Secondary Hypertension

Secondary hypertension
 Caused by an underlying disease process or medication that raises peripheral vascular

resistance or cardiac output.
 If the cause is identified and removed before permanent structural changes occur,
blood pressure returns to normal. Exam: kidney disease due to the retention of
sodium and water, adrenocortical hormonal imbalances such as primary
hyperaldosteronism and drugs (oral contraceptives, corticosteroids, antihistamines).
Isolated systolic hypertension

 Isolated systolic hypertension is typically defined as a sustained systolic BP >
140 mmHg and diastolic BP below 90 mmHg.
 Older than 65 years of age and is strongly associated with cardiovascular and
cerebrovascular events.
 An increased pulse pressure (systolic minus diastolic pressure) indicates reduced
vascular compliance of large arteries and is related to either an increase in cardiac
output (heart valve disease) or peripheral resistance (caused by atherosclerosis).
 Pharmacological management is required.
Complicated hypertension
 Cardiovascular complications of sustained hypertension include left ventricular
hypertrophy, angina pectoris, heart failure, coronary heart disease, myocardial
infarction and sudden death.
 Myocardial hypertrophy in response to hypertension is mediated by several
neurohormonal substances, including catecholamines from the sympathetic nervous
system (adrenaline and noradrenaline) and angiotensin II.
 Moreover, increased size of heart muscle increase demand for oxygen delivery over
time, contractility of the heart is impaired, and the individual is at increased risk for
heart failure.
 Vascular complications include the formation, dissection and rupture of aneurysms
(outpouchings in vessel walls) and atherosclerosis leading to vessel occlusion.
Microalbuminuria (small amounts of protein in the urine) occurs in 10–25% of
individuals with essential hypertension and an early sign of impending renal
dysfunction and significantly increased risk for cardiovascular events.
SITE OF INJURY MECHANISM OF INJURY POTENTIAL PATHOLOGICAL EFFECTS
Heart
Myocardium Increased workload combined with Left ventricular hypertrophy, myocardial ischaemia,
diminished blood flow through coronary left heart failure
arteries
Coronary arteries Accelerated atherosclerosis (coronary artery Myocardial ischaemia, myocardial infarction,
disease) sudden death
Kidneys Renin and aldosterone secretion stimulated by Retention of sodium and water, leading to increased
reduced blood flow blood volume and continuation of hypertension
Reduced oxygen supply Tissue damage that compromises filtration
High pressures in renal arterioles Renal failure
Brain Reduced blood flow and oxygen supply; Transient ischaemic attacks, cerebral thrombosis,
weakened vessel walls, accelerated aneurysm, haemorrhage, acute brain infarction
atherosclerosis
Eyes (retinas) Reduced blood flow Retinal vascular sclerosis
High arteriolar pressure Exudation, haemorrhage
Aorta Weakened vessel wall Dissecting aneurysm
Arteries of lower Reduced blood flow and high pressures in Intermittent claudication, gangrene
extremities arterioles, accelerated atherosclerosis
Clinical manifestations
 Hypertension a silent disease.
 The chance of developing primary hypertension increases with age. Although
hypertension is usually thought to be an adult health problem, occurs in children as
well.
 Increased peripheral resistance and early hypertension develop in the second, third
and fourth decades of life. If elevated blood pressure is not detected and treated, it
becomes established and may begin to accelerate its effects on tissues when the
individual is 30–50 years of age.
 Most clinical manifestations of hypertensive disease are caused by complications that
damage organs and tissues outside the vascular system. Besides elevated blood
pressure, the signs and symptoms therefore tend to be specific for the organs or
tissues affected.
 heart disease, renal insufficiency, central nervous system dysfunction, impaired
vision, impaired mobility, vascular occlusion or oedema can all be caused by
sustained hypertension.
Evaluation and treatment
REDUCE STROKE VOLUME REDUCE SYSTEMIC VASCULAR DECREASE HEART RATE
RESISTANCE
Thiazide diuretics Combined α, β-adrenergic blockers β-blockers
Chlorthalidone Carvedilol Atenolol
Hydrochlorothiazide Labetalol Metoprolol
Loop diuretics Angiotensin-converting enzyme (ACE) Combined α, β-adrenergic
Frusemide inhibitors blockers
Potassium-sparing diuretics Captopril Carvedilol
Amiloride Enalapril Labetalol
Spironolactone Angiotensin II receptor blockers
Angiotensin-converting enzyme (ACE) Irbesartan
inhibitors Losartan
Captopril Calcium channel blockers
Enalapril Diltiazem
Angiotensin II receptor blockers Verapamil
Irbesartan α-blockers
Losartan Prazosin
Centrally acting α-blockers
Clonidine
Methyldopa
Direct-acting vasodilators
Hydralazine
Minoxidil
Orthostatic hypotension
postural hypotension, refers to a decrease in both systolic and diastolic arterial blood pressure
on standing.
Normally when an individual stands up, the gravitational changes on the circulation are
compensated by mechanisms such as reflex arteriolar and venous constriction controlled by
the baroreceptors and increased heart rate. Furthermore, mechanical factors such as the
closure of valves in the venous system, pumping of the leg muscles and a decrease in
intrathoracic pressure assist in increasing venous return in the heart. Collectively, these
maintain blood pressure.
 The normal or compensatory vasoconstrictor response to standing is absent so that

there is blood pooling in the muscle vasculature, as well as in the splanchnic and renal
beds, leads to dizziness, blurry and vision loss
Orthostatic hypotension may be acute and temporary or chronic:
 Acute orthostatic hypotension is caused when the normal regulatory mechanisms are
sluggish as a result of (1) altered body chemistry, (2) drug action (e.g.
antihypertensives, antidepressants), (3) prolonged immobility caused by illness, (4)
starvation, (5) physical exhaustion, (6) any condition that produces volume depletion
(e.g. dehydration, diuresis, potassium or sodium depletion) or (7) venous pooling (e.g.
pregnancy, extensive varicosities of the lower extremities). The elderly are
particularly susceptible to this type of orthostatic hypotension.
 •
Chronic orthostatic hypotension may be (1) secondary to a specific disease or (2)

idiopathic or primary. The diseases that cause secondary orthostatic hypotension are
endocrine disorders (e.g. adrenal insufficiency, diabetes mellitus), metabolic disorders
(e.g. porphyria) or diseases of the central or peripheral nervous systems (e.g.
intracranial tumours, cerebral infarcts, Wernicke's encephalopathy, peripheral
neuropathies). It is more prevalent in the aged population and may be attributable to
an increase in mortality due to secondary effects of orthostatic hypotension, such as
falls. In addition to cardiovascular symptoms, associated impotence and bowel and
18
bladder dysfunction are common.
Although no curative treatment is available for orthostatic hypotension, often it can be

managed adequately with a combination of non-pharmacological and pharmacological
therapies. For both acute and chronic forms, hypotension resolves when the underlying
disorder is corrected.
Arteriosclerosis
Arteriosclerosis is a chronic disease of the arterial system characterised by abnormal
thickening and hardening of the vessel walls. Smooth muscle cells and collagen fibres
migrate into the tunica intima (internal layer of the arterial wall), causing it to stiffen and
thicken, gradually narrowing the arterial lumen (see Fig. 23.6 ). Changes in lipid, cholesterol
and phospholipid metabolism within the tunica intima also contribute to arteriosclerosis.
Although these changes may be part of normal ageing, pathophysiological conditions such as
hypertension, insufficient perfusion (blood flow) of tissues or weakening and outpouching of
arterial walls can be exacerbated by the changes to the arterial walls brought about by
arteriosclerosis.
Atherosclerosis
Atherosclerosis is the most common form of arteriosclerosis. It is characterised by soft
deposits of intra-arterial fat and fibrin in the vessels walls that harden over time.
Atherosclerosis is not a single disease entity but rather a pathological process that can affect
vascular systems throughout the body, resulting in ischaemic syndromes that can vary widely
in their severity and clinical manifestations. It is the leading cause of coronary heart and
cerebrovascular disease. (Atherosclerosis of the coronary arteries is described later in this
chapter, and atherosclerosis of the cerebral arteries leading to cerebrovascular disease is
described in Chapter 9 .)
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Pathophysiology
Inflammation plays a fundamental role in mediating all of the steps in the initiation and
progression of atherosclerosis formation. 19, 20, 21 Atherosclerosis begins with injury to the
endothelial cells that line the artery walls. Possible causes of endothelial injury include the
common risk factors for atherosclerosis, such as smoking, hypertension, diabetes mellitus,
increased levels of low-density lipoprotein (LDL) cholesterol and decreased levels of high-
density lipoprotein (HDL) cholesterol. Other possible causes of endothelial injury include
elevated C-reactive protein (CRP), increased serum fibrinogen, insulin resistance, oxidative
stress, infection and periodontal disease.
Injured endothelial cells become inflamed and cannot make normal amounts of antithrombic
and vasodilating substances. When the endothelium is injured, it loses the ability both to
prevent clotting and to vasodilate. This results in platelets aggregating when thromboxane
A 2 increases (refer to Chapter 16 ), and the release of serotonin and endothelin combines to
cause vasoconstriction. This leads to a decrease in blood flow and, ultimately, ischaemia. At
the same time, sympathetic nervous system activation causes vasoconstriction when
noradrenaline is released. The enzyme ACE in the endothelium also converts angiotensin I to
angiotensin II ( Fig. 23.7 summarises these events). Collectively, this leads to vasoconstriction
and increased clotting.
The next step in the formation of atherosclerosis occurs when inflamed endothelial cells
express adhesion molecules that bind monocytes and other inflammatory and immune cells.
Monocytes adhere to the injured endothelium and release numerous inflammatory cytokines
(e.g. tumour necrosis factor-alpha [TNF-α], interferons, interleukins and C-reactive protein)
and enzymes that further injure the vessel wall. Toxic oxygen radicals generated by the
22
inflammatory process cause oxidation (i.e. addition of oxygen) of LDL. Oxidised LDL is
engulfed by macrophages, which then penetrate into the intima of the vessel. These lipid-
laden macrophages are called foam cells and when they accumulate in significant amounts,
they form a lesion called a fatty streak (see Figs 23.8 and 23.9 ). Even small-sized lesions can
be found in the walls of arteries of most people, including young children. Once formed, fatty
streaks produce more toxic oxygen radicals and cause immunological and inflammatory
changes resulting in progressive damage to the vessel wall.
Macrophages also release growth factors that stimulate smooth muscle cell proliferation.
Smooth muscle cells in the region of endothelial injury proliferate, produce collagen and
migrate over the fatty streak forming a fibrous plaque (see Fig. 23.9 ). The fibrous plaque may
calcify, protrude into the vessel lumen and obstruct blood flow to distal tissues (especially
during exercise), which may cause symptoms such as angina or intermittent claudication (leg
pain with exercise) due to poor blood circulation.
Many plaques, however, are ‘unstable’, meaning they are prone to rupture even before they
affect blood flow significantly and are clinically silent until they rupture. Plaques that have
ruptured are called complicated plaques . Once rupture occurs, exposure of underlying tissue
results in platelet adhesion, initiation of the coagulation (or clotting) cascade and rapid
thrombus formation. The thrombus may suddenly occlude the affected vessel, resulting in
ischaemia and infarction. Aspirin or other antithrombotic agents are used to prevent this
complication of atherosclerotic disease.
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Atherosclerosis presents with symptoms and signs that result from inadequate perfusion of
tissues because of obstruction of the vessels that supply them. Partial vessel obstruction may
lead to transient ischaemic events, often associated with exercise or stress. As the lesion
becomes complicated, increasing obstruction with superimposed thrombosis may result in
tissue infarction. Obstruction of peripheral arteries can cause significant pain and disability.
Coronary heart disease caused by atherosclerosis (see Fig. 23.10 ) is the major cause of
myocardial ischaemia and is one of the most important health issues in Western countries,
including Australia and New Zealand. Atherosclerotic obstruction of the vessels supplying
the brain is the major cause of strokes.

