Cardiac Download

1996 Integrated Body Function 536-022: Volume III By Duy Thai
2nd Year Medicine Page 1 of 21
Integrated Body Function

1996
Volume III
CONTENTS
TOPIC PAGE NO.

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CARDIAC FAILURE
Essential concepts of ventricular performance

• Basic principles of cardiac function which should be understood:
• Heart rate
• The number of beats per unit time
• Preload
• The amount of tension in the ventricular wall due to stretch.
• Caused by a volume of blood in the ventricle (end diastolic volume)
• The end diastolic volume (EDV) is the volume of blood in the ventricle at the end of diastole (hence
the amount of blood just before systole)
• Afterload
• The pressure against which the heart must pump against to expel the blood from the left ventricle.
• The pressure is the aortic pressure and can be altered by changing the compliance of the aorta.
• Contractility
• Measured using the ejection fraction:
SV
EDV
• SV = EDV - ESV
• ESV is the end systolic volume and is the volume of blood left over in the ventricle after systole. i.e. it
is the remaining blood which has not been fully ejected from the contracting ventricle.
• Ventricular compliance
• Ability of the heart muscle to relax properly and expand to accommodate extra blood volume.
• Hypertrophy
• A disorder in any one of these may result in cardiac failure.
• One special thing to note is the difference between systolic heart failure and diastolic heart failure.
• Systolic heart failure
• Failure of ventricular contraction due to damaged heart muscle
• Diastolic heart failure
• Contraction is fine, but the filling of the ventricle during relaxation (diastole) is impaired.
• This may be due to stiffening of the heart muscle or hypertrophy, both of which make the heart less
compliant.
• The result: poor filling of the ventricle during diastole and hence a reduced end diastolic pressure
Definition of cardiac failure

• Cardiac failure is defined as being when the cardiac output is inadequate to meet the tissue requirements.
• It can be divided up into 2 types:
• Acute heart failure
• This is a sudden failure of the heart (such as a heart attack) and results in an immediate drop in cardiac
output which, if uncompensated, will result in shock due to poor tissue perfusion.
• However, this is not often occur due to compensatory mechanisms, preventing shock..
• Chronic heart failure
• The cardiac output may be normal but there is a reduced cardiac reserve.
• Cardiac reserve is the ability of the heart to increase its cardiac output (via increases in heart
rate, stroke volume - CO = HR X SV) during conditions such as exercise. This is influenced
by chronotropic (heart rate) and inotropic (force of contraction - stroke volume) factors.
• In the chronic heart failure patient, in order to achieve an increase in CO, more blood must be needed
to fill the heart and so the heart must expand a bit. This requires an increased venous return which
results in an increase in filling pressure (increased CVP).
Acute cardiac failure

• The normal cardiac output is 5L/min
• When you have heart failure, the heart is unable to pump properly and so the CO is reduced.
• A reduced CO results in:
• Reduced arterial pressure (MAP = CO X TPR)
• Damming up of blood in the right ventricle and systemic venous circulation (increased CVP)
• The compensatory mechanisms to prevent a prolonged decrease in CO are as follows:
• Immediate response:
• A reduction in CO leads to a decrease in arterial pressure.

• The baroreflex causes increased sympathetic stimulation.
• Increased sympathetic stimulation results in:
• Increased force and rate (contractility) of contraction
• These are performed by the non-damaged heart muscle and help to compensate for
the damaged heart muscle.
• As a result, you can detect a fairly rapid pulse.
• Increased peripheral vasoconstriction
• This occurs to increase the TPR.
• Vasoconstriction also helps to force blood back to the heart (increase venous
return).
• These 2 factors help to bring CO back up to normal
Chronic heart failure

• The increased sympathetic drive cannot go on indefinitely and so another mechanism must be involved to allow for
an increased CO without having the increase the force and rate of contraction to a considerable extent.
• A prolonged decrease in blood pressure is detected by the kidney’s due to a decreased GFR.
• A reduced GFR leads to a cascade of reactions which ultimately leads to the retention of water (and salts)
via aldosterone and angiotensin II.
• The fluid retention allows for an increased blood volume which helps increase the venous return. This
helps to increase the cardiac output.
• However, the venous pressure beforehand is already high (due to damming up of blood as a result of
inefficient pumping). Therefore, an increased blood volume not only increases the CO back towards normal
levels, it also increases the CVP even more above normal.
• The increased CVP leads to an increase in right ventricular size.
• If prolonged, and the right ventricle enlarges too much, you will eventually get weaker contraction of the
right ventricle due to length-tension relationships (remember them?)
• Prolonged fluid retention and an increase in blood volume will eventually lead to generalised oedema.
Precipitating factors in chronic heart failure

• Drugs which cause fluid retention
• Excess fluid or Na+ intake, thus increasing blood volume
• Arrhythmias
• Atrial or ventricular fibrillation
• Infection
• Leads to an increased need for blood by the damaged tissue, hence requiring an increase in cardiac output
• Pulmonary embolism
• These are common in bedridden patients who often get blood clots in their legs which makes its way
through the circulation, into the heart and gets lodged in the tiny pulmonary circulation.
• This causes pulmonary hypertension, enlargement of the right ventricle and an increased CVP.
Signs and symptoms of heart failure (left side)

• Pulmonary congestion/oedema
• Because the left ventricle is no longer able to pump blood effectively, the blood that it receives gets
jammed back.
• This blood comes directly from the pulmonary veins and so you get damming up of blood in the pulmonary
circulation. This leads to pulmonary hypertension.
• As a result of the increased pulmonary capillary pressures, more fluid is exudated from the capillaries into
the interstitium. The amount of fluid is too much for the lymphatics to handle and so the fluid passes into
the alveolae, resulting in pulmonary oedema.
• As a result, you are presented with a patient who has:
• Soboe
• Shortness of breath on exertion
• Orthopnoea
• Shortness of breath when lying down
• This occurs because lying down makes it easier for venous blood to go to the
heart and clog up the pulmonary circulation even more. Standing alleviates the
problem by reducing the ease by which venous blood can enter the right
ventricle
• Paroxysmal nocturnal dyspnoea

• Waking up in the middle of the night due to shortness of breath
• Low cardiac output
• Fatigue, lethargy, weakness, all as a result of not enough blood reaching the tissues.
• If there is not enough blood going to the brain you get syncope.
• Sympathetic response
• Tachycardia
• Pallor and cold due to peripheral vasoconstriction
Right heart failure

