Cardiovascular physiology The objectives are to know the following: 1. Functional anatomy of the heart 2. The basics of heart physiology& the origin of

heart beat 3. Changes that occur during cardiac cycle 4. Cardiac output & factors affecting it 5. Hemodynamics 6. Physiological abnormalities causing diseases

Cardiovascular system Functions of cardiovascular system include: 1. Transport of O2, glucose,A.A, F.A, vitamines,

drugs & water to the tissues. 2. Rapid washout of metabolic waste products like

CO2, urea & creatinine 3. CVS is part of a control system in that it

distributes hormones to the tissues & even secrete hormones by itself e:g ANP

4. Plays vital role in temperature regulation

Cardiovasular system Consists of: Heart: A pump that pumps blood under high

pressure A set of blood vessels for conduction of blood

from & back to the heart

Physiology of heartThe heart is a muscular organ. It’s wall consists of three layers:

1.Endocardium

2. Myocardium

3. Pericardium:

a.Visceral ( Epicardium)

b.Parietal:

1.Inner serous layer

2.Outer fibrous layer

PERICARDIUM&HEART WALL

Three Layers of Heart WallFrom the outside-in

- Epicardium- visceral pericardium

- Myocardium- the muscular wall

- Endocardium

Architecture Pericardial cavity Pericardium

Viscreal-epicardium-in direct contact with the heart

Parietal-surrounds heart, creating pericardial cavity

Pericardial cavity contains a small amount of fluid

Attached to diaphragm by fibers

Location Lies near anterior

chest wall, behind sternum

Tilted slightly to the left

Rotated slightly to the left

This causes the anterior surface to consist of the right atria and ventricle

Functional anatomy of heart Heart is divided into 2 halves: Rt.& Lt. Each half consists of an atrium & a ventricle Atrium & ventricle of the same side connect

through atrioventricular opening. AV opening guarded by presence of a valve

[ Atrioventricular valves- AV valves] Mitral valve on Lt.side Tricuspid valve on Rt.side

Heart ( functional anatomy) From Lt.ventricle arises the aorta From Rt.ventricle arises The pulmonary artery Openings of the large arteries are guarded by

semilunar valves: Aortic & pulmonary valves Valves are passive structures: they open when

there is a forward pressure to allow forward flow of blood

They close when there is a backward pressure to prevent backward flow of blood

Heart functional anatomy Blood reaches Rt. atrium via superior &

inferior vena cava Blood reaches Lt. atrium via pulmonary veins Opening of the veins are not guarded by

valves

Atrial Ventricular

Cardiac Muscle Almost totally dependant on aerobic

metabolism Each cell connected to its neighbor by

intercalated discs Gap junctions connect one cardiac muscle

fiber to another,act as functional syncytium- In the gap junction there is a channel that

allow movement between adjacent m.f- Diameter of channel is affected by

intracellular calcium concentration

FUNCTIONAL SYSCYTIUM

Cardiac muscle- Striated muscle- Arrangement of Actin, Myosin, Troponin &

Tropomyosin is similar to those in skeletal muscle.

- Excitation contraction coupling is similar to skeletal muscle

- Source of calcium ions: Sarcoplasmic reticulum+I.S.F through calcium channels

Cardiac muscle Because of presence of gap junctions, when

one cardiac muscle fiber is depolarized the wave of depolaization pass to other cardiac muscle fibers,acting as functional syncytium

All or None law applies to the whole cardiac muscle & not to a single muscle fiber as in skeletal muscle.

Sarcomeres are composed of myosin and actin

Several proteins mediate the interaction of myosin heads with the actin filament

Calcium signaling triggers contraction

ACTION POTENTIAL IN CARDIAC MUSCLE It is characterized by the presence of action potential

plateau ( 0.1-0.3 sec) Plateau keeps the membrane depolarized for longer

time than depolarization in skeletal muscle Plateau is due to inward calcium movement through

calcium channels Long refractory period No tetanization of cardiac muscle

REFRACTORY PERIOD

Conducting System Cardiac cells contract in the absence of neural

or hormonal stimulation. This is known as Self excitation or Rhythmicity.automaticity

Property of self excitation is obvious in the conducting system of the heart which is made of modified cardiac muscle fibers.

Path of the Action Potential Conducting system of heart: SA Node ( Pace maker of the heart)

- Atrial conducting pathways AV Node

- Impulse slows down to allow for blood movement and ventricular filling

Bundle of His Left and right bundle branches Purkinje fibers

Heart Physiology: Sequence of Excitation

Figure 18.14a

Heart Physiology: Intrinsic Conduction System Autorhythmic cells: Pace maker

Initiate action potentials Have unstable resting potentials called pacemaker

potentials Use calcium influx (rather than sodium) for rising

phase of the action potential

Pacemaker and Action Potentials of the Heart

Figure 18.13

Conducting system of heart Coducting system perform 2 functions: 1. Generation of impulses 2. Conduction of these impulses Rate of different parts of conductive system: SA node: 70-80/min AV node: 40-60/min Purkinje fibers: 15-40/min SA node dominates because of it’s high rate of

discharge & is the pace maker of the heart. The other parts function in conducting the impulses.