In evaluating individuals for the presence of atherosclerosis, a complete history (including
risk factors), physical examination and laboratory data are considered. The use of x-rays,
electrocardiography, ultrasonography, nuclear scanning and angiography may be necessary to
identify affected vessels, particularly coronary vessels.
The primary goal in the management of atherosclerosis is to restore adequate blood flow to
the affected tissues. If an individual presents with acute ischaemia, interventions are specific
to the diseased area (e.g. acute myocardial infarction due to occlusion of the coronary vessel).
In situations where the disease process does not require immediate intervention, management
focuses on removing the initial causes of vessel damage and preventing lesion progression.
This includes lifestyle modifications, such as increasing exercise levels, ceasing smoking and
controlling hypertension and diabetes mellitus where appropriate, and reducing LDL levels
by diet or medications, or both.
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Coronary heart disease
Coronary heart disease refers to conditions that affect the coronary blood vessels that
supply the heart with nutrients and oxygen (see Chapter 22 ). We have chosen to use the
term coronary heart disease to align with the terminology used by the Australian Institute of
Health and Welfare, the New Zealand Ministry of Health and the peak cardiac bodies in both
countries, the National Heart Foundation of Australia and the Cardiac Society of Australia
and New Zealand. In clinical practice you may see a variety of terms used for coronary heart
disease, such as ischaemic heart disease, coronary artery disease and heart disease. These
terms are essentially synonymous and are often used interchangeably. However, one of the
most important aspects to remember is that more than 90% of all cases of myocardial
ischaemia (a local state in which the cardiac cells are temporarily deprived of blood supply)
result from obstruction of the coronary arteries due to atherosclerosis. Persistent ischaemia or
complete occlusion of a coronary artery causes the acute coronary syndromes including
infarction or irreversible myocardial damage. Acute myocardial infarction constitutes the
often fatal event known within the community as a heart attack.
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The development of coronary heart disease
Approximately 3.0% of Australians (more than 685 000 people) have coronary heart disease.
It is associated with the elderly, as the prevalence of coronary heart disease increases with
age (see Fig. 23.1 ).
1
Numerous types of genetic susceptibilities to coronary heart disease have been identified in
individuals with a family history of heart disease. Risk factors can be categorised as
conventional (major) versus non-traditional (novel) and modifiable versus non-modifiable.
Much new information has been obtained about the conventional risk factors, which have
markedly improved prevention and management of the disease. Conventional risk factors for
coronary heart disease that are non-modifiable include:
 •
advanced age
 •
male or female after menopause
 •
family history.
Modifiable risk factors include:
 •
dyslipidaemia and atherosclerosis-promoting diet
 •
hypertension
 •
cigarette smoking
 •
diabetes mellitus and insulin resistance
 •
obesity and a sedentary lifestyle.
We now focus our attention on discussing these modifiable risk factors.
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Dyslipidaemia and atherosclerosis-promoting diet
The term lipoprotein refers to lipids, phospholipids, cholesterol and triglycerides bound to
carrier proteins. These carrier molecules assist in transporting lipid-based molecules through
the water-based environment of the blood. Lipids (cholesterol in particular) are required by
most cells for the manufacture and repair of plasma membranes. Cholesterol is also a
necessary component for the production of such essential substances as bile acids and steroid
hormones. Although cholesterol can easily be obtained from dietary fat intake, most body
cells can also produce cholesterol.
The cycle of lipid metabolism is complex. Dietary fat is packaged into particles known as
chylomicrons in the small intestine. Chylomicrons are required for absorption of fat; they
function by transporting lipid from the small intestine to the liver and peripheral cells.
Chylomicrons are the least dense of the lipoproteins and primarily contain triglyceride. Some
of the triglyceride may be removed from the blood and either stored by adipose tissue or used
by muscle as an energy source. The chylomicron remnants, composed mainly of cholesterol,
are taken up by the liver. A series of chemical reactions in the liver results in the production
of several lipoproteins that vary in density and function. These include very-low-density
lipoproteins (VLDL), primarily triglyceride and protein; low-density lipoproteins (LDL) ,
mostly cholesterol and protein; and high-density lipoproteins (HDL) , mainly phospholipids
and protein.
Dyslipidaemia refers to abnormal concentrations of serum lipoproteins. The National Heart

Foundation of Australia and the Cardiac Society of Australia and New Zealand (2005) have
classified the recommended target levels of lipoproteins in the blood (see Table 23.4 ).
LIPOPROTEIN
 •
Low-density lipoprotein cholesterol (LDL-C)
 •
High-density lipoprotein cholesterol (HDL-C)
 •
Triglyceride (TG)
 •
Non–high-density lipoprotein cholesterol (NHDL-C)
An increased serum concentration of LDL is considered a strong indicator of coronary risk.

Serum levels of LDL are normally controlled by hepatic receptors that bind LDL and limit
liver production of this lipoprotein. High dietary intake of cholesterol and fats, often in
combination with a genetic predisposition to accumulations of LDL, results in high levels of
LDL in the bloodstream. Oxidation of LDL, its migration into the vessel wall and
phagocytosis by macrophages are key steps in the pathogenesis of atherosclerosis (see Fig.
23.10 ). LDL cholesterol also plays a role in endothelial injury, inflammation and immune
responses that have been identified as being important in atherosclerosis
formation. Aggressive reduction of LDL with diet and cholesterol-lowering drugs, such as
23
HMG-CoA reductase inhibitors, more commonly referred to as statins, is associated with a

dramatic decrease in risk for coronary heart disease. 24
Low levels of HDL are also a strong indicator of coronary risk and high levels of HDL may
be more protective for the development of atherosclerosis than low levels of LDL. HDL is
25
responsible for ‘reverse cholesterol transport’, which returns excess cholesterol from the
tissues to the liver for metabolism. HDL also participates in endothelial repair and decreases
thrombosis. Exercise, weight loss, fish oil consumption and moderate alcohol use can result
26
in modest increases in HDL. LDL is often referred to as ‘bad’ cholesterol (atherogenic —

promoting development of atherosclerosis), while HDL is referred to as ‘good’ cholesterol
(for protection from atherosclerosis).
Other lipoproteins associated with increased cardiovascular risk include elevated serum
VLDL (triglycerides) and increased lipoprotein (a). Triglycerides are associated with an
increased risk for coronary heart disease, especially in combination with other risk factors
such as diabetes mellitus. Lipoprotein (a) is a genetically determined molecular complex
between LDL and a serum glycoprotein called apolipoprotein A and has been shown to be an
important risk factor for atherosclerosis, especially in women.
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Hypertension
Hypertension is responsible for a twofold to threefold increased risk of atherosclerosis. It
contributes to endothelial injury and can lead to myocardial hypertrophy, which increases
myocardial demand for coronary flow. This risk factor was discussed fully at the start of this
chapter.
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Cigarette smoking
Both direct and passive (environmental) smoking increase the risk of coronary heart disease.
Nicotine stimulates the release of catecholamines (adrenaline and noradrenaline), which
increase heart rate and peripheral vasoconstriction. As a result, blood pressure increases, as
do cardiac workload and oxygen demand. Cigarette smoking is also associated with an
increase in LDL and a decrease in HDL, and contributes to damage of the blood vessel
endothelial lining, blood vessel inflammation and thrombosis. It is likely that additional
mechanisms by which smoking increases atherosclerosis also occur.
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Diabetes mellitus and insulin resistance
Diabetes mellitus is an extremely important risk factor for coronary heart disease. Insulin
resistance and diabetes have multiple effects on the cardiovascular system, including
endothelial damage, thickening of the vessel wall, increased inflammation, increased
thrombosis and decreased production of endothelial-derived vasodilators such as nitric
oxide. Diabetes mellitus is also associated with dyslipidaemia. Diabetes mellitus is
27
discussed in Chapter 36 .
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Obesity and sedentary lifestyle
The prevalence of people who are overweight or obese is increasing steadily in Western
countries, and Australia and New Zealand are following this trend. In 2014–16, 63.4% of
Australians aged 18 years and over were overweight or obese. The prevalence of overweight
and obesity has increased in Australia over time, from 61.2% in 2007–8 and 56.3% in 1995.
In both countries the incidence of overweight and obesity is higher in the Indigenous than
non-Indigenous population. 1
Metabolic syndrome is a combination of central (abdominal) obesity, abnormal glucose

tolerance or impaired glucose tolerance, raised triglycerides, decreased HDL, elevated blood
pressure and insulin resistance (see Chapter 36 ). It is estimated that almost 30% of Australian
adults have metabolic syndrome. The combination of these risk factors considerably increases
the development of cardiovascular disease and confers an even higher risk for coronary heart
disease. Abdominal obesity has the strongest link with increased coronary heart disease risk
28
and is related to insulin resistance, decreased HDL, increased blood pressure and decreased
levels of adiponectin. Physical activity and weight loss offer substantial reductions in risk
29
factors for coronary heart disease.
Moreover, for a non-cardiac patient, exercise provides protection if there is a cardiovascular