• The right heart is unable to pump blood effectively through the pulmonary circulation.
• You have damming up of blood in the systemic venous circulation
• This leads to increased CVP
• Generalised oedema
• Raised JVP (Kussmal’s sign)
• Hepatomegaly
• This is enlargement of the liver due to liver congestion (the liver is congested with excess blood in
the systemic venous circulation).
• This also leads to right upper abdominal quadrant discomfort
• Positive hepatojugular reflux
• Normally when you press down on the liver to squeeze more blood out into the venous circulation
and towards the heart, not much will happen because the right ventricle is able to handle the
increased venous return.
• However, with right ventricular failure, the ventricle cannot handle the excess venous return and
so instead, it enters into the jugular vein and stays there.
PATHOPHYSIOLOGY OF CONGENITAL HEART DISEASE
Obstructive defects
• Dominant aortic stenosis
• The aortic valve does not open effectively when the left ventricle contracts, hence there is effectively a
constriction of the opening of the aorta.
• As a result, the left ventricle must pump harder in order push the blood into the aorta because of the
increased afterload (pressure against which the left ventricle must pump against).
• The left ventricular muscle then hypertrophies
• There may be reduced blood flow to the systemic circulation.
• This condition may result in damming up of blood in the left ventricle and atrium which leads on to the
pulmonary arteries. Hence, the pulmonary arteries may have an increased blood volume leading to an
increased pulmonary pressure.
• With further progression, pulmonary hypertension may lead to right ventricular hypertension because the
right ventricle has to push blood against a higher pressure in the pulmonary circulation.
• Pulmonary stenosis
• There is a constriction of the opening to the pulmonary trunk from the right ventricle.
• The right ventricle thus has to pump harder in order to push blood through the pulmonary valve, into the
pulmonary trunk and to the lungs (via the pulmonary veins)
• There is reduced blood flow to the lungs from the right ventricle
• As a consequence, you get right ventricular hypertrophy due to the increased load the right ventricle must
pump against. There is buildup of venous blood in the right ventricle, right atrium and systemic veins,
leading to elevated CVO.
• Note however that there should not be any pulmonary hypertension because the constriction
occurs before the pulmonary circulation.
Atrial Septal defects (ASD) - Acyanotic

• Persistent ductus arteriosus (DA)
• Normally shunts blood from pulmonary trunk → aorta in the foetus. This is because in utero, the
pulmonary circulation and lungs are inactive, collapsed and filled with fluid. Hence, the pressure in the
pulmonary circulation is higher than the pressure in the systemic circulation and you get shunting of blood
from pulmonary trunk to aorta.
• In the newborn, a patent DA causes shunting of blood from aorta to pulmonary trunk because now, the
situation is reversed. The lungs are filled with air and so the pulmonary circulation will be decreased in
pressure, causing blood to shunt from the high pressure aorta to the low pressure pulmonary circulation.
• Defects in the ventricular septum
• Shunting of blood from left ventricle to right ventricle during diastole due to a pressure difference between
the 2 ventricles
• Patent foramen ovale
• Shunting of blood from the left atrium to the right atrium during atrial diastole.
• Common features of these abnormalities:
• Increased blood flow into the pulmonary circulation since some blood from the aorta gets pumped into the
pulmonary circulation.
• As a result, there is increased vascularity which may be evident on the CXR as a pulmonary
plethora.
• Due to the increased volume load on the heart during diastole (more blood from the pulmonary
arteries entering the left atrium), the heart may increase in size.
• Pulmonary hypertension may result with a subsequent right ventricular hypertrophy.
• Blood in the systemic circulation is fully oxygenated because the blood has passed to the lungs for gas
exchange. Hence, these situations are called acyanotic.
Cyanotic defects
• The only way to have cyanotic effects is to have deoxygenated blood entering the systemic circulation.
• This can only occur if you have a right → left shunt.
• As mentioned previously, in the newborn, the systemic pressures are much greatly increased than
pulmonary pressure and so we have pressure moving from high areas (systemic circulation) → low areas
(pulmonary circulation).
• How then, can we get blood to pass in the opposite direction?
Right to left shunting of blood leading to cyanotic effects

• The only way this can happen is to have a combination of an ASD with some other additional factor. E.g.:
• A pulmonary stenosis (or anything which can lead to increased pressure in the right ventricle) causes the
pressure in the right ventricle/atrium to get larger. If the pressure gets large enough to oppose the pressures
in the left atrium/ventricle, the blood will be shunted from right to left (provided of course that there is a
way to shunt blood, i.e. there is an ASD.
• In order to have cyanotic effects, there must be co-existence of an ASD along with pulmonary stenosis
• In the CXR, the vascular markings of the lung are reduced (pulmonary oligemia)
Tetralogy of Fallot
• This condition has got 4 features:
• Pulmonary stenosis
• VSD
• Right ventricular hypertrophy due to high pressure in the right ventricle
• The aortic valve deviates to the right so that it lies half way between left and right ventricles (i.e. it lies
virtually at the interventricular septum). As a result, the right ventricle can pump deoxygenated blood
directly into the aorta and hence systemic circulation. At the same time, oxygenated blood can also enter
the aorta since it has communication with the left ventricle as well.
• An extreme case of Tetralogy of Fallot is when we have transposition of the major vessels.
• As described above, the aorta has deviated so that it receives blood from both left and right ventricles. If
the deviation is more severe, the aorta will lie completely in the right ventricle and the pulmonary trunk
will emerge from the left ventricle.
• Hence, deoxygenated blood from the systemic veins enters the right atrium, which pumps the blood to the
right ventricle. The right ventricle then pumps the deoxygenated blood into the aorta, back to the systemic
circulation. Also, oxygenated blood from the lungs, returns to the left atrium, but only to be pumped back
to the lungs again because the pulmonary trunk arises from the left ventricle.
• The only thing keeping these babies alive is an ASD (usually shunting between left and right atria via a
patent foramen ovale). Alternatively, there could be a patent ductus arteriosus.
• These shunts allow the cross flow of blood on which survival depends of. Oxygenated blood must
be able to enter the systemic circulation and the shunts allow shunting of oxygenated blood from
the left atrium into the right atrium or from the pulmonary trunk into the aorta.
• The pulmonary blood flow is normal in the CXR and this is a characteristic feature. Recall that all other
cyanotic defects result in pulmonary oligemia because deoxygenated blood is bypassing the lungs and
entering the systemic circulation. Blood to the lungs is thus reduced and you get loss of vascular markings.
• In this case, however, we do have blood flow into the lungs and so vascularity of the lungs is
normal.
Signs of neonatal heart disease

