Cardio Learning Topics Block 5

http://smp.sydney.edu.
au/compass/guide/handbook/block/5
LEARNING TOPICS - BLOCK 5
Cardiovascular Sciences
1. Activation of the heart

2. Assessing peripheral vascular disease
3. Atrial fibrillation
4. Causes of heart failure
5. Causes of tiredness
6. Chromosomal abnormalities and early development in Down syndrome
7. Chronic viral infections
8. Clinical and laboratory assessment in heart failure
9. Complications of ischaemic heart disease
10. Complications of rheumatic heart disease
11. Cyanosis: causes and consequences
12. Detecting alcohol abuse
13. Discovery of circulation: Harvey film (TIMETABLE)
14. Doctors' dilemmas: treating friends family
15. Drug therapy for stable effort angina
16. Essential Life Support
17. Features of Down syndrome
18. Flow and pressures in the circulation
19. Functions of the heart as a pump
20. Genesis of atheroma
21. Gross and fine anatomy of blood vessels
22. History of chronic fatigue syndrome
23. Immune mechanisms in rheumatic fever
24. Lifestyle modification in vascular disease
25. Long term management of childhood cardiac disease
26. Medicolegal issues in information-giving
27. Microbiology of endocarditis and rheumatic heart disease
28. Normal ECG
29. Oedema
30. Overview of cardiovascular function
31. Overview of congenital heart disease
32. Pathogenesis of hypertension
33. Pathophysiology of hypertension
34. Pathophysiology of ischaemia
35. Personality and coronary heart disease
36. Pregnancy and cardiovascular system
37. Prenatal Diagnosis and Down Syndrome
38. Regulation of cerebral blood flow
39. Short term regulation of blood pressure
40. Social roles: responses to health and illness
41. Structure of heart and great vessels
42. Support for carers
43. Syncope
44. The foetal circulation
45. Treatments for hypertension
46. Ventricular arrhythmias
LEARNING TOPIC - Activation of the heart
Activation of the heart includes
all the processes which determine and regulate the heart rate
the way in which electrical activity spreads across the heart
the processes which link electrical activity in the individual cardiac cells to their contraction.
Important clinical topics which depend on these concepts are the electrocardiogram and arrhythmias.
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The pacemakers
The heart rate is determined by the activity of small regions of spontaneously excitable tissue known as
pacemakers. Just as in other excitable tissues the electrical activity is a depolarisation of the membrane potential
Activation of the heart includes
http://smp.sydney.edu.au/compass/guide/handbook/block/5
all the processes which determine and regulate the heart rate
the way in which electrical activity spreads across the heart
the processes which link electrical activity in the individual cardiac cells to their contraction.
Important clinical topics which depend on these concepts are the electrocardiogram and arrhythmias.
The pacemakers
The heart rate is determined by the activity of small regions of spontaneously excitable tissue known as
pacemakers. Just as in other excitable tissues the electrical activity is a depolarisation of the membrane potential
known as the action potential. The activity of these pacemakers is modified by the autonomic nervous system;
this is the mechanism by which the heart rate increases when we are frightened and decreases during sleep. You
need to be familiar with
the name, intrinsic rate and site of the primary, secondary and tertiary pacemakers
be able to draw the action potential from a pacemaker cell and show how sympathetic transmitters
accelerate the heart rate and parasympathetic transmitters slow the heart rate
know the normal heart rate, the range over which it can change and the consequences for cardiac function
if you like more biophysical problems, understanding the currents which lead to spontaneous cyclical
activity is a fascinating issue
start to think about what will happen if one or other of the pacemaker stops working or goes too fast or too
slow (not many clocks run for 70 years without any problems and the heart is no exception).
The spread of electrical activity
The principle is that the primary pacemaker in the sinoatrial node determines the heart rate and the electrical
activity then spreads over the heart. For mechanical reasons the atria and the ventricles both need to contract
more or less synchronously whereas, because atrial contraction assists filling of the ventricles, it is important that
atrial contraction precedes ventricular contraction. To understand these issues, which are essential to
understanding the electrocardiogram, you need to be able to
describe and draw a diagram of the pathway by which electrical activity spreads over the heart
draw a table showing the parts of the pathway, their intrinsic rate if spontaneously active, the velocity of
conduction and the approximate delay
start to think about how all this leads to the electrocardiogram (a difficult issue unless you are an electrical
engineer used to describing currents in 3 dimensional space).
Excitation-contraction coupling
When the action potential gets to the individual myocytes it causes them to contract. Because the heart needs to
vary its force of contraction to get big or small outputs as required it has developed a method for varying the
force of contraction. Thus when the heart rate increases, or when the heart is stimulated, or when various drugs
are used, the force of every cell increases via the sympathetic nervous system. You need to know
the appearance of a typical ventricular action potential

how does the action potential trigger contraction in cardiac cells
how is it that the mechanism is variable
how drugs such as adrenaline or the cardiac glycosides lead to increased force.
the appearance of a typical pacemaker action potential
References
Use the textbooks in your Tutorial Room
Optional references:
Available in Medical Library: see Library Catalogue
Sherwood, L., 2007, Human physiology : from cells to systems, 6th ed., Thomson/Brooks/Cole, Australia
Berne, R. M., 2004, Physiology, 5th ed., Mosby, St. Louis.
Guyton, A. C. and J. E. Hall, 2006, Textbook of medical physiology, 11th ed., Elsevier Saunders, Philadelphia. .
Author: Professor David G Allen, Physiology
LEARNING TOPIC - Assessing peripheral vascular disease
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Peripheral Vascular Disease is a term used to describe symptomatic chronic arterial occlusion, usually in the lower
limbs. It is a disease that usually follows a slowly progressive course from intermittent pain on walking to
constant severe pain, ulceration, gangrene and limb loss.
LEARNING TOPIC - Assessing peripheral vascular disease
Peripheral Vascular Disease is a term used to describe symptomatic chronic arterial occlusion, usually in the lower
limbs. It is a disease that usually follows a slowly progressive course from intermittent pain on walking to
constant severe pain, ulceration, gangrene and limb loss.
The assessment of peripheral vascular disease is primarily a clinical task based on a careful history and physical
examination. Muscle pain (intermittent claudication) is the principal symptom.
In the early stage of the disease the pain is due to ischaemia of exercising muscle groups, most commonly the
calf muscles on running or walking, though depending on the anatomical distribution of the arterial occlusive
disease, other sites such as the buttock muscles or thighs may be the first to cause pain.
The arterial disease is usually due to atherosclerosis, and the pain typically fades away when the patient rests for
several minutes, allowing the flow of oxygenated blood to better match the needs of the muscles to return to
aerobic metabolism. At the same time, the blood pressure in the arteries distal to the obstruction, having fallen in
parallel with the onset of pain, rises again to the pre-exercise levels as the blood flow catches up with the
metabolic requirements of the vascular bed.
As the disease becomes more severe, pain may appear at rest and at this stage is largely due to ischaemia of
peripheral nerves. The patient may notice altered sensation in the feet and toes, worse after walking, and burning
numbness may become the dominant symptom as the nerves are subjected to constant ischaemia. The rest pain
is worse at night and may be relieved for short periods by getting up and walking around. Finally, tissue loss
secondary to minor trauma, infection or ischaemic gangrene completes the clinical course.
Clinical assessment of the new patient may be the only step required before commencement of treatment. The
nature of the pain is best confirmed by walking with the patient until the pain appears, and the examination
repeated then. Careful physical examination including palpation and auscultation of the arterial tree of the lower
limbs will demonstrate the level of the more proximal arterial occlusion or stenosis and. This is most commonly in
the femoro-popliteal arterial segment. Indeed this is often the only artery blocked in the patient who presents
with intermittent claudication.
Only by clinical or laboratory tests to define vessel patency at lower levels will the full extent of the occlusive
disease be revealed. Such tests must be considered in the severe claudicant and is always needed in the patient
with rest pain, who often has limb-threatening ischaemia. The presence or absence of flow in these distal
segments may be determined simply by the use of continuous wave Doppler examinations, usually with
segmental measurements of the systolic arterial pressure down the limb. Such Doppler pressure studies are most
informative and accurate when coupled with treadmill exercise, with systolic measurements performed before and
after exercise until the ankle arterial pressure returns to the pre-excise level. These may be compared with the
brachial artery systolic pressure to generate a ratio called the ankle/brachial index.
Other forms of assessment will demonstrate patent arterial segments (angiography by direct femoral puncture or
via intra-arterial catheters) or flow in open vessels (arterial duplex scanning of the lower limb arteries).
Angiography remains the most useful investigation before surgical intervention, which may be either radiological,
endoscopic or open. Arterial duplex studies are non-invasive and almost as accurate as arteriography and have
the additional advantage of being able to assess flow velocities to determine whether an arterial stenosis
contributes significantly to the symptomatic limitation of flow. Such studies may also better define the patient
who would benefit from angiographic interventional treatment, either balloon angioplasty or angiographic
stenting.
References
Burkitt, H. G. and C. Quick, 2002, Essential surgery : problems, diagnosis, and management, 3rd ed., Churchill
Livingstone, Edinburgh. Pages 459- 462 (Acute lower limb ischaemia)
Lawrence, P. F., et al., 2006, Essentials of general surgery, 4th ed., Lippincott Williams & Wilkins, Philadelphia
White, R. A. and L. H. Hollier, 1994, Vascular surgery : basic science and clinical correlationsed., Lippincott,
Philadelphia.
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Dormandy J, Maher M, Ascardy G et al. Fate of the patient with chronic leg ischaemia. J Cardiovasc Surg 1989; 10:28 AM
30(1): 50-57.
Peabody NC, Kannel WB, McNamara PM. Intermittent Claudication: Surgical Significance. Arch Surg 1974; 109(5):
Burkitt, H. G. and C. Quick, 2002, Essential surgery : problems, diagnosis, and management, 3rd ed., Churchill
Livingstone, Edinburgh. Pages 459- 462 (Acute lower limb ischaemia)
Lawrence, P. F., et al., 2006, Essentials of general surgery, 4th ed., Lippincott Williams & Wilkins, Philadelphia
White, R. A. and L. H. Hollier, 1994, Vascular surgery : basic science and clinical correlationsed., Lippincott,
Philadelphia.
Dormandy J, Maher M, Ascardy G et al. Fate of the patient with chronic leg ischaemia. J Cardiovasc Surg 1989;
30(1): 50-57.
Peabody NC, Kannel WB, McNamara PM. Intermittent Claudication: Surgical Significance. Arch Surg 1974; 109(5):
693-696.
Currie I, Wilson Y, Baird R, Lamont P. Treatment of Intermittent Claudication: The impact on quality of life . Eur J
Vasc Endovasc Surg 1995; 10(3):356-361.
Author: Associate Professor Peter Thursby, Surgery
LEARNING TOPIC - Atrial fibrillation
Atrial fibrillation (AF) is the most common of the cardiac arrhythmias. The prevalence increases with age, and
2-5% of those older than 60 have AF. AF may be paroxysmal or chronic. Paroxysmal episodes of AF often precede
chronic (permanent) AF.
Aetiology
Most types of heart disease can cause AF. The most important associations are mitral valve disease, hypertensive
heart disease, ischaemic heart disease, thyrotoxicosis, cardiomyopathy and idiopathic (lone fibrillation). In the
week following open heart surgery, 20 to 30% of patients experience transient AF.
Mechanism
AF is caused by multiple wandering wavelets of re-entry within the atria. Approximately 6 wavelets are required
for the development of sustained AF. The mechanism by which heart disease causes this phenomenon is
uncertain. It is probable that high atrial pressures lead to stretching of the atrium and atrial damage, this in turn
causes fibrosis which promotes the development of re-entrant circuits.
Not every impulse from the rapidly beating atria is conducted to ventricles. The AV node is bombarded randomly
by impulses, and only a proportion of these are conducted to the ventricles. Thus the ventricles contract
irregularly. In untreated AF the ventricular rate is usually between 150 and 200 beats per minute. If this rapid
rate continues for several days or if the patient has significant valvular or myocardial disease, the patient soon
develops cardiac failure.
Symptoms
The most common symptom of AF is that of rapid irregular palpitations. The patient may also feel fatigued. If
heart failure develops the patient may experience dyspnoea, ankle swelling and abdominal distension.
Signs
The pulse and heart beat are rapid and irregularly irregular. If the heart contracts rapidly several times in
succession, there will be insufficient time for cardiac filling, and each contraction will not generate a significant
pulse. Thus the pulse rate may be significantly lower than the heart rate. This is known as the 'pulse deficit'. In
addition, signs of cardiac failure may be present and one might find signs of the causative condition such as mitral
valve disease or thyrotoxicosis.
Diagnosis
AF is diagnosed on the electrocardiogram. P waves are absent and instead a finely undulating baseline is present.
These are known as fibrillation waves and have a frequency of 350-600 beats per minute. QRS complexes occur
irregularly with an average rate of 150 to 200 beats per minute in untreated AF.
Complications
Two major complications of AF are heart failure and embolism. Heart failure develops because of the rapid
ventricular rate. Lack of effective atrial contraction may also contribute.
Embolism may occur because the atrial contractions are feeble during AF, and this allows pockets of stasis
particularly in the left atrial appendage. This promotes thrombosis. Thrombi may detach themselves and lodge in
the systemic circulation.
Treatment
Several methods are used to treat AF. It is important to treat the cause of the atrial fibrillation, eg thyrotoxicosis,
4 of 57 valvular or hypertensive heart disease. Methods of treatment include drug treatment and DC cardioversion.16/10/10 10:28 AM
Drug Treatment
Two strategies are used to treat AF. The first is to control the ventricular rate. This is done by increasing the
ventricular rate. Lack of effective atrial contraction may also contribute.
Embolism may occur because the atrial contractions are feeble during AF, and this allows pockets of stasis
particularly in the left atrial appendage. This promotes thrombosis. Thrombi may detach themselves and lodge in
Treatment
Several methods are used to treat AF. It is important to treat the cause of the atrial fibrillation, eg thyrotoxicosis,
valvular or hypertensive heart disease. Methods of treatment include drug treatment and DC cardioversion.
Drug Treatment
Two strategies are used to treat AF. The first is to control the ventricular rate. This is done by increasing the
degree of block in the AV node. Drugs which are used for rate control include digoxin, verapamil and beta
blockers.
The second strategy is to give drugs to revert the AF and thereafter to decrease the frequency of further
episodes. Drugs used for this purpose include sotalol, amiodarone and flecainide.
DC Cardioversion
If a patient is severely compromised with AF, an alternative treatment is DC cardioversion (DC shock to the
praecordium designed to revert the arrhythmia).
Anticoagulation
AF significantly increases the risk of systemic embolism and embolic stroke. The risk of stroke depends on the
type of heart disease causing the AF. In patients with rheumatic valve disease and AF, the incidence of stroke is
increased between 15 and 20 times above that of the general population but patients with AF and no heart
disease do not have an increased risk of stoke. Treatment with warfarin is effective, but carries an increased the
risk of bleeding. The risk of serious thromboembolism in patients with AF is about 5% per year. Warfarin
decreases this risk to about 1% per year. The risk of serious haemorrhage whilst taking warfarin is < 1% per
year. Patients with lone AF are not given warfarin. Aspirin has also been used to decrease the risk of
thromboembolism but is only about 25%-50% as effective as warfarin.
Curative Procedures
A number of curative procedures have been developed to control AF. The most effective is the 'maze' procedure.
This is an 'open-heart' surgical procedure in which a number of incisions are placed in the atria to create lines of
block so that the multiple reentrant circuits cannot develop. This procedure is not widely performed because of
the discomfort and risk posed by open-heart surgery. Several catheter ablation techniques have also been
developed but currently these are regarded as investigational since the safety and efficacy have not yet been
determined.
AV Nodal Ablation and Implantation of Pacemaker