event. Exercise training improves major cardioprotection mechanisms including increased
30
nitric oxide generation, decreased cytokine production and increased antioxidant defences.
Similarly, research suggests that some foods or food components can decrease cardiovascular
risk, and/or improve existent coronary heart disease. Beneficial nutrients include those found
in fruits and vegetables and omega-3 polyunsaturated fatty acids. 31, 32
Coronary heart disease, myocardial ischaemia and acute myocardial infarction form a
pathophysiological continuum that impairs the pumping ability of the heart by depriving the
heart muscle of blood-borne oxygen and nutrients. We now explore how coronary heart
disease results in myocardial dysfunction and possible cardiac cell death.
Myocardial ischaemia
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Pathophysiology
The coronary arteries supply blood flow sufficient to meet the demands of the myocardium
during normal levels of cardiac activity, as well as when the heart is working harder (such as
during exercise). Oxygen is extracted from these vessels with maximal efficiency. If demand
increases, healthy coronary arteries dilate to increase the flow of oxygenated blood to the
myocardium. Various pathological mechanisms can interfere with blood flow through the
coronary arteries, giving rise to myocardial ischaemia . Narrowing of a major coronary
artery by more than 50% impairs blood flow enough to interfere with cellular metabolism
(see Fig. 23.11 ).
Myocardial ischaemia develops if blood flow or oxygen content of coronary blood is

insufficient to meet the metabolic demands of myocardial cells. Imbalances between coronary
blood supply and myocardial demand can result from a number of conditions. The most
common cause of decreased coronary blood flow and myocardial ischaemia is the formation
of atherosclerotic plaques in the coronary circulation. As the plaque increases in size, it may
partially occlude the vessel, thus limiting coronary flow and causing ischaemia (see Fig.
23.12 ). This is common when metabolic demand increases, such as during exercise. Some
plaques are ‘unstable’, meaning they are prone to ulceration or rupture. When this occurs,
underlying tissues of the vessel wall are exposed, resulting in platelet adhesion and thrombus
formation. This can suddenly cut off blood supply to the heart muscle, resulting in acute
myocardial ischaemia and, if the vessel obstruction cannot be reversed rapidly, ischaemia will
progress to infarction (death of the cells). Myocardial ischaemia can also result from other
causes of decreased blood and oxygen delivery to the myocardium, such as coronary spasm,
hypotension, arrhythmias and decreased oxygen-carrying capacity of the blood, such as
anaemia. Common causes of increased myocardial demand for blood include tachycardia,
exercise and valvular disease.
In coronary heart disease, ischaemia can develop within 10 seconds of coronary occlusion.
Myocytes (cardiac muscle cells) do not have the capacity to store a large amount of
adenosine triphosphate (ATP). Therefore, myocytes need a constant supply of blood that
carries oxygen and nutrients, so that ATP can be manufactured continually. If coronary artery
blood flow is impeded, after several minutes, the heart cells lose the ability to contract, thus
hampering pump function and depriving the myocardium of a glucose source necessary for
aerobic metabolism. Anaerobic processes take over and lactic acid accumulates. Cardiac
muscle cells remain viable for approximately 20 minutes under ischaemic conditions. If
blood flow is restored, aerobic metabolism resumes, contractility is restored and cellular
repair begins. If perfusion is not restored, then myocardial infarction occurs (see Fig. 23.11 ),
which causes death to those deprived cardiac cells. These cells do not regenerate and remain
as non-contractile scar tissue, no longer able to contribute to cardiac function.
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Individuals with reversible myocardial ischaemia can present clinically in several ways.
Chronic coronary obstruction results in recurrent predictable chest pain called angina
pectoris (commonly referred to as angina ). Abnormal vasospasm of coronary vessels results
in unpredictable chest pain called Prinzmetal's angina (also known as variant angina ).
Myocardial ischaemia that does not cause obvious and detectable symptoms is called silent
ischaemia .
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Angina
Angina is chest pain caused by myocardial ischaemia. The discomfort is usually transient,
lasting approximately 3–5 minutes. If blood flow is restored, no permanent change or damage
results. Angina is typically experienced as substernal chest discomfort, ranging from a
sensation of heaviness or pressure to moderately severe pain. Individuals often describe the
sensation by clenching a fist over the left sternal border. Discomfort may radiate to the neck,
lower jaw, left arm and left shoulder or, occasionally, to the back or down the right arm.
Discomfort is commonly mistaken for indigestion. The pain is presumably caused by the
build-up of lactic acid or abnormal stretching of the ischaemic myocardium that irritates
myocardial nerve fibres. These afferent sympathetic fibres enter the spinal cord from levels
C3 to T4, accounting for the variety of locations and radiation patterns of angina. Pallor,
diaphoresis (excessive sweating) and dyspnoea may be associated with the pain. Stable
angina is caused by gradual luminal narrowing and hardening of the arterial walls, so that
affected vessels cannot dilate in response to increased myocardial demand associated with
physical exertion or emotional stress.
Prinzmetal's angina is chest pain attributable to transient ischaemia of the myocardium that
occurs unpredictably and often at rest. Pain is caused by vasospasm of one or more major
coronary arteries, with or without associated atherosclerosis. The pain often occurs at night
during rapid eye movement sleep and may have a cyclic pattern of occurrence. The angina
may result from hyperactivity of the sympathetic nervous system, increased calcium flux in
arterial smooth muscle or endothelial dysfunction with impaired production or release of
prostaglandin or thromboxane and abnormal responses to acetylcholine. 33
Myocardial ischaemia may not cause detectable symptoms such as angina. Ischaemia may be
totally asymptomatic, referred to as silent ischaemia . Individuals may complain only of
fatigue, dyspnoea or a feeling of unease. Silent ischaemia and atypical symptoms are more
common in women (see ‘Research in Focus: Women and coronary heart disease’). In
addition, individuals who experience angina often have additional silent episodes of
myocardial ischaemia.

Many individuals with reversible myocardial ischaemia will have a normal physical
examination between events. However, in those with chronic ischaemia, the examination may
disclose rapid pulse or extra heart sounds, indicating impaired left ventricular function during
ischaemia. The presence of xanthelasmas (small fat deposits; see Fig. 23.13 ) around the
eyelids or arcus senilis of the eyes (a yellow lipid ring around the cornea) suggests
dyslipidaemia and possible atherosclerosis.
Electrocardiography is a critical tool for the diagnosis of myocardial ischaemia. Because

many individuals have normal electrocardiograms when there is no pain, diagnosis requires
that electrocardiography be performed during an episode of angina or during stress testing.
The ST segment and T wave segment of the electrocardiogram correlate with ventricular
contraction and relaxation. Transient ST segment depression and T wave inversion are
characteristic signs of subendocardial ischaemia. ST elevation, indicative of transmural (full
thickness of the heart wall) ischaemia, is seen in individuals with Prinzmetal's angina and
transmural myocardial infarction (see Fig. 23.14 ). The ECG may also indicate which coronary
artery is involved. Exercise stress testing is useful in differentiating angina from other types
of chest pain, as well as detecting ischaemic changes that occur in the absence of angina pain.
Coronary angiography helps determine the anatomical extent of coronary heart disease.
The procedure involves threading a small aperture catheter into the coronary arteries, via
arterial cannulation (usually using the femoral artery), and injecting dye directly into the
coronary arteries. Sophisticated x-rays allow visualisation of the vessels and the extent of
disease can be determined.
The primary aim of therapy for myocardial ischaemia and angina is to reduce myocardial
oxygen consumption by favourably altering its various determinants. The factors most
amenable to pharmacological manipulation are blood pressure, heart rate, contractility and
left ventricular volume. Medications that reduce vasospasm, lower cholesterol and prevent
clotting are also useful. These drugs include nitrates, β-adrenergic blocking agents, calcium
channel blockers, ACE inhibitors, lipid-lowering agents (statins) and antiplatelet agents. Such
drugs are recommended by the National Heart Foundation of Australia and the Cardiac
Society of Australia and New Zealand. It has also been demonstrated that long-acting
34
calcium channel blockers reduce the risk of stroke, angina pectoris and heart failure in
patients with coronary heart disease.35
One of the main treatment options for cardiac tissue that is affected by myocardial ischaemia
includes percutaneous (through the skin) coronary intervention, which involves accessing the
coronary arterial system in a similar manner to performing coronary angiography as
described above. Percutaneous coronary intervention includes angioplasty and stenting.
Percutaneous transluminal coronary angioplasty (PTCA) is a procedure whereby stenotic

