Chapter 14

CARDIOVASCULAR RESPONSES IN PATHOLOGICAL

SITUATIONS

Learning Objectives

After reading this chapter you should be able to:

1. Define hypertension
2. Classify hypertension
4. Describe the characteristic features of shock.
5. List the different categories of shock.
6. Describe the consequences of a hemorrhage.
7. Describe the compensatory responses to hemorrhage – short term and long term.
8. Explain syncope.
9. Define chronic congestive cardiac failure.
10. Describe the consequences of cardiac failure.
11. Describe the compensatory responses to mild cardiac failure.
12. Describe the outcome of moderate to severe cardiac failure.

Hypertension
Hypertension is a chronic, progressive raised arterial pressure. It afflicts more than 50
million Americans and is a leading cause of morbidity and mortality. It is not just a
cardiovascular disease since it can damage other organs notably the kidneys, brain and
eye. Unfortunately, hypertension is often asymptomatic until end-organ damage has
actually occurred (i.e. stroke, myocardial infarction, renal dysfunction and visual
disturbances) and is picked up during routine investigations.
If BP was measured in a population we would find a continuous spectrum (a bell shaped
distribution). Consequently it has been difficult to define hypertension since there is no
clear dividing line between normotensive and hypertensive. One has to judge whether
blood pressure is sufficiently high enough to cause end-organ damage. Treatment of
hypertension with drugs also carries with it its own set of risks and side effects. A
pragmatic definition of hypertension is „that level of blood pressure above which
investigation and treatment do more good than harm‟. Guidelines for defining and
treating hypertension are however laid down by various societies. A recent report (the 7th
Joint National Committee Report on the Prevention, Detection, Evaluation and Treatment
of High Blood Pressure) was published by the National Institute of Health.

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Table 1: The Seventh Joint National Committee Report on the Prevention,
Detection, Evaluation and Treatment of High Blood Pressure. (www.nhlbi.nih.gov)

A prehypertensive state (SBP 120 – 139; and DBP 80 – 89 mm Hg) is now recognized
where lifestyle modification is more than encouraged. However in the presence of
chronic renal disease or diabetes drug therapy is indicated with the aim of reducing the
BP to <130/80 mm Hg. A SBP of 140 – 159, and DBP of 90 – 99 mm Hg is classified as
Stage 1 hypertension and drug treatment is advocated for all individuals. A SBP of > 160
and a DBP of > 100 mm Hg is classified as Stage 2 hypertension and successful drug
therapy is achieved usually with at least two drugs.

Classification of Hypertension

1. Essential hypertension: No single definable cause

(i) Benign essential hypertension: Commonest form

Slowly progressive
Symptomless

(ii) Malignant hypertension: Rarer

Rapidly progressive

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2. Secondary Hypertension: Identifiable cause

(i) Renal artery stenosis: RAS is activated

Atheromatous plaques cause stenosis of the renal artery. This reduces the pressure
at the afferent arteriole which stimulates the release of rennin by the kidney. This
leads to an increase angiotensin II which results in a generalized vasoconstriction
and an increase in salt and water retention via aldosterone.

(ii) Renal disease (e.g. diabetic nephropathy, glomerulonephritis)

When the nephrons are damaged their ability to handle sodium and water is
impaired resulting in salt and water retention thus increasing blood volume and
blood pressure.

(iii) Hyperaldosteronism (Conn’s syndrome): ↑ed Na+ and H2O retention

The increased secretion of aldosterone by an adrenal adenoma causes renal

retention of sodium and water thereby increasing blood volume and arterial
pressure.

(iv) Pheochromocytoma: ↑ed secretion of epinephrine

A tumor of the adrenal medulla results in high levels of circulating

catecholamines resulting in α1-mediated vasoconstriction and β1- mediated cardiac
stimulation – both of which increase arterial pressure.

(v) Pre-eclampsia : ↑ed BP in pregnancy (occurs in ~ 5%)

It results from increased blood volume and tachycardia. It is unclear why some
women develop this. The hypertension usually disappears after parturition.

(vi) Hyperthyroidism: Systemic vasoconstriction and↑ed cardiac activity

(vii) Cushing’s Syndrome: Excessive glucocorticoids

Glucocorticoids act synergistically with catecholamines on blood vessels.