In some patients with AF the ventricular rate remains high despite drug therapy. In these patients the ventricular
rate may be controlled by intentionally destroying the AV node using catheter ablation techniques. A pacemaker
must be implanted to treat the resulting bradycardia. Since the atria continue to fibrillate, anticoagulation must
be continued after this procedure.
References
Author: Clinical Associate Professor Mark Mcguire, Medicine
LEARNING TOPIC - Causes of heart failure
Heart failure can be defined as the inability of the heart to maintain a cardiac output appropriate to systemic
metabolic requirements. Heart failure may be a low output state, where forward pump function of the heart is
impaired and cannot meet normal metabolic needs, or more rarely, a high output state, where pump function of
the heart is normal but systemic metabolic needs are excessive. Examples of low output failure include impaired
pump function due to cardiomyopathy or myocardial infarction. Examples of high output failure include
thyrotoxicosis and beri-beri.
Heart failure is usually a chronic condition, but in some circumstances may be acute, as in acute valvular
regurgitation. In chronic heart failure, the heart adapts and remodels in an attempt to compensate. This
remodelling includes ventricular dilatation and eccentric myocardial hypertrophy. In acute heart failure,
ventricular dilatation does not have time to develop and the major compensation is an increase in heart rate.
In a patient presenting with heart failure, it is important to distinguish between the underlying cause and the
immediate precipitating cause. The underlying cause is the pathological process affecting the heart and leading to
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impaired myocardial pump function. A precipitating cause is a factor or event which results in decompensation of
the heart and symptoms. Typical precipitating causes are factors placing an additional load upon the heart such
as fever, anaemia or systemic infection. In addition, arrhythmias such as atrial fibrillation, may precipitate overt
heart failure.
Heart failure is usually a chronic condition, but in some circumstances may be acute, as in acute valvular
regurgitation. In chronic heart failure, the heart adapts and remodels in an attempt to compensate. This
remodelling includes ventricular dilatation and eccentric myocardial hypertrophy. In acute heart failure,
ventricular dilatation does not have time to develop and the major compensation is an increase in heart rate.
In a patient presenting with heart failure, it is important to distinguish between the underlying cause and the
immediate precipitating cause. The underlying cause is the pathological process affecting the heart and leading to
impaired myocardial pump function. A precipitating cause is a factor or event which results in decompensation of
the heart and symptoms. Typical precipitating causes are factors placing an additional load upon the heart such
as fever, anaemia or systemic infection. In addition, arrhythmias such as atrial fibrillation, may precipitate overt
heart failure.
There are many potential underlying causes of heart failure, which should be sought in patients who present with
symptoms of heart failure. These causes include impaired blood supply due to coronary artery disease, with or
without myocardial infarction, and increased haemodynamic load on the heart due to valve disease, such as aortic
stenosis or aortic or mitral regurgitation. Often heart failure is due to an intrinsic dysfunction of the systolic
contractile function of the myocardium, known as a cardiomyopathy, and this results in dilatation of the cardiac
chambers. Causes of dilated cardiomyopathy include alcohol abuse, previous myocarditis, hereditary defects in
myocardial metabolism and metabolic abnormalities such as hyper/hypo-thyroidism, or haemochromatosis.
Occasionally drugs or heavy metal poisoning can cause cardiomyopathy. An important drug cause is the
anti-cancer drug, adriamycin.
A less common cause of heart failure is a restrictive cardiomyopathy. These patients typically have thickened and
stiff ventricular myocardium, due to fibrous infiltration or deposition of abnormal glycoproteins. The most common
cause in Australia is amyloidosis which is manifest mostly in older women. In patients presenting with heart
failure it is important to look for the precipitating cause as this may be readily treatable and can result in rapid
clinical improvement for the patient. It is also important to look for the underlying cause of heart failure, as this
may be reversible in some cases, such as by coronary artery bypass grafting in coronary artery disease or by
stopping alcohol intake.
References
Kumar, V., et al., 2005, Robbins and Cotran pathologic basis of disease, 7th ed., Elsevier Saunders, Philadelphia.
[Available as a E-Book]
Boon, N. A. and S. Davidson, 2006, Davidson's principles & practice of medicine, 20th ed., Elsevier/Churchill
Livingstone, Edinburgh ; New York.
Author: Professor Richmond Jeremy, Medicine
LEARNING TOPIC - Causes of tiredness
Tiredness is a very common presentation in medical practice, comprising 5-10% of all presentations in general
practice. Although the cause is usually found to be psychological or social in nature (in 50-80% of cases), an
over-riding initial concern is to exclude physical causes requiring treatment.
Psychosocial factors
Most people presenting to their doctor with tiredness will have a psychosocial cause, and most of those people will
have associated features of depression (e.g. insomnia, morning tiredness, loss of interest, poor self esteem) or
anxiety (e.g. worry, apprehension, or irritability). Depression is very common and should always be considered
and excluded by specific questioning. Anxiety is often related to lifestyle (e.g. relationships, family, work,
financial), and this can usually be identified by empathic inquiry.
Physical causes
Almost any medical condition can cause tiredness, but certain medical conditions cause persistent tiredness as a
major manifestation. These conditions usually have associated symptoms and signs which should be sought by
careful initial history and physical examination. The most common associated symptoms (and conditions) include:
weight loss (malignancy, chronic infection, diabetes, hyperthyroid), polydipsia, polyuria (diabetes), fever
(infection, malignancy), cold intolerance (hypothyroidism), melaena or menorrhagia (anaemia), amenorrhoea,
nausea and mastalgia (pregnancy), hypertension and/or dyspnoea (heart failure), snoring and/or daytime
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somnolence (sleep apnoea).
Infections which commonly cause persistent tiredness include: infectious mononucleosis, HIV, hepatitis C,
tuberculosis, subacute bacterial endocarditis (SBE).
Physical causes
Almost any medical condition can cause tiredness, but certain medical conditions cause persistent tiredness as a
major manifestation. These conditions usually have associated symptoms and signs which should be sought by
careful initial history and physical examination. The most common associated symptoms (and conditions) include:
weight loss (malignancy, chronic infection, diabetes, hyperthyroid), polydipsia, polyuria (diabetes), fever
(infection, malignancy), cold intolerance (hypothyroidism), melaena or menorrhagia (anaemia), amenorrhoea,
nausea and mastalgia (pregnancy), hypertension and/or dyspnoea (heart failure), snoring and/or daytime
somnolence (sleep apnoea).
Infections which commonly cause persistent tiredness include: infectious mononucleosis, HIV, hepatitis C,
tuberculosis, subacute bacterial endocarditis (SBE).
The use of prescribed and non-prescribed drugs (for example, alcohol, B-blockers, anticonvulsants, anxiolytics
and NSAIDS) can cause tiredness and should be carefully sought in the history.
Physiological tiredness, due to excessive physical or psychological activity is common in day to day life, but
uncommon in medical practice. The cause is usually obvious (sometimes to everyone except the affected person),
although physical and psychological causes must first be excluded in the history and examination. Inquiry should
centre on day to day patterns of work, rest and recreation.
Chronic fatigue syndrome should be considered in patients with fatigue lasting longer than six months in whom
other diseases have been excluded.
References
Murtagh, J., 2007, John Murtagh's general practice, 4th ed., McGraw-Hill Australia, Sydney
A good comprehensive introduction to the diagnosis and management of a patient presenting with fatigue.
McWhinney, I. R., 1997, A textbook of family medicine, 2nd ed., Oxford University Press, New York
A useful supplement to Murtagh. Emphasises a diagnostic approach to presentations of fatigue in general practice.
Useful recent journal articles:
Dick ML, Sundin J. Psychological and psychiatric causes of fatigue. Assessment and management. Australian
Family Physician 2003;32(11):877-881.
Murtagh J. Fatigue : a general diagnostic approach. Australian Family Physician 2003;32(11):873-876.
Murdoch JC. Chronic fatigue syndrome. The patient centred clinical method--a guide for the perplexed. Aust Fam
Physician. 2003;32(11):883-887.
Author: Professor Simon Willcock, General Practice
LEARNING TOPIC - Chromosomal abnormalities and early development in Down syndrome
The human chromosome complement was established as recently as 1956 as 23 pairs, i.e. 46 chromosomes. This
is called the diploid number of chromosomes. Down syndrome was the first disorder in which a chromosome
abnormality was discovered by Lejeune and colleagues in 1958. They established that the majority (95%) of
Down syndrome subjects had an additional 21 chromosome. More sophisticated cytogenetic techniques reveal
that a variety of different chromosomal mechanisms result in Down syndrome although these all share the
common abnormality of triplication of chromosome 21 genes.
Cytogenetic Mechanisms Responsible for Down Syndrome
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Trisomy 21 95 %
is called the diploid number of chromosomes. Down syndrome was the first disorder in which a chromosome
abnormality was discovered by Lejeune and colleagues in 1958. They established that the majority (95%) of
Down syndrome subjects had an additional 21 chromosome. More sophisticated cytogenetic techniques reveal
that a variety of different chromosomal mechanisms result in Down syndrome although these all share the
common abnormality of triplication of chromosome 21 genes.
Cytogenetic Mechanisms Responsible for Down Syndrome
Trisomy 21 95 %
Translocation 2.5%
Mosaicism 2.5%
Other <1%
What are the Mechanisms which Produce Trisomy 21
During meiosis (the formation of germ cells), the chromosome complement is halved to 23. This is called the
haploid number. There are 2 steps, Meiosis I in which the diploid number is halved to 23, and Meiosis II in which
the chromosomes are replicated similar to a mitotic step. Non-disjunction, i.e. the non-segregation of paired
sister chromosomes to 2 daughter cells, results in a germ cell with 24 chromosomes and a corresponding germ
cell with 22 chromosomes.
Molecular Cytogenetic and DNA polymorphism studies demonstrate that the error occurs in maternal meiosis I in
75% and meiosis II in 25% of patients. When the error occurs in paternal meiosis the ratios are reversed meiosis
I (25%) and II (75%). Epidemiologic studies show that an increased incidence of trisomy 21 Down syndrome is
strongly connected with the maternal age >37 years. Errors occur in meiosis in women at all ages. At 40 years,
the incidence of Down syndrome is approximately 1:100 compared with an incidence of 1:1000 in women 29
years.
Translocation
Physical fusion of two chromosomes (or part of chromosomes) is known as translocation. This anomaly may be
stably inherited. Fusion between chromosomes which have their centromere at one end (acrocentrics) i.e.
chromosomes 13, 14, 15, 21 and 22 are known as Robertsonian translocations. A Robertsonian translocation
which does not affect the absolute number (dosage) of chromosome 21 causes no phenotypic effects. Balanced
translocations may be stably inherited. However balanced translocations result in abnormal pairing at meiosis and
in gametes with an unbalanced composition (excess or insufficiency). Unbalanced Robertsonian translocation is
responsible for 2-3% of Down syndrome, in which half those affected are inherited. Recurrence risks vary. The
21;21 translocation when present in a parent results in 100% Down syndrome offspring (the monosomic
conceptus is previable lethal).
Mosaicism
About 2.5% of patients have a mixture of body cells, normal cells with 46 chromosomes and Down syndrome cells
with 47 chromosomes. There is a wide variation in intellectual disability (if any) and phenotypic effects. Some
individuals with Down syndrome mosaicism commence life as full trisomic embryos but one 21 is lost by anaphase
lag in early embryogenesis. This is sometimes known as “trisomic rescue”.
Other
Patients have been described with partial trisomy (duplication) for a region of the long arm of chromosome 21.
The region of chromosome 21, 21q 22.13-22.2 is responsible for most of the phenotype. Partial trisomy may be
undetectable by standard methods of chromosomal (cytogenetic) analysis such as G banding and Fluorescence in
situ hybridisation (FISH) employing probes for a region of chromosome 21. Tiny duplications may be detected by
interphase FISH and Comparative Genomic Hybridisation Array technology (CGH array) (Ronan et al 2007).
References
Antonarakis S, Lyle R, Dermitzakes ET, Reymond A, Deutsch S. Chromosome 21 and Down Syndrome: from
8 of 57 genomics to pathophysiology . Nature Reviews Genetics 2004; 5(10):725-737. 16/10/10 10:28 AM
Gardner, R. J. M. and G. R. Sutherland, 2004, Chromosome abnormalities and genetic counseling, 3rd ed., Oxford
University Press, New York. Pages 249-263
References

