National Academy of Family Medicine

Pakistan Society of Family Physicians

www.pakjfm.com

240026,217067,234836,221035,254216

Contents 

Board

Of 

Management

Editorial



Board

Chapter One

Chairman: Dr Fazal Mehmood Uppal

Tel no: 217067

Finances: Dr M Akram Awan

Tel no: 215215

Some Definitions

Saleem Akhtar Rana

Mean cardiovascular pressure The CVS is filled with liquid at a positive mean pressure ("mean cardiovascular pressure"), which exists independent of the pumping action of the heart. Mean cardiovascular pressure is the pressure related to the blood volume and the compliance of the entire elastic cardiovascular compartment

Pulse Pressure Pulse pressure is the difference between systolic and diastolic arterial pressure.

Chief Editor: Dr Saleem Akhtar Rana

Tel no 240026

Editors: Dr Ehsan Assad Tel no: 254216

Dr Arshad Javaid Sh Tel no: 221035

Dr Mehboob Ashraf Tel no: 234836

Mean Arterial Pressure (MAP) An indicator of tissue perfusion.

MAP = Diastolic arterial pressure + (pulse pressure / 3)

MAP = CO x SVR

MAP is the product of cardiac output (CO) and systemic vascular resistance (SVR):

If cardiac output falls, for example when venous return decreases in hypovolaemia, MAP will also fall unless there is a compensatory rise in SVR by vasoconstriction of the arterioles.

352 Pakistan Society of Family Physicians

E Sattelite Town Gujranwala Pakistan

Tel no 0431 / 240026,217067,215215,234836,254216,221035

WWW.pakjfm.com, saleem@pakjfm.com, drsar@brain.net.pk, ehsanassad@hotmail.com

Systolic Pressure: Peak pressure reached during systole in left ventricle. Not the mean pressure.

Diastolic Pressure: Lowest pressure during diastole in Aorta.It is never zeroed. It is never less than that of intrathoracic pressure.

Frank Starling Relationship: It is also described as Frank starling law. It refers to one essential factor related to contracting force of heart. It states that force of contraction is directly proportional to the initial length of muscle fibre. These fibres are streched by the end diastolic volume of blood. So greater is the volume, greater is going to be the length of muscle fibre at the onset of contraction. This will determine the force of contraction, so establishing a link between end diastolic volume and force of contraction. This law is termed as relationship nowadays because we know that this effect is only upto a certain limit. Beyond this limit this effect is no more there so increasing the end diastolic volume will not increase the force of contraction, rather it will have a negative effect.

Isometric (isovolumic) Contraction: This refers to the period of early systole when all valves are closed. At the start of ventricular systole, the mitral and tricuspid valves close. Ventricular muscle initially shortens relatively little, but intraventricular pressure rises sharply as the myocardium presses on the blood in the ventricle. This period is known as isovolumic or isometric ventricular contraction. Importance of this duration is because of AV valves bulge in the atria and this causes a small but sharp rise in the atrial pressure.

Ventricular Ejection: When ventricular pressure rises enough to open the aortic and pulmonary valves then blood starts flowing to these great vessels. This phase of ejection is known as ejection phase.

End Diastolic Ventricular Volume: At the end of diastole approximately 130 mls gather in the cavity. Against the capacity of 85 mls. So it stretches the walls, i.e, muscle fibres. This is end diastolic ventricular volume.

Endsystolic Ventricular Volume: During systole whole of this 130 mls is not ejected. Only part of this is propelled in the vessels.50 mls remains behind. This is important to remember. As under pathological conditions where contraction starts becoming less and less efficient, this endsystolic volume start rising, making less and less room for the blood coming from atria.

Ejection Fraction: It is the percentage of the end-diastolic ventricular volume that is ejected with each stroke. This is normally 65 %. As discussed above this is a valuable index of cardiac function. This is readily available, but much underutilized. This is one of the echocardiographic findings.

Stroke Volume: Volume of blood pumped out of each ventricle per beat .It is about 70 mls during resting conditions in average sized male in supine position.

Isovolumic ventricular relaxation: At the end of systole obviously ventricular pressure does not drop immediately. It does so in appreciable time (0.04 sec). Until the pressure drops enough for opening of atrial valves, volume of ventricles remains constant. This is the period of isovolumic relaxation.

Cardiac Output: The output of the heart per unit time is the cardiac output. There is a correlation between body surface area and cardiac output. In average sized man it is about 5 lts/min/72 beats. One can calculate cardiac output in the same way by multiplying stroke rate times stroke volume. Stroke volume and heart rate only measure output. These variables are not determinants of output.

Cardiac Index: The cardiac output per minute per square meter of body is known as cardiac index. Average is 3.2 lts. Activity, temperature, anxiety, eating, pregnancy, and many many condition specific and non-specific to CVS affact this measurement.