Heart Physiology: Sequence of Excitation Sinoatrial (SA) node generates impulses about

75 times/minute Atrioventricular (AV) node delays the

impulse approximately 0.1 second (allow atria to contract before ventricles)

Impulse passes from atria to ventricles via the atrioventricular bundle (bundle of His)

Heart Physiology: Sequence of Excitation AV bundle splits into two pathways in the

interventricular septum (Rt.& Lt.bundle branches) Bundle branches carry the impulse toward the

apex of the heart Purkinje fibers carry the impulse to the heart apex

and ventricular walls ( fast conduction allow the ventricle to contract as one unit)

Extrinsic Innervation of the Heart

Heart is stimulated by the sympathetic cardioacceleratory center

Heart is inhibited by the parasympathetic cardioinhibitory center

Figure 18.15

Cardiac cycle An action potential generated in the SA

node,travelling to the atria depolarizing them & bringing contraction of atria.

Action potential spreading to the ventricles through AV node,bundle of His & bundle branches depolarizing the ventricles & bringing contraction of the ventrices.

Contraction will be followed by relaxation

Cardiac Cycle Cardiac cycle refers to all events associated

with blood flow through the heart Cardiac cycle consists of systole &diastole

Systole – contraction of heart muscle Diastole – relaxation of heart muscle Duration: 0.8 sec if HR 72 ( 60/72) SYS: atrial (0.1sec), ventricular (0.3sec) DIAS: atrial (0.7sec), ventricular (0.5sec)

FUNCTIONAL ANATOMY OF HEART

Phases of the Cardiac Cycle Ventricular systole

Atria relax

1.Isometric ventricular contraction (0.06 sec)Rising ventricular pressure results in closure of AV

valves (1st heart sound)

Rising ventricular pressure opens semilunar valves

2.Ventricular ejection phase begins (0.21sec)

Phases of the Cardiac Cycle Ventricular diastole 1.Protodiastole (0.02 sec) ends by closure of semilunar

valves(2nd heart sound) 2.Isometric ventricular relaxation (0.05 sec) ends by

opening of AV valves 3.Rapid ventricular filling (0.16sec) 4.Slow ventricular filling (0.23sec) 5.Atrial systole (0.1sec) a new wave of depolarization

Changes during cardiac cycle 1. PRESSURE CHANGES A. in ventricles Rt ventricle 22/0 mm Hg Lt ventricle 120/0 mm Hg B. Aorta 120/80 mm Hg C. Pulmonary artery 22/8 D. Atria Rt.4-6, Lt.7-8 mmHg (a,c,v waves)

Changes during cardiac cycle 2.VOLUME CHANGES End Diastolic Volume (120-130ml) Stroke Volume 70 ml End Systolic Volume (50-60ml)

EDV- SV= ESV

Changes during cardiac cycle 3.HEART SOUNDS First heart sound LUP at beginning of systole Second heart sound DUP at beginning of

diastole Third heart sound(some times)-rapid

ventricular filling Fourth heart sound( atrial systole)

Changes during cardiac cycle 4.ELECTRICAL CHANGES Electrical changes originating in the heart

spreads to the surrounding tissue & some reaches the body surface & can be recorded

ELECTROCARDIOGRAPHY ECG

Phases of the Cardiac Cycle

Figure 18.20

Electrocardiography Electrical activity is recorded by

electrocardiography (ECG) P wave corresponds to depolarization of SA node QRS complex corresponds to ventricular

depolarization T wave corresponds to ventricular repolarization Atrial repolarization record is masked by the

larger QRS complex

Electrocardiography

Figure 18.16

Action potential in ventricular muscle

Heart Excitation Related to ECG

Figure 18.17

Recording ECG Recording is done by using two types of leads. 1. Bipolar leads: The potential difference between 2

active electrodes is recorded. Also called standard limb leads: Lead I,II,III

2. Unipolar leads: One active electrode called Exploring electrode is put on different points on body surface. The other electrode( indifferent electrode) is kept at zero potential

A. Unipolar limb leads( aVR, aVL, aVF) B. Unipolar chest leads( precordial leads):

V1,V2,V3,V4,V5,V6

Standard limb leads & Einthoven triangle

Einthoven law: I + III = II

Unipolar chest leads( precordial)

Precordial leads

Augmented limb leads: waves inverted in aVR

Waves & Intervals P wave: duration:0.1sec,voltage, 0.1-0.3mv P-R interval: 0.12-0.2 sec ORS complex: duration 0.08sec, voltage 0.5-

1.5mv T wave: duration 0.27sec, voltage 0.2-0.3mv Q-T interval: 0.35sec

++++----

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++++----

++++---- ++++---- ++++--------++++

--++--++--++--++----++++

++++----++++----

++++----++++

---- ++++---- ++++--------++++

--++--++--++--++----++++

++++----++++ ++++---- ----++++

----++++---- ++++--------++++

--++--++--++--++----++++

++++++++ --------++++ ++++---- ----++++----++++---- ++++++++ --------

----++++

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Most ventricular activity that is recorded is activity in the left ventricle. The same activity gives different shapes in different leads because a wave of depolarization moving toward an electrode will cause an upward deflection on the ECG needle while if depolarization is moving away from an electrode that electrode records a negative wave.