(narrowed) coronary vessels are dilated with a balloon. As the balloon is inflated
(temporarily) a number of times, the plaque becomes compressed, thereby increasing the
blood vessel lumen. Several different types of catheters with balloons can be used to open the
blocked vessel. PTCA is generally used to treat single-vessel disease, but it can be effective
with multiple-vessel disease or restenosis (reocclusion) of a coronary artery bypass graft.
Restenosis of the artery is the major complication of the procedure. 36, 37
Improved outcomes following PTCA have been achieved by the use of coronary stenting.
Following balloon treatment during PTCA, a small cylinder of metal called a stent is inserted
into the artery — this remains permanently within the coronary vessel. Multiple stents are
often used where a few blockages are treated. Although the stent initially maintains the vessel
lumen, stents have been thrombogenic (tending to produce a thrombus [clot]) in nature and
have tended to promote hypertrophy of vessel endothelium as well as platelet plug
formation. Use of antiplatelet drugs such as abciximab (pronounced ‘ab-sick-see-mab’) has
37
improved outcomes. Furthermore, stents can be coated with drugs that are slowly released to
36
reduce the restenosis.
Coronary heart disease and associated ischaemic events can be surgically treated
using coronary artery bypass graft . This technique uses grafts from blood vessels (for
example, the internal mammary artery or saphenous vein from the leg) to oversew the
diseased coronary artery portion, such that blood flow to the myocardium can be restored.
The surgery can be performed either using cardiopulmonary bypass (the heart is stopped and
blood is circulated and oxygenated external to the body using a bypass circuit and artificial
pump) or without bypass. The requirement for this surgical treatment is based on the degree
of symptoms arising from myocardial ischaemia (angina), the extent of coronary heart
disease in multiple vessels and which coronary arteries are affected. This treatment option
would be used when coronary occlusions are severe (only a small lumen remaining open) or
widespread (affecting a number of vessels).
FOCUS ON LEARNING
 1
Define atherosclerosis and briefly describe how it forms.
 2
Discuss why hypertension and increased cholesterol increase the risk of developing
coronary heart disease.
 3
Discuss the relationships among myocardial ischaemia, angina and silent ischaemia.
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The acute coronary syndromes
The acute coronary syndromes are one of the most common causes of acute medical
admissions to Australian hospitals. The syndromes are a continuum of clinical presentations
38
that encompasses unstable angina without myocyte death through to myocardial infarction
with and without ST segment elevation. However, the terminology used to describe the acute
coronary syndromes has been changing to match clinical approaches that are more
appropriate to the patient's condition, rather than forming a definitive diagnosis upon
presentation (see Fig. 23.15 ).
FIGURE 23.15
The acute coronary syndromes: clinical presentation and possible changes to the initial working diagnosis.
The initial ECG provides a working diagnosis, which is later confirmed (or not confirmed), depending on
the ECG and presence of cardiac biomarkers in the blood. ECG = electrocardiogram.
The process of atherosclerotic plaque progression can be gradual, taking several decades
before angina manifests. Eventually plaque formation will ensue, which can be either stable
and result in stable angina, or unstable and prone to rupture and thrombus formation. When
there is sudden coronary obstruction caused by thrombus formation over a ruptured
atherosclerotic plaque, the acute coronary syndromes result. Thrombus formation on a
ruptured plaque that disperses in less than 20 minutes leads to transient ischaemia and
unstable angina. If vessel obstruction is sustained, myocardial infarction with inflammation
and necrosis of the myocardium results (see Fig. 23.16 ).
FIGURE 23.16
The pathophysiology of the acute coronary syndromes.
Atherosclerosis may lead to stable angina or unstable angina. If the ischaemia is sustained, it can lead to
myocardial infarction.
Unstable angina is the result of reversible myocardial ischaemia and is a strong indicator of
impending myocardial infarction. Acute myocardial infarction (AMI) results when there is
prolonged ischaemia causing irreversible damage to the myocytes (heart muscle cells).
Plaque disruption occurs because of shear forces, inflammation with release of multiple
inflammatory mediators, secretion of macrophage-derived degradative enzymes, immune cell
activation and apoptosis of cells at the edges of the lesions (see Fig. 23.17 ). 21, 22, 39, 40 The
underlying layer of plaque is then exposed and this causes activation of the coagulation
cascade. The resulting thrombus can form quickly. The thrombus may break up before
permanent myocyte damage has occurred (unstable angina) or it may cause prolonged
ischaemia by impeding blood flow past the thrombus and causing lack of oxygen and
nutrients to the myocardium, resulting in infarction of the heart muscle (acute myocardial
infarction; see Fig. 23.18 ). Acute myocardial infarction can be further subdivided into non-ST
elevation MI (non-STEMI) and ST elevation MI (STEMI) . Sudden cardiac death can
occur as a result of any of the acute coronary syndromes.
FIGURE 23.17
The pathogenesis of unstable plaques and thrombus formation.
Atherosclerosis can be affected by inflammation and other processes that can cause plaque rupture, with
further complications promoting vasoconstriction which further decreases the oxygen supply to the heart
muscle.
FIGURE 23.18
Acute coronary syndromes and thrombus formation resulting in angina, myocardial infarction or sudden
death.
Schematic representation of sequential progression of coronary artery lesion morphology, beginning with
stable chronic plaque responsible for typical angina and leading to the various acute coronary syndromes.
There are also alternative descriptions for the acute coronary syndromes, which are STEACS
(ST elevated MI), and NSTEACS (non-ST elevation acute coronary syndromes). NSTEACS
includes unstable angina if there is no evidence of heart cell death (by cardiac biomarkers in
the blood), and it also includes MI where there is no ST elevation. These terms are also
described below in the section ‘ Evaluation and treatment ’.
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Unstable angina
Unstable angina is a form of acute coronary syndrome that results from reversible myocardial
ischaemia. It is important to recognise this syndrome, because it signals that the
atherosclerotic plaque has become complicated and infarction may soon follow. Unstable
angina occurs when a fairly small fissuring or superficial erosion of the plaque leads to
transient episodes of thrombotic vessel occlusion and vasoconstriction at the site of plaque
damage. This thrombus is unstable and may occlude the vessel for no more than 10–20
minutes, with return of perfusion before significant myocardial necrosis occurs. Unstable
angina presents as new-onset angina, angina occurring at rest or angina that is increasing in
severity or frequency. Individuals may experience increased dyspnoea (difficulty breathing),
diaphoresis (excessive sweating) and anxiety as the angina worsens. Physical examination
may reveal evidence of ischaemic myocardial dysfunction such as tachycardia. The ECG
most commonly reveals ST segment depression and T wave inversion during pain that
resolves as the pain is relieved (see Fig. 23.14 ). Approximately 20% of individuals with
unstable angina will progress to acute myocardial infarction or death. Management of
unstable angina usually requires some form of antithrombotic therapy. In most cases,
individuals are given aspirin and clopidogrel when percutaneous coronary intervention (PCI)
is anticipated — these drugs are used to prevent platelet aggregation and therefore avoid
platelet plug formation.
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Acute myocardial infarction
When coronary blood flow is interrupted for an extended period of time, myocyte necrosis
occurs. This results in acute myocardial infarction. Pathologically, there are two major types
21
of myocardial infarction: subendocardial infarction and transmural infarction. Plaque

progression, disruption and subsequent clot formation are the same for acute myocardial
infarction as they are for unstable angina (see Figs 23.16, 23.17 and 23.18 ). In this case,
however, the thrombus is lodged in the coronary artery and occludes the vessel for a
prolonged period, such that myocardial ischaemia progresses to myocyte necrosis and death.
 •
If the thrombus breaks up before complete distal tissue necrosis has occurred, the
infarction will involve only the myocardium directly beneath the endocardium
( subendocardial infarction ).
 •
If the thrombus lodges permanently in the vessel, the infarction will extend through
the myocardium all the way from the endocardium to the pericardium, resulting in
severe cardiac dysfunction ( transmural infarction ).
Clinically, it is important to identify those individuals with transmural infarction, who are at
highest risk for serious complications and should receive definitive intervention without
delay. These individuals usually have marked elevations in the ST segments on ECG and are
categorised as having STEMI. Those without ST segment elevation are more likely to have
subendocardial infarction and are said to have non-STEMI (see Fig. 23.14 ).
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Pathophysiology
CELLULAR INJURY
Cardiac cells can withstand a lack of oxygen and blood flow for about 20 minutes before
cellular death takes place. After only 30–60 seconds of hypoxia (low oxygen levels in the
tissues), electrocardiograph changes are visible. Yet even if cells are metabolically altered
and non-functional, they can remain viable if blood flow is restored within 20 minutes.
After 8–10 seconds of decreased blood flow, the affected myocardium becomes cyanotic and
cooler. Myocardial oxygen reserves are used quickly (within about 8 seconds) after complete
cessation of coronary flow. Glycogen stores decrease as anaerobic metabolism begins.
Glycolysis can supply only 65–70% of the total myocardial energy requirement and produces
much less ATP than aerobic (oxygen-dependent) processes. Hydrogen ions and lactic acid
accumulate. Because myocardial tissues have poor buffering capabilities and myocardial cells
are sensitive to low cellular pH (build-up of acid), accumulation of these products further
compromises the myocardium. Acidosis may make the myocardium more vulnerable to the
damaging effects of lysosomal enzymes and may suppress impulse conduction and
contractile function, thereby leading to heart failure.
Oxygen deprivation is also accompanied by electrolyte disturbances, specifically the loss of

potassium, calcium and magnesium from inside the cell. Myocardial cells deprived of
necessary oxygen and nutrients lose contractility, thereby diminishing the pumping ability of
the heart. Normally, the myocardium takes up varying quantities of catecholamines
(adrenaline and noradrenaline). Significant coronary artery occlusion causes the myocardial
cells to release catecholamines, predisposing the individual to serious imbalances of
sympathetic and parasympathetic function, irregular heartbeat (arrhythmia) and heart failure
(see Fig. 23.19 ). Catecholamines mediate the release of glycogen, glucose and stored fat from
body cells. Therefore, plasma concentrations of free fatty acids and glycerol rise within 1
hour after the onset of acute myocardial infarction. Excessive levels of free fatty acids can
have a harmful effect on cell membrane structure. Noradrenaline elevates blood glucose
levels through stimulation of liver and skeletal muscle cells and suppresses pancreatic beta-
cell activity, which reduces insulin secretion and elevates blood glucose further. Not
surprisingly, hyperglycaemia is noted approximately 72 hours after acute myocardial
infarction. 41
FIGURE 23.19
Cellular and systemic events occurring after acute myocardial infarction.
This figure shows the changes caused by acute myocardial infarction. The systemic changes are shown in
pink and cellular changes in blue. ATP = adenosine triphosphate; CK-MB = myocardial band of creatine
kinase; LDH = lactate dehydrogenase.
Angiotensin II is released during myocardial ischaemia and contributes to the pathogenesis of

myocardial infarction in several ways. First, it promotes catecholamine release and causes
coronary artery spasm. Second, it results in peripheral vasoconstriction and fluid retention.
Finally, it is a growth factor for vascular smooth muscle cells, myocytes and cardiac
fibroblasts, resulting in structural changes in the myocardium called ‘remodelling’. 42
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Cellular death
After about 20 minutes of myocardial ischaemia, irreversible hypoxic injury causes cellular
death and tissue necrosis. This lack of blood flow deprives myocytes of oxygen and nutrients,
and ultimately damage to the sarcolemma (cell membrane in myocytes) and coagulation and
necrosis develop (see Chapter 4 ). This results in the release of intracellular enzymes such as
creatine kinase and myocyte proteins such as the troponins through the damaged cell
membranes into the interstitial spaces, and the lymphatic vessels pick up the enzymes and
transport them into the bloodstream, where they can be detected by blood tests.
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Structural and functional changes
With infarction, ventricular function is abnormal and the ejection fraction (the percentage of
blood ejected from the ventricles with each heartbeat, usually about 65%) falls, which results
in increases in ventricular end-diastolic volume. If the coronary obstruction involves the
perfusion to the left ventricle, pulmonary venous congestion ensues; if the right ventricle is
ischaemic, increases in systemic venous pressures occur.
Myocardial infarction results in both structural and functional changes of cardiac tissues
(see Figs 23.20 and 23.21 ). Gross tissue changes at the area of infarction may not become
apparent for several hours, despite the almost immediate onset (within 30–60 seconds) of
electrical conduction changes. Cardiac tissue surrounding the area of infarction also
undergoes changes that can be categorised into:
 1
myocardial stunning — a temporary loss of contractile function that persists for

hours to days after perfusion has been restored
 2
hibernating myocardium — tissue that is persistently ischaemic and undergoes

metabolic adaptation to prolong myocyte survival until perfusion can be restored
 3
myocardial remodelling — a process mediated by angiotensin II, aldosterone,