Preload: Muscle lenght effects on contractility are well known as Frank Starling relationship. End diastolic volume determines what is going to be the radius (so the length of individual muscle fibres) of the ventricular cavity. Ventricular stiffness, innate capacity for being able to be stretched, if changed effects this equation negatively. All these factors taken together are known as preload.

Afterload: Heart contrcats against multiple forces. Collective effect is negative on stroke volume and is known as after load.

These are followings.

Aortic impedence of resistance
Peripheral vascular Resistance.
Arterial wall resistance
Mass of column of blood in Aorta.

Viscosity of blood.

Chronotropic action: Any drug or physiological or pathological state, which increases the heart rate, is known as chronotropic. This action is known as chromotropic action.

Inotropic Effects: These effects refer not to the rate of contractions but to the strength of contractions. Factors that increase the strength are known as positive inotropic effects and those, which decrease the strength of contractions, are known as negative inotropics.

Getz Pharma

Manufacturers

Ribazole and Uniferon

Chapter Two

Heart as A Pump

Dr Mehboob Ashraf

The cardiovascular system has few characteristics that make it an unusually complicated hydraulic system. These unique characteristics peculiar to the cardiovascular system are:

The system is elastic rather than rigid.Diameter of ducts can be changed.This increases or decreases resistance to the flow of blood through these.
The system is filled with liquid at a positive mean pressure ("mean cardiovascular pressure"), which exists independent of the pumping action of the heart.
The heart fills passively, rather than by actively sucking.
As a consequence of the heart's passive filling, the circulation rate is normally regulated by peripheral-vascular factors, rather than by cardiac variables.
The flow from the heart is intermittent, while the flow to it is continuous.
The slowing effect of any vascular resistance on flow rate depends on its location, with reference to available compliance (i.e the length of vessels after the vaso or venoconstriction), as well as its magnitude.

VENTRICLES (THE PUMPS)

The cardiac cycle

With heart rate of 72/m each cycle has about 0.8 seconds. This is the time taken for following components of a typical cardiac cycle.

Origin of impulse at SA node.
Atrial contraction. During this period, impulse reaches at AV node.
Impulse is delayed at AV node for 0.1 sec before it travels down the Bundle of His.
First left branch is reached so left ventricular contraction occurs little earlier than right ventricular contraction
Impulse travels down both branches of Bundle of His till it reaches Purkinjie fibres.From here onward immpulse rapidly spreads to whole myocardium and makes it to contract.Contraction is complete in 0.08-0.1 sec.

After contraction muscle fibres are refractory to further stimulation for a certain period. This is refractory period. It is for the first portion absolutely refractory. Later portion is relatively refractory meaning that any stimulation can cause contraction if it is stronger than ordinary impulse. This is the period during which muscle fibres relax and achieve a surface potential which was there before these were stimulated by the preceding impulse.

Events during Cardiac Cycle

Previous Cycle: For understanding these events we have to start from a point in the previous cycle. Early in the diastole when pressure in the ventricles have come down and it is now lower than that of atria. Atrial valves open in the ventricles and these start filling up. Now myocardium is completely relaxed. Atrial valves are open and allowing blood to move freely in the ventricles.

Diastole of previous cyle and origin of new cardiac impulse: Blood, coming through pulmonary veins and both venae cavea to atria, starts flowing to venticles directly, without any storage period in atria. Most of the ventricular filling, 70-80 %, is in this fashion. Now ventricles are filled and muscle fibres are stretched again. Before there is a contraction due to intrinsic capability of muscle fibres and Purkinjie system next normal impulse from SA node is born.