Generation of the ECG complexes

READING ECG 1. Find heart rate 2. Detection of conduction defects 3. Detection of abnormality in rhythm

(arrhythmias) 4. Detection of signs of ischemia 5. Detection of atrial or ventricular

hypertrophy

Heart rate Is found by dividing 300 by the no. of large

squares between 2 successive R waves Normal HR 60-90/min Below 60/min. Bradycardia Above 90/min. Tachycardia

Calculation of heart rate

CONDUCTION DEFECTS 1.SA node .Sick sinus syndrome ( Stoke’s Adam

syndrome) :atrial escape.Corrected by artificial pacemaker. 2. AV node,bundle of His. (Heart block) a. Incomplete heart block: 1. 1st degree HB ( prolongation of P-R interval) 2. 2nd degree HB ( 2:1 or 3:1 block) b. Complete heart block (3rd degree HB) ( ventricular escape ventricles beat by their idioventricular

rhythm) 3. Bundle branch block ( RBBB, LBBB)

Sinoatrial block with AV nodal rhythm

First degree heart block

Second degree heart block

Complete heart block

ARRHYTHMIAS 1. SUPRAVENTRICULR a. Sinus ( tachycardia, bradycardia) b. Atrial ( extrasystole, paroxysmal atrial

tachycardia, atrial flutter, atrial fibrillation) 2. VENTRICULAR ( extrasystole, tachycardia, fibrillation)

Arrhythmias If the irritable ectopic focus discharges once,

the result will be a premature beat or extrasystole

If the focus discharges repetitively at a rate more rapid than SA node, it produced rapid regular tachycardia

A very rapidly & irregularly discharging focus or more likely group of foci can produce fibrillation

Sinus tachycardia

Sinus bradycardia

Supraventricular extrasystole (premature beat)

Ventricular extrasystole

Paroxysmal atrial tachycardia

Paroxysmal ventricular tachycardia

Ventricular fibrillation

Circus movement A common cause of paroxysmal arrhythmias

is a defect in conduction that permits a wave of excitation to propagate continuously within a closed circuit producing circus movement or Re-entry movement

Re-entry ( circus movement)

Atrial flutter & atrial fibrillation

SIGNS OF ISCHEMIA Decreased blood flow to the myocardium Angina pectoris Myocardial infarction

Signs of ischemia

Atrial hypertrophy Right atrial hypertrophy: Tall & peaked p

wave

Left atrial hypertrophy: Broad & Bifid p wave

Ventricular hypertrophy Estimating the electrical axis of the heart or

the main direction of the cardiac vector Estimated from the QRS deflection in 2

standard limb leads usually lead 1 & lead 3 Normal electrical axis of the heart +59

degrees [ normal range (-30)-(+110) ]

Visualization of the generation ofthe Left Ventricular portion ofthe ECG complex in Lead II

1. Septum depolarizes from the inside out and the resulting depolarization wave moves away from the electrode recording Lead II

2. The rest of the ventricle depolarizes counter-clockwise from the inside out and creates the (large arrow) which is essentially, the algebraic sum of all of the small depolarization vectors. This vector is, in a normal heart, almost always moving directly toward Lead II, generating a mostly positive QRS complex

main cardac vector

Lead II electrode60 downwardrotation angle from the horizontal 0

o

o

60o

Note: compared tothe left ventricle, the right ventricle is muchsmaller and contributeslittle to the overall mainvector of depolarization

(DEPOLARIATION)

Cardiac vector

Estimation of electrical axis

Electrical axis of different leads

Electrical axis estimated from 2 bipolar leads

Electrical axis of heart

Left axis deviation

Right axis deviation

Cardiac Output (CO) and Reserve CO is the amount of blood pumped by each

ventricle in one minute CO is the product of heart rate (HR) and stroke

volume (SV) HR is the number of heart beats per minute SV is the amount of blood pumped out by a

ventricle with each beat Cardiac reserve is the difference between resting

and maximal CO

Cardiac Output: Example CO (ml/min) = HR (75 beats/min) x SV (70

ml/beat) CO = 5250 ml/min (5.25 L/min) Change in HR or change in SV or change in

both of them can change the CO

Regulation of Stroke Volume SV = end diastolic volume (EDV) minus end

systolic volume (ESV) EDV = amount of blood collected in a

ventricle during diastole ESV = amount of blood remaining in a

ventricle after contraction

Factors Affecting Stroke Volume Preload – amount ventricles are stretched by

contained blood[EDV] .increase EDV increases SV Contractility – cardiac cell contractile force due to

factors other than EDV Afterload – Is the resistance to ventricular ejection

caused by resistance to flow in systemic circulation Increase afterload decreases SV

Frank-Starling Law of the Heart Preload, or degree of stretch, of cardiac muscle

cells before they contract is the critical factor controlling stroke volume. The heart can pump a small or a large volume of blood depending on blood reaching it.

Slow heartbeat and exercise increase venous return to the heart, increasing SV

Blood loss and extremely rapid heartbeat decrease SV

Venous return to the heart Venous return &EDV increase by: 1. Skeletal muscle contraction 2. Increased negative intrathoracic pressure

during inspiration 3. venoconstriction 4. Increased blood volume

Venous return Venous return & EDV decrease following: 1. Prolonged standing 2. Excessive bleeding 3.Costrictive pericarditis

Preload and Afterload

Figure 18.21

Contractility of myocarium Contractility is the increase in contractile

strength, independent of preload & afterload Increase in contractility comes from:

Increased sympathetic stimuli Certain hormones:g Noradrenaline Ca2+ and some drugs ( sympathomimetic drugs)

Contractility and Norepinephrine

Sympathetic stimulation releases norepinephrine and initiates a cyclic AMP second-messenger system

Figure 18.22

Afterload Resistance offered to ventricular ejection Hypertension, Aortic stenosis Stroke volume is inversely proportional to

afterload

Regulation of Heart Rate Positive chronotropic factors increase heart

rate Negative chronotropic factors decrease heart

rate HR is affected by: Nervous & Hormonal

factors

Sympathetic nervous system (SNS) stimulation is activated by stress, anxiety, excitement, or exercise. Increases HR

Parasympathetic nervous system (PNS) stimulation is mediated by acetylcholine and opposes the SNS. Decreases HR

PNS dominates the autonomic stimulation, slowing heart rate and causing vagal tone