~95% of hypertensives have essential hypertension, the remaining have secondary

hypertension. Fortunately of those with essential hypertension only a small proportion
have malignant hypertension which is much more serious and life threatening.

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Pathology of essential hypertension

MAP = CO x TPR

Hypertension is caused by either an increase in systemic vascular resistance (TPR) or an

increase in cardiac output. Both are usually raised in hypertension. To sustain a high
blood pressure it is necessary to increase blood volume through renal retention of sodium
and water. Acute elevations of TPR would elicit a reflex natruiesis (renin-angiotensin
system) resulting in a fall in blood volume and restoration of the blood pressure. In
chronic hypertension, natruiesis response is shifted to the right such that a higher arterial
BP is required to maintain sodium balance. The elevated pressure is sustained by an
increase in blood volume. These changes in the renal handling of sodium and water are
brought about by changes in sympathetic activity and changes in circulating hormones
such as angiotensin II, aldosterone and vasopressin. Renal disease can also lead to
hypertension since renal handling of sodium and water can be impaired.

There is no single hypothesis explaining the pathogenesis of essential hypertension. It is

related to hereditary, age, race and socioeconomic status.

However, two theories have been proposed to account for the raised systemic vascular
resistance.

Salt imbalance - renal hypothesis

There is a small but sustained discrepancy between salt intake and salt excretion
which ↑ extracellular Na+ and consequently, ECF leading to an ↑ed plasma
volume, filling pressure, EDV, SV and BP which evokes hypertrophy of vascular
smooth muscle and a rise in TPR.
Normally a high salt intake and fluid retention reduce the levels of angiotensin II
and aldosterone which promotes salt and water excretion and restores the balance.
However, in a subgroup of hypertensives angiotensin II and aldosterone levels are
increased rather than depressed.

Neurogenic or Stress Hypothesis

Exaggerated alerting responses cause excessive sympathetic outflow which
initiates bouts of reversible hypertension. The excess sympathetic effects cause
peripheral vasoconstriction, increased cardiac output, increased release of
epinephrine from the adrenal medulla as well as increased circulation of
aldosterone, angiotensin II and vasopressin. The repeated bouts of
vasoconstriction eventually cause hypertrophy of vascular smooth muscle.

Whatever the cause of the hypertension, hypertrophy of the vascular smooth muscle
occurs which then triggers a self-perpetuating positive feedback mechanism - the
narrowed arteries increase BP and the increased BP results in more vascular hypertrophy.

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As well as the hypertrophy, secondary changes also occur in which the elastin
defragments and the arteries start to resemble the arteriosclerotic arteries of the elderly.
This stiffening causes a reduction in arterial compliance resulting in large increases in
systolic BP. Note that the baroreceptor reflex still operates in hypertension, but at a new
set point.

Consequences of Hypertension

1. ↑ work load of the LV – eventually causing cardiac failure.

This stimulates the release of growth factors that cause a compensatory

hypertrophy of the myocardium. Initially, this helps but eventually congestive
cardiac failure with dilatation of the heart supervenes.

2. ↑ risk of vascular disorders: intracerebral hemorrhage

subarachnoid hemorrhage
dissecting aortic aneurysms

Data suggest that 62% of cerebrovascular disease and 49% of ischemic heart
disease are due to inadequate management of hypertension.

3. Damage to renal arterioles due to deposition of proteins – leads to loss of

nephrons and eventually chronic renal failure which further exacerbates the
hypertension.

4. ↑ risk of developing atheroma and coronary artery disease.

It is essential to treat the asymptomatic state before the following occur:

Cardiac failure
Cerebrovascular accidents (CVA)
Coronary artery disease
Chronic renal failure

If untreated, 50% develop cardiac failure; 25% renal failure and 25% CVAs. Globally, ~7
million individuals die prematurely as a result of hypertension.