catecholamines, adenosine and inflammatory cytokines that causes myocyte
hypertrophy and loss of contractile function in the areas of the heart distant from the
site of infarction. 42 , 43 , 44 , 45
FIGURE 23.20
A schematic representation of myocardial infarction after acute coronary artery occlusion.
Necrosis begins in a small zone of the myocardium beneath the endocardial surface in the centre of the
ischaemic zone. This entire region of myocardium (shaded) depends on the occluded vessel for perfusion
and is the area at risk. Note that a very narrow zone of myocardium immediately beneath the endocardium
is spared from necrosis because it can be oxygenated by diffusion from the ventricle. The end result is
necrosis of the muscle that was dependent on perfusion from the obstructed coronary artery. Nearly the
entire area at risk loses viability.
FIGURE 23.21
Evidence of acute myocardial infarction of the left ventricle.
The large arrow at the top indicates an area of necrosis, coloured yellow. The far edge (right side) of the
myocardial infarction contains a myocardial haemorrhage that was associated with cardiac rupture. An old
infarct is also evident (arrowhead).
All these changes can be limited through the rapid restoration of coronary flow and the use of
ACE inhibitors or angiotensin receptor blockers and β-blockers after acute myocardial
infarction, although the magnitude of tissue damage will influence the degree of repair.
The severity of functional impairment depends on the size of the lesion and the site of
infarction. Functional changes can include: (1) decreased cardiac contractility with abnormal
wall motion; (2) altered left ventricular compliance; (3) decreased stroke volume; (4)
decreased ejection fraction; (5) increased left ventricular end-diastolic pressure; and (6)
sinoatrial node malfunction. Life-threatening arrhythmias and heart failure often follow
myocardial infarction.
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Repair
Acute myocardial infarction causes a severe inflammatory response that ends with wound
repair. Damaged cells undergo degradation, fibroblasts proliferate and scar tissue is produced.
Many cell types, hormones and nutrient substrates must be available for optimal healing to
proceed. Within 24 hours, leucocytes infiltrate the necrotic area and proteolytic enzymes
from scavenger neutrophils degrade necrotic tissue. The collagen matrix that is deposited is
initially weak, mushy and vulnerable to re-injury. Unfortunately, it is at this time in the
recovery period (10–14 days after infarction) that individuals may feel like increasing their
activities and so may stress the newly formed scar tissue. After 6 weeks, the necrotic area is
completely replaced by scar tissue, which is at full strength but cannot contract and relax like
healthy myocardial tissue.
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The first symptom of acute myocardial infarction is usually sudden, severe chest pain. The
pain is similar to angina pectoris but more severe and persistent and is not relieved by
medication or rest. It may be described as heavy and crushing. Pain radiating to the neck, jaw,
back, shoulder or left arm is common. Some individuals, especially those who are elderly or
have diabetes mellitus, experience no pain, thereby having a ‘silent’ infarction. Infarction
often simulates a sensation of unrelenting indigestion. Nausea and vomiting may occur
because of reflex stimulation of vomiting centres by pain fibres. Reflexes from the area of the
infarcted myocardium may also result in stimulation of the gastrointestinal tract via
parasympathetic nervous system reflexes. Catecholamine release results in sympathetic
stimulation, producing diaphoresis (excessive sweating) and peripheral vasoconstriction that
cause the skin to become cool and clammy.
Various cardiovascular changes are found on physical examination:
 1
Blood pressure initially decreases.
 2
The sympathetic nervous system is reflexively activated to compensate, resulting in a

temporary increase in heart rate and blood pressure.
 3
Abnormal extra heart sounds reflect left ventricular dysfunction.
 4
Pericardial friction rub (roughened membranes rubbing against each other) and
cardiac murmurs may result from inflammation.
 5
Pulmonary findings of congestion, including dullness to percussion and inspiratory

crackles at the lung bases, can occur if the individual develops pulmonary oedema.
The number and severity of post-infarction complications depend on the location and extent
of necrosis, the physiological condition of the individual before infarction and the availability
of rapid therapeutic intervention, such as thrombolysis. Sudden cardiac death may occur in
individuals with myocardial ischaemia even if infarction is absent or minimal and is a
multifactorial problem. Risk factors for sudden death are related to three factors: ischaemia,
left ventricular dysfunction and electrical instability. Table 23.5 lists the most common
complications from acute myocardial infarctions.
TABLE 23.5
Complications from acute myocardial infarctions
TYPE CHARACTERISTICS
Arrhythmias Disturbances of cardiac rhythm, which affect 90% of cardiac infarction patients
Caused by ischaemia, hypoxia, autonomic nervous system imbalances, lactic acid
electrolyte abnormalities, alterations of impulse conduction pathways or conducti
abnormalities, drug toxicity or haemodynamic abnormalities
Left ventricular failure Characterised by pulmonary congestion, reduced myocardial contractility and abn
wall motion
Cardiogenic shock can develop
Inflammation of the Includes pericardial friction rubs
pericardium Often noted 2–3 days later and associated with anterior chest pain that worsens w
(pericarditis) effort
Organic brain syndrome Can occur if brain blood flow is impaired secondary to acute myocardial infarctio
Transient ischaemic Occur if thromboemboli break loose from clots that form in the cardiac chambers
attacks or stroke valves
Rupture of heart Caused by necrosis of tissue in or around papillary muscles
structures Affects papillary muscles of chordae tendineae cordisPredisposing factors include
wall, poor collateral flow, shearing effect of muscular contraction against stiffene
area, marked necrosis at terminal end of blood supply and ageing of myocardium
laceration of myocardial microstructure
Rupture of wall of Can be caused by aneurysm formation when pressure becomes too great
infarcted ventricle
Left ventricular Late (month to years) complication of acute myocardial infarction that can contrib
aneurysm failure and thromboemboli
Infarctions around septal Occur in those structures that separate the heart chambers and lead to septal ruptu
structures Associated with audible, harsh cardiac murmurs, increased left ventricular end-dia
pressure and decreased systemic blood pressure
Systemic May disseminate from debris and clots that collect inside dilated aneurysmal sacs
thromboembolism infarcted endocardium
Pulmonary Usually from deep venous thrombi of legs
thromboembolism Reduced incidence associated with early mobilisation and prophylactic anticoagu
Sudden death Arrhythmias frequently causative, particularly ventricular fibrillation
Risk of death increased by age more than 65 years, previous angina pectoris, hypo
cardiogenic shock, acute systolic hypertension at time of admission, diabetes mell
arrhythmias and previous acute myocardial infarction
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The diagnosis of acute myocardial infarction is made on the basis of the history, physical
examination, ECG and serial enzyme alterations. The cardiac enzymes, troponin I (cTnI) and
troponin T (cTnT), are the most specific indicators of an acute myocardial infarction; these
are measured from blood tests and are referred to as cardiac biomarkers. A transient rise in
these plasma enzyme levels can confirm the occurrence of acute myocardial infarction and
indicate its severity. Other enzymes released by myocardial cells include creatine kinase-
myocardial band (CK-MB) and lactate dehydrogenase. Cardiac troponins will be within
normal levels when tissue other than cardiac muscle is damaged, therefore, troponin I and
troponin T are more specific and are elevated soon after infarction and remain elevated for
longer than other enzymes (see Fig. 23.22 ). Clinically, repeated measures of elevated troponin
and isoenzymes (enzymes with slightly different structures) over time are essential to
determine if an acute myocardial infarction has occurred. Elevation of troponin, CK-MB and
lactate dehydrogenase may be noted at characteristic times and laboratory confirmation that
an infarction has occurred may be delayed up to 12 hours.
FIGURE 23.22
Serum cardiac enzymes (biomarkers) after acute myocardial infarction.
A Graphical representation of changes in enzymes (cardiac specific and nonspecific) over
time. B Recommended times for measuring cardiac enzymes (biomarkers) when acute myocardial
infarction is suspected.
Myocardial infarction can occur in various regions of the heart wall and may be described as
anterior, inferior, posterior, lateral, subendocardial or transmural, depending on the
anatomical location and extent of tissue damage from infarction. Twelve-lead
electrocardiograms help localise the affected area through identification of Q waves and
changes in ST segments and T waves (see Fig. 23.23 ). The infarcted myocardium is
surrounded by a zone of hypoxic injury, which may progress to necrosis or return to normal.
Adjacent to this zone of hypoxic injury is a zone of reversible ischaemia. Ischaemic and
injured myocardial tissue causes ST and T wave changes. If the thrombus breaks up before
complete distal tissue necrosis has occurred, the infarction will involve only the myocardium
directly beneath the endocardium. This type of myocardial infarction most often presents
with no elevation of the ST segment on ECG and therefore is termed non-STEMI. 21, 40 A
non-STEMI is also known as a NSTEACS. It is especially important to recognise this form of
acute coronary syndrome because recurrent clot formation on the disrupted atherosclerotic
plaque is likely, with resultant infarct expansion. If the thrombus lodges more permanently in
the vessel, the infarction will extend through the myocardium from endocardium to
pericardium, resulting in severe cardiac dysfunction. This usually presents with significant
ST segment elevation on ECG (STEMI). Often a characteristic Q wave will develop on ECG
some hours later. An ST elevated myocardial infarction (STEMI) requires rapid intervention
to prevent serious complications and sequelae. STEMI is also referred to as STEACS, as it
represents a ST elevation acute coronary syndrome.
FIGURE 23.23
Electrographic changes associated with different zones of myocardial infarction.
The pattern of changes in the ECG resemble the time course of progression from ischaemia (T wave
inversion), injury (ST elevation), and finally infarction (deep Q wave).
Additional laboratory data may reveal leucocytosis, elevated sedimentation rate and C-
reactive protein, all of which indicate inflammation. The blood glucose level is usually
elevated and the glucose tolerance level may remain abnormal for several
weeks. Hypoxaemia may also accompany heart failure.
41
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Treatment
Acute myocardial infarction requires admission to hospital, often directly into an acute
cardiac unit. The individual may be given aspirin immediately, with sublingual glyceryl
trinitrate providing both pain relief as well as promoting coronary vasodilation to improve
oxygenation to the heart muscle cells. Pain relief is of utmost importance, and frequently also
involves the use of intravenous morphine. Continuous monitoring of cardiac rhythms and
enzymatic changes is essential, because the first 24 hours after onset of symptoms is the time
of highest risk for sudden death. Both non-STEMI and STEMI are frequently managed with
the urgent administration of thrombolytics or by percutaneous coronary intervention along
with antithrombotics. Further management may include ACE inhibitors and β-blockers
depending on haemodynamic state. Individuals who are in shock require aggressive fluid
resuscitation, inotropic drugs (drugs that increase contraction of the myocardium) and
possible emergency invasive procedures (see the section on shock later in this chapter).
FOCUS ON LEARNING
 1
Describe the coronary heart disease–myocardial ischaemia continuum.
 2
Describe the pathophysiology of a myocardial infarction.
 3
Detail complications associated with the period after infarction.
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Aneurysm
An aneurysm is a localised dilation or outpouching of a vessel wall or cardiac chamber.
Aneurysms form in arteries when there is disruption of the wall of the vessel associated with
changes in collagen and elastin, which make the vessel more vulnerable to intravascular
pressures. The aorta is particularly susceptible to aneurysm formation because of constant
stress on the vessel wall. Some 75% of all aneurysms occur in the abdominal aorta (see Fig.
23.24 ). Atherosclerosis is the most common cause of arterial aneurysms because plaque
formation erodes the vessel wall and contributes to inflammation that can further weaken the
vessel. Hypertension also contributes to aneurysm formation by increasing wall stress.
FIGURE 23.24
Aortic aneurysm.
An abdominal aortic aneurysm (*) is distal to the renal arteries (white arrows). The large pouching of the
artery occurs due to atherosclerosis weakening the wall, and the high pressure of the arterial system causes
the bulging of the vessel. Aortic aneurysms tend to enlarge over time and if undiscovered or untreated can
rupture, often leading to death.
Aortic aneurysms are often asymptomatic until they leak and and possibly rupture,
when they become painful. Aortic aneurysms are often
asymptomatic until they leak and possibly rupture, when they
become painful. Symptoms of dysphagia (difficulty swallowing) and
dyspnoea (breathlessness) are caused by the pressure of a thoracic
aneurysm on surrounding organs. An aneurysm that impairs flow to
an extremity causes symptoms of ischaemia. Cerebral aneurysms
are associated with signs and symptoms of increased intracranial
pressure and can relate to stroke. (Cerebral aneurysms are
described in Chapter 9 .)
The diagnosis of an aneurysm is usually confirmed by