Regulation of Heart Rate: Autonomic Nervous System

Atrial (Bainbridge) Reflex Atrial (Bainbridge) reflex – a sympathetic

reflex initiated by increased blood in the atria Causes stimulation of the SA node Stimulates baroreceptors in the atria, causing

increased SNS stimulation

Chemical Regulation of the Heart The hormones epinephrine and thyroxine

increase heart rate Intra- and extracellular ion concentrations

must be maintained for normal heart function

Factors Involved in Regulation of Cardiac Output

Figure 18.23

MEASUREMENT OF CO Clinical exam. Gives a good indication of

cardiac function. For example: Skin temperature Capillary refill. Pulse rate & pulse volume. Urine output level of consciousness are reliable markers of

CO

Measurement of C.O 1. Fick method ( O2 consumption method) Total O2 consumption in one min. C.O= Art.O2 content- Venous O2 content

250ml/min e:g =5L/min 190-140

Measurement of C.O 2. Dye dilution method A known amount of dye or radioactive isotope is

injected to an arm vein & the concentration of the indicator in serial samples of arterial blood is determined

mg dye injected C.O= mean conc. X time from appearance to

disappearance of dye

Measurement of C.O 3.Doppler method with Echocardiography Pulses of ultrasound are directed at the blood

flowing in ascending aorta & reflected back to the probe by red cells in the blood. The velocity of blood in aorta is measured & if the cross sectional area of aorta is measured by echocardiography the stroke volume & C.O can be calculated

Effect of various conditions on C.O NO CHANGE: 1. Sleep 2. Moderate change in environmental temp.

Increase C.O 1.Anxiety & excitement 50-100% 2.Eating 30% 3.Exercise up to 700% 4.High environmental temp. 5.pregnancy

Decrease C.O 1.Sitting or standing from lying position 20-30% 2.rapid arrhythmias 3.Heart disease

Oxygen consumption of the heart At rest: 9ml/100gm/min [ normal wt.250-300gm] Increases during exercise & in a no. of different conditions Cardiac muscle obtain energy mainly from metabolism of

fatty acids & to a lesser extent from glucose & lactate. Energy expenditure determined by: 1. Heart rate 2. Arterial B.P Energy expenditure can increase when these 2 parameters

increase even though the cardiac output is not changed.

Vascular system

Circulation

Systemic circulation

HEMODYNAMICS Include the study of : 1. Mean pressure 2. Type of flow 3. Speed of flow In different parts of the circulation [systemic

circulation]

HemodynamicsBLOOD VESSELS:

 [anatomical & functional classification]

A.  Arteries (high pressure vessels)[conducting vessels]

1.  structure            a.  thick-walled            b.  large diameter c.  elastic

                     

HEMODYNAMICS

B.  Arterioles [resistance vessels][1].  structure         a.  small diameter         b.  smooth muscle in wall          1.  vasoconstriction, vasodilatation  2.  vascular tone[2].  function:  to regulate blood flow to capillary beds    

HEMODYNAMICS

C.  Capillaries [exchange vessels] 1.  structure      a.  thin-walled;  porous      b.  narrow      c.  Large surface area 2.  function: exchange 3.  capillary blood flow: regulated by presence of    a.  precapillary spincters            

HEMODYNAMICS

D.  Veins [storage or capacitance vessels]1.  low pressure vessel2.  structure    a.  large diameter    b.  distensible  c.  thin-walled d. Valve3.  function: storage4.  venous return mechanisms   a.  skeletal muscle pump   b.  sympathetic vasoconstriction c. Thoracic pump                                   

Blood Flow Blood flow is defined as the quantity of blood

passing a given point in the circulation in a given period and is normally expressed in ml/min

Overall blood flow in the total circulation of an adult is about 5000 ml/min….The cardiac output

FORWARD BLOOD FLOW

Mechanisms – Movement of Blood1.Forces imparted by rhythmic contractions of the heart2.Elastic recoil of arteries following filling by the action

of the heart3.Squeezing of blood vessels during body movements4.Peristaltic contractions of smooth muscle surrounding

blood vessels5. Negative I.T.pre.during inspiration

FACTORS AFFECTING BLOOD FLOW

Forward blood flow

Conductance and vessel diameter

Slight changes in the diameter of a vessel cause tremendous changes in the vessel's ability to conduct blood when the blood flow is streamlined

Although the diameters of these vessels increase only fourfold, the respective flows are 1, 16, and 256 ml/mm, which is a 256-fold increase in flow. Thus, the conductance of the vessel increases in proportion to the fourth power of the diameter

Peripheral resistance Blood flow is determined by: 1. Pressure difference between the 2 ends of

the vessel 2. Peripheral resistance: A. Vessel diameter: Resistance is inversely

proportional to the fourth power of radius B. Blood viscosity: determined by no. of RBC

& by plasma proteins

HEMODYNAMICS Mean pressure: average pressure during the

whole cardiac cycle In the arteries it is obtained by : 1 systolic pressure+2diastoloic pressures 3 The mean pressure is important for proper

tissue perfusion.

MEAN PRESSURE Arteries: 95mmHg Beginning of arterioles: 85mmHg Leaving arterioles: 30mmHg Venular end of capillary: 10mmHg Rt atrium: around zero mmHg All these values are for blood vessels at the

level of the heart.