Risk factors for developing hypertension

Family history
Race
Salt intake
Obesity
Alcohol intake

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Drug Treatment of Hypertension

Drugs used:

Peripheral vasodilators: Ca channel blockers

(↓ TPR) α1 receptor antagonists

Diuretic Drugs: ↓ ECF and hence BP

ACE inhibitors: ↓ Angiotensin II (and indirectly aldosterone)

↓ vascular tone and ECF volume

β adrenergic blockers: ↓ CO and hence BP

Hypotension and Shock

Hypotension is defined as a systolic BP of < 90 mm Hg and a diastolic of < 60 mm Hg. It
results from a decrease in either cardiac output or systemic vascular resistance, or both. A
reduction in cardiac output could be due to a fall in heart rate (e.g AV block) or a fall in
stroke volume. The reduction in SV could be due to a reduced contractility (e.g heart
failure) or a fall in preload (e.g hemorrhage). As a consequence there is an acute failure
of the cardiovascular system to adequately perfuse the tissues of the body. Hypotension
often happens acutely and the individual is said to be “in shock”.

Characteristic Signs and Symptoms of Shock

(some are due to the compensatory mechanisms)

Pale, cold, sweaty and clammy skin (↑sympathetic discharge, venoconstriction)

Rapid and weak pulse (due to tachycardia and a small SV)

↓ Pulse pressure (MAP may be normal)

Rapid and shallow breathing

↓ Urine output

Often, altered consciousness, confusion, muscular weakness and collapse.

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Categories of Shock

Hypovolemic Shock: ↓ Blood volume (due to hemorrhage) or internal fluid loss

(due to diarrhea, vomiting, extensive burns). A fall in blood
volume reduces preload, which reduces SV and CO.

Cardiogenic shock: Acute failure of the heart to pump blood (following an M.I.
or arrhythmias) resulting in pump failure and a fall in SV
and CO.

Septic shock: Systemic Inflammatory Response Syndrome – caused by a

bacterial infection of blood; bacterial endotoxins activate
the immune system causing a massive release of TNF and
NO which cause vasodilation and a reduction in systemic
vascular resistance.

Analphylactic shock: Intense allergic reaction to antigens resulting in a fall in

systemic vascular resistance.

Although the responses to each vary slightly there is a common pattern of response. We
will focus on hemorrhagic shock (hypovolemic shock) since it is a common medical
emergency.

Hemorrhagic Shock

Normal blood volume is ~ 5L, with 65% of blood being in the venous compartment.

The consequences of a rapid loss of blood volume:

5 – 10% (after blood donation): No significant fall in MAP

15 – 20%: Modest ↓ MAP; homeostatic mechanisms result in a full recovery

20 – 30% MAP 60 – 80 mm Hg; characteristics of mild hemorrhagic shock

Rarely fatal.

30 – 40% MAP falls to 50 – 70 mm Hg; serious shock responses which could

become irreversible

> 50% Usually fatal.

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Consequences of Hemorrhage

Immediate Effects:

Loss of Blood Volume

↓ CVP

↓ VR and ↓ EDV

↓ SV and ↓ CO

↓ MAP Inadequate Tissue Perfusion

A 20% reduction in blood volume causes CO to fall to ~ 3L/min.

Compensatory Responses
The immediate responses to a hemorrhage are the triggering of reflexes which will
restore the arterial blood pressure thus ensuring adequate cerebral and myocardial
perfusion (often at the expense of reduced blood flow to less essential organs). The
reflexes elicited include:

1. Baroreceptor Reflex

↓ MAP → ↑ Sympathetic and ↓ Parasympathetic discharge

↑ sympathetic discharge causes: Peripheral vasoconstriction and ↑ TPR

↑ Contractility and ↑ HR, and ↑ CO

The ↑ TPR and ↑ CO restore the MAP.

Note that the peripheral vasoconstriction affects cutaneous, splanchnic, skeletal

muscle and renal circulations whereas the coronary and cerebral circulations are
generally preserved. The sympathetically-mediated venoconstriction increases the
filling pressure which will try and restore the VR. Unfortunately, the filling
pressure may still be low, resulting in a still lower than normal EDV and SV.
However, the increased HR will restore CO to a large extent if the blood loss is
not too severe (< 20%).

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 These sympathetically-mediated responses explain the clinical manifestations of
shock: the cold, clammy skin and the rapid and weak heart beat. The intense
vasoconstriction may also cause some degree of peripheral cyanosis.