Antonarakis S, Lyle R, Dermitzakes ET, Reymond A, Deutsch S. Chromosome 21 and Down Syndrome: from
genomics to pathophysiology . Nature Reviews Genetics 2004; 5(10):725-737.
Gardner, R. J. M. and G. R. Sutherland, 2004, Chromosome abnormalities and genetic counseling, 3rd ed., Oxford
University Press, New York. Pages 249-263
Patterson D, Costa AC. Down syndrome and genetics - a case of linked histories . Nature Reviews Genetics 2005
Feb; 6(2):137-47.
Ronan A, Fagan K, Christie L, Conroy J, Nowak NJ and Turner G. Familial 4.3 Mb duplication of 21q22 sheds new
light on the Down syndrome critical region. J. Med. Genet. 2007 44(7):448-51.
Author: Professor David Sillence, Genetic Medicine
LEARNING TOPIC - Chronic viral infections
Many viruses establish long-term relationships with their human hosts, and everyone carries a substantial number
which have little impact on their health.
The mechanisms allowing them to achieve persistence vary. Some, such as the herpes viruses which cause cold
sores chicken pox and glandular fever, produce an acute infection with a vigorous host response, but then
become latent. During acute infection they produce progeny virus and kill their host cells, but during latency only
one or two viral genes are transcribed. Such viruses can be reactivated and may then cause quite a different
disease picture (compare chicken pox with shingles, glandular fever with Burkitt's lymphoma).
Viruses from some other taxonomic groups cause little acute disease, but evade the host response and continue
to replicate and cause on-going cell damage in their target organ. Hepatitis C and HIV are good examples of this
group. They characteristically mutate to form 'quasi-species' in response to immune pressure.
Yet another group of chronic viral diseases are caused by persistence of defective virus in the tissues. Subacute
sclerosing panencephalitis following measles and squamous carcinoma due to papillomavirus are two famous
examples.
These mechanisms are not mutually exclusive For instance hepatitis B and papillomaviruses may use two or even
all three. Many examples of chronic virus infection (such as cytomegalovirus) have come to notice in immune
deficient patients and cause major problems in their management. Unrestrained viral replication produces severe
tissue injury and also high levels of infectivity to contacts. Some viruses, such as poliomyelitis and human
parvovirus which are eliminated by normal people, become chronic in the immune deficient.
Chronic viral infections may
cause apparently acute illness, particularly by reactivation

