purkinje system Slow response AP Fast response AP

Phases of fast response AP

4 = Resting Membrane Potential

0 = Rapid Depolarization

1 = Initial Repolarization

2 = Plateau

3 = Repolarization

Phases of fast response APPhase 0 - Rapid depolarization

- due to opening of the fast Na+ channels and the

subsequent rapid increase in the membrane conductance to

Na+ (gNa

) and a rapid influx of Na+ ions into the cell

The fast Na+ channel

made up of two gates at rest

m gate closed

h gate open

Upon electrical stimulation of the cell, the m gate opens

quickly while simultaneously the h gate closes slowly

For a brief period of time, both gates are open and Na+ can

enter the cell across the electrochemical gradient

Phases of fast response AP

Phase 1 – Initial repolarization - occurs with the inactivation of the fast Na+ channels - the transient net outward current causing the small downward deflection of the action potential is due to the movement of K+ and Cl- ions - Cl- ions movement across the cell membrane results from the change in membrane potential, from K+ efflux, and is not a contributory factor to the initial repolarization ("notch").

Phases of fast response AP

Phase 2- Plateau phase

- sustained by a balance between inward movement of Ca2+ (ICa) through L-type calcium channels and outward movement of K+ through the slow delayed rectifier potassium channels, Iks.

Phases of fast response APPhase 3 - Rapid Repolarization phase - L-type Ca2+ channels close, while the slow delayed rectifier (IKs) K+ channels are still open - this ensures a net outward current, corresponding to negative change in membrane potential, thus allowing more types of K+ channels to open - this net outward, positive current (equal to loss of positive charge from the cell) causes the cell to repolarize - the delayed rectifier K+ channels close when the membrane potential is restored to about -80 to -85 mV

Slow response AP

Phases

4 - Spontaneous depolarization

0 - Triggered depolarization

3 - Repolarization

Phases of slow response APPhase 4 – Spontaneous Depolarization

- Prepotential

- Slow diastolic depolarization• depolarization by themselves• the resting potential of a pacemaker cell

(-60mV to -70mV) is caused by;

= a continuous outflow or "leak" of K+ through ion channel proteins in the membrane that surrounds the cells

= a slow inward flow of Na+, called the funny current

= an inward flow of calcium• This relatively slow depolarization continues until the

threshold potential is reached• Threshold is between -40mV and -50mV

Phases of slow response APPhase 0 – Upstroke

- Triggered depolarization

- The SA and AV node do not have fast sodium channels like neurons, and the depolarization is mainly caused by a slow influx of calcium ions

- The calcium is let into the cell by voltage-sensitive calcium channels that open when the threshold is reached.

Phases of slow response AP

Phase 3 - Repolarization

• The Ca++channels are rapidly inactivated, soon after they open

• Sodium permeability is also decreased

• Potassium permeability is increased, and the efflux of potassium (loss of positive ions) slowly repolarizes the cell

Ion channel inhibitor/blocker• Na+ channel = phase 0 (fast response

- Tetrodotoxin

• Ca++ channel = phase 0 (slow response AP) and phase 2 (fast response AP)

- Verapamil

- Nifidipine

- Manganese

• K+ channel = phase 3

- Amiodarone

Refractory period

• Absolute refractory period

- duration when Na

channel is closed

• Relative refractory period

- m gate closing and

h gate opening

• Super normal period

- membrane potential close to the RMP

effective refractory period (ERP)

• absolute refractory period (ARP) of the cell

• during the ERP, stimulation of the cell by an adjacent cell undergoing depolarization does not produce new, propagated AP → nontetanization of the heart

• ERP acts as a protective mechanism in the heart by preventing multiple, compounded action potentials from occurring → limits the frequency of depolarization and therefore heart rate.