MEAN PRESSURE

TYPE & SPEED OF FLOW Arteries:Pulsatile flow Capillaries & Veins: Continuous flow Systolic BP-Diastolic BP= Pulse pressure Pulse pressure enables us to feel pulse Arteries: speed of flow 40cm/sec Capillaries: 0.07cm/sec Veins: 10cm/sec

LAMINAR & TURBULENT BLOOD FLOW Normally blood flow is laminar flow[silent] If blood passes by an obstruction or rough

surface or if it’s speed increases , it changes to Turbulent flow[ noisy flow]

Modes of flow in vessles Blood flow can either be laminar or turbulent

Laminar Flow

When blood flows through a long smooth vessel it flows in straight lines, with each layer of blood remaining the same distance from the walls of the vessel throughout its length

When laminar flow occurs the different layers flow at different rates creating a parabolic profile

The parabolic profile arises because the fluid molecules touching the walls barely move because of adherence to the vessel wall. The next layer slips over these, the third layer slips over the second and so on.

LAMINAR or STREAMLINE FLOW

P2P1

P1 > P2

-Cone Shaped Velocity Profile-Not Audible with a Stethoscope

Turbulent flow

When the rate of blood flow becomes too great, when it passes by an obstruction in a vessel, when it makes a sharp turn, or when it passes over a rough surface, the flow may then become turbulent

Turbulent flow means that the blood flows crosswise in the vessel as well as along the vessel, usually forming whorls in the blood called eddy currents. When eddy currents are present, the blood flows with much greater resistance than when the flow is streamline because eddies add tremendously to the overall friction of flow in the vessel.

Turbulent blood flow Turbulent blood flow is a noisy flow It produces sounds that can be heard by a

stethoscope The fact that turbulent flow produces sound is used

in measurement of arterial blood pressure Sounds produced by turbulence to blood flow during

blood pressure measurement are called : Korotkoff sounds

BLOOD PRESSURE Arterial blood pressure: It is the force of blood on the wall of arteries.

Blood pressure is important because it provides a forward driving force to the flow of blood & it ensures proper blood perfusion to all organs in the body specially the vital organs :

[brain, heart, kidneys]

Blood pressure Systolic BP: pressure of blood on the wall of

arteries during ventricular systole. Normal range is 100-140 mmHg

Diastolic BP: pressure of blood on wall of arteries during ventricular diastole. Normal range is 60-90 mmHg

Pulse pressure: difference between systolic & diastolic BP

BLOOD PRESSURE

Factors affecting blood pressure: 1.Cardiac output C.O[ HR, SV] 2.Peripheral resistance [ blood viscosity, diameter of arteriole] 3.Total blood volume

Peripheral Resistance Blood viscosity Diameter of arterioles: Vasomotor tone [sympathetic tone] Arterioles are kept in a state of partial

vasoconstriction because of activity of VMC through sympathetic NS

Increased sympathetic activity= vasoconstriction Decreased sympathetic activity= vasodilatation There is no parasympathetic supply to blood vessels

BLOOD PRESSURE

B.P = C.O X P.R Changes in C.O affect systolic B.P Changes in P.R affect diastolic B.P

Neural regulation of blood pressure

Regulation of blood pressure 1. Neural control [ VMC, Sympathetic, Baroreceptors] Baroreceptors found in aortic arch & carotid sinus They are stimulated by increased blood pressure When stimulated they cause inhibition of VMC Inhibition of VMC decrease sympathetic discharge to blood

vessels This leads to vasodilatation and decreased peripheral

resistance = decreased blood pressure Baroreceptors have a buffering action on blood pressure

Aortic & carotid baroreceptors

Effect of increased BP on baroreceptor stimulation

Regulation of B.P 2. Hormonal regulation A. Epinephrine & Norepinephrine B. Antidiuretic hormone [ ADH] or

vasopressin C. Renin-Angiotensin- Aldosterone

system

The Adrenal MedullaActs very much like a part of the sympathetic

nervous system (fight or flight)Secretes two amines:

norepinephrine (20%) epinephrine (80%)

Stimulated by preganglionic neurons directly, so controlled by the hypothalamus as if part of the autonomic nervous system.

Effects of ADH

Renin-Angiotensin –Aldosterone system Decrease in BP or Decrease plasma sodium Stimulates cells in Juxtaglomerular apparatus

in the kidney to secrete renin Renin acts on angiotensinogen to form

angiotensin I Angiotensin I is activated to Angiotensin II

by the Angiotensin converting enzymes( ACE)

Angiotensin II Functions: 1. Arteriolar vasoconstriction= increase PR 2. Venoconstriction= increase venous return

to heart =Increase CO 3. Stimulates adrenal cortex to secrete

Aldosterone which increases sodium reabsorption from renal tubules

Regulation of BP by renin-angiotensin

Regulation of BP by Renin-angiotensin

Blood pressure Effect of gravity on blood pressure: (+) or (-) 0.77mmHg/cm distance from heart level It is (+) for blood vessels below heart level It is (– )for blood vessels above heart level All values mentioned for mean blood pressure are

for blood vessels at level of heart Critical closing pressure: Blood flow stops if the pressure difference between

the 2 ends of a vessel is lower than peripheral resistance

Effects of gravity on arterial and venous pressures.Each cm of distance produces a 0.77 mmHg change.