• Cyanotic
• Breathlessness
• Fluid retention in the lungs
• Enlarged liver
• Accumulated fluid in the portal veins
• Cardiovascular collapse (cardiogenic shock)
• Reduced cardiac output
• Acidosis
• Oedema
• Due to increased pressure in the venous system as a result of increased pulmonary pressure and right heart
failure.
The transition state

• The move from intra uterine life to the outside world involves many changes.
• Loss of placental circulation
• Pulmonary vasodilation and a fall in pulmonary resistance when the first breath is taken
• Increased pulmonary blood flow
• Constriction of the DA due to a rise in PaO2
• Increased volume load on the left ventricle
• Functional closure of the foramen ovale.
• This does not occur immediately and so a baby who has transposition of the great vessels does not
die at birth because we still have a way to get oxygenated blood to the systemic circulation.
However, if the foramen ovale closes, you will die.
Other less common defects

• Pulmonary atresia with VSD and persistent DA
• Pulmonary atresia means that the pulmonary valve is completely blocked so blood in the right ventricle has
nowhere to go except to the left ventricle via the VSD.
• The deoxygenated blood is pumped into the aorta and then enters the DA to go to the pulmonary veins. The
blood is thus oxygenated in an indirect way rather than entering the pulmonary veins directly from the right
ventricle
• The only thing keeping this child alive is the ASD and DA
• Interruption of the aorta
• The arch of the aorta stops after giving off the left subclaivan. (In normal people, the aorta continues as the
descending aorta).
• The descending aorta in this case is the DA which becomes the descending aorta rather than connecting to
the arch of the aorta.
• The blood to the regions where the descending aorta supplies thus gets a lack of oxygenated blood.
• Coarctation of the aorta
• This is a less severe form from the above. Instead of a complete separation between arch of aorta and
descending aorta, there is just a narrowing.
How to keep the ductus arteriosus patent

• In the foetus, the DA stays open because of the high levels of PGE1.
• PGE1 inhibits the vasoconstriction of ductal smooth muscle.
• In pregnancy, levels of PGE decreases but the level of PaO2 is low (~ 35mmHg)
• At birth, the combination of low PGE and high PaO2 results in closure of the DA.
• Hence, if we want to keep the DA patent, we infuse with PGE1.
Some notes to think about

• A newborn infant will often be:
• Hypoxic
• Hypoxic conditions in the womb
• Hypocapnic
• Due to the baby hyperventilating to get more O2 in
• Polycythemia
• Due to the hypoxia, more erythropoeitin is produced to increase the Hb concentration.
• this results in:
• Increased blood viscosity
• More concentration of deoxy Hb in the blood leading to cyanotic effect
• Relatively large right ventricle
• The newborn baby’s heart was effectively pumping at equal pressures between right and left
ventricle in utero.
• When born, there is a change in pressure so that the left ventricle will start to have to do more
work that the right hear. With age, the left heart will outgrow the right heart to a much greater
extent (provided everything goes OK).
• Slightly acidotic since hypoxic tissues generate lactic acid
CARDIAC DYSRHYTHMIA
Normal contraction of the heart

• As you can see in the above diagram, the heart is synchronised to enable rhythmical and simultaneous contraction of
the atria and ventricles.
• Normally, the atria contract first.
• During diastole, the atria relax and blood begins to fill them. Blood from the systemic venous system
(deoxygenated) fills the right atrium and blood from the pulmonary veins (oxygenated) fills the right
atrium.
• At the start of systole, the atria contract first (atrial systole) to “prime” the ventricles with blood before
ventricular contraction. During ventricular systole, the ventricle contract and push blood into the aorta or
pulmonary arteries. The pressure which has built up in the ventricles during this time closes the mitral and
tricuspid valves to prevent regurgitation of blood back into the atria.
• Remember that the tricuspid valve separates right atrium and ventricle
• The mitral valve separates left atrium from ventricle
• The time between atrial contraction and ventricular contraction is 0.16 sec (REMEMBER THIS - VERY
IMPORTANT!)
• The way the heart coordinates all this is via the electrical conduction system
The origin of the conducting system

• Nearly all cells of the heart have an inherent rhythmicity. This means that they are capable of self depolarisation,
without the need for external nervous innervation.
• This is possible because the cells are continuously more leakier to Na+ in resting state.
• Remember that the normal cell has a resting membrane potential of -80mV.
• This is due to the movement of K+ out of the cell (making the inside negative) and little movement
of Na+ into the cell.
• In a cardiac cell, the resting membrane potential is much higher (-60mV) because there is a greater
movement of Na+ into the cell, tending to make the inside more positive. However, the movement of K+ out
of the cell still predominates and so the inside is still negative (although not as negative as a normal cell)
• A resting membrane potential of -60mV is close to the threshold potential and so the cell will be easy to
excite.
• Another special property of these cells is that they are continuously leaky to Na+ and Ca2+. As Na+ and Ca2+
enter the cells, the inside of the cell is made more positive due to the entry of positive ions (Na+ and Ca2+)
The membrane potential moves towards positive. When the membrane potential reaches threshold (approx.
-40mV), Na+ channels open and allow for a massive influx of Na+, causing the cell to depolarise.
• The Na+ channels are then closed, and K+ channels opened, allowing for a massive exit of K+ from the cell,
repolarising the membrane towards negative again.
• The cycle begins again.
• Most cardiac cells have this inherent rhythmicity.
• It is the cell which fires action potentials at the fastest rate which controls the firing of all the other cells.
This cell is known as the pacemaker.
• The normal pacemaker is the SA node.
• If the SA node is stuffed up, the 2nd fastest cells will take up the job as being pacemaker. These cells are
usually at the AV node.
Electrical conduction system of the heart

• The conduction pathway is as follows:
SA node (pacemaker)
Internodal pathway through atria
AV node (there is a delay here)
Bundle of His
Left branch Right branch
Purkinje fibres of left ventricle Purkinje fibres of right ventricle
• Some important points to note:

• As the electrical signal passes from SA node to AV node, the atria are being depolarised, and so this is the
stage of atrial contraction.
• The reason why we have an AV node delay is to allow for sufficient emptying of atrial contents into the
ventricle before the ventricle has time to contract.
• In the bundle branches, signals move from the left branch to the right branch and then pass down to the tip
of the ventricle. This gives rise to the Q wave seen on ECG. (ask me for clarification of this point if you
don’t understand)
• As the signal passes to the purkinje fibres, the ventricles are depolarised, and so this is the stage of
ventricular contraction.
• The left purkinje fibre system is stronger than the right (because the left side of the heart has more muscle
to innervate. Therefore in ECG, the depolarisation of the left purkinje fibres is detected rather than the
right.
External innervation of the heart

• Sympathetic innervation
• Sympathetic innervation is mediated by noradrenaline which acts on β1 adrenergic receptors on the heart to
increase heart rate and force of contraction.
• Major innervation is to the ventricles
• Shortens the time between SA nodal action potentials by increasing Na+ conductance
• Parasympathetic innervation
• Acts via the vagus nerves which release Ach
• Innervates mainly the SA and AV nodes, with a bit to the atria
• Decreases the rate of the SA node firing (by reducing Na+ conductance and increasing K+ loss, causing
hyperpolarisation.
• Increases the AV nodal delay
The ECG
• The ECG is measured using 3 standard limp leads (I, II, III) which form Einthoven’s triangle.
• In addition, extra exploratory leads (V1, V2, V3 ... etc.) can be placed directly over certain parts of the heart to
analyse cardiac myopathies.
• Don’t worry about these details, just know that the 3 standard limb leads form a triangle around the heart.
• The 3 standard limb leads measure slightly different views of the electrical activity of the heart, but for our
purposes, they can be considered virtually the same. The only thing we are interested in is the time course/duration
of the electrical signals which indicate when the atria and ventricles have contracted. The “average” of the pictures
observed in each of the 3 leads is:
R
Not drawn to scale!
Ask me about the mechanisms of how
P the ECG. I don’t know if you need to
T know it but it would help if you did. It
is too complicated to write down here.
Q S
Interpretation of the ECG

• The P wave represents atrial depolarisation (the start of atrial contraction
• The flat line between P and Q represents the time of AV nodal delay
• The Q wave represents the movement of current from left bundle branch to right bundle branch.
• The QRS complex represents ventricular depolarisation and hence the start of ventricular contraction.
• The T wave represents ventricular repolarisation
• Some important values you need to know:
) If the ECG is printed on graph paper, every small bow represents

0.04 sec and every big, bold box represents 0.2 seconds.
) The distance between the start of P and the start of Q (or R if Q is

not present) equals 0.16 sec. Recall that this is the time between atrial
contraction and ventricular contraction.
) The distance between Q (or R) and the end of T is 0.35 sec and
represents the time of ventricular contraction.
) The distance between two P waves (indicating the time between 2

heart beats) is often around 0.75 sec. This means 1 beat per 0.75 sec
which works out to be around 80 bpm.
• Any variation in these times results in characteristic ECG patterns of arrhythmia
Arrhythmias
• Causes of arrhythmias
• Abnormal rhythmicity of pacemaker
• Ectopic pacemaker
• Blocks of electrical resistance
• Abnormal pathway of transmission (e.g. re-entrant loops)
• Spontaneous generation of abnormal impulses
Tachycardia
• A heart rate > 100 bpm
• Can be due to:
• Increased body temperature (e.g. in fever) which increases the metabolism of the heart, causing it to pump
faster.
• Increased sympathetic stimulation
• Toxic conditions of the heart
• Reentry
• Enhanced automaticity of an ectopic focus which is faster than the SA node
• Normally, the SA node is firing very fast and the bundle of His does a good job in slowing the rate down for the
ventricles to cope. If this pathway is bypassed then there will be no His bundle slowing down and the ventricles will
contract wildly at the same pack as the SA node.
• If there is an ectopic focus in the atria (supraventricular tachycardia), the problem is not as bad as if there were and
ectopic focus in the ventricles. This will cause the ventricle to contract out of sync with the atria - a bad case.
• What are 2 mechanisms which can normally protect against excessive tachycardia?
• One has been mentioned: the bundle of His slowing down the SA signal
• Refractory period of cells - they can’t elicit an AP immediately after the first (need a refractory period
when no AP can be elicited). A disorder which shortens the refractory period may be able to bypass this
control mechanism.
• Seen as a reduction in the P - P interval (i.e. shortened time between heart beats)
Bradycardia
• A heart rate < 60 bpm
• Caused by:
• Parasympathetic vagal stimulation
• Carotid massage which tricks the body into thinking it has a high blood pressure and so causes widespread
parasympathetic responses.
• Seen as an increase in the P - P interval
• Often, with too much vagal stimulation, the heart can stop beating altogether because the SA and AV nodes have
been too depressed (recall that parasympathetic fibres innervate mainly the SA and AV nodes). Under these
circumstances, the heart stops beating for about 5 -30 sec before a new pacemaker starts up in the ventricles (often
in the purkinje system). This is known as ventricular escape and allows the ventricles to pump independently of the
atria - not good!
SA block
• Impulses from the SA node can’t enter the atria via the interatrial fibres.
• Therefore there is no depolarisation of the atria (No P wave)
• The next fastest node (AV node) becomes the new pacemaker and is able to cause ventricular contraction (but not
atrial contraction because the signal can’t pass backwards).
AV block
• Incomplete 1st degree:
• Prolonged P-R interval (>0.2 msec; normal is 0.16 msec)
• Incomplete 2nd degree
• Sometimes the signal can pass through the AV node, sometimes they cant.
• Will get dropped beats if the signals cannot pass to the ventricle, so only the atrial contract (only P wave)
• Complete block (3rd degree)
• No signals at all from AV node to ventricle.
• Ventricle stop pumping but atria pump normally.
• After a while, the ventricles display ventricular escape and so tend to pump independently of the atrial
pumping
• Get asynchonisation of atrial contraction with ventricular contraction.
SHOCK
• Shock is defined as a condition when the cardiac output of the heart is unable to meet the metabolic requirements of
the tissues
Types of shock
• Hemmorhagic shock
• Loss of blood volume due to heavy bleeding
• Hypovolemic shock
• Loss of plasma fluid due to:
• Dehydration, vomiting, diarrhoea
• Severe burns
• Cardiogenic shock (pump failure)
• The heart is unable to pump effectively and so the CO is reduced
• Septic shock
• Due to bacterial infections which release vasodilator chemicals (e.g. prostaglandins, bradykinin).
Vasodilator agents cause venous pooling and hence prevent venous return back to the heart.
• Infected tissues which become damaged have an increased metabolic requirement and hence, even though
the cardiac output may be normal at 5L/min, it is not enough to provide adequate perfusion.
• Neurogenic shock (anaesthesia, spinal injury)
• Loss of vasomotor tone resulting in vasodilation, and a huge fall in TPR (and hence CO).
• Vago-vagal syncope (fainting)
• Not really a type of “shock” but the physiological effects do mimic shock.
• There is increased parasympathetic signals which slow down the heart and cause vasodilation. All these can
be triggered as a result of emotional states of the individual.
• Anaphylactic shock
• Due to an allergic reaction which causes the release of histamine especially.
• Histamine acts as a vasodilator as well as increasing capillary permeability
• You get transudation of fluid from the capillaries into the interstitium. Blood volume decreases as a result.
Stages of shock
• Non progressive (compensated)
• This is the stage where a loss in blood volume/reduced CO, does not result in significant variations in
arterial blood pressure.
• Progressive (decompensated)
• The reduction in CO and blood pressure is too great for the compensatory mechanisms to be effective any
more.
• Irreversible
• Death is close because there is just too much tissue damage.
Compensatory mechanisms in shock