Sympathetic activity also causes the release of epinephrine from the adrenal
medulla. Epinephrine also, like norepinephrine, increases cardiac contractility and
heart rate and causes vasoconstriction (but to a lesser extent than norepinephrine).

2. Activation of the Renin-Angiotensin System

The renin-angiotensin system is activated by increased renal sympathetic activity,

reduced renal artery pressure and the reduced Na load in the macula densa. As a
result, the powerful vasoconstrictor, angiotensin II is produced. Angiotensin II
also stimulates aldosterone production which causes retention of sodium and
water. ADH secretion is stimulated by reduced atrial stretch, sympathetic
stimulation and angiotensin II. ADH causes water retention and stimulates thirst.
The reduced atrial stretch results in less ANF released which favours water and
salt retention.

The vascular responses to angiotensin II occur rapidly whereas the renal effects of
these hormones occur more slowly – over a few hours to days.

3. Movement of interstitial fluid into the blood - “internal transfusion”

The fall in arterial BP, due to the hemorrhage, causes a reduction in capillary
hydrostatic pressure, and since the oncotic pressure is unchanged the Starling
forces result in the movement of fluid from the interstitium to the blood. As the
sympathetic activity increases, glycogen breakdown in the liver is enhanced and
blood glucose increases, this increases the osmolarity of blood and the interstitial
fluid which then results in the movement of intracellular fluid to the interstitium.
If ~ 1000 ml of blood is lost, this “internal transfusion” will cause ~600 ml of
fluid to enter the blood over the course of ~10 min. The plasma oncotic pressure
will gradually fall as the blood becomes more diluted with the interstitial fluid but
at the same time, the capillary hydrostatic pressure is increasing due to the
internal transfusion. Eventually a new equilibrium well be established between
the Starling forces and the internal transfusion will stop.
A consequence of the internal transfusion is that the blood becomes more dilute
and hematocrit falls – this reduces the viscosity of blood which makes it easier for
it to flow round the body but it also lowers the resistance to blood flow and could
contribute to a further fall in blood pressure. The reduced oxygen carrying
capacity of the blood as a result of the hemodilution will restrict O2 delivery to
already poorly perfused tissues.

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 Hemorrhage
+CVP +CVP
+CO + + +CO
↑Bld volume ↓Arterial Pressure +SVR
+Thirst
↑ ADH +Symp
↑ TPR +Symp

↑ Na+ and H2O ↑ Ang II ↑ Renin ↑ Catecholamines

retention

↑ Aldosterone

Figure 1 Neurohumoral Responses to Hemorrhage

Longer Term Responses

The short term responses preserve the perfusion of the heart and brain. But the patient is
left with a reduced perfusion to other organs due to an overall loss of body water,
electrolytes, plasma proteins and red cells. These deficiencies are gradually corrected
over days and weeks.

Water and salt deficits are corrected first by the kidney. Increased sympathetic activity
causes vasoconstriction of the renal afferent arterioles. This reduces the glomerular
filtration rate leading to salt and water retention. As mentioned above, the sympathetic
activity increases renin production resulting in formation of angiotensin II. This
stimulates aldosterone which further increase salt and water retention, thus enhancing
blood volume. A blood loss of 1L could be replaced within 3 days, with a normal salt and
water intake.

The liver increases its production of plasma proteins and they could be completely
replenished a week after a moderate hemorrhage.

The reduced red cell mass is detected by the kidneys, which respond by increasing
production of erythropoietin (Epo). Epo stimulates the production of red blood cells in
the bone marrow. The red cells would be replaced in ~ 4 – 6 wks. Hematocrit is then
restored, provided iron intake is adequate. (After a blood donation, individuals are given
iron tablets).

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The above responses occur due to a mild to moderate loss of blood. Most people could
recover from a 25% loss by purely physiological means, although clinical intervention
will accelerate recovery and minimize end organ damage.

The Effects of Severe and Prolonged Hypotension (Decompensated Shock)

If the patient has lost >30% of blood and there is a 3 – 4 delay before fluid replacement
has begun then the patient may enter the syndrome of decompensated or irreversible
shock. In this situation, shock enters a second phase where restoration of blood volume
by transfusion, may not save his life. Although there is an initial reflex increase in
sympathetic activity due to baroreceptor reflex (in which the BP may be maintained), in
severe shock the sympathetically-mediated vasoconstriction is followed by a profound
peripheral vasodilation which further lowers BP. No heroic measure can now raise the
BP. This fall in BP results from the activation of decompensatory mechanisms (which
here are examples of positive feedback mechanisms).