Atrial Contraction: Beginning of Systole: Right atrium contracts little earlier than left one as it is stimulated earlier. Both atria contract when stimulated by this impulse and send 20-30 % of end diastolic volume of blood to ventricles. Volume of blood in each venticle is approximately 130 mls. This is end diastolic volume. This determines the diameter of ventricular cavity (so length of individual muscle fibre) immediately before contraction. So this determines the force of contraction. (Frank Starling Relationship). End diastolic volume, under normal conditions, is determined by extra cardiac factors.
Start of Ventricular Contractions: Impulse has reached AV node. It is delayed for sometime before passing to Bundle of His.There is no other communication between atria and ventricles. As these are separated by fibrous tissue. Left ventilce contracts first. Cardiac impulse on reaching the Purkinjie fibres stimulates muscle fibres when these have recoverd properly from previous contraction and are optimally stretched due to end diastolic volume. Now contraction of ventricles starts and goes through following stages.
Closure of Atrioventricular Valves: Myocardium starts contracting. Ventricular pressure starts rising. Once it is higher than that in atria, blood rushes towards atria, and pushes the cusps of these valves alongwith it. Under this pressure atrial valves close down and even slightly pushed inside the atrial cavities. But chordae Tendinae, which also contract as part of myocardial contraction, keep these valves in mid position and closed. Closure of mirtal valve produces first heart sound.
Isometric or isovolumic Contraction: Now atrioventricular valves, aortic and pulmonary valves are closed. Blood is trapped and it can not leave under this initial rise in pressure. Myocardium contracts on this trapped blood. Pressure keeps on rising. Size of cavity does not change untill Aortic and Pulmonary valves open. This is known as isometric contraction.
Opening of Aortic and Pulmonary Valves: Pressure keeps on going up and up due to force of contraction of muscle fibres of ventricles. Once it rises above that in Aorta (80 mm of Hg) and Pulmonary Artery (10 mm of Hg), this pushes their valves open. Pulmonary valve opens before aortic valve. So ejection begins on right side first. Blood start flowing to these great vessels. It will further rise to Systolic pressure, which are measured in limbs as 120 mm or so.
Ejection Phase: Blood starts flowing in these vessels. This is ejection phase. Most of the blood is ejected in first one third of this phase. In next part of contraction phase rest of the stroke volume is ejected. Ventricular cavity is not emptied fully. Some blood remains in the cavity of ventrilce at the end of contraction. This is known as end systolic volume. Fraction ejected is known as ejection fraction. It is 65 %-70 % of end diastolic volume, i.e, 70-80 mls. This is known as stroke volume. This is an important indicator of left ventricular function. Echography is easily available investigation, which measures it.
Closure of Aortic and Pulmonary Valves.End of Systole: Start of Diastole: When contraction stops pressure in ventricular chambers does not drop immediately. Obviously it occurs slowly. First it becomes lower than that in Aorta (< 80 mm). Once it is lower than 80 mm, Aortic and pulmonary valves close when blood tries to flow from higher pressure in vessels to lower pressure in ventricles. This is end of systole. Closure of Aortic valve produces second heart sound.
Isometric or Isovolumic Relaxation: Now there is an interval when ventricular pressure falls down further from 80 mm to 10 mm. Both sets of valves are closed during this interval. So size of ventricular cavity remains same inspite of relaxation leading to lowering of pressure from 80 to 10 mms. This interval is known as isometric relaxation period.
Opening of Atrial Valves: Pressure keeps on going down till it is lower than that in atria. At this moment due to pressure gardient blood starts flowing from atria to ventricles on opening of atrioventricular valves. Initial filling is rapid and may give rise to third sound in children and young adults.
Till the end of Diastole: Ventricular Filling: Now myocardial muslce fibres are completely relaxed. Intracardiac pressure is never zeroing. It is always higher than intrathoracic pressure. Electrochemical changes inside and outside the cell walls revert back to where these were before stimulation by the cardiac impulse. Duration is 0.5 sec. Blood is freely flowing to ventricles from Pulmonary Veins and Superior and Inferior Venae Cavae, traveling through atria. Before the origin and propagation of next cardiac impulse ventricles will be filled upto 70 % of their end diastolic volume.we must note one thing. Whole of the ventricular filling is completed in one cardiac cycle.70-80 % is achieved during ventricular diastole and 20-30 % is achieved in adjacent atrial systole.
Origin of next cardiac impulse and beginning of next Cardiac Cycle: Next impulse takes origin from SA node and spread to atria.Atrial muslces contract and push the rest of the 20-30 % volume of blood to complete the ventricular filling.In the meantime impulse has crossed to Bundle of His and ventricular muscle fibres start getting tense and ready for next contraction.

Duration of Cardiac Cycle

And its relationship with Heart Rate

At Heart Rate of 75/m, Duration of one typical cycle under normal conditions = 0.8sec

Diastole = 0.53 sec

Systole = 0.27 sec

At the H/R of 65/m Systole = 0.3 sec

At the H/R of 200 Systole = 0.14 sec

Diastole = 0.16 sec

Duration of systole is much more fixed than diastole. If duration of systole is shortened to a critical limit than obviously storke volume will decrease. Increase in heart rate may compensate for this. Uptill heart rate of 180 /m increase in heart rate compensates for smaller stroke volume due to shorter systole. But further increase in heart rate can not be usually compensated and symptoms of insufficient cardiac output appear.

Diastole is important on two accounts. Firstly most of the filling occurs in diastole. Secondly blood supply to subendocardial myocardium of left ventrilce is mostly during diastole. So after a limit these two important functions of diastole start suffering. Duration of diastole is much more compromised than that of systole, whenever heart rate is increased.

Oxygen Consumption by the Heart

The basal consumption of myocardium, when heart is not beating, is 2ml/100 gm/m. It is considerable larger than the skeletal muscles. This is 9ml/100 gms/m by the beating heart. Under resting conditions myocardium extracts upto 65%-70 % of oxygen from arterial blood. So little extra can be extracted during increased requirements like exercise. Extra oxygen can only be supplied by increasing blood flow.

The O2 consumption by the heary is determined by

Intramyocardial tension: End diastolic volume: Radius of Ventricular cavity.
Contractile state of myocardium
Heart Rate.
Afterload i.e pressures in the vessels.