• The body attempts to maintain arterial pressure above all else. Hence it tends to sacrifice tissue perfusion for
maintenance of arterial pressure.
• The following evens occur:
• Increased sympathetic stimulation
• Results in increased heart rate and force of contraction (due to stimulation of β2 receptors in the
heart.
• Generalised vasoconstriction.
• Stimulation of the adrenal medulla to release adrenaline and noradrenaline.
• Increased water retention
• A reduced blood pressure triggers the kidney’s to respond by releasing renin.
• Angiotensin II is produced, causing vasoconstriction. Angiotensin II also stimulated the release of
aldosterone from the adrenals to aid in fluid and sodium reabsorption.
• ADH is also released and this aids in water reabsorption from the collecting duct and generalised
vasoconstriction.
• Increased peripheral vasoconstriction
• Vasoconstriction aids to increase the TPR which results in an increased blood pressure because
MAP = CO x TPR
• Venoconstriction (constriction of the veins) aids to increase venous return to the heat, helping to
raise the cardiac output slightly.
• Note that the two most important organs necessary for survival (heart and lungs), are unresponsive to the
compensatory mechanisms because we want to maintain as well as possible, the perfusion to these organs.
• As shock progresses, there is a final last ditch effort to maintain blood pressure constant known as the cerebral
ischemic response.
• This is just a more powerful sympathetic stimulation throughout the body and is only used when the blood
pressure has dropped significantly (<50mmHg)
Signs and symptoms of shock

• Hypotension
• In hypovolemic shock, the plasma volume is reduced due to loss of fluid.
• Hyperventilation
• Tissues are crying out for oxygen which is taking too long to reach them. The body responds by thinking
that there is a lack of oxygen and so increases the ventilatory rate. Ventilation is also stimulated as a result
of the increased CO2 in the blood.
• Oliguria
• The increased water retention leads to a reduced urine output.
• Acidosis
• Since the perfusion to tissues is reduced, there is a decreased delivery of O2 to metabolising tissues. The
tissues thus have to undergo anaerobic metabolism which results in a large lactic acid buildup.
• Since perfusion is slow at the tissue level, CO2 produced by the tissues dissolved in the blood and forms
HCO3- and H+, thus further adding to the acidosis.
• Remember that the exchange of O2 and CO2 at the lungs is fine, it is just the transport of oxygen through
the body which is impaired.
• Tissue necrosis
• In end stage failure, tissues will be so deprived of oxygen that they will die. An example is the kidney,
where a markedly reduced renal perfusion will lead to tubular necrosis.
• Hypoxic tissues produce lots of prostaglandins and bradykinins which have a large role in causing capillary
permeability.
Feedback systems in the non-progressive vs. progressive stages of shock

• Negative feedback systems act to maintain blood pressure as a result of acute and chronic shock
• Baroreflex
• Chemoreceptors
• Vasoconstriction
• Cerebral ischaemic response
• Fluid retention
• Positive feedback mechanisms act to increase the adverse aspects of shock and hence are not very good for the
patient
• Reduced coronary blood flow
• Initially, the body tries very hard to maintain adequate flow to the heart and brain above all else. It
does this by causing peripheral vasoconstriction but vasodilation in the coronary and cerebral
circulations.
• Blood is hence redirected from relatively unimportant tissues to the more important brain and
heart.
• If the blood pressure falls too low, there will be inadequate perfusion to the cardiac muscle and so
you will get loss of cardiac muscle tissue. Impaired myocardial contractility results, further
worsening the scenario.
• Increased capillary permeability
• Acidosis
• Due to lactic acid buildup as a result of anaerobic metabolism
• Venous dilation (vasomotor failure)
• A result of poor perfusion to the vasomotor areas of the brain
• Depression of the reticuloendothelial system
• Due to cortisol
• Release of toxins from ischaemic tissues
• Blockage of circulation
• Since the flow of blood is moving so slowly, there is congestion of the circulation
• Adrenal collapse
• Loss of aldosterone and cortisol
Principles of treatment
• Plasma replacement therapies
• This is only of benefit if you have hypovolemic shock.
• Oxygen therapy
• Note that the problem is NOT inadequate ventilation, but inadequate transport of oxygen through the body.
• Cortisol
• Cortisol maintains the reactivity of the vasculature to changes in tone via vasoconstrictor agents.
• Antihistamines
• Stop the vasodilating effects of histamine and well as its tendency to increase capillary permeability.
• Antibiotics
• Used to fight against the bacterial infections which may arise
• Sympathomimetic agents
• These are only useful for neurogenic or anaphylactic shock. They are not useful for cardiogenic shock
because in these cases, the sympathetic response will already have been maximally stimulated.
• These agents act to mimic sympathetic agents by increasing heart rate and contractility in an attempt to
increase the cardiac output.
HYPERTENSION I
Variability of blood pressure readings