Electrical PropertiesB. Automaticity and Rhythmicity =

Chronotropy

- rate and rhythm

prepotential = phase 4

Heart RateNormal range

Bradycardia – vagal stimulation

Tachycardia – sympathetic effect

Vagal tone

Heart Rate at Rest

Age Group Beats per Minute

Newborn 140

Young Child 100-120

Adult 60-100

Mechanism of change in heart ratePrepotential:

RMP

TP

Slope

RMP TP Slope

Parasympathetic ↓ ↓

Sympathetic ↓

Automaticity Pacemaker Discharge rate

1. SA node = 70 – 80 beats/min

= primary pacemaker

2. AV node = 40 – 60 beats/min

3. Purkinje fibers = 30 – 40 beats/min

Ectopic beat – successful impulses coming from other pacemaker cells and not from SA node

Arrhythmia• when the heart rate is too fast or too slow or

when the electrical impulses travel in abnormal pathways is the heartbeat considered abnormal

An arrhythmia may occur for one of several reasons:

• Instead of beginning in the sinus node, the heartbeat begins in another part of the heart

• The sinus node develops an abnormal rate or rhythm

• A patient has a heart block

Abnormal Heart RhythmsCondition Symptoms Possible causes

Tachycardia HR > 100 bpm Elevated body temperature, excessive sympathetic stimulation

Bradycardia HR < 60 bpm Athletes: increased SV, excessive vagal stimulationCarotid sinus stimulation

Sinus arrhythmia HR varies with respiration Ischemia, inflammation, cardiac failure

Paroxysmal atrial tachycardia

Sudden increase in HR to 95 – 150 bpm P wave precedes QRS complex

Excessive sympathetic stimulation, increased cardiac permeability to Ca++

Atrial flutter As many as 300 P waves and 125 QRS complexes/min

Ectopic beats in the atria

Atrial fibrillation No P waves, complex normal QRS complex and T waves

Ectopic beat in the atria

Symptoms of Arrhythmia • Heartbeats are fast or slow, regular or irregular or

short or long • Person feels dizzy, light-headed, faint or even

loses consciousness • Person is experiencing chest pain, shortness of

breath or other unusual sensations along with the palpitations

• Palpitations happen when the patient is at rest or only during strenuous or unusual activity

• Palpitations start and stop suddenly or gradually

Electrical PropertiesC. Conductivity = DromotropyConducting tissues:1. SA node2. AV node3. Internodal tract4. Interatrial tract or Bachmann’s bundle5. Atrial muscles6. Bundle of His7. Bundle branches8. Purkinje fibers9. Ventricular muscles

Tissue Diameter (μm)

Conduction velocity (m/sec)

SA node 2 – 7 0.05

Atrial muscles 8 – 10 0.3 – 0.5

Internodal tract 16 – 20 1.0

AV node Variable 0.02 – 0.05

Purkinje fibers 70 – 80 2.0 – 4.0

Ventricular muscles

10 - 16 <1.0

Conduction time

Conduction of impulses• Physiologic delay – occurs at the AV node

Mechanisms:

1.Size of the fibers - small

a. interatrial tracts - enter the AV node

b. His-nodal tract – leaves AV node

2.Contains fewer gap junctions

Significance: allows time for ventricular filling

Conduction of impulses

Fastest conduction velocity - purkinje fibers

Mechanism: fibers have the largest diameter

Significance: ensures an almost simultaneous contraction of ventricles

Characteristics of conduction

Mechanism1. One way direction ARP 2. Decremental sizes of fibers

3. Indefatigable ARP

ECG

P wave QRS T wave

complex

Basic Information derived from ECG tracings

1. Heart rate

2. Origin of excitation

3. Rhythm = regular or irregular

4. Conduction velocity = PR interval

= normal, delayed or blocked

5. Mean Electrical Axis

6. Primary cardiac impairment = ST segment

7. Blood supply = large Q wave, ST segment and T wave

EKG

ECG

Large boxes are used to estimate heart rateMeasure from QRS to QRS

1 large box = 300 bpm2 large boxes = 150 bpm3 large boxes = 100 bpm4 large boxes = 75 bpm5 large boxes = 60 bpm

EKGNormal Sinus Rhythm (NSR) • originates in the SA node and follows the appropriate

conduction pathways. • rate is normal, and the rhythm is regular• every beat has a P wave followed by QRS complex

• EKG CriteriaRate: 60-100 bpm

Rhythm: Regular P waves: look the same and originate from the same locus (SA node) PR interval: 0.12 - 0.20 sec QRS: 0.08 -0.12 sec, narrow