Aortic pressure is seven times more than in pulmonary artery. So O2 consumption is 7 times of left ventricle than in right ventricle. Pressure in Aorta causes more consumption than in ventricular volume. In Aortic Stenosis (increased pressure needed to push blood through aortic valve) left ventricle needs much more O2 than in Aortic incompetence (increase in end diastolic volume).

Cardiac Cycle and Arterial Pulse.

When blood is forced in Aorta with a pressure it expands aortic walls. This wave of pressure and expansion of arterial walls travel throughout arterial system and is felt, as pulse whereever arteries are accessible to fingers. Rate of travel of this pressure wave is following in different sized and arteries in different locations.

Aorta = 4 meters/sec

Large Arteries = 8 m/sec

Small arteries in young patients = 16 m/sec

With advancing age arteries become rigid. This increases the speed of this pressure wave. Strength of pulse, felt by fingers, depends upon the pulse pressure.
Pulse is very strong if stroke volume is large and it is weak and thready during shock.
When pulse pressure is high the pulse wave may be large enough to be felt or even herd by the patient. This is palpitation.
In Aortic sufficiency the pulse is quite strong and is called as collapsing or corrigon or water hammer pulse.

Atrial Pressure Changes and Jugular Pulse.

Atrial pressure rises during atrial systole.
After this it again rises when AV valve is closed and somewhat pushed in the atrial cavity.
After this event the valve is again pushed downwards by chordae tendinae as part of myocardial contraction. This lowers atrial pressure.
Valves remain closed during ventricular contraction but blood keeps on flowing inside atria. This raises atrial pressure.
Finally AV valves open during ventricular diastole and blood starts flowing in the ventricles. This lowers atrial pressure.
These changes are transmitted to great veins. These produce three characteristic changes in the pulse if jugular pressure is recorded.

“a” wave is due to atrial systole
“C” wave is due to bulge of tricuspid valve in atrial cavity after closure of this valve.
“V “ wave is due to rise in atrial pressure caused by filling with blood while tricuspid valve is closed during ventricular systole.

Cerebral Circulation (Continued from page 24)

Two vertebral arteries join to form basilar artery.This in turn forms circle of Willis with two internal carotid arteries,below the hypothalamus.The Circle of Willis gives rise to six large arteries to cerebral cortex.Internal Carotids carry most of the blood supply and vertebral arteries carry little blood.Pressure on both sides of Circle is equal.So flow is not mixed to sizeable extent in the circle.Substances injected in one internal carotid usually remains on the same side of cortex.Occlusion of one internal carotid artery usually causes serious problem.There are precapillary anastomis between different arterioles but this is not sufficient enough when one cerebral artery is blocked.The venous drainage from brain occurs mainly to internal jugular veins through deep veins and dural sinuses.A small amount goes through opthalmic and pterygoid venous plexuses.

Blood Brain Barrier: The tight junctions between capillary endothelial cells in the brain and between the epithelial cells in the choroid plexus effectively prevent proteins from entering the bain in adults and slow the penetrations of smaller molecules.The rate of passage is directly proportional to their lipid solubility and inversely proportionate to their size.There is little vesicular transport across cerebral capillaries but there are many carrier mediated transport systems in the cerebral capillaries.Movement from brain to blood is freer than in the opposite direction.Water,CO2,O2 penetrate the brain with ease.So do the lipid soluble free forms of steroid hormones.Protein bound forms and all proteins,polypeptides do not move freely.Physicians must know upto what extent drugs cross this barrier.This barrier tends to break down in the areas of infection or injury and tumours.

Stroke: There are two types of strokes.Hemorrhagic and ischaemic.Hemorrhagic stroke occurs when some artery or arteriole ruptrues,sometimes at the site of aneurysm.Ischaemic stroke occurs when flow in the vessels is compromised by atherosclerotic patches where thrombi form or thrombi from distant sites lodge.Untill recently nothing much could be done to affact the course of disease.Now it is known that in penumbra, the area surrounding the most severe brain damage,ischaemia reduces glutamate uptake and the increase in local glutamate causes excitotoxic damage and death of neurons.Drugs that prevent this excitotoxic damage significantly,reduce the effects of stroke.In addition clot lysing drugs such as t-PA are of benefit.Both antiexitotoxic treatment and t-PA are of of benefit.But these should be given early in the course of disease.That is why stroke is now a condition where rapid diagnosis and treatment has become significant.It has become paramount to know whether stroke is hemorrhagic or ischaemic because clot lysic drugs are contraindiacted in the hemorrhagic stroke.

Chapter Three

Cardiac Output

Dr Mehboob Ashraf

Dr Saleem Akhtar Rana

There are two aspects to Cardiac Output

How to measure it?
Which factors determine the size of cardiac output?

Measurement. Cardiac Output = Heart Rate X Stroke volume.

Even under normal conditions heart has to vary cardiac output very frequently to meet the demands of moment to moment changes in posture, physical activity, emotional status etc. Hear rate is the principal instrument, which is manipulated inside the heart to change the output. To maintain a certain output if heart rate increases then stroke volume has to go down and if stroke volume increases due to certain adjustments, like postural change, than heart rate has to come down. These two factors are not the determinents of cardiac output rather these are reciprocally related to anyone size of cardiac output. These can be measured easily.