• The blood pressure distribution of a population is a normal distribution with the curve skewed to the right. The
average value of blood pressure being 126mmHg for males and 118mHg for females.
• The typical medical model likes to draw a line between what it perceives to be normal and what is abnormal. In
reality, no actual defining line can be drawn. Hence, when we talk about a level at which a person is diagnosed as
hypertensive, we are really selecting an arbitrary value.
• Blood pressure is a difficult thing to measure, because we are not measuring a solid end point like height or weight
for instance. There is enormous variability of BP among different people, the population and also within an
individual throughout the day.
• During the day your blood pressure fluctuates continuously from high to low, minute to minute.
• There is also a generally diurnal pattern of BP, with high levels in the morning and low levels in the
evening and during sleep.
• During the day you may get some peaks of high blood pressure and some periods of low blood pressure,
but these are perfectly normal.
• It goes to show why blood pressure measurements must not be diagnosed on one measurement but on
several taken over different visits.
• Factors which can affect blood pressure and lead to its variability:
• Diurnal
• Seasonal
• In summer blood pressure is usually lower due to vasodilation
• Errors
• Measurement technique of the doctor
• Equipment error
• Observer variation
• Fear of the doctor (white coat hypertension)
• A doctor taking an initial measurement on a new patient may get a very high blood pressure
reading simply because the patient is not comfortable yet with the doctor. It is therefore wrong to
diagnose the patient with hypertension from this measurement. What you will see is a regression
towards the mean, i.e. subsequent measurements will tend towards more normal values because
the patient becomes more comfortable around the doctor.
• If it was found that a person has a high BP on the first visit, subsequent visits would result in:
• 1/3 having a higher value
• 1/3 staying the same
• 1/3 having a lower value
Blood pressure and gender/body size

• The mean population’s blood pressure increases with age.
• The increase is most rapid in childhood and adolescence due to the rapid increase in body size during the
growth spurt. (Increased body size means more blood needs to be pumped around the body and hence a
higher BP)
• Blood pressure is variable in adult life, i.e. it does not stay the same. Changes depend on location and
lifestyle
• In a western society, blood pressure tends to increase gradually with age
• In a non-western society, blood pressure tends to plateau off and remain relatively stable with age
rather than increase.
• Blood pressure is also dependent on gender
• Females get an increase in blood pressure sooner than males during growth because they reach puberty
earlier. However, males will tend to have a higher blood pressure in adulthood because they are generally
larger in body size.
Location and lifestyle

• Migration studies have shown a change in blood pressure in all people who have migrated. The changes affect everyone
and at all different blood pressures. This means that a person with low blood pressure would have an increase in blood
pressure, the same as with a person with already high blood pressure.
• Essentially, the population distribution of blood pressure follows a normal curve and if the whole population moves to a
western society, the whole curve will be shifted towards the higher end of the blood pressure scale.
• With people in the middle ranges, it may be possible to attribute the increase in BP due to lifestyle changes such as the
type of food eaten. But for people in the extremities, the same cannot apply.
• Hence, the mean blood pressure (average of the whole population) depends on environment.
• What determines where an individual will lie on the population curve? Will they be at the extremes or in the middle
ranges?
• Genetic factors may affect an individual's rank in the population. This means that we may be genetically
predisposed to having high blood pressure.
• Montreal adoption studies found that there is a higher correlation between natural siblings having similar BP
than adopted ones. This may be due to them sharing the same intrauterine environment.
• Studies may show that growth in the uterine environment sets a certain level which may determine the
levels set in adulthood. e.g. if in utero you were set to have a high BP, you will ultimately end up with
a high BP in adulthood.
Death and society as a whole

• When we look at hypertension and the relative death rate, we can see a correlation between an increased BP leading to
an increased risk factor of dying. Does this mean we should concentrate on the people with a high blood pressure and try
to help them?
• However, if you look at the absolute death rate for the whole population, the number of people dying from high BP is not
as much as the number of people dying from other causes who have a perfectly normal blood pressure.
• i.e. A high risk level X a low number of people dying from the risk = a log risk in general
• Therefore, it is more beneficial to try and educate the whole population (not just those who have high BP, because they
represent a minority).
• If you can shift the whole population's blood pressure down by 8mmHG, it would be the equivalent of spending the same
amount of time and money just to get the same result in only half of the people in the high risk group.
• e.g. say you spent $5 million educating the whole community and you ended up lowering the population BP down by
8mmHg.
• Now, say you spent $5 million educating only the people in the high risk group. You would only get half of the group to
be able to reduce their BP by 8mmHg.
• A common misconception of hypertension is that it is related to stress (hyper = high, tension = stress). However, stress
seems to play a very small role in high BP. Hence, hypertension in a bit of a misnomer. It should be called high blood
pressure.
HYPERTENSION II
Causes of hypertension
• The kidney lies at the center of nearly every disorder.
• The kidney's control the body's fluid balance and hence plasma volume.
• The kidney also secretes substances which can alter the circulation and hence blood pressure (e.g. renin,
erythropoietin)
• The kidney controls acid base balance in conjunction with the lungs
• Most cases of hypertension can be traced back to a restriction of renal blood flow as a result of:
• A cyst in the kidney
• Atheroma of the renal artery
• If not, then it can be attributed to an adrenal tumor (or a pituitary one, but these are rare) leading to increased production
of:
• Aldosterone
• Most common
• Leads to retention of salt and water by the kidneys resulting in an increased ECF (plasma volume) and
cardiac output.
• Also leads to excessive loss of K.
• Cortisol
• As mentioned in the endocrinology notes (see volume 1), cortisol has some mineralocorticoid effects
similar to aldosterone.
• Most excess cortisol is a result of a pituitary tumor releasing too much ACTH.
• Catecholamines
• Increased vasoconstriction (increase TPR) leading to an increased BP, HR and contractility due to the
sympathetic response.
Polycystic kidney disease