lead to 'non-communicable' diseases including malignancies (Burkitt's lymphoma and cancer of the cervix
for example ) and degenerative CNS syndromes (eg progressive multifocal leucoencephalopathy (PML) ,
tropical paraparesis)
produce continuing long-term damage to their target organ, either directly or by inducing immunological
destruction of infected cells
Recognition of the large number and variety of chronic virus infections has led to attempts to implicate them in
numerous 'non-infectious' syndromes. Theses especially include degenerative diseases of the CNS such as
multiple sclerosis and malignancies including lymphomas and cancer of the breast. Animal diseases often provide
clues in making such disease associations, but most remain controversial and unproved.
Chronic viral infections also induce on-going production of lymphokines such as interferon, and lymphocyte
proliferation may also be found. Non-specific symptoms, particularly fatigue, muscle aches and low grade fever
may result. Fatigue may be the presenting symptom in patients with cumulative tissue damage, eg hepatitis C or
HIV, but the clinical association of fatigue with viruses which are carried by most healthy people is difficult to
prove either for individual patients or the community. Molecular techniques continue to reveal 'new' viruses (eg
HHV6, HHV8, and hepatitis G) which cause chronic infection, but whose disease load is still very uncertain. As
each is discovered renewed attempts are made to associate virus infections with these unexplained syndromes.
The control of chronic viral infections is difficult because asymptomatic people are likely to remain infectious for
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many years and treatment regimes, if available, are very long term.
References
proliferation may also be found. Non-specific symptoms, particularly fatigue, muscle aches and low grade fever
may result. Fatigue may be the presenting symptom in patients with cumulative tissue damage, eg hepatitis C or
HIV, but the clinical association of fatigue with viruses which are carried by most healthy people is difficult to
prove either for individual patients or the community. Molecular techniques continue to reveal 'new' viruses (eg
HHV6, HHV8, and hepatitis G) which cause chronic infection, but whose disease load is still very uncertain. As
each is discovered renewed attempts are made to associate virus infections with these unexplained syndromes.
The control of chronic viral infections is difficult because asymptomatic people are likely to remain infectious for
many years and treatment regimes, if available, are very long term.
References
Look up the viruses listed above in Mims [Available as an E-book] and compare the mechanisms and
manifestations of acute and chronic infection for each.
Mandell, G. L., R. G. Douglas, et al., 2005, Mandell, Douglas, and Bennett's principles and practice of infectious
diseases, 6th ed., Elsevier/Churchill Livingstone, New York. [Available as an E-Book]
Author: Professor Peter McMinn, Infectious Diseases
LEARNING TOPIC - Clinical and laboratory assessment in heart failure
The assessment of a patient with heart failure is directed towards determining both the severity and the cause of
heart failure. Clinical assessment is based upon the patient's symptoms, including dyspnoea, orthopnoea, fatigue
and exercise tolerance. The severity of clinical symptoms can be graded according to criteria of the New York
Heart Association, from Class 1 (mild symptoms) to Class 4 (severe restriction of activity). The NYHA Class is an
important prognostic indicator as well as a useful description of the patient's functional status. The clinical
assessment also includes physical examination with emphasis upon the signs of heart failure, including peripheral
oedema, elevation of the jugular venous pressure, displacement of the apex beat of the heart and auscultatory
signs such as atrial or ventricular gallop sounds and murmurs of aortic or mitral regurgitation. Clinical assessment
usually reveals the severity of the patient's heart failure and may reveal the underlying cause, such as a history
of myocardial ischaemia, or physical signs of chronic liver disease and alcohol abuse.
Simple investigations can provide further information. The electrocardiogram may reveal previous myocardial
infarction or signs of left ventricular hypertrophy or document an arrhythmia (eg atrial fibrillation). The chest
X-ray provides an indication of cardiac size and is important for assessment of pulmonary congestion, with
evidence of upper lobe venous distension or interstitial oedema. Biochemical tests are directed towards evaluating
consequences of heart failure (ie blood electrolytes and creatinine) and also towards possible causative factors,
such as anaemia (full blood count), alcohol abuse (liver function tests), endocrine abnormalities (thyroid function
tests).
In many cases, the physician will seek to document the degree of impairment of cardiac function. This entails
cardiac imaging, usually by echocardiography or equilibrium radionuclide ventriculography. These imaging studies
provide information about cardiac size and pump function, which is often quantitated by the ejection fraction
(ejection fraction = strake volume/end-diastolic volume). The normal adult left ventricular ejection fraction is
50-70%. In general, patients with an ejection fraction below 25% have severe heart failure.
In specific circumstances, other more specialised investigations may be required, such as myocardial perfusion
scanning with radionuclides or coronary angiography to detect coronary artery disease. It is to be emphasised
that heart failure is not a diagnosis in itself, but rather a symptom complex indicative of cardiac disease. It is
therefore necessary to undertake an appropriate clinical and investigative assessment to define the severity and
causes of heart failure in order to rationally plan treatment for the patient which can relieve symptoms and may
even restore cardiac pump function in certain cases.
References
10 of 57 16/10/10 10:28 AM

LEARNING TOPIC - Complications of ischaemic heart disease
The major complication of coronary artery disease is myocardial infarction. This results from thrombotic occlusion
of a major coronary artery. In patients who develop myocardial infarction, a number of serious complications may
follow, either acutely or in the healing phase. These include:-
Arrhythmias:
In the acute stages, conduction disturbances may result from infarcts which involve the conduction system and
usually produce bradyarrhythmias while tachyarrhythmias result from myocardial irritability or re-entry.
Transmural infarcts in the posterior wall of the left ventricle are especially likely to lead to bradyarrhythmias. In
the convalescent phase and late after infarction, ventricular tachcardia and fibrillation result from reentry around
the edges of scar, and are a major cause of sudden death.
Left ventricular dysfunction:
This may lead to left-sided cardiac failure, pulmonary congestion and oedema. A large, transmural infarct
involving 40% of the left ventricular wall or more may be followed by profound ventricular dysfunction, acute
"pump failure" and cardiogenic shock.
Rupture of the myocardium:
Infarcted myocardium undergoes softening especially during the acute inflammatory response to the necrosis.
This can lead to its rupture in the following locations:
The free or external ventricular wall. Haemopericardium will result from escape of blood from the left
ventricle.
The interventricular septum. Shunting of blood between the ventricles usually left to right, occurs.
The papillary muscle with acute onset of mitral regurgitation. Papillary muscle dysfunction may result from
ischaemia without rupture of the muscle. Rupture of the papillary muscle leads to sudden onset mitral
regurgitation, and may be heralded by acute pulmonary oedema.
Mural thrombosis:
This occurs most frequently in the left ventricle, and is caused by stasis of blood due to ventricular hypokinesis or
endocardial injury in the area of infarction. Such thrombus may embolise into the systemic circulation with
possible impaction for example in a cerebral vessel.
Patients with myocardial infarction are at high risk of development of hypercoagulability of blood. They are
predisposed to the development of deep venous thrombosis and pulmonary embolism.
The propensity toward certain complications depends greatly on the proportion of the myocardial wall damaged
by infarction. As noted above, patients with large transmural infarcts tend to be more susceptible to develop
arrhythmias and shock while a transmural infarct of the free wall may rupture more readily.
Mostly, myocardial infarction will commence in the subendocardial region which is the least well-perfused part of
the myocardium. However within a few hours, this infarct can progress along a wavefront of necrosis to become
transmural. This wavefront necrosis may be modified by prompt thrombolysis and coronary reperfusion.
Patients with transmural myocardial infarction in particular may develop an acute fibrinous pericarditis
within a few days of occurrence of the infarction
Infarct extension. The zones bordering an area of recent infarction while still viable, may exhibit changes of
sublethal injury reflecting a lesser degree of ischaemic injury. These zones are unstable due to ischaemia
and in the days or weeks following the original infarct there may be extension of necrosis into these
adjoining areas.
Cardiac remodelling. In some patients, myocardial infarction is followed by a series of changes involving
both the area of infarction and the adjoining wall and culminating in a change in ventricular shape and
dimensions. This involves infarct expansion which begins as early as within 24 hours after occurrence of
11 of 57 16/10/10
infarction and in which the area of infarction undergoes disproportionate stretching and thinning. This
10:28 AM
differs from infarct extension in that further necrosis is not a prerequisite. A similar but less pronounced
thinning and dilatation occurs in the adjoining non-infarcted region. It has been shown that most of the
thinning in the infarcted region and all of the thinning in the non-infarcted zone is due to rearrangement of
Infarct extension. The zones bordering an area of recent infarction while still viable, may exhibit changes of
sublethal injury reflecting a lesser degree of ischaemic injury. These zones are unstable due to ischaemia
and in the days or weeks following the original infarct there may be extension of necrosis into these
adjoining areas.
Cardiac remodelling. In some patients, myocardial infarction is followed by a series of changes involving
both the area of infarction and the adjoining wall and culminating in a change in ventricular shape and
dimensions. This involves infarct expansion which begins as early as within 24 hours after occurrence of
infarction and in which the area of infarction undergoes disproportionate stretching and thinning. This
differs from infarct extension in that further necrosis is not a prerequisite. A similar but less pronounced
thinning and dilatation occurs in the adjoining non-infarcted region. It has been shown that most of the
thinning in the infarcted region and all of the thinning in the non-infarcted zone is due to rearrangement of
myocytes or "cell slippage" with a reduction in layers of myocytes in the ventricular wall.
As a result the ventricle dilates, its volume increases as do the stresses on its wall. Such patients have higher
mortality than those in whom remodelling is not observed because of development of congestive heart failure and
ventricular arrhythmias. It is believed that remodelling may be modified by treatment which reduces preload or
afterload stress and that coronary reperfusion may also be beneficial.
Author: Dr Suchitra Chandar, Cardiology
LEARNING TOPIC - Complications of rheumatic heart disease
Rheumatic heart disease is the sequel to one or more attacks of acute rheumatic fever. In up to 50% of patients
with the condition there is no history of a documented episode of rheumatic fever, whereas a significant
percentage of those who have had rheumatic fever do not develop chronic rheumatic involvement of the heart,
especially if the acute attack is accompanied by only mild carditis.
Chronic valvular disease is the most important consequence of rheumatic fever. The mitral valve is most often
affected, and it is unusual to have rheumatic heart disease in the absence of mitral involvement. Aortic valve
disease often co-exists with mitral valve disease and may be the predominant valve affected. Less often the
tricuspid valve is also affected, although it is often functionally regurgitant. The affected valves may be either
stenosed or regurgitant, and you should read how the heart responds to these mechanical lesions, how they can
be assessed by clinical examination and investigation (ECG, chest X-ray, echocardiogram and cardiac
catheterisation), and the indications for medical, balloon and surgical treatments.
Arrhythmias are a common complication of chronic rheumatic heart disease, with atrial fibrillation being the most
frequently observed. This arrhythmia is most often seen in patients with mitral valve disease and left atrial
dilatation due to chronic pressure and volume overload. The onset of atrial fibrillation is accompanied by a fast
and irregular ventricular response, and treatment is directed towards control of the ventricular rate. The loss of
atrial systole and its effect on cardiac performance, and the increased risk of thrombo-embolism are the major
adverse complications of this arrhythmia. Your reading should be directed towards understanding the
pathogenesis and treatment of patients with atrial fibrillation, including the drugs that are used to slow the
ventricular rate and the management strategy involved in re-establishing sinus rhythm.
Thrombo-embolism is a complication which particularly occurs in patients with mitral valve disease and atrial
fibrillation. The most devastating consequence is embolic stroke. Life-long anticoagulation is the most important
prophylactic measure. The maintenance of sinus rhythm is another important treatment goal. Occasionally the
thrombus which forms in the left atrium is so large that it obstructs the mitral valve orifice. Your reading should
include the management of patients on long-term oral anticoagulation.
Infective endocarditis is a serious but often preventable complication of chronic valvular disease. Its presentation
varies from an acute rapidly progressive illness to a subacute more indolent condition. Your reading should
include prophylactic measures, diagnosis of endocarditis and the medical and surgical treatment of the condition
and its complications.
Recurrent attacks of acute rheumatic fever are particularly prevalent in those countries where its prophylaxis is
suboptimal. Prophylaxis includes public health measures, the prompt treatment of streptococcal upper respiratory
infections, and the continuous antibiotic use up to the age of approximately 30 years in all individuals who have
had a documented attack of acute rheumatic fever. Recurrent episodes of rheumatic fever can produce further
valve and myocardial damage. The latter can manifest later as impaired left ventricular function out of keeping
with the degree of valvular dysfunction. Your reading should include the aetiology, pathology and prevention of
acute rheumatic fever and its occurrences.
References