Determinants of Cardiac Output

Whatever can change heart rate and stroke volume determines the ultimate size of cardiac output.

Factors affacting Heart Rate

Heart rate is influenced maily by autonomic nervous system. This in turn is manipulated by baro-receptors present in multiple sites. These are stimulated by changes in blood pressure. Required adjustment is made through efferent limb of sympathetic or parasympathetic systems.

Autonomic Nerve Supply: This is the major influence on heart rate. Many drug which affact heart rate act through this system. Sympathetic stimulation increases the heart rate and at the same time it increases the strenght of contraction. So it is chronotropic and positively ionotropic as well. Parasympathetic stimulation (through vagus nerves) acts on both these parameters i.e heart rate and strength of contraction, but in opposite direction. Parasympathetic stimulation decreases heart rate and diminishes the force of contraction.

Factors affacting Stroke Volume

How much blood can be ejected per contraction, depends upon many factors. These are mostly extracardiac. Only contractility of myocardium is intracardiac factor. Followings are important factors affacting the size of stroke volume.

Pre-load = End diastolic volume & Myocardial Contractility.Main determinant of end diastolic volume is Mean cardiovascular pressure.
After-Load (impedence to blood flow from heart)

Pre-load: End diastolic Volume

Force of contraction depends upon the diameter of ventricular cavity, i.e, how much blood is there to stretch the ventrilcular walls. It is about 130 mls of blood, which is present in each ventricle just before contraction, under resting conditions. This determines the force of contractility upto a certain extent.

End diastolic volume is determined maily by mean cardiovascular pressure. This takes into account of blood volume, viscosity, total extracellular volume, interaction of different fluid compartments and compliance of cardiovascular system.70 % of blood volume is in venous bed. Only 15 % are circulating in arterial system. Taking all these factors together which affact the end diastolic volume positively i.e enhancing makes up mean cardiovascular pressure.

Myocardial Contractility: ~Sympathetic and vagal (parasympathetic) stimulation produce above-mentioned effects.

~Total number of muscle fibres (remember loss in infarction) is an absolute essential for contraction.

~Blood Supply to myocardium is again essential for optimum contraction.

Many drugs and disease states affact contractility.

Beta Blockers.Decrease heart rate and force of contractility.
Xanthines like coffee and theophylline are positively ionotropic.
Digoxin is positively ionotropic.
Quinidine,procainamide and barbiturates depress force of contractility
Hypercapnia, Hypoxia and Acidosis are negatively ionotropic.
Heart failure itself reduces force of contration due to intrinsic depression.

Following condition damages cardiac muscles and produce wasting.

Atrophy in IHD
Myocarditis
Myopathy
Pericardial effusion reduces the space for streching of myocardium by end diastolic volume.

Following factors increase end diastolic volume (consequently force of contraction).

Stronger atrial contraction
Increased total blood volume
Increased pumping action of skeletal muscles.
Increased negative intrathoracic pressure.

Following factors decrease end diastolic volume.

Standing
Increased intrapericardial pressure

Decreased ventricular compliance (as in AMI stiffness is increased)

After-load

It is the resistance against which blood is expelled. This resistance comprises of

Resistance and (2) Elasticity

The elasticity of the vascular system makes location of the resistance a significant parameter. Because of the elasticity of the circle, the location of any particular resistance determines to what extent that resistance has on impeding blood flow. A given resistance may have little or no effect in determining cardiac output if it is near the outlet of the ventricles, yet the same magnitude of resistance may have tremendous slowing effect on circulation if located near the inlets of the heart. Resistance sites that have little compliant vascular bed “upstream” (arteriolar resistance), increase pump work but may not affect cardiac output significantly. The heart, except during failure, exerts enough energy to force the blood past any resistance near its outlet, with no hold up in flow. On the other hand, resistance located near the ventricular inlet has a tremendous effect on flow rate by slowing blood return to the ventricles. Venous sided resistance is a major inhibitor of circulation rate. Thus, venous sided resistance is a major determinant of cardiac output, but arterial resistance is not. Interpolation of the additive effect of all resistance points in the circle on cardiac output must include the amount of compliant bed available after resistance point.

All resistance factors — including blood viscosity,cross-section area of any vascular bed,margination of blood constituents, etc.play roles in flow rate determination only when linked with their location to compliance after the resistance point. Adding venous sided resistance of a magnitude that results in only a few mm. Water pressure gradients may cause a marked reduction of flow. Whereas, increasing arteriolar resistance to the point of severe arterial hypertension may not appreciably change cardiac output.

(3) Impediment to Ventricular Filling

The end-diastolic pressure: Ventricles offer an impediment to filling. The left ventricle has thicker and stiffer walls than the right, so it tends to retard filling more than the right ventricle. Catheterization data shows end-diastolic pressure of five to ten centimeters of water above intrathoracic pressure. The intracardiac pressure is always above that intrathoracic pressure.