ultrasonography, CT scan, MRI or angiography. The goals of medical
treatment of aneurysms are to maintain a low blood volume and low
blood pressure to decrease the mechanical forces thought to
contribute to vessel wall dilation. Medical treatment is indicated for
slow-growing aortic aneurysms, particularly in the early stages, and
includes smoking cessation, reducing blood pressure and blood
volume. For those aneurysms that are dilating rapidly, surgical
treatment is often indicated. Surgery may be considered when
aortic aneurysms become large and usually includes replacement
with a prosthetic graft. New endovascular surgical techniques make
aneurysm repair possible for more individuals.
4.2
Heart failure
Heart failure is a syndrome encompassing several different types of cardiac dysfunction that
result in inadequate perfusion of tissues with oxygen and blood-borne nutrients. Providing a
definition of heart failure is difficult because consensus has been hard to achieve; however, it
is now considered that both clinical features and an objective measure of abnormal
ventricular function are required to adequately diagnose heart failure. The National Heart
Foundation of Australia and the Cardiac Society of Australia and New Zealand have
formulated the following definition:
Heart failure is a complex clinical syndrome that is frequently, but not exclusively,
characterised by an underlying structural abnormality or cardiac dysfunction that impairs the
ability of the left ventricle (LV) to fill with or eject blood, particularly during physical
activity. Symptoms of CHF (congestive heart failure) (e.g. dyspnoea and fatigue) can occur at
rest or during physical activity.
66
Heart failure occurs in up to 1.5–2% of all Australians; with over one-third with the
66
condition aged 75 years or over. Most causes of heart failure result from dysfunction of the
left ventricle (systolic and diastolic heart failure). The right ventricle may also be
dysfunctional, especially in pulmonary disease (right ventricular failure). Coronary heart
disease and acute myocardial infarction are documented in about two-thirds of systolic heart
failure patients. Essential hypertension is also strongly associated with heart failure and is
present in approximately two-thirds of all newly diagnosed cases. In the following sections
66
we examine heart failure and its relationship to other cardiovascular diseases.
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Left heart failure
Left heart failure , commonly called congestive heart failure , can be further categorised as
systolic heart failure or diastolic heart failure. These two types of heart failure can occur
together or in isolation.
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Systolic heart failure
Systolic heart failure is defined as an inability of the heart to generate adequate cardiac
output to perfuse vital tissues. Cardiac output depends on the heart rate and stroke volume.
Stroke volume is influenced by three major determinants: contractility, preload and afterload
(refer to Chapter 22 ).
Contractility is reduced by diseases that disrupt myocyte activity. Myocardial infarction is the
most common primary cause of decreased contractility; other causes include myocarditis and
the cardiomyopathies. Secondary causes of decreased contractility, such as recurrent
myocardial ischaemia and increased myocardial workload, contribute to inflammatory,
immune and neurohumoral changes that mediate a process called ventricular
remodelling (see ‘Research in Focus: Inflammation, immunity and humoral factors in the
pathogenesis of heart failure’). 16, 67 Ventricular remodelling results in hypertrophy and
dilation of the myocardium and causes progressive myocyte contractile dysfunction over time
(see Fig. 23.41 ). When contractility is decreased, stroke volume falls and ventricular end-
diastolic volume increases. This causes dilation of the heart and an increase in preload.
RESEARCH IN FOCUS
Inflammation, immunity and humoral factors in the pathogenesis of heart failure
The treatment of the haemodynamic abnormalities of heart failure can provide short-term
improvement in symptoms but will not prevent the progression of myocardial dysfunction
over time. Studies have shown that neurohumoral responses to heart failure (including
changes in the renin-angiotensin-aldosterone system, catecholamines, natriuretic peptides,
endothelin and nitric oxide) exert direct cardiotoxicity that results in progressive damage to
the heart muscle. Drugs such as ACE inhibitors, angiotensin II receptor blockers and β-
blockers can slow disease progression and are now the standard of care for heart failure. In
2016, a new treatment was approved for clinical use that combines an angiotensin II receptor
antagonist with a neprilysin (protease) inhibitor. Inflammatory cytokines such as tumour
necrosis factor-alpha (TNF-α) and interleukins have been implicated in the pathogenesis of
heart failure and its systemic complications. However, trials with anticytokine drugs have
failed to show significant improvements.
FIGURE 23.41
The pathophysiology of ventricular remodelling.
Myocardial dysfunction activates the renin-angiotensin-aldosterone and sympathetic nervous systems
releasing neurohormones (angiotensin II, aldosterone, catecholamines and cytokines). These
neurohormones contribute to ventricular remodelling.
Preload increases with decreased contractility or an excess of plasma volume (intravenous

fluid administration, renal failure, mitral valvular disease). Increases in preload can actually
improve cardiac output, but as preload continues to rise, it causes a stretching of the
myocardium that eventually can lead to dysfunction of the sarcomeres and decreased
contractility. This relationship is described by the Frank-Starling law of the heart, which
details the length–tension relationship between end-diastolic volume and stroke volume in the
ventricle. (This was reviewed in Chapter 22 .)
However, with sarcomere dysfunction resulting in decreased contractility, increases in end-

diastolic volume do not result in increases in stroke volume. In fact, decreased contractility
leads to further increases in preload (see Fig. 23.42 ), which causes a lowering of cardiac
output for a given ventricular end-diastolic volume (see Fig. 23.43 ). In this scenario, across
the range of end-diastolic volumes, cardiac performance is less than normal, as increases in
stroke volume do not occur to the same magnitude as the normal heart because of the damage
to the myocytes.
FIGURE 23.42
The effect of elevated preload on myocardial oxygen supply and demand.
Increased preload beyond optimal levels, causes excess myocardial stretching and ischaemia, which may
decrease contractility.
FIGURE 23.43
The relationship between ventricular end-diastolic volume and stroke during normal contraction and heart
failure.
The Frank-Starling law of the heart is the relationship between length (end-diastolic volume) and tension
(stroke volume) in the heart. In the normal heart, increases in end-diastolic volume cause an increase in
stroke volume, thereby increasing cardiac output. In heart failure, decreased contractility leads to reduced
cardiac output, as increases in end-diastolic volume do not cause similar increases in stroke volume.
Therefore, the curve is shifted downwards over the range of end-diastolic volumes.
Increased afterload is most commonly a result of increased peripheral vascular resistance,