EKG: Heart BlockFirst degree: regular rhythm PR interval > 0.12 sec

Second degree: Mobitz I: Wenkebach: Rhythm: Irregular

PR interval: Progressive lengthening followed by dropped beat

QRS's appear to occur in groups. Mobitz II: PR interval: Constant on conducted complexes until a sudden block of AV conduction = P wave is abruptly not followed by a QRS

Third degree: P wave: Independent P waves and QRS's (AV dissociation)

QRS: wide (>0.12 sec) and slower (30-40 bpm) with ventricular escape rhythm.

EKG

Limb leads Precordial leads

Mean Electrical Axis

-30° to +110° limb leads

Mean Electrical AxisLead with the tallest QRS complex

Perpendicular to the lead with equipotential QRS complex

Complimentary Leads:

I and aVF

II and aVL

III and aVR

Mechanical PropertiesA. Contractility – Inotropy Cardiac wall

Sarcomere length = 2.2 – 2.6 μm

Excitation-Contraction Coupling

Contractility = Inotropy

Systole = ejection of blood into the circulation

Systole = contraction

• Stroke volume = amount of blood ejected per contraction (beat)

• Cardiac output = amount of blood ejected per minute

Inotropism(+) = greater force of contraction → more blood

ejected

= results from an increased Ca++ concentration

- sympathetic stimulation = via β2 receptors

- epinephrine and norepinephrine

- cardiac glycosides (digitalis)

(-) = weaker force of contraction → less blood ejected

- parasympathetic stimulation

- hypoxia

- acidosis

Diastole = ventricular filling

Diastole = relaxation

= Lucidotropy

• End Diastolic Volume (EDV) – amount of blood contained in the ventricle at the end of diastole

• End Systolic Volume (ESV) – amount of blood left in the ventricle at the end of systole

• SV = EDV - ESV

Frank-Starling Law of the heart

- relationship between the initial length of the ventricular myocardia at the end of diastole and the force of contraction

= initial length - dependent on the EDV

= force of contraction → SV

- ability of the heart to change its force of contraction and therefore stroke volume in response to changes in venous return

Cardiac cycle

Cardiac cycle

Cardiac cycle

• Phase 1 = Atrial systole

• Phase 2 = Isovolumetric contraction

• Phase 3 = Rapid ejection

• Phase 4 = Reduced ejection

• Phase 5 = Isovolumetric relaxation

• Phase 6 = Rapid filling

• Phase 7 = Reduced filling

Heart sounds• S1

= closure of semilunar valves

aortic and pulmonic component

= isovolumetric relaxation

= sounds like “dub”

• S2

= closure of semilunar valves

aortic and pulmonic component

= isovolumetric relaxation

= sounds like “dub”

Heart sounds

• S3

- during rapid filling

• S4

- during atrial systole

Not normal in adults

Murmur – turbulent blood flow• Valvular defect

• Congenital abnormalities

Patent Ductus Arteriosus

Septal defect: ASD VSD

Valve Abnormality Timing of murmur

Semilunar valves

StenosisInsufficiency

SystolicDiastolic

AV valves StenosisInsufficiency

DiastolicSystolic

Effects of valvular lesions on circulation

• Reduction of cardiac output

• Additional cardiac work = due to extra volume load

• Backflow of blood is produced

Pressure Volume Loop Pressure (mm Hg) Points

A = opening AV valves

D C B = closure AV valves

SV C = opening of SL valves

D = closure of SL valves

A B

Volume (ml)

Lines

AB = Ventricular filling

BC = Isovolumetric contraction

CD = Ejection

DA = Isovolumetric relaxation

Cardiac OutputCO = SV X HR

Factors affecting cardiac function1. Preload2. Afterload3. Contratility4. Heart rate

Ejection Fraction = SV/EDV x 100 ≥ 55%

Preload = End Diastolic Volume

Regulation of cardiac activity

1. Intrinsic control – autoregulation

= regulation of SV

2. Extrinsic regulation

= regulation of heart rate

Autoregulation (SV = EDV – ESV)