Inertia of Intermittent Blood Flow Offset by “The Atrial Effect”

Atrial function facilitates circulation by preventing the retarding effect that would otherwise occur from the intermittent inflow to the intermittent outflow from ventricles. By being partially empty and distensible, atria prevent the interruption of venous flow to the heart that would occur during ventricular systole if the veins ended at the inlet valves of the heart.

Atria have four essential characteristics that cause them to promote continuous venous flow.

There are no atrial inlet valves to interrupt blood flow during atrial systole.
The atrial systole contractions are incomplete and thus do not contract to the extent that would block flow from the veins through the atria into the ventricles. During atrial systole, blood not only empties from the atria to the ventricles, but blood continue to flow uninterrupted from the veins right through the atria into the ventricles.
The atrial contractions must be gentle enough so that the force of contraction does not exert significant backpressure that would impede venous flow.

The “let go” of the atria must be timed so that they relax before the start of ventricular contraction, to be able to accept venous flow without interruption.

By preventing the inertia of interrupted venous flow that would otherwise occur at each ventricular systole, atria allow approximately 75% more cardiac output than would otherwise occur. The fact that atrial contraction is 15% of the amount of the succeeding ventricular ejection has led to the false conclusion that atria have their benefit by pumping up the ventricles (the so-called “atrial kick”). The real benefit is in preventing inertia and allowing uninterrupted venous flow.

The 20% to 25% increases in cardiac output from synchronized atrial

Function over that of atrial fibrillation doesn’t belie the 75% contribution of the atrial effect, as atrial fibrillation eliminates only part of that effect. Atrial compliance, elasticity, and gravity help in emptying the atria at ventricular diastole during atrial fibrillation. Also, cardiac output during atrial dysfunction is buffered: the initial fall in circulation rate during atrial fibrillation reduces renal flow, thereby causing retention of water and the subsequent rise in mean cardiovascular pressure, which then partially offsets the slowing effect on circulation.

Thus, four factors impede the flow of blood around the cardiovascular circle:

resistance in the vessels
upstream compliance,slowing down circulation
Ventricular non-compliance. Actual cavity would accommodate only 80 cc but it is streching which allows 120-130 msl end diastolic volume.
Inertia if there is intermittent venous flow.

The combined effect of these factors that impede the flow of blood to the inlet of the ventricles and, therefore, determine cardiac output in a negative way will be referred to as inlet impedance.

Resistance and Capacitance Vessels.

Normally most of the veins are partially collapsed. Large amount of blood or fluid can be injected before an end point is reached or local pressures rises to the extent that no more fluid can be injected. Veins are known as capacitance vessels. Small arteries and arterioles are known as resistance vessels because these are the principal sites of peripheral resistance. When extra blood is transfused, only 1 % goes to arterial system (High-pressure system). Rest of it goes to systemic veins, pulmonary circulation and right ventricle.

Characteristics of different vessels

Vessels	Lumen diameter	Wall thickness	Approximate total cross sectional area in whole bodycm2)	Percentage of total blood volume in these vessels
Aorta	2.5 cms	2 mm	45	2
Arteries	0.4 cms	1mm	20	8
Arterioles	30 micro m	20 micro m	400	1
Capillaries	5 micro m	1 micro m	4500	5
Venules	20 micro m	2 micro m	4000	54
Veins	0.5 cm	0.5 mm	40
Vena Cava	3 cm	1.5 mm	18

Additional 12 % of blood are in heart and 18 % in the pulmonary circulation.

Regulatory Mechanisms.

Local Regulatory Mechanisms:

Autoregulation: Most vascular beds have a capacity to maintain the perfusion pressure at a constant by manipulating local resistance of arterioles.

Vasodilator Metabolites: Decreases in O2 and pH produce vasodilatation. Increased K+ and lactate concentrations also produce vasodilatations. Increases and decreases in local temperature cause dilatation and constriction respectively. Injured vessels constrict due to serotonin production from platelets.

Prostacyclin & Thromboxane A2: endothelial cells produce Prostacycline and this inhibits platelet aggregation and vasodilation. Thrombaxane A2 by the platelets and promotes platelet aggregation and venoconstriction. A balance between these two plays is important homeostatic function.

Nitric Oxide (NO): This is produced by endothelial cells and plays a key role in vasodilation.

Adenosine, ANP, and histamine act via H2 receptors and produce vasodilatation.

Endothelins: A group of similar polypeptides produced by the endothelial cells. Very powerful vasoconstrictors.

Systemic Regulation

Circulating Hormones:

Vasodilators: VIP, Kinins, and ANP

Vasoconstritors: Vasopressin, Norepinephrine, Epinephrine, and Angiotension 11.

(Splanchic Circulation from page 28)

These sinusoids are highly permeable as there are large gaps between sinusoidal cells.Liver comprises of approximately 100,000 acini.These are well oxygenated in the centre and less well oxygenated as you move towards periphery.