If MAP falls below 60 mm Hg, coronary perfusion is reduced (this level falls below the
coronary autoregulatory range). Reduced coronary blood flow leads to myocardial
hypoxia which impairs contractility. The impaired contractility further reduces MAP by
reducing stroke volume and cardiac output which cause a further decrease in coronary
perfusion. The fall in BP also decreases organ blood flow and the sympathetically
mediated vasoconstriction reduces blood flow further. The more hypoxic a tissue
becomes the greater the build up of vasodilator metabolites which eventually override the
sympathetically mediated vasoconstriction (sympathetic escape) and blood flow begins to
increase within the organ. However this vasodilation will cause a fall in arterial pressure
which further reduces organ perfusion which leads to further vasodilation and
hypotension.

Severe Hemorrhage

↓Cardiac Output ↓Tissue Blood Flow

↓ Inotropy ↓ Arterial Pressure ↓Tissue Hypoxia

Vasodilation
↓ Coronary Perfusion (Sympathetic Escape)

Figure 2 Positive feedback loops leading to irreversible (decompensated) shock

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Other positive feedback mechanisms contribute to irreversible shock: tissue hypoxia
results in metabolic acidosis; an increased [H+] impairs contractility and
vasoconstriction; cerebral hypoxia eventually results in depression of the cardiovascular
centres and reduced sympathetic output.

In summary:
The body responds to hypotension and shock by activating neurohumoral mechanisms
that operate as negative feedback systems. With severe hypotension positive feedback
mechanisms become dominant and the state of shock becomes irreversible.

Management of Shock

Ensure adequate lung ventilation and provide extra oxygen.

Restore blood volume by infusion of blood or other fluids
Use interventions that improve cardiac performance.

Correct recognition of the signs and symptoms of shock helps to avoid the consequences
of catastrophic circulatory failure.

Syncope (Fainting)

This is a sudden, transient loss of consciousness due to a fall in BP resulting in reduced

cerebral perfusion. Syncope could be triggered by hypvolemia, standing up suddenly
(particularly if the patient is taking α1 antagonists) or a psychological stress (fear, pain or
horror – [psychogenic fainting]).

In psychogenic fainting (vasovagal syncope) the individual starts to “feel faint”; he has
tachycardia, muscle vasodilation and skin vasoconstriction; he looks pale and sweaty and
is hyperventilating. These responses are a typical “alerting response”. Then suddenly
there is a large increase in vagal outflow causing a profound bradycardia accompanied by
a sudden peripheral vasodilation (due to a fall in sympathetic drive). As a result the BP
falls sharply, reducing cerebral perfusion and causing a loss of consciousness which can
last a couple of minutes. The mechanism that causes the sudden increase in vagal tone is
not clear. It is similar to the “playing possum” (playing dead) response seen in small
animals.

When a person faints he falls to the ground and becomes supine. The supine position
helps him to recover. The intrathoracic blood volume increases, increasing filling
pressure, EDV and stroke volume and this together with the baroreceptor reflex soon
restores the cardiac output and the blood pressure.

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An individual who is feeling faint should lie down or put his head between his knees. On
no account should he be propped up since then you would be depriving him of the
benefits of the Frank-Starling mechanism. Sometimes loss of consciousness can be
avoided when the individual who on feeling faint, lies down immediately.

Chronic (Congestive) Cardiac Failure

Definition: A pathophysiological state in which an abnormality of cardiac function is
responsible for the failure of the heart to pump blood at a rate
commensurate with the requirements of the metabolising tissues.
(Brunwald, 1980; A textbook of cardiovascular medicine)

Variables that determine CO:

Preload Events (Filling Pressure, EDV)

Contractility (associated with [Ca++] and [H+] levels)

Afterload Events (resistance to blood leaving the heart)

Heart rate regulation

Preload, contractility and afterload determine the SV of the heart.

Heart rate regulation is mainly by the baroreceptor reflex which keeps arterial BP fairly
constant.