Sphincters protectcapillaries

VENOUS PUMP keeps PV < 25 mm Hg

Veins Arteries

190 mm Hg

100 mm Hg0

HYPERTENSION Blood pressure levels above the generally

accepted normal according to age. 20 year: 140/90mmHg 50 year: 160/95mmHg 70 year: 170/105 Exercise,anxiety,discomfort & unfamiliar

surrounding can lead to to a transient rise in BP

ETIOLOGY OF HYPERTENSION 85-90% : Essential HT 10-15%: Secondary HT ,could be due to: 1. Renal diseases 2. Endocrine disorders& hormone therapy 3. Pregnancy 4. Coarctation of aorta( Ht in upper limb &

normal pressure in lower limb)

COMPLICATIONS OF H.T. 1. Left ventricular hypertrophy & MI 2. hypertensive encephalopathy & CVA 3. Hypertensive retinopathy 4. Hypertensive nephropathy Treatment aims at decreasing CO, or PR

or total blood volume & eventually decreasing BP

CAPILLARY CIRCULATION Types of capillaries: Throughfare, True Receives 5% of total CO Thin walled Speed of flow: 0.07cm/sec Exchange: by diffusion ( lipid sol.,water sol.),

pinocytosis. Water movement: by Filtration

Filtration of water Depends on Starling forces: 1. Filtration pressure= Hydrostatic pressure in capillaries-hydrostatic

pressure in I.S.F. 2. Osmotic pressure gradient= Colloid osmotic pressure in plasma-colloid

osmotic pressure in I.S.F.

Filtration

Filtration

ACTIVE & INACTIVE Capillaries Normally flow is through the throughfare vessels When there is an increased demand for blood flow,

blood pass through true capillaries as well. Vasodilator metabolites can cause capillary

dilatation.e:g Increased CO2, increased H+ , increased lactic acid

Decreased sympathetic activity: Vasodilatation & relaxation of precapillary sphincter

VENOUS CIRCULATION Function: 1. Storing large quantities of blood(64%) of total C.O 2. Regulating C.O

Factors affecting venous flow: 1. Skeletal muscle contraction[ muscle pump] 2. Negative I.T.pre. During inspiration[thoracic pump] 3. Sympathetic venoconstriction 4. Presence of valves in limb veins.

VENOUS PRESSURE Central venous pressure is affected by a balance

between: 1. Pumping of blood by heart 2. Venous return Rt.atrial pressure & hence central venous pressure is

increased in: 1. Serious HF 2. Following massive transfusion of blood 3. Straining While it decreases in shock

VENOUS PRESSURE Effect of gravity on venous pressure is the

same as on arterial pressure Veins collapse when their pressure is zero or

below zero Measurement of venous pressure: Central venous pressure Peripheral venous pressure

LYMPHATIC CIRCULATION Constitute a one way route for the movement

of I.S.F to blood Lymphatic system; made of an extensive

network of thin vessels resembling veins arise as a group of blind end lymph capillaries permeable to all I.S.F. constituents

LYMPH FLOW Assisted by: 1. Pumping action of skeletal muscles 2. Effect of respiration on I.T.Pressure 3. Presence of valves 4. Rhythmic contraction of walls of large

lymph ducts

Functions of lymphatic system 1. Return of excess fluid from the

I.S.compartment 2. Return of proteins [ some capillaries are

permeable to protein] 3. Specific transport function for fat 4. lymph nodes & defence

Protein content in lymph Source of lymph Protein%

Choroid plexus 0 Skeletal muscle 2 Skin 2 Lung 4 G.I.T 4.1 Heart 4.4 Liver 6.2

INTERSTITIAL FLUID VOLUME I.S.F volume affected by: 1. Capillary pressure 2. Plasma oncotic pressure 3. Capillary permeability 4. Lymph flow

EDEMA Accumulation of fluid in I.S.space Causes: 1. Increased capillary pressure e:g CHF [Increased venous

pressure]

2. Hypoproteinemia: a.decreased protein intake b.decreased synthesis by liver c.increased loss through kidney or GIT

3. Increased capillary permeability e:g Kinin,Histamine

4. Lymphatic obstruction e;g Filariasis or Elephantiasis

Cardiovascular regulatory mechanisms The aim of these mechanisms is to: 1. Increase blood supply to active tissues. 2. To increase or decrease heat loss from the

body by redistributing the blood. 3. In the face of challenges, e:g hemorrhage,

they maintain blood flow to vital organs at the expense of the rest of the body.

Cardiovascular regulatory mechanisms Cardiovascular adjustments are affected by: 1. Altering the cardiac output. 2. Changing the diameter of resistance vessels 3. Or changing the amount of blood pooled in

the capacitance vessels

Cardiovascular regulatory mechanisms Diameter of arteiole & amount of blood flow

can be regulated by; 1. Systemic regulation [affecting large

segment of circulation] 2. local regulation [ Auto-regulation]

affecting small segment of circulation

Systemic regulation 1. Neural [VMC, Sympathetic N.S] 2. Hormonal: vasodilator or vasocostrictor

hormones Vasodilator Vasoconstrictor Kinin Adr & Norad ANP Angiotensin II VIP ADH, Natriuretic F

AUTOREGULATION [local] Most tissues have an intrinsic capacity to

compensate for moderate changes in perfusion pressure by changes in vascular resistance so that blood flow remains constant.

This capacity is well developed in the kidneys,skeletal muscle, brain, liver & myocardium

Myogenic theory of autoregulation

AUTOREGULATION Local autoregulation could be due to: 1. Accumulation of metabolites: [ metabolic theory of autoregulation] Increase : CO2, H+, K+, lactic acid, Adenosine.

Or decrease O2

All lead to vasodilatation

AUTOREGULATION 2. Substances secreted by endothelium: a. Prostacycline [ vasodilatation] b. Endothelin [ vasoconstriction].Stretching of

blood vessels causes the release of endothelin c. EDRF [ Nitric oxide NO ]: vasodilatation

EndothelinEndothelin Biosynthesis Endothelin (ET-1) is a 21 amino acid peptide that is

produced by the vascular endothelium from a 39 amino acid precursor, through the actions of an endothelin converting enzyme (ECE) found on the endothelial cell membrane. ET-1 formation and release are stimulated by angiotensin II antidiuretic hormone (ADH), thrombin, cytokines, reactive oxygen species, and shearing forces acting on the vascular endothelium. ET-1 release is inhibited by prostacyclin and

atrial natriuretic peptide as well as by nitric oxide.