Portal venous pressure is 10 mm Hg while in hepatic vein is 5 mmHg.Mean Pressure in hepatic arteries is 90 mm Hg.Pressure in sinusoids is less than that in portal vein.At rest circulation in peripheral portions of liver is sluggish and only a portion of liver is actively perfused.During the drop in systemic pressure intrahepatic portal radicles constrict,portal pressure rises,and blood flow through liver is brisk,bypassing most of the organ.Constriction of hepatic arterioles shifts most of the blood to systemic circulation.In severe shock blood flow through liver may be so much decreased that there may be patchy necrosis of liver.When systemic pressure rises portal vein radicles dilate passively and blood in the liver increases.In CCF congestion is at the extreme.

Circulation through Skin

The amount of heat loss from the body is regulated to a large extent by varying the amount of blood flow through the skin.The fingers,toes,palms and earlobes contain well innervated anastomotic connections between arterioles and venules.Blood flow in response to thermoregulatory stimuli can vary from 1 to 150 ml/100 gms of skin.The subdermal capillary and venous plexus is a blood reservoir of some importance.Noradrenergic nerve stimulation and circulating epinepherine and norepinepherine constrict cutaneous blood vessels.There are no vasodilator nerve fibres.Vasodilation is brought on by varying constrictor tone and production of bradykinin and other vasodilator metabolites in sweat glands.Skin colour and temperature depends upon the state of capillaries and venules.A cold blue or grey skin is one in which the arterioles are constricted and capillaries are dilated.A warm and red skin is one in which both are dilated.Shock is more profound in patients with elevated temperature due to cutaneous vasodilation.Patient in shock should not be warmed to the extent that it raises their temperature.

(Continued on Page 11)`

Ternelin for painful muscle spasm

From

Novartis

Chapter Five

The circulation

Dr Saleem Akhtar Rana

Dr Hamid Jawad

Arteries supply blood to the organs at high pressure, whereas arterioles are smaller vessels with muscular walls, which allow direct control of flow through each capillary bed. Capillaries consist of a single layer of endothelial cells, and the thin walls allow exchange of nutrients between blood and tissue.

Blood flow

In blood vessels flow is pulsatile rather than continuous, and viscosity varies with flow rate. Small changes in radius result in large changes in flow rate. In both arterioles and capillaries changes in flow rate are brought about by changes in tone and therefore vessel radius.

Viscosity describes the tendency of a fluid to resist flow. At low flow rates the red blood cells stick together, increasing viscosity, and remain in the centre of the vessel. The blood closest to the vessel wall (which supplies side branches) therefore has a lower haematocrit. This process is known as plasma skimming. Viscosity is reduced in the presence of anaemia, and the resulting increased flow rate helps maintain oxygen delivery to the tissues.

Distribution of Blood Flow:

Pulsatile Blood Flow and Arteriolar Resistance

Pulsatile arterial blood flow tends to result in diffuse, fairly equal distribution of blood to all tissues of the body. This phenomenon would not occur with a non-pulsatile steady flow. Arteriolar resistance variability from time to time and from place to place, superimposed on the otherwise diffuse distribution, controls preferential blood flow to specific areas, with physiologic benefit. The diverting of a greater portion of cardiac output to the digestive tract after meals and the increased flow to muscles during exercise are examples of changes in distribution of blood flow controlled by variable arteriolar resistance. Peripheral arteriolar resistance, rather than having a cardiac output control function, has its physiological significance by its determination of distribution of blood flow

Control of the systemic circulation

Arterial Blood Pressure

In young adults, in sitting or lying posture, systolic pressure is 120 mm and diastolic is 70 mm of brachial artery. Gravity affects blood pressure. In standing posture pressure in vessels above heart level decreases while in vessels below heart it increases. Thus in adult human being in standing position, systolic pressure at heart level is 100mm,mean pressure in large artery in head it will be 62 mm and in large artery of foot it will be 180 mm. It is lower at night. It is lower in women. Because of nervousness about 20 % of patients have higher blood pressure in the doctor’s room.

Arterial Blood Pressure is a product of Cardiac output and resistance. Cardiac output is in turn a product of heart rate and stroke volume.

So Arterial Blood Pressure depends upon

Heart Rate
Stroke Volume (Mean cardiovascular pressure and resistance)
Peripheral Resistance

Manipulation of these factors can influence the BP in any desired direction. Most of the antihypertensive therapy is affacting these factors.

Arteriolar tone determines blood flow to the capillary beds. A number of factors influence arteriolar tone, including followings.

Control of arterial pressure

Systemic arterial pressure is controlled closely in order to maintain tissue perfusion. The mean arterial pressure (MAP) takes account of pulsatile blood flow in the arteries, and is the best measure of perfusion pressure to an organ. MAP is defined:

MAP = Diastolic arterial pressure + (pulse pressure / 3)
MAP = CO x SVR

Where pulses pressure is the difference between systolic and diastolic arterial pressure.