12 of 57 16/10/10 10:28 AM
Zipes, D. P. and E. Braunwald, 2005, Braunwald's heart disease : a textbook of cardiovascular medicine, 7th ed.,
had a documented attack of acute rheumatic fever. Recurrent episodes of rheumatic fever can produce further
valve and myocardial damage. The latter can manifest later as impaired left ventricular function out of keeping
with the degree of valvular dysfunction. Your reading should includehttp://smp.sydney.edu.au/compass/guide/handbook/block/5
the aetiology, pathology and prevention of
acute rheumatic fever and its occurrences.
References
W.B. Saunders, Philadelphia, Pa. [Available as an E-Book]
Kasper, D. L. and T. R. Harrison, 2005, Harrison's principles of internal medicine, 16th ed., McGraw-Hill, Medical
Pub. Division, New York. [Available as an E-Book]
Additional detail on acute rheumatic fever
W.B. Saunders, Philadelphia, Pa. [Available as an E-Book] Chapter 82 (Rheumatic diseases and the
cardiovascular system)
Author: Clinical Associate Professor David Richmond, Medicine
LEARNING TOPIC - Cyanosis: causes and consequences
Cyanosis refers to an abnormal dusky blue discolouration of the skin and/or mucous membranes due to a higher
than normal concentration of deoxygenated or unsaturated haemoglobin (deoxyhaemoglobin) in the tissue
capillaries. Haemoglobin changes colour from red to blue as it unloads oxygen from the capillaries into the
tissues. Normally, the high proportion of saturated haemoglobin in the capillaries of visible tissues imparts the
usual pink colour while the veins draining these tissues appear blue. Cyanosis arises through two basic
mechanisms; either 1) the arterial blood entering these capillaries is less saturated than normal or 2) the
circulation may be slowed so that more extraction of oxygen per gram of haemoglobin occurs, hence increasing
the concentration of deoxyhaemoglobin in the capillaries. Both mechanisms may operate together.
Cyanosis is classified as peripheral or central. When extremities appear blue but the warm buccal mucosa and
conjunctivae appear pink it is usually due to slowing of the circulation causing peripheral cyanosis and this is most
often associated with cold induced vasoconstriction. More important pathological causes of peripheral cyanosis are
reduced circulation due to atheromatous or traumatic narrowing of arteries (eg diabetic vasculopathy) or
abnormal arterial spasm (eg Raynaud's phenomenon). Central cyanosis affecting the warm mucous membranes is
more important because this usually implies mechanism 1) above and this means that the systemic arterial blood
perfusing the whole body is deficient in oxygen. It is essential to appreciate that, by the time cyanosis is
detectable, the oxygen deficiency (hypoxaemia) in the arterial blood is very severe and potentially life
threatening, particularly if it is acute. Arterial hypoxaemia arises when venous blood from the tissues, finally
mixing in the right side of the heart (mixed venous blood), is not normally oxygenated by passage through the
lungs to the left side of the heart and thence the systemic arteries. Direct shunting of blood from the right to the
left side of the heart, bypassing the lungs (as in this case), or perfusion of abnormal shunt vessels in the lungs
which have no contact with alveolar gas are the "shunt" causes of cyanosis. The more common cause, however, is
an imbalance or mismatch between ventilation and blood flow among the gas exchanging units of the lung
(ventilation-perfusion inequality) which occurs to some degree in most diseases affecting the lungs.
The detection of central cyanosis means that in systemic arterial blood the partial pressure of oxygen (PaO 2 in
mmHg), the percentage saturation of haemoglobin (SaO 2 in % oxyhaemoglobin / total haemoglobin), and the
content of oxygen (CaO 2 in ml/dL of blood) are lower than normal. Useful normal values to remember for a young
adult breathing air at sea level are PaO 2 97 mmHg, SaO 2 97% and CaO 2 20.4 ml/dL, the latter given a normal
(total) haemoglobin concentration of 150 gm/L. There is a complex sigmoid relation between PaO 2 as the
independent variable and SaO 2 or CaO 2 as the dependent variable known as the oxyhaemoglobin dissociation
curve. The most important features of this curve are that PaO 2 must fall to 60 mmHg before SaO 2 falls below
90% but, thereafter, SaO 2 falls quite steeply such that a PaO 2 of 40 mmHg corresponds with an SaO 2 of 75%.
Central cyanosis cannot usually be detected until there is a concentration of 50 gm/L of deoxyhaemoglobin in the
arterial blood. It can be seen, from the above relations, that a patient with a normal total haemoglobin
concentration of 150 gm/L would need the SaO 2 to fall to 67% (PaO 2 35 mmHg) before cyanosis could be
detected and this is a very dangerous level of hypoxaemia below the normal mixed venous PO 2 of 40 mmHg.
Cyanosis may be detected at a less extreme degree of hypoxaemia when the patient has a high haemoglobin.
Detection of cyanosis in the mildly anaemic subject corresponds with a desperately low PaO 2 .
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The importance of early detection of hypoxaemia lies in the fact that the body has very small stores of oxygen
and most tissues are critically reliant on a continuous adequate arterial content especially the brain and the heart.
The oxygen partial pressure (PO ) in the capillary is the immediately critical factor, as oxygen moves along a
90% but, thereafter, SaO 2 falls quite steeply such that a PaO 2 of 40 mmHg corresponds with an SaO 2 of 75%.
Central cyanosis cannot usually be detected until there is a concentration of 50 gm/L of deoxyhaemoglobin in the
arterial blood. It can be seen, from the above relations, that a patient with a normal total haemoglobin
concentration of 150 gm/L would need the SaO 2 to fall to 67% (PaO 2 35 mmHg) before cyanosis could be
detected and this is a very dangerous level of hypoxaemia below the normal mixed venous PO 2 of 40 mmHg.
Cyanosis may be detected at a less extreme degree of hypoxaemia when the patient has a high haemoglobin.
Detection of cyanosis in the mildly anaemic subject corresponds with a desperately low PaO 2 .
The importance of early detection of hypoxaemia lies in the fact that the body has very small stores of oxygen
and most tissues are critically reliant on a continuous adequate arterial content especially the brain and the heart.
The oxygen partial pressure (PO 2 ) in the capillary is the immediately critical factor, as oxygen moves along a
pressure gradient to the mitochondria in the cells where the prevailing partial pressure of oxygen is probably less
than 2 mmHg. However, the oxyhaemoglobin saturation and oxygen content of the arterial blood entering the
capillaries are crucial in maintaining an adequate driving pressure as the oxygen is consumed. For example, the
anaemic patient with normal lungs may have a normal PaO 2 and SaO 2 but the low CaO 2 means that the PO 2
(and saturation) fall much more rapidly as oxygen is taken up from the capillaries. The precise relation between
oxygen content and pressure in determining oxygen delivery is incompletely understood.
The important principle is that the causes of hypoxaemia should be rapidly identified and corrected, particularly
when it is acute. Compensatory mechanisms play an important role in minimising the deleterious effects of
chronic hypoxaemia. The patient in this case is likely to develop these mechanisms including a high cardiac output
and a high total haemoglobin concentration, but these compensations bring other complications.
References
West JB. Respiratory physiology : the essentials. 8th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams &
Wilkins; 2008
West JB. Pulmonary pathophysiology : the essentials. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2008
West, J. B., 1990, Ventilation/blood flow and gas exchange, 5th ed., Blackwell Scientific
Fauci AS. Harrison's principles of internal medicine. 17th ed. New York: McGraw-Hill Medical; 2008. [ Available as
an E-Book] Chapter 35 (Hypoxia and Cyanosis)
Shapiro BA, Harrison RA, Cane RD, Templin R. Clinical Application of Blood Gases. (4th ed.) Chicago: Year Book
Medical Publishers, 1989.
Author: Clinical Professor Iven Young, Medicine
LEARNING TOPIC - Detecting alcohol abuse
Alcohol problems can present to a medical practitioner in a multitude of ways. One in six adults presenting to
general practitioners will be drinking in a hazardous or harmful manner. It has been shown that most of these
problems or potential problems are undetected and unknown to the doctor. This learning topic addresses this
area, so students will be familiar with current methods of detection of alcohol related illness.
Medical Presentations of Alcohol Related Problems