Cardiac failure is a complex syndrome and may be the main manifestation of any form of
heart disorder. Left ventricular failure is more common than RV; RV failure is associated
with pulmonary disease, but it more commonly occurs as a consequence of LV failure.

Clinical Features: Exertional dyspnea

Tiredness
Pulmonary and Systemic Edema

Prevalence: 1% at age 50
9% at age 80

50% mortality within 5 years of diagnosis.

Deaths are due to pump failure and/or arrhythmias.

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Causes of Cardiac Failure

 Reduced myocardial contractility

Conditions which lead to reduced myocardial contractility:

 Diffuse coronary artery disease

 Reduced myocardial mass following an infarct

 Chronically increased afterload due to hypertension, aortic valve disease

Consequences of a fall in contractility:

↓ SV → ↓ Ejection Fraction → ↑ EDV

↑ EDV → ↑ Venous Pressure → ↑ Capillary Hydrostatic Pressure → Edema formation

↑ EDV → Dilation of the heart

Cardiac failure can be due to primarily to LV failure (commoner) or to RV failure.

Left sided failure is however, the commonest cause of right heart failure.

Characteristic Features of LV Failure

↑ Pulmonary vein pressure → Pulmonary Congestion

Pulmonary congestion → Difficulty in inflating lungs → Breathlessness (Dyspnea)

Note that the dyspnea is worst when supine (because of the greater increase in pulmonary
venous pressure when supine)

Characteristic Features of RV Failure

↑ CVP → ↑ capillary hydrostatic pressure in tissues → peripheral edema

→ ankle swelling (pitting edema)

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The ↑ CVP is reflected in an increase in the jugular venous pressure which can be
estimated in an individual. The pulsing jugular vein will be visible in the neck when the
individual is semi-recumbent.

Basically, because the heart is not pumping adequately there is an increase in back
pressure (from veins to arteries) throughout the circulation. If the primary defect is the
RV then the back pressure is felt through the systemic circulation and if it is LV failure,
then the pulmonary pressures increase.

Systolic Failure vs Diastolic Failure

Cardiac failure could be primarily systolic failure or diastolic failure.

Systolic failure: ↓ Contractility → ↓ SV

Diastolic failure: ↓ Ventricular filling (e.g. stenosis of A-V valves)

→ ↓ EDV and ↓ SV

Systolic failure is more common than diastolic; however an individual can exhibit both.

Consequences of LV failure on the RV (and vice versa)

Imagine the scenario when the LV starts to fail. The healthy RV continues to pump blood
into the lungs until LV preload is increased enough to restore the ventricular balance i.e.
the CO from the two sides of the heart. This balance is achieved at the price of a raised
left atrial and pulmonary venous and capillary pressure (causing formation of pulmonary
edema). Also the increase in pulmonary capillary pressure results in an increase in
pulmonary artery pressure. This increases the afterload on the RV and eventually the RV
starts to fail. In fact, the commonest cause of RV failure is left heart failure!
The same situation also arises when RV starts to fail.

Other causes of RV failure are lung disorders which lead to pulmonary hypertension.
(Inadequate oxygenation leads to hypoxic vasoconstriction).

The cardiac function curve (Starling curve) in the figure below is depressed in the failing
heart. As you can see from the graph, the disparity between the normal heart and the
failing heart is much greater during exercise.

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 100 Normal LV

Exercise
80

Stroke Volume (ml)

Failing LV
60 Rest

40

20

0 10 20 30
End-Diastolic Pressure (cm H2O)

Figure 1 Effects of cardiac failure on the cardiac function curve.

Chronic cardiac failure is a progressive disease. Initially when the heart starts to fail
compensatory mechanisms come into play which can restore the cardiac output to normal
and the individual is still asymptomatic. Gradually, as the myocardial contractility
continues to decline, the compensatory mechanisms become inadequate and
breathlessness, exercise intolerance and edema become manifest. At this stage the heart is
said to be decompensated.

Mild cardiac failure: Compensatory mechanisms

The initial compensatory mechanism in the failing heart is the Frank-Starling mechanism:
as the SV falls, the EDV increases and this stretches the myocardial fibres resulting in a
greater force of contraction, thus restoring the SV.