MAP is the product of cardiac output (CO) and systemic vascular resistance (SVR):

If cardiac output falls, for example when venous return decreases in hypovolaemia, MAP will also fall unless there is a compensatory rise in SVR by vasoconstriction of the arterioles. A fall in blood pressure causes reduced stimulation of the baroreceptors, and consequent reduced discharge from the baroreceptors to the vasomotor centre. This causes an increase in sympathetic discharge leading to vasoconstriction, increased heart rate and contractility, and secretion of adrenaline. Conversely, rises in blood pressure stimulate the baroreceptors, which leads to increased parasympathetic outflow to the heart via branches of the vagus nerve, causing slowing of the heart. There is also reduced sympathetic stimulation to the peripheral vessels causing vasodilation.

Baroreceptor responses provide immediate control of blood pressure; if hypotension is prolonged, other mechanisms start to operate, such as the release of angiotensin II and aldosterone from the kidneys and adrenal glands, which leads to salt and water being retained in the circulation.

Relationship of Pulmonary and Systemic Blood Volumes.

The relative size and compliance of the two circuits and, to a minor extent determine the blood volume equilibrium, by the relative impediment of flow to the two pumps.

It has been noted that the output of the two sides of the heart is never equal because there are physiological shunts, which connect one vascular bed to the other. The largest of these shunts, in normal physiology, are the bronchial arteries, which go from the systemic circuit to the lungs. The bronchial blood flow is a left-to-right shunt that accounts for the left ventricular output normally being at least 10% larger than the right. As blood going to lungs via bronchial arteries never enters right ventricle. This amount is circulating from left ventricle to lung to left ventricle again. Because of the shunt, more blood returns to the left ventricle than the right, the left ventricle passively fills more than the right, thereby causing it to produce a greater output and thus the equilibrium is maintained.

A dramatic illustration of this volume equilibrium, automatically being maintained during a massive discrepancy in output of the two pumps, is seen in atrial septal defects. In this case, the right ventricular output may be four or five times that of the left. Yet, the volume equilibrium is maintained. A large atrial septal defect virtually results in a single atrium above the two ventricles. The shunt occurs during ventricular diastole, because the right, thin walled ventricle is more distensible than the non-compliant thicker walled left ventricle. The blood in the common atrium goes the way of least resistance. The greater filling into the more compliant right ventricle results in greater right ventricular output. The greater right output goes to the lungs and then directly backs to the right ventricle, returning again through the septal defect. Because of the passive filling, this results in no progressive increase in the blood volume in the lungs, and no disturbance in the maintenance of the blood volume equilibrium. After closure of the septal defect, resulting in much smaller right heart output, the volume equilibrium remains. This equilibrium, which persists after such sudden, massive changes in right heart output, occurs automatically because of the passive-filling characteristic of the ventricles.

It is the physical characteristics of the two vascular beds (e.g., relative size, compliance, and impediment to flow), that determine the volume balance with passive filling ventricles.

Exercise and Corresponding increase in Output.

Following factors cause the increase in cardiac output during exercise.

Exercise causes the cardiovascular impedance to be decreased and the mean cardiovascular pressure to be increased. The intermittent skeletal muscle contractions around venous beds, which contain one-way valves, act as a peripheral pump, which overcomes significant impedance to flow.

Neuro-humeral reflexes speed the heart rate, which slightly lowers the inlet impedance to the heart, by lowering the end-diastolic pressure over what it would otherwise be.
The increased heart rate guarantees excess energy expenditure, thus preventing cardiac power failure at the higher circulation rate. The neuro-humeral response to exercise also throws the vascular system into spasm, thereby increasing the mean cardiovascular pressure from the "G-suit" effect of tensing the body in general.

Blood vessels dilate in exercising muscle groups because of increased metabolism, and blood flow increases. This increases venous return and right ventricular preload. Consequently more blood is delivered to the left ventricle and cardiac output increases. There will also be increased contractility and heart rate from the sympathetic activity associated with exercise, further increasing cardiac output to meet tissue requirements.

Splanchnic Circulation

The blood from the intestines, spleen and pancreas drains via portal vein to liver and from the liver via hepatic veins to inferior vena cava. Liver recieves about 1000ml/m from portal vein and another 500ml/m from hepatic artery.

Intestinal Circulation: There is extensive anastomosis between vessels but there can be infarction of part of intestine by blockage of large intestinal artery. The blood flow to mucosa is larger than rest of the bowel wall. Circulation responds to changes in the metabolism of the gut. It doubles up during meal and there is similar increase in portal vein. It lasts for 3 hours. The intestinal circulation is capable of extensive autoregulation.

Hepatic Circulation: Terminal branches of Hepatic Artery and portal vein converge on sinusoids which in turn empty via terminal hepatic veins.

(Continued on Page no 19)

March 2002

Pakistan Journal of Family Medicine

Cardiovascular Medicine

Basics Volume 2