Medical practitioners need to have a high index of suspicion regarding the possibility of alcohol related conditions
and be aware of the presentations where alcohol is likely to be a causative or contributory factor. Teaching needs
to emphasize the spectrum of possible presentations of alcohol problems.
• Possible Early Problems

o accidents
o injuries
o trauma
o depression, anxiety
o psychological problems
o social, relationship, family problems
14 of 57 o employment difficulties, legal problems 16/10/10 10:28 AM
o hypertension
o arrhythmias
o dyspepsia
o accidents
o injuries http://smp.sydney.edu.au/compass/guide/handbook/block/5
o trauma
o depression, anxiety
o psychological problems
o social, relationship, family problems
o employment difficulties, legal problems
o hypertension
o arrhythmias
o dyspepsia
o minor gastrointestinal problems
• Later Stage Problems - In addition to the above -

o major gastrointestinal disease - cirrhosis, pancreatitis
o neurological disease - alcohol related brain damage, peripheral neuropathy
o major cardiovascular disease - cardiomyopathy
o dependence and withdrawal
History
Consumption, alcohol related problems, features of dependence. Approach to interviewing with regard to possible
alcohol problems, motivational interviewing.
Examination Findings
Physical signs of possible early alcohol problems, and signs of later problems
Assessment of an alcohol problem

Hazardous drinking, harmful drinking, alcohol related problems, alcohol dependence
Pathology Tests and Biochemical Markers

Gamma Glutamyl Transpeptidase (GGT), Mean Red Cell Volume,
Questionnaires as Screening Instruments
References
Latt, N., Conigrave, K., Saunders, J., Nutt, D., (eds), 2009, Addiction Medicine. OUP
Hulse, G., White, J., Cape, G., (eds.), 2002, Management of alcohol and drug problems, OUP, South
Melbourne.
Audit Questionnaire. See Learning topic: Early intervention for harmful drinking Problem 2.03 New
wheels
Australian Alcohol Guidelines

www.nhmrc.gov.au/publications/synopses/_files/ds10-alcohol.pdf
15 of 57 Author: Dr Ken Curry, Addiction Medicine 16/10/10 10:28 AM
LEARNING TOPIC - Discovery of circulation: Harvey film (TIMETABLE)

Author: Dr Ken Curry, Addiction Medicine
LEARNING TOPIC - Discovery of circulation: Harvey film (TIMETABLE)
William Harvey is regarded as the originator of modern medical science, and the video will show how
he came to his revolutionary conclusion that the blood flows in a continuous circle around the body.
Like Copernicus he made his great discovery without recourse to novel scientific instruments, but
stimulated by the intellectual freedom of the Renaissance he encountered during his student years in
Padua.
Although Harvey broke out of the belief in tidal flow of blood through (non-existant) holes in the
interventricular septum which had endured unchallenged from ancient times, he remained politically
conservative and retained many of the other scientific ideas developed by Aristotle and Galen. For
instance he not only dedicated his book to King Charles I, but in his preface compared the monarchy
and its role in society to the heart which was the source of the "innate heat" which distinguished the
living from the dead.
That is, Harvey looked both forwards and backwards as we all still do. New discoveries and concepts
are assimilated into the paradigms passed on from our predecessors and in the process must be
related to our view of the world. Lag in this process of incorporation of new medical ideas into the
culture of a society affects the relationship between patients and doctors and is important in shaping
goverment health policies
Please see timetable for time and location of film
References
University of Sydney. Dept. of Infectious Diseases. 1990, 'The Four Elements and the four humours' in
History and philosophy of medicine for medical students , The Department, Sydney, N.S.W.
Aubrey, J., 1999, "William Harvey" in Aubrey's Brief lives. O. L. Dick (ed.) Boston, Mass.
LEARNING TOPIC - Doctors' dilemmas: treating friends family
Treating family and friends.
There is a long-standing prejudice against treating family and friends, because the relationship
between the carer and the ill person is too close. It is not illegal, but it is discouraged. Why should it
matter? It might even be argued that the closeness and understanding should lead to better
management, rather than to problems. To understand why there is a very real problem, we need to
examine why people consult doctors, how patients and doctors conduct their transactions and how
the relationship of family or friend may interfere with these transactions.
Why do people consult doctors ?
People ask for medical help for more reasons than might seem obvious. The reasons can be
conveniently considered under seven headings. Most obviously, they have developed symptoms
and/or signs which obviously threaten their autonomy and quality or duration of life (abdominal pain,
swollen joints, sore throat, depression, for example). Others have a symptom/sign complex which
does not cause any obvious ill health, but threatens to do so in the future (symptomless breast lump,
symptomless hypertension). A third group have no evidence of disease, but have reason to fear that
they will develop a more or less serious illness (family history of colon cancer, hepatitis B exposure,
16 of 57 16/10/10
relationship with HIV sufferer). A fourth group will be in good health and wants to stay that way by 10:28 AM
ensuring health screening and health advice (health maintenance plan, breast screening). A fifth will
have developed patterns of coping with life which involve using illness as a shelter (abnormal illness
behaviour, some chronic pain syndromes). A sixth will not perceive that they are ill, but are sent by
People ask for medical help for more reasons than might seem obvious. The reasons can be
conveniently considered under seven headings. Most obviously, they have developed symptoms
and/or signs which obviously threaten their autonomy and quality or duration of life (abdominal pain,
swollen joints, sore throat, depression, for example). Others have a symptom/sign complex which
does not cause any obvious ill health, but threatens to do so in the future (symptomless breast lump,
symptomless hypertension). A third group have no evidence of disease, but have reason to fear that
they will develop a more or less serious illness (family history of colon cancer, hepatitis B exposure,
relationship with HIV sufferer). A fourth group will be in good health and wants to stay that way by
ensuring health screening and health advice (health maintenance plan, breast screening). A fifth will
have developed patterns of coping with life which involve using illness as a shelter (abnormal illness
behaviour, some chronic pain syndromes). A sixth will not perceive that they are ill, but are sent by
family or friends who do perceive a change (occult cerebral tumour, alcoholism). Finally, a seventh
group present because they find themselves overwhelmed by anxiety or other symptoms of angst
(anxiety states, grieving, burnout).
The nature of the clinical transaction
Doctor and patient work within an agency relationship, in which the patient entrusts the doctor to
become his/her agent in order to secure something which s/he desires. All such relationships are
based on trust. Doctor and patient use language and signs to communicate and elucidate the problem
of the illness. The doctor translates the patient's account into his/her own language, and then back to
the patient's language when s/he comes to explain what is wrong and what should be done. By the
use of language and signs, doctor and patient should ideally achieve an intersubjective relationship,
whereby the doctor understands the nature of the illness and how it affects this particular individual.
Within this relationship, doctor and patient decide together what the right action may be. The
transaction begins with the power markedly unbalanced in favour of the doctor and should end with a
restoration of power to the patient.
The problems of treating family and friends.
Family and friends do not stand in an agency relationship with you as a doctor. They may trust you,
but may also find it difficult to accept your authority when you give advice. It is likely that they will
appeal to your special relationship and to make special judgements which may not accord with your
own perceptions of right action. The language you commonly use with family and friends is not the
language of medicine, and linguistic communication is easily distorted. It is particularly hard to offer
probabilistic advice to family and friends who want to know what will happen to them as unique
individuals. It is also hard to break bad news without offering false hopes. This all occurs because
intersubjectivity is replaced by sympathy and identification with the other. You are connected with
the other by special social and emotional bonds.
References
Little, J. M., 1995, Humane medicine., Cambridge University Press, Cambridge, U.K. pp. 15-29,
61-73,141-159.
Broyard, A., 1992, Intoxicated by my illness : and other writings on life and death, Fawcett
Columbine, New York
Ingelfinger F. Arrogance. New Engl J Med 1980; 303(26): 1507-1511.
Rabin D. Occasional notes: Compounding the ordeal of ALS: isolation from my fellow physicians. New
Engl J Med 1982; 307(8): 506-509.
Author: Dr Narelle Shadbolt, General Practice
LEARNING TOPIC - Drug therapy for stable effort angina
It is important to understand the mechanism of symptoms in order to treat angina. Effort related
angina pectoris is the symptom produced by myocardial ischemia. Effort angina results from 'demand
ischemia' -- an increase in myocardial oxygen demand in excess of the ability of the coronary
circulation to increase blood flow and supply oxygen.
17 of 57 The major determinants of myocardial oxygen demand are 16/10/10 10:28 AM