such as that seen with hypertension. With increased afterload, there is resistance to
ventricular emptying and more work for the ventricle, which results in myocardial
hypertrophy. Hypertrophy is mediated by angiotensin II and catecholamines and results in an
increase in oxygen demand by the thickened myocardium. A state of relative ischaemia
develops, which further contributes to changes in the myocytes themselves and ventricular
remodelling (see Fig. 23.44 ). In addition, hypertrophy results in the deposition of collagen
between the myocytes, which can disrupt the integrity of the muscle, decrease contractility
and make the ventricle more likely to dilate and fail.
FIGURE 23.44
The role of increased afterload in the pathogenesis of heart failure.
Increased afterload causes increased resistance in the aorta and other arteries, and as a result it is more
difficult for the left ventricle to eject blood. As a result, the cardiac output from the left side is insufficient,
which can lead to impairment of blood flow to the kidneys. In turn, this activates the renin-angiotensin-
aldosterone system and sympathetic nervous system. Together, these lead to ventricular remodelling which
can decrease contractility.
As cardiac output falls, renal perfusion diminishes with activation of the renin-angiotensin-
aldosterone system, which acts to increase both peripheral vascular resistance and plasma
volume, thus further increasing afterload and preload. In addition, baroreceptors in the central
circulation detect the decrease in perfusion and stimulate the sympathetic nervous system to
cause yet more vasoconstriction and the hypothalamus to produce antidiuretic hormone. The
neurohumoral aspects of systolic heart failure suggest that treatment must include inhibition
of angiotensin, aldosterone and catecholamines to prevent long-term damage to the
myocardium. 16, 67 Immune and inflammatory processes also play an important role in the
pathogenesis of heart failure and its systemic complications. This vicious cycle of decreasing
contractility, increasing preload and increasing afterload causes progressive worsening of
systolic heart failure (see Fig. 23.45 ).
FIGURE 23.45
The vicious cycle of heart failure.
Insufficient ventricular function leads to increased vasoconstriction, and decreased renal perfusion leading
to fluid retention. Together, these increase the workload of the heart, leading to further ventricular
dysfunction.
Source: Reproduced with permission from Guidelines for the prevention, detection and management of
chronic heart failure in Australia Updated October 2011. © 2011 National Heart Foundation of Australia.
The clinical manifestations of systolic heart failure are the result of pulmonary vascular
congestion and inadequate perfusion of the systemic circulation. Individuals experience
dyspnoea, orthopnoea (experiencing dyspnoea when lying flat — individuals compensate by
sitting upright), cough of frothy sputum, fatigue, decreased urine output and oedema.
Physical examination often reveals pulmonary oedema (see Chapter 25 ), hypotension or
hypertension and evidence of underlying coronary heart disease or hypertension. The
diagnosis can be further confirmed with echocardiography revealing decreased cardiac output
and cardiomegaly.
Management of systolic left heart failure is aimed at interrupting the worsening cycle of
decreasing contractility, increasing preload and increasing afterload. The acute onset of
66
systolic left heart failure is most often the result of acute myocardial ischaemia and must be
managed in conjunction with managing the underlying coronary disease. Oxygen, nitrate and
morphine administration improves myocardial oxygenation and helps relieve coronary spasm
while lowering preload through systemic venodilation. Intravenous inotropic drugs, such as
dopamine or dobutamine, increase contractility and can help raise the blood pressure in
hypotensive individuals. Diuretics reduce preload and ACE inhibitors, angiotensin receptor
blockers and aldosterone blockers reduce both preload and afterload by decreasing
aldosterone levels and reducing peripheral resistance. Short-acting intravenous β-blockers
also have been found to reduce mortality in selected people.
Management of chronic left heart failure also relies on increasing contractility and reducing
preload and afterload. The current evidence-based standard of care for individuals in
Australia and New Zealand is outlined in Tables 23.12 and 23.13 .
TABLE 23.12
Non-pharmacological management of heart failure
GRADE OF
RECOMMENDAT
Regular physical activity is recommended. All patients should be referred to a B
specifically designed physical activity program, if available
Patient support by a doctor and pre-discharge review and/or home visit by a nurse is A
recommended to prevent clinical deterioration
Patients frequently have coexisting sleep apnoea and, if suspected, patients should be D
referred to a sleep clinician as they may benefit from nasal CPAP
Patients who have an acute exacerbation, or are clinically unstable, should undergo a D
period of bed rest until their condition improves
Dietary sodium should be limited to below 2 g/day C
Fluid intake should generally be limited to 1.5 L/day with mild to moderate symptoms, C
and 1 L/day in severe cases, especially if there is coexistent hyponatraemia
Alcohol intake should preferably be nil, but should not exceed 10–20 g a day (1 or 2 D
standard drinks)
Smoking should be strongly discouraged D
Patients should be advised to weigh themselves daily and to consult their doctor if their D
weight increases by more than 2 kg in a 2-day period, or if they experience dyspnoea,
oedema or abdominal bloating
Patients should be vaccinated against influenza and pneumococcal disease B
High-altitude destinations should be avoided. Travel to very humid or hot climates C
should be undertaken with caution, and fluid status should be carefully monitored
Sildenafil and other phosphodiesterase V inhibitors are generally safe in patients with C
heart failure. However, these medications are contraindicated in patients receiving
nitrate therapy, or those who have hypotension, arrhythmias or angina pectoris
GRADE OF
RECOMMENDAT
Obese patients should be advised to lose weight D
A diet with reduced saturated fat intake and a high fibre intake is encouraged in D
patients with chronic heart failure
No more than 2 cups of caffeinated beverages per day recommended D
Pregnancy should be avoided in patients with chronic heart failure D
CPAP = continuous positive airway pressure.
*GRADE OF RECOMMENDATION DESCRIPTION
A Rich body of high-q
data
B Limited body of RC
high-quality non-RC
C Limited evidence
D No evidence availab
consensus judgmen
RCT = randomised control trial.
TABLE 23.13
Pharmacological management of heart failure
Source: Reproduced with permission from Guidelines for the prevention, detection and management of
chronic heart failure in Australia Updated October 2011. © 2011 National Heart Foundation of Australia.
RECOMMENDATIONS FOR PREVENTING CHF AND TREATING ASYMPTOMATIC GRADE OF
LV DYSFUNCTION RECOMMEN
All patients with asymptomatic systolic LV dysfunction should be treated with an ACEl A
indefinitely, unless intolerant
Anti-hypertensive therapy should be used to present subsequent CHF in patients with A
elevated blood pressure
Preventive treatment with an ACEI may be considered in individual patients at high risk of B
ventricular dysfunction
Beta-blockers should be commenced early after an Ml, whether or not the patient has B
systolic ventricular dysfunction
Statin therapy should be used as part of a risk management strategy to prevent ischaemic B
events and subsequent CHF in patients who fulfil criteria for lipid-lowering
RECOMMENDATIONS FOR PHARMACOLOGICAL TREATMENT OF GRADE OF
SYMPTOMATIC CHF RECOMME
First-line agents
ACEIs. unless not tolerated or contraindicated, are recommended for all patients with A
systolic heart failure (LVEF < 40%), whether symptoms are mild, moderate or severe
Every effort should be made to increase doses of ACEIs to those shown to be of benefit in B
RECOMMENDATIONS FOR PREVENTING CHF AND TREATING ASYMPTOMATIC GRADE OF
LV DYSFUNCTION RECOMMEN
major trials. If this is not possible, a lower dose of ACEI is preferable to none at all
Diuretics should be used, if necessary, to achieve euvolaemia in fluid-overloaded patients. D
In patients with systolic LV dysfunction, diuretics should never be used as monotherapy, but
should always be combined with an ACEl to maintain euvolaemia
Beta-blockers are recommended, unless not tolerated or contraindicated, for all patients A
with systolic CHF who remain mildly to moderately symptomatic despite appropriate doses
of an ACEI
Beta-blockers are also indicated for patients with symptoms of advanced CHF B
Aldosterone receptor blockade with spironolactone is recommended for patients who B
remain severely symptomatic, despite appropriate doses of ACEIs and diuretics
Aldosterone blockade with eplerenone should be considered in systolic heart failure B
patients who still have mild (NYHA Class II) symptoms despite receiving standard therapies
(ACEl, beta- blocker)
Angiotensin II receptor antagonists may be used as an alternative in patients who do not A
tolerate ACEIs due to kinin-mediated adverse effects (e.g. cough). They should also be
considered for reducing morbidity and mortality in patients with systolic CHF who remain
symptomatic despite receiving ACEIs
Direct sinus node inhibition with ivabradine should be considered for CHF patients with B
impaired systolic function and a recent heart failure hospitalisation who are in sinus rhythm
where their heart rate remains ≥ 70 bpm despite efforts to maximise dosage of background
beta-blockade
Second-line agents
Digoxin may be considered for symptom relief and to reduce hospitalisation in patients with B
advanced CHF. It remains a valuable therapy in CHF patients with AF
Hydralazine-isosorbide dinitrate combination should be reserved for patients who are B
truly intolerant of ACEIs and angiotensin II receptor antagonists, or for whom these agents
are contraindicated and no other therapeutic option exists
Fish oil (n-3 polyunsaturated fatty acids) should be considered as a second-line agent for B
patients with CHF who remain symptomatic despite standard therapy which should include
ACEIs or ARBs and beta-blockers if tolerated
Other agents
Amlodipine and felodipine can be used to treat comorbidities such as hypertension and B
CHD in patients with systolic CHF. They have been shown to neither increase nor decrease
mortality
Iron deficiency should be looked for and treated in CHF patients to improve symptoms, B
exercise tolerance and quality of life
* Refer to Table 23.12 for description of grades of recommendation.
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Diastolic heart failure
Diastolic heart failure is also known as heart failure with preserved systolic function.
Diastolic heart failure can occur in isolation or along with systolic heart failure. Isolated
diastolic heart failure is common and may account for up to 40% of all chronic heart failure
cases. It is defined as pulmonary congestion (see Chapter 25 ) despite a normal stroke volume
66
and cardiac output. It results from decreased compliance of the left ventricle and abnormal
diastolic relaxation such that a normal left ventricular end-diastolic volume results in an
increased left ventricular end-diastolic pressure. This pressure is reflected back into the
pulmonary circulation and results in pulmonary oedema. The major causes of diastolic
dysfunction include hypertension-induced myocardial hypertrophy and myocardial ischaemia
with resultant ventricular remodelling.
Individuals with diastolic dysfunction present with dyspnoea on exertion, fatigue and
evidence of pulmonary oedema. There may also be evidence of underlying coronary heart
disease, hypertension or valvular disease. Diagnosis is made initially by echocardiography,
which demonstrates poor ventricular filling with normal ejection fractions. Management is
aimed at improving ventricular relaxation and prolonging diastolic filling times to reduce
diastolic pressure.
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Right heart failure
Right heart failure can result from left heart failure when an increase in left ventricular
filling pressure is reflected back into the pulmonary circulation. As pressure in the pulmonary
circulation rises, the resistance to right ventricular emptying increases (see Fig. 23.46 ). The
right ventricle is poorly prepared to compensate for the increased afterload and dilates and
fails. When this happens, pressure rises in the systemic venous circulation, resulting in
peripheral oedema and hepatosplenomegaly (enlarged liver and spleen). Treatment relies on
management of the left ventricular dysfunction. When right heart failure occurs in the
absence of left heart failure, it is caused most commonly by diffuse hypoxic pulmonary
disease such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, cor
pulmonale and adult respiratory distress syndrome (ARDS) (see Chapter 25 ). These disorders
result in an increase in right ventricular afterload.
FOCUS ON LEARNING
 1
Differentiate between systolic and diastolic heart failure.
 2
Outline the process of ventricular remodelling.
 3
Describe the vicious cycle of systolic heart failure.
FIGURE 23.46
Right-sided heart failure.
Lung disease is a main cause of right-sided heart failure, as it increases the work required by the right side
of the heart to eject blood into the dysfunctional lungs. The lung disease alters the blood pressure in the
pulmonary circuit, increasing the workload for the right side of the heart. RA = right atrial; RV = right
ventricular.
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Shock
In shock , the cardiovascular system fails to perfuse the tissues adequately, resulting in
widespread impairment of cellular metabolism. Because tissue perfusion can be disrupted by
any factor that alters heart function, blood volume or blood pressure, shock has many causes
and various clinical manifestations. Ultimately, however, a vicious cycle ensues and shock
progresses to organ failure and death unless compensatory mechanisms reverse the process or
clinical intervention succeeds. Untreated severe shock overwhelms the body's compensatory
mechanisms through positive feedback loops that initiate and maintain a downward
physiological spiral.
The term multiple organ dysfunction syndrome (MODS) describes the failure of two or
more organ systems after severe illness and injury and is a frequent complication of severe
shock. The disease process is initiated and perpetuated by uncontrolled inflammatory and
stress responses. It is progressive and is associated with significant mortality.
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Impairment of cellular metabolism
The final common pathway in shock of any type is impairment of cellular metabolism. Fig.
23.47 illustrates the pathophysiology of shock at the cellular level.
FIGURE 23.47
Impaired cellular metabolism in shock.
Significant alterations in oxygen and glucose usage lead to severely dysfunctional cell metabolism.
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Impairment of oxygen use
In all types of shock, the cell either is not receiving an adequate amount of oxygen or is
unable to use oxygen. Without oxygen, the cell shifts from aerobic to anaerobic metabolism.
Anaerobic metabolism decreases ATP stores and affects the pH of the cell. Without ATP, the
cell cannot operate the Na + -K + pump such that cells of the nervous system and myocardium
cannot function properly. The lack of pH control leads to metabolic acidosis. Enzymes
necessary for cellular function dissociate under acid conditions. Enzyme dissociation stops
cell function, repair and division. As lactic acid is released systemically, blood pH drops,
reducing the oxygen-carrying capacity of the blood. Therefore, less oxygen is delivered to the
cells. Further acidosis triggers the release of more lysosomal enzymes because the low pH
disrupts lysosomal membrane integrity — and the vicious cycle continues.
Three positive feedback loops further impair oxygen use: (1) activation of the coagulation
cascade; (2) decreased circulatory volume; and (3) toxin (lysosomal enzyme) release. The
coagulation cascade activates the inflammatory response and causes clotting in the peripheral
venous circulation leading to a decrease in venous return. Decreased blood volume causes the
second positive feedback loop and magnifies decreased tissue perfusion in all types of shock.
Toxin release, the third positive feedback loop, not only injures the cell that released it but
also injures adjacent cells. By damaging the mechanisms of the surrounding cells, the
lysosomal enzymes that leak from the cells extend the areas of impaired metabolism and
cellular injury.
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Impairment of glucose use
Impaired glucose use can be caused by either impaired glucose delivery or impaired glucose
uptake by the cells. Cells shift to alternative processes (namely glycogenolysis,
gluconeogenesis and lipolysis) to generate fuel for survival. The energy costs of
glycogenolysis and lipolysis are considerable and contribute to cellular failure. When
gluconeogenesis causes proteins to be used for fuel, these proteins are no longer available to
maintain cellular structure, function, repair and replication. As proteins are broken down,
ammonia and urea are produced. Ammonia is toxic to living cells. Uraemia (high urea levels)
develops and uric acid further disrupts cellular metabolism. Serum albumin and other plasma
proteins are consumed for fuel first. Serum protein consumption decreases capillary osmotic
pressure and contributes to the development of interstitial oedema, creating another positive
feedback loop that decreases circulatory volume.
A final outcome of impaired cellular metabolism is the build-up of metabolic end products in
the cell and interstitial spaces. Waste products are toxic to the cells and further disrupt
cellular function and membrane integrity. Once a sufficiently large number of cells from vital
organs have damage to their cellular membranes, leakage of lysosomal enzymes and ATP
depletion, shock can be irreversible.
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Types of shock
There are several different types of shock: cardiogenic, hypovolaemic, neurogenic,
anaphylatic and septic shock. Cardiogenic shock is defined clinically by ‘myocardial
dysfunction and tissue hypoxia in the presence of adequate intravascular volume’ and most
cases follow acute myocardial infarction. Hypovolaemic shock is caused by a large loss of
fluid volume, whether it be blood, plasma or interstitial fluid. Neurogenic or vasogenic shock
is the result of vasodilation that results from parasympathetic overstimulation and
sympathetic understimulation. Anaphylatic shock results as an allergic reaction to an allergen
and leads to similar physical alterations as neurogenic shock. Septic shock is part of the
systemic inflammatory response syndrome (SIRS). It begins with an infection that progresses
to bacteraemia, then sepsis, severe sepsis and septic shock. All shocks may lead to multiple
organ dysfunction syndrome (MODS). Table 23.14 summarises the key components of the
different types of shock.
TABLE 23.14
Types of shock
TYPE CAUSE PHYSIOLOGICAL ADAPTATIONS
Hypovolaemic Loss of fluid volume Heart rate ↑, peripheral resistance Failed compensation and
shock ↑, cardiac output ↑, tissue perfusion, poor skin turgo
perfusion ↑ (initially), water oliguria, low preload, tach
TYPE CAUSE PHYSIOLOGICAL ADAPTATIONS
retention ↑ (initially) thready pulse, ↓ mental st
Cardiogenic Myocardial dysfunction, Heart rate ↑, preload ↑, stroke ↓ mental status, dusky ski
shock tissue hypoxia volume ↑, systemic and hypotension, oliguria, dys
pulmonary oedema ↑
Neurogenic Trauma to spinal cord or Interrupted sympathetic activity, Bradycardia
shock medulla, Interrupted supply relative hypovolaemia to
of oxygen or glucose to the vasodilation, peripheral vascular
medulla, depressive drugs, resistance ↓, tissue hypoperfusion
anaesthetic agents, severe
emotional stress and pain
Anaphylatic Anaphylaxis Vasodilation, peripheral pooling, Sudden and progression to
shock hypovolaemia, tissue mins, anxiety, difficulty b
hypoperfusion gastrointestinal cramps, o
burning and itching of ski
pressure, ↓ mental status
Septic shock Microorganism Activated complement system and Tachycardia, systemic inf
coagulation cascade, activated response syndrome (SIRS
kinins, activated inflammatory pressure, temperature inst
response, widespread deranged renal function, g
vasodilation, cardiac output ↑, mucosa changes that allow
myocardial contractility ↓, into the blood stream, jaun
hypoperfusion, low peripheral abnormalities, deterioratio
vascular resistance, systemic status, adult respiratory di
oedema syndrome
Share
Cardiogenic shock
Cardiogenic shock is defined as ‘decreased cardiac output and evidence of tissue hypoxia in
the presence of adequate intravascular volume’. Most cases of cardiogenic shock follow acute
myocardial infarction, because the myocardium is damaged and therefore contractions are
inadequate. Cardiogenic shock is often unresponsive to treatment, with a mortality of more
than 70% reported. The pathophysiology of cardiogenic shock is outlined as a concept map
in Fig. 23.48 .
FIGURE 23.48
Cardiogenic shock.
Shock becomes life threatening when compensatory mechanisms (in blue) cause increased myocardial
oxygen requirements. Renal and hypothalamic adaptive responses (i.e. renin-angiotensin-aldosterone and
antidiuretic hormone) maintain or increase blood volume. The adrenal gland releases catecholamines (e.g.
mostly adrenaline, some noradrenaline), causing vasoconstriction and increases in contractility and heart
rate. These adaptive mechanisms, however, increase myocardial demands for oxygen and nutrients. These
demands further strain the heart, which can no longer pump an adequate volume, resulting in shock and
impaired metabolism. SVR = systemic vascular resistance.
The clinical manifestations of cardiogenic shock are caused by widespread impairment of
cellular metabolism. They include impaired mentation, elevated preload in the systemic and
pulmonary vasculature, systemic and pulmonary oedema, dusky skin colour, hypotension,
oliguria (low urine output) and dyspnoea. Management of cardiogenic shock includes careful
fluid and catecholamine administration.