Other mechanisms that come into play are:

Baroreceptor reflex – activated by the fall in CO and arterial pressure. Response is an ↑

sympathetic drive.

↑ Sympathetic activity will:

↑ HR: not always helpful in a failing heart since it ↑ work load of the heart.

↑ Contractility of the heart (activation of β1 receptors).

↑ Venoconstriction → ↑ VR and ↑ EDV

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 Peripheral vasoconstriction (α1 receptors) – helps divert blood to the heart and
brain (since these organs have few α1 receptors)

↑ Renin secretion → ↑ salt and water retention → ↑ Plasma volume→↑ EDV

When the failure is mild, the patient is asymptomatic but the right atrial pressure may be
increased and the heart may be enlarged.

Moderate to Severe Cardiac Failure: The Decompensated Heart

As the disease progresses the compensatory mechanisms become inadequate:

As the SV and CO continue to fall, the EDV gets larger and larger, and the heart
now operates on the plateau of the ventricular function curve. The ejection
fraction can fall to ~10 – 20%.

The increase in EDV also results in dilation of the heart and as the heart becomes
more and more dilated, the contractions get weaker and weaker (as a result of
Laplace‟s relationship).

The A-V orifices in the dilated heart are widened causing A-V valve leakage,
which compounds the problem.

The continuing sympathetic drive increases the HR which further increases the
workload of the heart.

Down regulation of the β1 receptors occurs - the heart responds less and less to
sympathetic activity.

The expansion of plasma volume (renin-angiotensin system) now increases the

filling pressure and the capillary hydrostatic pressure – favoring edema.

Overproduction of Ang II has a deleterious effect on the structure of the heart

itself.

At the cellular level, there is an increased production of various cytokines which

cause cardiac hypertrophy.

Explanations of the characteristic features of cardiac failure

Exercise Intolerance
The failing heart cannot raise its output to a normal degree due to an inadequate increase
in SV and HR. The large EDV has stretched the fibres beyond the level at which
increased contractility can occur. The increased sympathetic drive of exercise cannot
exert its full effects because of the down regulation of the β1 receptors.

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Pulmonary Edema: LV failure
Pulmonary edema is due to a raised capillary hydrostatic pressure in the pulmonary
circulation. This is due to a raised pulmonary venous pressure. The edema is exacerbated
by a fall in plasma oncotic pressure due to expansion of the plasma following salt and
water retention due to activation of the renin-angiotensin system. Pulmonary edema
causes crackles (heard during auscultation). In severe pulmonary edema, fluid
accumulates in the alveoli too, impairing O2 transport – this is potentially fatal.
The net effect of pulmonary edema is to make the lungs stiffer and more difficult to
inflate – this causes dyspnea – and a feeling of breathlessness which becomes worse
when lying down at night and may wake the patient up. Such patients find it more
comfortable to sleep propped up by several pillows.

Peripheral (Systemic) Edema: RV failure

In RV failure, the venous pressure throughout the systemic circulation increases resulting
in an increase in CVP. This causes distension of the jugular veins which can be observed
when the patient is semi-recumbent. The peripheral edema is worse in the dependent
regions – ankles and feet. The edema is said to be “pitting”.
The characteristic features of RV failure are then pitting edema in the ankles and a raised
jugular pressure.

Cardiac failure eventually affects both ventricles and patients then exhibit pulmonary
congestion and peripheral edema.

Management of Cardiac Failure

Objectives: To reduce the clinical symptoms of edema and dyspnea

To improve cardiovascular function to enhance organ perfusion and
increase exercise capacity
To reduce mortality

4 pharmacological approaches are taken:

1. To reduce venous pressure (reduce edema and dyspnea)

Diuretics (reduce blood volume), ACE inhibitors (venodilation)

2. Reduce afterload by dilating the systemic blood vessels

ACE inhibitors and angiotensin rec antagonists (dilate bld vessels)

3. To improve contractility: Digoxin

4. β receptor antagonists:
It is known that long term sympathetic activation of the heart is deleterious. Beta
blockers may be beneficial in heart failure by blocking the effects of the
sympathetic on the heart.
Beta blockers and ACE inhibitors appear to provide long term benefit through
ventricular remodeling and have improved mortality.

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