Endothelin Intracellular Mechanisms Once ET-1 is released by the endothelial cell, it binds to

receptors on the target tissue (e.g., adjacent vascular smooth muscle). There are two basic types of ET-1 receptors: ETA and ETB. Both of these receptors are coupled to a G-protein and the formation of IP3 . Increased IP3 causes calcium release by the sarcoplasmic reticulum, which causes smooth muscle contraction. In blood vessels, the ETA receptor is dominant under normal conditions in terms of ET-1 effects on contraction.

Nitric Oxide in the Muscular Nitric Oxide in the Muscular SystemSystem NO was orginally called EDRF (endothelium

derived relaxation factor) NO signals inhibition of smooth muscle contraction

Ca+2 is released from the vascular lumen activating NOS

NO is synthesized from NOS III in vascular endothelial cells

This causes guanylyl cyclase to produce cGMP A rise in cGMP causes Ca+2 pumps to be activated,

thus reducing Ca+2 concentration in the cell This causes muscle relaxation

Nitric Oxide in the Circulatory Nitric Oxide in the Circulatory SystemSystem

NO serves as a vasodilator Released in response to high blood flow rate and

signaling molecules (Ach and bradykinin) Highly localized and effects are brief If NO synthesis is inhibited, blood pressure rises During O2 delivery, NO locally dilates blood

vessels to aid in gas exchange

Nerve cells target the endothelial cells lining of blood vessels

Acetylcholine activates NO synthase & production of NO in endothelial cells that surround the smooth muscle cells surround the blood vessel.

Role of NO in smooth muscle relaxation of blood vessel walls

NO diffuses into smooth muscle, binds to heme group in guanylyl cyclase and activated synthesis of cGMP

Nitroglycerin is used to prevent chest pain (angina) because it is rapidly converted to NO

Synthesis of Nitric Oxide Nitric oxide is synthesized from L-arginine This reaction is catalyzed by nitric oxide

synthase, a 1,294 aa enzyme

COO-

C

(CH2)3

NH

C

H2N

H

NH2+

+H3N

Arginine

NOS

NADPH

+ O2

NAD+

COO-

C

(CH2)3

NH

C

H+H3N

N+

H2NH

OH

N-w-Hydroxyarginine

COO-

C

(CH2)3

NH

H+H3N + NO

NOS

C

O NH2

Citrulline

Types of NOS NOS I

Central and peripheral neuronal cells Ca+2 dependent, used for neuronal communication

NOS II Most nucleated cells, particularly macrophages Independent of intracellular Ca+2 Inducible in presence of inflammatory cytokines

NOS III Vascular endothelial cells Ca+2 dependent Vascular regulation

Synthesis & release of nitrous oxide (NO)

Nitric oxide synthase (NOS) catalyzes the synthesis of NO from the terminal nitrogen atom of L-arginine in the presence of O2

Once synthesized, NO can freely diffuse across plasma membranes reaching neighboring cells

NO acts locally, and has a very short half-life (5-10 secs)

PULMONARY CIRCULATION Receives same cardiac output= 5L/min Pulmonary a: Thin [1/3rd that of aorta] Branches of pulmonary a., smaller a. &

arterioles have larger diameter than corresponding systemic vessels.

Thinness+ Distensibility= very large compliance which permits the pul.a. to accommodate the C.O. of Rt.ventricle

PULMONARY CIRCULATION Pulmonary veins : compliance to similar to

those in systemic circulation Bronchial a.[oxygenated blood] : supply

connective tissue, septa, large & small bronchi. It empties in pul.vein & enters Lt. atrium.[ decreasing arterial PO2=physiological shunt]

The pulmonary circulation

tissue

CO2 O2

Pulmonary artery

RV

LA

Pulmonary vein

Pulmonary capillaries

PULMONARY CIRCULATION Pulmonary pressure= 22/8 mmHg Pulse pressure= 14 mmHg Pulmonary capillary pressure= 7mmHg Mean pressure at Lt.atrium & major

pul.veins= 2mmHg Blood volume in the lungs: 450ml[9% of CO] 70 ml of this blood is in the capillaries Remainder in the a. & v.

PULMONARY CIRCULATION Blood flow regulation: Local factors [ major role] & autonomic N.S.

[minor role] Pul.blood vessels constrict when PO2

decreases[ in systemic circulation there is vasodilatation when PO2 decreases]

Increase Lt.atrial pressure= slows venous return=increased pul. Cap.pre.=pul.edema

CIRCULATION THROUGH SPECIAL REGIONS

CORONARY CIRCULATION Coronary blood: 5% of resting C.O Major coronary vessels travel in the

epicardium & subdivide sending separate branches through the myocardium.