1. Homeometric autoregulation = ↑ contractility →↓ ESV → ↑ SV

Systole

Diastole

2. Heterometric autoregulation = ↑ EDV →

↑ SV

= Frank-Starling’s Law of the heart

Extrinsic regulation of the heart = effect on Heart Rate

• Neural1. Extrinsic nerves to the heart vagal tone2. Cardiac centers: CIC and CAC3. Higher centers: cerebral cortex, limbic system4. Cardiac reflexes Baroreceptor - bradycardia Chemoreceptor Bainbridge Somatic afferent hot temperature – tachycardia cold temperature - bradycardia

Nerve supply to the heart• Parasympathetic nervous system – vagus

Right vagus = SA node, AV node, Atrial

muscles

Left vagus = AV node, Atrial muscle, SA

node

• Sympathetic nervous system

Right nerve = SA node, AV node, Atrial

muscles and Ventricular muscles

Left nerve = AV node, SA node, Atrial

muscles and Ventricular muscles

Nerve supply to the heart• Parasympathetic nervous system – vagus

Right vagus = SA node, AV node, Atrial

muscles

Left vagus = AV node, Atrial muscle, SA

node

• Sympathetic nervous system

Right nerve = SA node, AV node, Atrial

muscles and Ventricular muscles

Left nerve = AV node, SA node, Atrial

muscles and Ventricular muscles

Baroreceptors

• Marey’s Law Sinoaortic reflex

• Stimulus = high BP

• Receptors = carotid and aortic sinuses

• Afferent nerve = IX and X nerves

• Center = medulla

• Efferent nerve = X nerve

• Effector = SA node

• Effect = slowing HR

Chemoreceptors• Peripheral

Stimulus = hypoxia

Receptors = carotid and aortic bodies

Effect = increase in HR

• Central

Stimulus = high H+ in CSF

Receptor = medulla

Effect = increase in HR

Extrinsic regulation of the heart

• Humoral Tachycardia Bradycardia

1. Hormones

Epinephrine, NE Acetylcholine

2. Ions

Ca++ (Ca ++ rigor) K+ (K+ inhibition)

2. Gases

↑ CO2 ↓ O2

CIRCULATION• Pulmonary = from

RV to the lungs for

Oxygenation

• Systemic = from

LV to different organs

of the body

Blood Vessels

Functions of blood vessels

• Aorta – windkessel vessel• Large arteries – conducting vessels• Medium arteries – distributing vessels• Small arteries and arterioles – resistance

vessels • Capillaries – exchange vessels• Veins = capacitance vessels• Vena cava = conduits

Distribution of blood at rest

60 – 70 % veins and venules

10 – 12% pulmonary circulation

8 – 11% heart

10 – 12% arteries

4 - 5% capillaries

HEMODYNAMICS• Blood Flow (Q) = amount of blood from point

1 to point 2 in one minute = Poiseuille’s Equation = ml/min Q = ΔP/R R = 8 η l η = viscocity π r4 l = vessel length r = vessel radius Q = π ΔP r4

8 η l

HEMODYNAMICS• Character of flow = Reynold’s Number (Re # = ρ V D η ρ = blood density V = velocity of blood flow D = vessel diameter

> Laminar or Streamlined = flow of components of blood runs parallel to the wall of blood vessel

> Turbulent = flow of components of blood runs tangential to the wall

producing eddy currents

Hemodynamics• Wall Tension (T) Laplace’s Law

T = Pr

P = transmural pressure

r = vessel radius

Relationship of velocity of blood flow and total cross sectional area

Blood PressureQ = ΔP/R ΔP = Q x R BP = CO x TPR

Methods:1 Palpatory2 Auscultatory3 Oscillometric

SPDP

Korotkoff sounds

Components of BP

Arterial Pressure

• Pulse Pressure = SP – DP

• Mean Arterial Pressure

MAP = DP + 1/3PP

Categories for Blood Pressure Levels in Adults (in mmHg)

The ranges in the table apply to most adults (aged 18 and older) who don't have short-term serious illnesses

CategorySystolicPressure

 DiastolicPressure

Normal < 120 And < 80

Prehypertension 120–139 Or 80–89

High blood pressure

     Stage 1 140–159 Or 90–99

     Stage 2 ≥ 160 Or ≥ 100

.