• The kidney's develop large cysts which compress the flow of the renal arteries and hence reduce the blood flow to the
remaining kidney tissue.
• This reduced blood flow causes an increased renin release which causes the release of aldosterone (via angiotensin II)
• Aldosterone acts on the principal cells of the collecting duct to increase the production of Na+ channels. Hence
aldosterone acts to alter the rate of genetic transcription and hence is a long acting hormone (acting on the cell
nucleus).
• The increased Na+ channels are inserted into the plasma membrane and increase the rate of NA reabsorption
(and hence water retention).
• The increased reabsorption of Na+ causes a negative lumen potential, resulting in the increased loss of K and H
into the lumen, down an electrochemical gradient.
• Increased fluid retention also causes an increase in plasma volume. This leads to a slight elevation in systolic
blood pressure.
• The baroreceptors detect and increased BP and respond by slowing down the heart rate.
• The whole process keeps on going until the cause is removed (i.e. the cysts in the kidney's).
Liddle's syndrome
• A mutation in the gene coding for Na+ channels results in excessive production which occurs independent of aldosterone.
Since there is a high Na+ retention, the kidney's stop renin release (and hence aldosterone is reduced)
• We thus have a way to distinguish between two syndromes.
• One type results in the excess production of aldosterone
• The other leads to a dampening down of aldosterone release.
Body size and insulin

• People with excessive carbohydrate intake will stimulate their pancreas to work overtime in releasing excessive amounts
of insulin. Over time, this can result in insulin resistance by tissues (type II diabetes) because there is so much circulating
insulin.
• Insulin can also affect the kidney to cause increased reabsorption of water and Na+
• Insulin is also able to act on the brain (the brain is not desensitized to high insulin levels) to increase the sympathetic
nervous system.
• This results in an increased HR
• Remember that NA is the brain's sympathetic mediator acting as a neurotransmitter. Andrenaline, on the other
hand acts as a hormone produced by the adrenal medulla as a result of increased sympathetic nervous activity.
• Normally, an increase in insulin is a result of increased glucose intake. Usually, hi plasma glucose levels inhibit the
release of adrenaline (since adrenaline acts to increase blood glucose by breaking down glycogen stores during
hypoglycemia).
• In people with a predisposition to high BP, there may be a genetic mechanism making the adrenals more
sensitive to the sympathetic response (by NA released by the brain due to insulin acting on the CNS). This
causes the adrenal medulla to release adrenaline when insulin is high (despite high glucose levels)
• Adrenaline acts on beta receptors of the kidney to release renin which causes the release of
angiotensin II (and hence aldosterone).
• Angiotensin II also acts to increase peripheral vasoconstriction (hence increasing TPR and blood
pressure). It also leads to greater constriction of the efferent arteriole than afferent and hence a
damming up of blood in the glomerula capillary. This increases the filtration pressure in the
glomerulus which leads to an increased GFR.
• Young people with an increased predisposition to hypertension have the following:

• Increased body weight and body fat
• Elevated insulin levels after a glucose meal
• Increased adrenaline after glucose (normally adrenaline is reduced)
• This is genetic and due to NA (the brain's sympathetic response) being released via insulin
stimulation. The adrenals have an increased sensitivity to NA activation which allows the NA to
override the homeostatic mechanisms.
• Adrenaline activates beta receptors in the:
• Kidney: Release of renin
• Heart: Increased heart rate
• Increased GFR due to effects of angiotensin II constricting the efferent arteriole > afferent arteriole.
CARDIAC HYPERTROPHY
• Cardiac hypertrophy is an increase in size of the heat due to an increase in size of the myocardial cells (NOT an increase
in the number of cells which is called hyperplasia).
Normal hypertrophy (growth): Macroscopic

• The size of the heart parallels body growth
• In utero, both chambers of the heart are equal in size (2ml) since both sides pump against equal pressures. However, at
birth and during the years to follow, the left ventricle will enlarge to a greater extent than the right ventricle. This is
because the right ventricle must now pump against a low pressure pulmonary circulation whereas the left ventricle has to
pump much harder against the high pressure, systemic circulation.
• Hence, high pressure is an important factor for growth.
• In pulmonary hypertension (increased pressure in the pulmonary capillaries), the right ventricle will have to
pump against a higher pressure and so it will get larger.
Growth on the microscopic scale

• In the early formative months of the foetus, the number of myocardial cells is set (What is set in the early formative
months echoes what will happen in the future adult life - same theory as the predisposition in utero to hypertension in
adult). Thereafter, the myocardial cells are unable to divide and multiply. Hence, any growth of the heart muscle is a
result of cell growth, rather than cell proliferation.
• Other cells (other than myocardial cells) grow as well, but these cells (fibroendothelial cells) are able to multiply in
number, so that at birth, the fibroendothelial:myocyte ratio is 1:1. But during growth, the ratio may change to 2.5:1.
• (In a heart attack, the damaged myocytes are unable to divide to replace the damaged cells. Hence, people who were
born with a large number of cells to start off with are better off than people born with a small number.
• There is also growth of the intracellular matrix (connective tissue) of the myocardium.
• In normal growth, there is an increased growth in all 3 components of the myocardium:
• Myocytes
• Fibroendothelial cells
• Intracellular matrix
Normal growth
• The control of growth of heart muscle is via:
• Non hemodynamic stimuli (independent of CO and BP)
• Number of cells (determined at birth)
• Hypothalamo-pituitary axis
• GH/IGF
• IGF’s mediate the growth effects of GH. i.e. GH itself does not affect growth
directly, it acts via an intermediate - IGF’s
• Thyroxine
• Thyroxine and GH both need to be present to enable growth of the heart. If one
is lacking, the other cannot do its job.
• Hemodynamic stimuli
• Body size
• This is related to CO and BP
• As the body grows, not only does its organs grow as well, but so does the amount of
blood needed to be pumped around the body.
• Since we need more blood pumped, the cardiac output must be increased as a result of
increased blood volume, which also tends to raise blood pressure. These 2 factors put a
stress on the heart, making it work harder, resulting in growth of heart muscle.
Heart size in young adults