Secondary Hypertension

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Secondary Hypertension

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Secondary hypertension

 Caused by an underlying disease process or medication that raises peripheral vascular

Isolated systolic hypertension

 The normal or compensatory vasoconstrictor response to standing is absent so that

Orthostatic hypotension may be acute and temporary or chronic:

Chronic orthostatic hypotension may be (1) secondary to a specific disease or (2)

bladder dysfunction are common.

Although no curative treatment is available for orthostatic hypotension, often it can be

Evaluation and treatment

male or female after menopause

Modifiable risk factors include:

dyslipidaemia and atherosclerosis-promoting diet

diabetes mellitus and insulin resistance

obesity and a sedentary lifestyle.

We now focus our attention on discussing these modifiable risk factors.

Dyslipidaemia refers to abnormal concentrations of serum lipoproteins. The National Heart

Low-density lipoprotein cholesterol (LDL-C)

High-density lipoprotein cholesterol (HDL-C)

Non–high-density lipoprotein cholesterol (NHDL-C)

An increased serum concentration of LDL is considered a strong indicator of coronary risk.

HMG-CoA reductase inhibitors, more commonly referred to as statins, is associated with a

in modest increases in HDL. LDL is often referred to as ‘bad’ cholesterol (atherogenic —

Metabolic syndrome is a combination of central (abdominal) obesity, abnormal glucose

factors for coronary heart disease.

Moreover, for a non-cardiac patient, exercise provides protection if there is a cardiovascular

Myocardial ischaemia develops if blood flow or oxygen content of coronary blood is

Evaluation and treatment

Electrocardiography is a critical tool for the diagnosis of myocardial ischaemia. Because

Percutaneous transluminal coronary angioplasty (PTCA) is a procedure whereby stenotic

reduce the restenosis.

Define atherosclerosis and briefly describe how it forms.

of myocardial infarction: subendocardial infarction and transmural infarction. Plaque

Oxygen deprivation is also accompanied by electrolyte disturbances, specifically the loss of

Angiotensin II is released during myocardial ischaemia and contributes to the pathogenesis of

myocardial stunning — a temporary loss of contractile function that persists for

hibernating myocardium — tissue that is persistently ischaemic and undergoes

myocardial remodelling — a process mediated by angiotensin II, aldosterone,

Various cardiovascular changes are found on physical examination:

Blood pressure initially decreases.

The sympathetic nervous system is reflexively activated to compensate, resulting in a

Abnormal extra heart sounds reflect left ventricular dysfunction.

Pulmonary findings of congestion, including dullness to percussion and inspiratory

Describe the coronary heart disease–myocardial ischaemia continuum.

Describe the pathophysiology of a myocardial infarction.

Detail complications associated with the period after infarction.

The diagnosis of an aneurysm is usually confirmed by

we examine heart failure and its relationship to other cardiovascular diseases.

Preload increases with decreased contractility or an excess of plasma volume (intravenous

However, with sarcomere dysfunction resulting in decreased contractility, increases in end-

Increased afterload is most commonly a result of increased peripheral vascular resistance,

* Refer to Table 23.12 for description of grades of recommendation.

Differentiate between systolic and diastolic heart failure.

Outline the process of ventricular remodelling.

Describe the vicious cycle of systolic heart failure.

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