heart rate
wall stress: the product of left ventricular diastolic dimension and afterload (systolic blood
pressure and arterial distensibility)
It is important to understand the mechanism of symptoms inhttp://smp.sydney.edu.au/compass/guide/handbook/block/5
order to treat angina. Effort related
angina pectoris is the symptom produced by myocardial ischemia. Effort angina results from 'demand
ischemia' -- an increase in myocardial oxygen demand in excess of the ability of the coronary
circulation to increase blood flow and supply oxygen.
The major determinants of myocardial oxygen demand are
heart rate
wall stress: the product of left ventricular diastolic dimension and afterload (systolic blood
pressure and arterial distensibility)
myocardial contractility
All of these increase with physical effort, and emotion or sexual intercourse, and provoke demand
ischemia which may result in angina.
The main reason for limitation of coronary blood flow is atherosclerotic obstruction to the epicardial
coronary arteries of > 50% lumen diameter reduction. Microvascular abnormalities secondary to
endothelial dysfunction may also limit vasodilator reserve. Because coronary blood flow occurs mostly
in diastole, and because tachycardia reduces diastolic time, tachycardia itself may limit coronary
blood flow.
Both the doctor and the patient should understand that angina is merely a symptom of ischemia so
drug therapy should not aim to merely relieve pain but must reduce ischemia. This can be
accomplished by reducing the myocardial oxygen demand through blockade of the heart rate increase
with exercise, and reduction in afterload and ventricular volume with a vasodilator. Exercise training
may have a similar effect. The other approach to management of angina is the obstruction to coronary
blood flow with bypass surgery or percutaneous coronary intervention (balloon angioplasty usually
with stenting).
Treatment of angina using antianginal drugs may relieve symptoms but will not necessarily improve
prognosis. Almost 1 in 3 patients in primary care with stable angina have weekly angina, and this
impairs quality of life, making it important for us to assess this and appropriately manage angina.
Because patients with coronary disease have an increased risk of death and myocardial infarction,
drugs which can reduce this risk should be given. These include aspirin, the statins, angiotensin-
converting enzyme inhibitors and probably fishoils. Lifestyle measures such as exercise, exercise
training, diet and smoking cessation should also be advised. These measures may reduce angina in
addition to improving the prognosis.
Antianginal drugs
1. Nitrates. These drugs relax vascular smooth-muscle through a cyclic GMP mechanism and are
both arterial and venodilators. Afterload and ventricular dimension are both reduced, and
collateral blood flow increased. The short acting nitrates such as nitroglycerin sublingual tablets
or spray, or isosorbide dinitrate sublingual tablets can be taken in the mouth (not swallowed)
immediately angina is experienced. They are also very effective if taken prophylactically just
before angina. NB limited shelf-life, and instability of nitroglycerin tablets if removed from the
original glass container. The long acting nitrates including sustained release preparations of
isosorbide mononitrate and isosorbide dinitrate and nitroglycerin transcutaneous preparations,
can be used to provide a more sustained effect than the short acting preparations. Unfortunately
long acting nitrates will produce tolerance within 24 hours unless a nitrate-free or nitrate-poor
period of approximately 10 hours (often overnight) is provided in the regimen.The main side
effect of nitrates is headache due to vasodilatation. Nicorandil is a novel nitrate with an
additional potassium channel opening effect and may have a beneficial effect on prognosis.
2. Beta-blockers. These drugs reduce the heart rate and blood pressure at rest and during exercise
and are very effective in patients with angina. They may also improve prognosis, but probably
only if there is left ventricular dysfunction. The drugs most used are the beta-1 selective
blockers (atenolol , metoprolol and bisoprolol) which have a lesser tendency to aggravate
asthma or peripheral vascular disease than the non-selective beta-blockers. Metoprolol has a
large first-pass metabolism and the drug dose must be titrated to achieve the desired heart rate
response. The beta-blockers may also cause unwanted effects such as fatigue, loss of libido and
impotence, and bad dreams.
3. Calcium entry blockers. These drugs are arterial dilators and reduce blood pressure and
afterload. Verapamil and diltiazem also have some heart rate slowing and myocardial depressant
effects which may be useful in treatment of angina. The long acting dihydropyridine drugs
nifedipine (only in a sustained release formulation) and amlodipine are more potent vasodilators
18 of 57 16/10/10 10:28 AM
with minimal heart rate and myocardial effects. All drugs in this class can produce vasodilator
side effects such as flushing, hypotension, and edema. They can be combined with beta-blockers
although combinations may produce adverse effects including hypotension (all) and
brachycardia, heart block and heart failure (verapanil and dilatiazem). These drugs should not
response. The beta-blockers may also cause unwanted effects such as fatigue, loss of libido and
impotence, and bad dreams.
3. Calcium entry blockers. These drugs are arterial dilators and reduce blood pressure and
afterload. Verapamil and diltiazem also have some heart rate slowing and myocardial depressant
effects which may be useful in treatment of angina. The long acting dihydropyridine drugs
nifedipine (only in a sustained release formulation) and amlodipine are more potent vasodilators
with minimal heart rate and myocardial effects. All drugs in this class can produce vasodilator
side effects such as flushing, hypotension, and edema. They can be combined with beta-blockers
although combinations may produce adverse effects including hypotension (all) and
brachycardia, heart block and heart failure (verapanil and dilatiazem). These drugs should not
be used in patients with stable angina who also have heart failure.
4. Perhexiline. This is a carnitine palmityl transferase-2 inhibitor which reduces the myocardial
requirement for aerobic metabolism. The drug is very useful in refractory cases but blood levels
must be monitored closely because a significant proportion of the population are genetically
determined very slow drug metabolisers and will achieve very high blood levels which are both
hepatotoxic and neurotoxic. Another metabolic agent not available in Australia is Ranolazine.
5. Ivabradine. This is a novel drug that blocks the If channel in the sinus node, and slows the heart
rate at rest and during exercise. It therefore has a similar action to the beta-blockers, but
without beta adrenoreceptor blockade. The only side effect (uncommon) is phosphenes, a yellow
coloration of vision which is reversible.
6. Angiogenic drugs, genes, stem cells. A number of angiogenic cytokines, genes and stem cells are
currently under investigation in patients with end-stage coronary artery disease. The hope is
that angiogenesis will be induced to provide new collateral vessels and an increase in coronary
blood flow without the need for revascularisation.
7. Intractable angina. Patients with angina refactory to drug therapy, lifestyle measures, and are
who unsuitable for revascularization, may benefit from a period of external counterpulsation
(pumps applied to limbs and torso timed to inflate or deflate according to the cardiac cycle).
Other alternatives include spinal chord stimulation, TENS, and cervical sympathectomy.
References
See relevant sections of:
Rang, H. P. and M. M. Dale, 2007, Rang and Dale's Pharmacology, 6th ed., Churchill Livingstone,
Edinburgh
Boon, N. A. and S. Davidson, 2006, Davidson's principles & practice of medicine, 20th ed.,
Elsevier/Churchill Livingstone, Edinburgh ; New York
Author: Professor Ben Freedman, Medicine
LEARNING TOPIC - Essential Life Support
Learning Topic: Essential Life Support
Dr Michele Franks MBBS, FACEM. Northern Clinical School, USyd

Discipline of Emergency Medicine
Essential life support is the maintenance of airway, breathing and circulation in the person who has
suddenly become extremely unwell or severely injured.
Objectives for the BLS topic are to:
1. Effectively care for a patient that suddenly becomes unconscious or very unwell in the
19 of 57 community setting; 16/10/10 10:28 AM
2. Demonstrate appropriate airway opening manoeuvres, jaw thrust / head tilt / chin lift;
3. Demonstrate correct mouth to mouth / mask and bag-valve –mask ventilation;
Essential life support is the maintenance of airway, breathing and circulation in the person who has
suddenly become extremely unwell or severely injured.
Objectives for the BLS topic are to:
1. Effectively care for a patient that suddenly becomes unconscious or very unwell in the
community setting;
2. Demonstrate appropriate airway opening manoeuvres, jaw thrust / head tilt / chin lift;
3. Demonstrate correct mouth to mouth / mask and bag-valve –mask ventilation;
4. Demonstrate effective external chest compression;
5. Explain safety precautions associated with using defibrillation;
6. Demonstrate operation of an AED (automatic external defibrillator);
7. Demonstrate management of unconscious person including positioning;
8. Identify complications that may arise during BLS
In general, the clinical signs of critical illness are similar whatever the underlying process, because
they reflect failing respiratory, cardiovascular and neurological systems. The initial approach to the
collapsed patient is always the same using the algorithm DRABC.
D - Danger… Is the area safe? Are there electrical cables, broken glass, traffic? Is the patient in
water, on unstable ground? Remove patient from danger while maintaining your own safety.
R - Response…Talk to the patient. No response?... then try to awaken the person by tapping
your hand on their shoulder, then calling their name. Call for help – 112 on mobile, 000 on
landline… yell out to other bystanders.
A - Airway… Look in the mouth; remove any foreign object (eg food). Open the airway, head
tilt/chin lift. Jaw thrust if cervical spine injury suspected.
B - Breathing… Look, listen and feel. If no breathing or inadequate breathing, ventilate using
expired air resuscitation, mouth to mask or bag-valve –mask ventilation, attach supplemental
oxygen if available. Give 2 breaths.
C - Circulation…Check carotid pulse or if no signs of life, start chest compressions – ratio 30

compressions to 2 breaths, at a compression rate of 100/minute. Attach AED as soon as
available and follow prompts. Continue CPR until help arrives, patient shows signs of life or you
can no longer sustain resuscitative efforts. AEDs are designed to be used by untrained or
minimally trained personnel. AEDs are usually found in crowded areas such as airports, sporting
stadiums, etc. If person starts to breath and has a pulse they can be put into the recovery
position.
Author: Dr Michele Franks, Medicine
LEARNING TOPIC - Features of Down syndrome
Down syndrome is diagnosed where there is effectively trisomy for chromosome 21 (see learning
topic on Chromosomal abnormalities and early development in Down syndrome).
The features which Dr Langdon Down identified in 1866 as 'mongoloid' are present in many but not all
patients with Down syndrome. The dysmorphic, i.e. abnormal craniofacial features, are modified by
familial and ethnic facial features. Down syndrome may be found in children and adults in every
ethnic group throughout the world. The dysmorphic features which are identified with Down
20 of 57 syndrome may be found in a large number of other syndromes. Thus the presence of the features 16/10/10 10:28 AM
singly or in combination is never diagnostic, but a suspicion of Down syndrome should always be
confirmed by chromosomal study.
Features which are commonly seen in the Newborn with Down syndrome:
Down syndrome is diagnosed where there is effectively trisomy for chromosome 21 (see learning
topic on Chromosomal abnormalities and early development in Down syndrome).
The features which Dr Langdon Down identified in 1866 as 'mongoloid' are present in many but not all
patients with Down syndrome. The dysmorphic, i.e. abnormal craniofacial features, are modified by
familial and ethnic facial features. Down syndrome may be found in children and adults in every
ethnic group throughout the world. The dysmorphic features which are identified with Down
syndrome may be found in a large number of other syndromes. Thus the presence of the features
singly or in combination is never diagnostic, but a suspicion of Down syndrome should always be
confirmed by chromosomal study.
Features which are commonly seen in the Newborn with Down syndrome:
Hypotonia
Excessive skin folds at the back of the neck
Maxillary (malar) underdevelopment (hypoplasia)
In curving of the little finger (clinodactyly)
Hypoplasia of the middle phalanx of the 5th finger - recognised by a short middle segment or a
single interphalangeal crease.
Wide gap between the first or second toes (sandal gap)
Features which may be seen in normal newborns
Epicanthic folds (prominent skin folds at the inner canthi of the eyes) which are usually seen in babies
of African and Asian descent and not uncommonly in European infants.
Single transverse palmar crease
Down syndrome Normal
Bilateral 45% 1%
Unilateral 4%
Major malformations in the Newborn with Down syndrome
Congenital Heart Anomalies (40%)

Atrio-ventricular canal (13%)
Ventricular septal defects (13%)
Tetralogy of Fallot (7%)
Atrial septal defects (10%)
Gastrointestinal Anomalies (10-18%)
Duodenal atresia
Hirschsprung disease
Undescended testes (21%)
Features commonly seen in childhood
Delayed psychomotor development