Risk factors of developing hypertension

• Family history of high blood pressure, heart disease, or diabetes• Age greater than 55• Overweight• Not physically active (sedentary)• Alcohol excessive drinking• Smoking• Food high in saturated fats or sodium use• Race• Gender• Certain medications such as NSAIDs, cocaine decongestants

Composition of microcirculation• ArteriolesMetarterioles

• Capillaries

• Venules

• Terminal lymphatic vessels

Fluid Exchange = governed by Starling’s forces

Filtration occurs mainly through the intercellular junctions of the small pore system

As formulated is Starling’s hypothesis:

- the fluid filtered across a capillary membrane is proportional to the net filtration pressure

- the sum of hydrostatic pressures and the colloidal osmotic pressure

- expressed as:

Vf  =  kf [(Pc - Pif) - (πc - πif)]

or = kf [(Pc+ πif) - (πc+ Pif)]

Fluid exchange

Veins• Capacitance vessels

• Reservoir of blood

• Low pressure

• Low resistance

Factors affecting Venous Return• Muscle contraction - rhythmical contraction of limb muscles

as occurs during normal locomotory activity (walking, running, swimming) = promotes venous return by the muscle pump mechanism

• Decreased venous compliance - following Sympathetic activation of veins, increases central venous pressure and promotes venous return indirectly by augmenting cardiac output through the Frank-Starling mechanism = increases the total blood flow through the circulatory system

• Respiratory activity - during respiratory inspiration, the decrease in right atrial pressure = increases the venous return  

• Vena cava compression - increases vena cava resistance which occurs when the thoracic vena cava becomes compressed during a Valsalva maneuver or during late pregnancy = decreases return

• Gravity - the effects on venous return when a person stands up, the hydrostatic forces cause the venous pressure in the dependent limbs to increase = venous return decreases

Regulation of blood flow• Local regulation

1. Intrinsic

a. Myogenic theory

b. Endothelial derived =Nitric Oxide,

Endothelin, Thromboxane

2. Metabolic

a. Oxygen demand

> active hyperemia - ↑ O2 consumption

> reactive hyperemia – hypoxia due

previous occlusion of blood supply

b. Vasodilator agents = H+, histamine, kinins

Extrinsic regulation of blood flow• Neural Sympathetic tone Vascular centers: VCC and VDC Cardiovascular reflexes: Baroreceptor = ↓ TPR• Humoral 1. Hormones Vasodilators : ACh, Epinephrine Vasoconstrictors: Epinephrine, NE, Angiotensin, ADH, Serotonin 2. Ions Ca++ – vasoconstriction H+ and K+ - vasodilation 3. Gases ↑CO2 and ↓O2 - vasodilation

Delayed regulation of blood flow

• Opening of collaterals

- blood flowing to more blood vessels

• Angiogenesis

- formation of more arteries

Neural mechanisms• ANS on vessel caliber

- sympathetic tone - parasympathetic = vasodilatation

• Vasomotor centers - medulla- Vasoconstrictor center- Vasodilator center

• Higher centers- cerebral cortex- limbic system

• Vasomotor reflexes- baroreceptor- chemorecpetor- somatosympathetic

Humoral mechanismsVasoconstrictor agents Vasodilator agents

Epinephrine (on alpha receptors)

Epinephrine (on beta receptors)

Angiotensin Acetylcholine

Vasopressin Histamine

Serotonin Prostaglandin

Endothelin 1 ANP

Calcium Nitric oxide

Thromboxane Ions = H+, K+

CO2

Low O2

Bradykinin

Lactic acid

BP regulation - Onset of action

• Immediate

Cardiovascular reflexes

CNS ischemic effect• Intermediate

Capillary fluid shift

Renin-Angiotensin system• Delayed

Aldosterone

Renal vascular system

Effect of :• Acute pain → increased sympathetic

stimulation• Deep pain → increased parasympathetic

stimulation

Vasoconstriction Vasodilation• pH decreased increased• Temperature low high