• Body size
• The bigger you are, the bigger your heart.
• Lean body mass tends to be a better indicator because lean body mass is a measure of your muscle mass
(excluding fat). Since heart is a muscle, it is understandable that is you have a high lean body mass, you
will have a larger heart.
• Systolic blood pressure
• The heart has to pump against systolic blood pressure, because this is the period where the heart is open to
the arterial circulation and “sees” the pressure in the aorta (the aortic valve is open). During diastole, the
aortic valve is closed and so the pressures in the aorta are “hidden” from the left ventricle and therefore
have no influence on left ventricular growth.
• Angiotensin II
• Vasoconstrictor, hence raising peripheral resistance and increasing blood pressure. The heart must therefore
pump harder against the increased afterload.
• AII also leads to an increased plasma volume due to fluid retention (via aldosterone). This increases the CO
of the heart.
• Catecholamines
• Increases in NA and adrenaline have inotrophic and chronotrophic effects on the heart, causing it to work
harder.
• They are also trophic to heart cells
• Genetic influences
• Set the number of myocytes we are destined to have
• Most hearts at rest work well below their maximum capacity. That means that the heart is larger than required when
working under normal conditions. However, when the need arises for increased blood flow, the reserve capabilities
of the heart are enable, thus allowing the heart to pump faster and harder without being too stressed.
• This implies that normal, resting heart size is not determined entirely by the basal workload. I.e. the conditions of
the body at rest are not the sole influences on the size of the heart. If this were so, the heart will only be as big as it
needs to in order to fulfill its role under normal conditions. Under danger conditions, where the heart is required to
pump faster and harder to accommodate increased blood flow, it simply wont be able to cope because it is not large
enough.
• Again, genetic components may be involved (natural selection). E.g. a caveman with a heart size just big enough to
pump effectively under normal conditions will surely die if chased by a dinosaur because the heart cannot cope with
the extra load put on it. The caveman with a larger than necessary heart under normal conditions, will have the right
sized heart when it comes to strenuous activities (such as being chased by a dinosaur)and so he will survive.
(survival of the fittest)
Hypertrophy
• Due to increased load (the pressures the heart has to face)
• Especially due to increased afterload
• Afterload is the pressures in the aorta (and systemic system in general) against which the left ventricle has
to pump in order to expel blood during ventricular contraction (systole)
• This leads to high strain on individual muscle cells and ventricular wall. The result is what is known as
concentric hypertrophy.
• Concentric hypertrophy is when the lumen of the ventricle stays the same but the wall thickens.
• This is often due to a high arterial blood pressure or aortic stenosis (thickening of the outflow of
the left ventricle (so it has to pump harder to pump blood past the obstruction in the ascending
aorta).
• Another condition, known as eccentric hypertrophy, is when the ventricular wall remains the same thickness but the
lumen of the ventricle increases in size.
• This is a result of a volume overload (too much blood)
• Anaemia
• The need for a greater cardiac output to deliver the same number of blood cells to tissues.
• Mitral incompetence (valve between the left atrium and ventricle)
• When the left ventricle contracts to expel blood into the aorta, the mitral valve closes to
prevent blood from regurgitating into the right atrium. If this valve fails, whenever the
ventricle contracts, some blood enters the aorta and some blood enters the atrium, adding
to the volume of blood already in the atrium. In the next diastole, the increased volume of
blood in the atrium is transferred to the ventricle, which needs to get larger to
accommodate the increased volume.
• Aortic incompetence
Response to hypertrophy
• Cellular response
• Increased myocardial cell size
• Increased number of fibroendothelial cells
• This occurs especially around the coronary vessels, tending to constrict them and reduce coronary
blood flow to some parts of the heart
• Increased interstitial matrix
• Subcellular response
• Increased number of mitochondria (increased energy demands)
• Extra myofibrils (contractile elements)
• Extra sarcoplasmic reticulum (to synchronise contraction with relaxation via the movement of Ca2+).
• Switch from low to high ATPase myosin
• Pumping characteristics
• Myocardial cells develop less tension at a given length (remember the length tension curve)
• When stretched to a slight degree, the muscle fibres are able to contract with greater force because the actin
and myosin will be arranged in optimum configuration. However, if stretched any further, the actin and
myosin will be out of alignment again and will not be able to develop a forceful contraction.
• Consequences of hypertrophy
• Adaptation/compensation
• An athlete may deliberately want to increase the size of their heart so that under normal resting
conditions, the heart does not have to pump as hard and as fast to get the necessary quantities of
blood to the tissues. With activity however, the heart is large enough to cope with the increased
strain due to the demands of increased CO and HR.
• There is an increased left ventricular end diastolic volume (the volume of blood in the left
ventricle after diastole/before systole). There is also an increase in the left ventricular end diastolic
pressure. In an average person, the above 2 signs are indicative of heart failure.
• Failure
• Low workload:mass ratio. i.e. the heart has all this extra mass but is not being put to good use
unless you have a large workload all the time.
• Cardiovascular risk
• A larger heart means that some coronary arteries may not be able to reach some parts of the heart
and so some areas of the heart get O2 deprivation.
• Increased number of fibroendothelial cells can disrupt the electrical circuitry of the heart.
End of Volume III

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1996 Integrated Body Function 536-022: Volume III By Duy Thai

2nd Year Medicine Page 1 of 21

Integrated Body Function

TOPIC PAGE NO.

Essential concepts of ventricular performance

Definition of cardiac failure

Acute cardiac failure

• A reduction in CO leads to a decrease in arterial pressure.

Chronic heart failure

Precipitating factors in chronic heart failure

Signs and symptoms of heart failure (left side)

• Paroxysmal nocturnal dyspnoea

Right heart failure

PATHOPHYSIOLOGY OF CONGENITAL HEART DISEASE

Atrial Septal defects (ASD) - Acyanotic

Right to left shunting of blood leading to cyanotic effects

Signs of neonatal heart disease

The transition state

Other less common defects

How to keep the ductus arteriosus patent

Some notes to think about

Normal contraction of the heart

The origin of the conducting system

Electrical conduction system of the heart

Internodal pathway through atria

AV node (there is a delay here)

Left branch Right branch

Purkinje fibres of left ventricle Purkinje fibres of right ventricle

• Some important points to note:

External innervation of the heart

Interpretation of the ECG

) If the ECG is printed on graph paper, every small bow represents

) The distance between the start of P and the start of Q (or R if Q is

) The distance between two P waves (indicating the time between 2

• Any variation in these times results in characteristic ECG patterns of arrhythmia

Compensatory mechanisms in shock

Signs and symptoms of shock

Feedback systems in the non-progressive vs. progressive stages of shock

Variability of blood pressure readings

Blood pressure and gender/body size

Location and lifestyle

Death and society as a whole

Polycystic kidney disease

Body size and insulin

• Young people with an increased predisposition to hypertension have the following:

Normal hypertrophy (growth): Macroscopic

Growth on the microscopic scale

Heart size in young adults

End of Volume III

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