During Systole the myocardial wall tension compresses the vessels increasing resistance to flow

Coronary arteries

Factors affecting coronary blood flow Aortic pressure Coronary arteriolar resistance myocardial

metabolic activity (autoregulation) Extravascular compression

importance L > R (lower RV pressures) maximal L flow in early diastole

Coronary circulation Maximum flow in left coronary vessels

occurs during isometric ventricular relaxation while the arterial pressure is still relatively high & the myocardium is relaxed

Control of coronary flow: 1. Autoregulation [ Adenosine] 2. Sympathetic stimulation through ß

receptors

Coronary blood flow

SNS stimulation Receptors:

(vasoconstrictor) (vasodilator)

Direct SNS effect: vasoconstriction Overcome by vasodilation due to

metabolic activity (local regulation dominant)

Coronary circulation Energy obtained mostly through aerobic

pathway Normally Hb releases approximately half of

it’s arterial O2 content to myocardium in contrast to the remainder of the body [25%]

Becomes even higher during exercise or stress

Coronary circulation PO2 % Hb saturationArterial B 95mmHg 97%Venous B 40mmHg 75%Coronary 25-30mmHg 50%Venous BDuring exercise cardiac O2 consumption may increase

5-6 folds in well trained athletes due to:1. Increase coronary blood flow2. Widening of arterio-venous O2 difference

Cutaneous circulation Low metabolism

Blood flow serves mainly thermoregulatory role

Numerous AV anastomoses

Thick muscular layer Rich nerve supply No basal tone (can constrict maximally) No metabolic autoregulation Exclusively under SNS control (can close

completely) thermoregulation

Skin circulation

Effect of changes in environmental temp. on heat conductance from body core to skin surface

Cerebral circulationUnique features:

contained within rigid structure inflow/outflow inbalance pressure Cushing’s phenomenon: systemic BP with intracranial pressure

(e.g. tumor) - by ischemic stimulation of vasopressor center in medulla (helps maintain brain flow)

Absolute requirement for adequate flow tissue least tolerant to ischemia

5 sec ischemia loss of consciousness 3-4 min permenant brain damage

glucose-dependent

Cerebral circulation Important features: 1. Intracranial pressure [ Cushing reflex] 2. Effect of gravity 3. Blood Brain Barrier [BBB]: A. Protect against changes in ionic composition B. Protection of brain from endogenous &

exogenous toxins C. Prevention of escape of neurotransmitters into the

general circulation

Cushing reflex

Neural regulation of brain vessels Minimal importance (local mechanisms

predominate)

SNS (along carotid & vertebral arteries) - weak vasoconstriction

Parasympathetic fibers from facial nerve - weak vasodilation

Local regulation of brain vessels Hypoxia Very sensitive to CO2 (vasodilation via

changed pH) H+ cannot cross blood-brain barrier

cerebral vasodilation by: local CO2/pH changes blood CO2 not blood pH (if = CO2)

Brain flow auto-regulation Excellent between 60 and 140 mmHg

Below 60 mmHg: syncope

Above 160 mmHg: cerebral edema

Hepatic circulation

Hepatic blood flow ~ 25% CO 1/4 of that from hepatic artery 3/4 of that via portal vein

little O2

mean pressure ~10 mmHg small driving pressure gradient hepatic (and central) venous pressure easily transmit upstream

liver edema transudation to peritoneal cavity (ascites)(also with portal resistance due to fibrosis in cirrhosis)

Hepatic circulation

Regulation of liver circulation

Autoregulation not in portal system hepatic arterioles autoregulate

SNS constriction of resistance vessels in portal venous & hepatic

arterial systems constriction of capacitance vessels more important (blood

reservoir) liver contains ~ 15% of all blood 50% of that can be rapidly expelled by SNS

FETAL CIRCULATION 2 umbilical arteries[branches of int.iliac] carry blood

to placenta Exchange between fetal & maternal blood Return through umbilical vein Some blood pass through liver, remaining through

ductus venosus enter inf.vena cava Reach right atrium Go through foramen ovale to left atrium,left

ventricle & aorta Remaining go to right ventricle, pulmonary artery

High fetal pulmonary vascular resistance

Low O2 hypoxic vasoconstriction No ventilation undistended, convoluted

vessels Shunts ~90% of CO of right ventricle enters

aorta through ductus arteriosus Aorta carries mixed blood to different parts of

circulation

Birth

Umbilical vessels closed by trauma (if not tied) Ductus venosus closes [ligamentum venosum] CO2 breathing,expansion of lungs decrease

pulmonary resistance arterial PO2 constricts ductus arteriosus (via

vasodil. PGs, Bk, also K channels) Closure of placental bed[ increase systemic

resistance] Increase afterload closes foramen ovale

Heart FailurePhysiological definition : Failure of the heart to

pump blood normally & to maintain adequate CO

Etiology:

1. Ventricular outflow obstructon.e:g Systemic HT, or Pulmonary HT,or aortic & pulmonary stenosis

Heart Failure Etiology[cont.] 2. Ventricular inflow obstruction e:g Mitral &

Tricuspid stenosis 3. Impaired ventricular function.e:g

Myocarditis,Myocardial infarction& subsequent fibrosis.

4. Volume overload.

Heart Failure Symptoms: 1. Backward failure e;g edema 2. Forward failure e;g weakness &

exercise intolerence

Heart Failure Symptoms of Lt.HF: 1. Orthopnoea 2. Paroxysmal nocturnal dyspnoea 3. Crepitation at the base of lung Symptoms of Rt.HF: 1. Raised jugular venous pressure 2. Peripheral edema

SHOCK A term used to describe the clinical

syndrome that develops when oxygen delivery is inadequate to meet the metabolic needs of the tissues due to some form of acute circulatory failure

Clinical features of shock 1. Sweating 2.reduced conscious level:drowsiness 3. Tachypnoea 4. Hypotension 5. Tachycardia with weak pulse 6. Cold skin 7. Oliguria

Causes & Types of Shock 1. Fainting [Syncope] or vasovagal attack Caused by pain,stress ,fear ,excessive heat or

sight of blood 2. Hypovolemic shock 3. Cardiogenic shock 4. Anaphylactic shock 5. Septic shock