Intellectual disability
Prominence of the tongue (due to a small mouth)
Persistent epicanthic folds
Flattening of the back of the head (brachycephaly)
Short stature
Brushfield spots (speckling around the rim of the iris) except in subjects with brown irides
Joint hypermobility
Preventive health maintenance in childhood
Leukoerythroblastic anaemia
Acute Leukaemia
Hypothyroidism
Atlanto-Occipital Instability
Preventive health maintenance in adults
21 of 57 Leukoerythroblastic anaemia 16/10/10 10:28 AM

Acute Leukaemia
Hypothyroidism
Acute Leukaemia
Hypothyroidism
Preventive health maintenance in adults
Acute Leukaemia
Hypothyroidism
Specific terminologic notes
By international convention the term 'mongolism' had been abandoned

Syndromes are named without the possessive ie Down syndrome, Edwards syndrome etc.
'Simian' means 'pertaining to a monkey'. It is an inappropriate (obsolete) term for 'single
transverse palmar crease' or 'bridged transverse palmar crease' which should be distinguished
from the Sydney line which is a proximal complete transverse palmar crease in the presence of a
partial distal palmar crease.
References
Chromosomal syndromes : common and/or well-known syndromes in 2001, Syndromes of the head
and neck, Oxford Monographs on Medical Genetics NO. 42, ed. R. J. Gorlin, et al. New York, Oxford
University Press: Pages 35-42.
Gardner, R. J. M. and G. R. Sutherland, 2004, Chromosome abnormalities and genetic counseling, 3rd
ed., Oxford University Press, New York. Pages 249-263
Selikowitz, M., 1997, Down syndrome : the facts, 2nd ed., Oxford University Press, Oxford ; New York,
204 pp.
Antonarakis S, Lyle R, Dermitzakes ET, Reymond A, Deutsch S. Chromosome 21 and Down Syndrome:
from genomics to pathophysiology. Nature Reviews Genetics 2004; 5(10): 725-737.
There is extensive literature on the molecular mechanisms resulting in Down syndrome. This review
gives an extensive coverage of the information on the correlation between molecular mechanisms and
phenotype.
LEARNING TOPIC - Flow and pressures in the circulation
The flow of blood around the body is driven by pressure, generated by the pump action of the heart's
ventricles. Within the circulation, the arteries contain blood under high pressure but there is a marked
reduction in pressure within the microcirculation and capillaries. The veins are a low pressure system
for return of blood to the heart. The pulmonary circulation normally operates at a lower pressure than
The cardiac cycle consists of two major phases: diastole, when the ventricles are being filled with
blood and systole when the ventricles contract to eject blood from the heart. In diastole the ventricles
are relaxed and fill from the atria with blood flowing across the open atrio-ventricular valves. The
walls of the ventricle are distended as it fills. With the onset of systole, an electrical impulse causes
the walls of the ventricle to begin contracting. As the ventricle contracts, the pressure within the
chamber rises and forces the atrio-ventricular valve shut. The ventricle continues to contract
(isovolumic contraction period) and pressure within the chamber rises further before forcing the
semi-lunar valve open and ejecting blood into the aorta (or pulmonary artery). The blood ejected from
the ventricle is the stroke volume. At the end of this ejection period, pressure within the ventricle
begins to fall as the muscle relaxes. The semilunar valve closes and ventricular chamber pressure falls
further (isovolumic relaxation). During this time the atria have been collecting blood from the veins,
ready for the next beat. When ventricular pressure falls below the atrial pressure, the atrio-
22 of 57 ventricular valve opens and blood flows from the atrium to the ventricle to begin the next cycle.16/10/10 10:28 AM
Mechanical systole is the period from onset of rise of ventricular pressure to the closure of the
semi-lunar valve.
chamber rises and forces the atrio-ventricular valve shut. The ventricle continues to contract
(isovolumic contraction period) and pressure within the chamber rises further before forcing the
semi-lunar valve open and ejecting blood into the aorta (or pulmonary artery). The blood ejected from
the ventricle is the stroke volume. At the end of this ejection period, pressure within the ventricle
begins to fall as the muscle relaxes. The semilunar valve closes and ventricular chamber pressure falls
further (isovolumic relaxation). During this time the atria have been collecting blood from the veins,
ready for the next beat. When ventricular pressure falls below the atrial pressure, the atrio-
ventricular valve opens and blood flows from the atrium to the ventricle to begin the next cycle.
Mechanical systole is the period from onset of rise of ventricular pressure to the closure of the
semi-lunar valve.
2
In adults, the normal end-diastolic left ventricular volume is approximately 70 ± 20 ml/m s and the
2
normal residual volume in the ventricle at end-systole is 25 ± 10 ml/m s. The ejection fraction is the
proportion of the end-diastolic volume which is ejected during each systole and is typically 50-70%
for the left ventricle. The cardiac output is the amount of blood pumped from the heart each minute
and is the stroke volume per beat multiplied by the heart rate.
The flow of blood between heart chambers is dependent upon the pressures within each chamber. The
atria are low pressure chambers with mean right atrial pressure being 3-5 mmHg and mean left atrial
pressure being 5-10 mmHg. In diastole the ventricles have low chamber pressures, being 1-3 mmHg
at the onset of ventricular filling. During diastole, ventricular filling pressure increases to 5-7 mmHg
in the right ventricle and 8-10 mmHg in the left ventricle by end-diastole. During systole there is a
marked increase in ventricular chamber pressures to approximately 20-25 mmHg in the right ventricle
and 110-130 mmHg in the left ventricle. Normal pulmonary artery pressures are approximately 25/12
mmHg and normal aortic pressures are approximately 120/80 mmHg, because the systemic arterial
vascular resistance is higher than the pulmonary vascular resistance.
References
Elsevier/Churchill Livingstone, Edinburgh ; New York.
LEARNING TOPIC - Functions of the heart as a pump
Structure of the Myocardium
Understand the macroscopic structure of the myocardium as a syncytium of myocytes containing

contractile myofilaments. Myofilaments contain both contractile proteins (actin and myosin) and
regulatory proteins (such as troponin and tropomyosin). These proteins are assembled into
sarcomeres, which are the contractile units of the myocardium. The structure of the sarcomeres is
maintained by additional proteins, such as titin. Refresh your knowledge of the structure of the actin
and myosin molecules and how they are believed to interact to generate contractile force. The
interaction of the myosin head with an exposed actin binding site is central to the contractile process.
After binding to actin and myosin, the myosin molecule bends at the head-rod junction and this
protein deformation shortens the myofilament (power stroke). Repetition of the power stroke
shortens the muscle. This process requires hydrolysis of ATP at the rate of 1 ATP molecule per power
stroke per myosin molecule. Understand the role of regulatory proteins, including tropomyosin and
Troponin-T in the actin-myosin interaction.
Pump action of the heart
The heart functions as a pump in systole to eject blood into the circulation. During diastole, the
ventricle fills with blood from the atrium. At end-diastole, the mitral valve closes and ventricular
pressure rises. The aortic valve opens and blood is ejected into the circulation. At end-systole, the
ventricle begins to relax, ventricular pressure falls and the aortic valve closes and then the mitral
valve opens to begin the next cardiac cycle. The volume of blood ejected from the ventricle is the
stroke volume and the cardiac output is the product of stroke volume and heart rate. The work done
23 of 57 by the heart in each beat is the integral product of the stroke volume and ventricular pressure 16/10/10 10:28 AM
generated during systole.
The degree to which a sarcomere shortens is dependent upon its initial load (preload) and the load
against which it must contract (afterload). In the heart, an increase in venous return to the ventricle
The heart functions as a pump in systole to eject blood into the circulation. During diastole, the
ventricle fills with blood from the atrium. At end-diastole, thehttp://smp.sydney.edu.au/compass/guide/handbook/block/5
mitral valve closes and ventricular
pressure rises. The aortic valve opens and blood is ejected into the circulation. At end-systole, the
ventricle begins to relax, ventricular pressure falls and the aortic valve closes and then the mitral
valve opens to begin the next cardiac cycle. The volume of blood ejected from the ventricle is the
stroke volume and the cardiac output is the product of stroke volume and heart rate. The work done
by the heart in each beat is the integral product of the stroke volume and ventricular pressure
generated during systole.
The degree to which a sarcomere shortens is dependent upon its initial load (preload) and the load
against which it must contract (afterload). In the heart, an increase in venous return to the ventricle
will cause it to stretch the sarcomere during diastole. As a result the sarcomere will shorten more in
the next systole. This is the Frank-Starling principle and it is an important physiological modulator of
the force of cardiac contraction. In patients with heart disease, who have a reduced contractile
function of the heart, the Frank-Starling mechanism is used to partly restore contractile function. The
Frank-Starling mechanism does not usually fully compensate for depressed cardiac function in
patients with heart failure and it is not possible to stretch sarcomere indefinitely. If the sarcomere is
overstretched, contractile force declines. If diastolic pressure in the left ventricle becomes too high,
then the patient will suffer pulmonary congestion.
The degree of afterload on the ventricle is important. Afterload is a multifactorial identity, influenced
by arterial pressure, aortic valve function and arterial impedance. An increase in afterload will result
in a reduction of the degree of shortening of the sarcomere and a reduction in stroke volume and
cardiac output.
References
LEARNING TOPIC - Genesis of atheroma
Atherosclerosis involves cellular proliferation, inflammation, intracellular and extracellular deposition

of lipoprotein-derived lipid (principally cholesterol and cholesteryl ester), deposition of extracellular
matrix, and, of particular importance in the clinical management of ischaemic heart disease,
thrombotic occlusion of coronary vessels. Diabetes, hypercholesterolaemia, smoking, hypertension,
male sex, increasing age, positive family history, sedentary lifestyle and obesity are all established
risk factors for coronary atherosclerosis.
Native or modified (oxidised, glycosylated or aggregated) low density lipoprotein (LDL) in the arterial
intima may induce monocyte infiltration to initiate atherosclerosis. Arterial branch points are
predisposed to atherosclerosis. This appears due to increased turbulence, cell turnover and
permeability of endothelium at branch points.
Endothelium is normally non-thrombogenic and non-adherent for leukocytes. The expression of

adhesion molecules by endothelial cells is critical for the initial reversible rolling and subsequent
irreversible firm adhesion and diapedesis by monocytes. Cytokines augment leukocyte-endothelial cell
adhesion by promoting the expression of endothelial adhesion molecules (eg VCAM-1) and monocyte
ligand molecules (eg integrins). The endothelium maintains vascular tone by releasing prostacyclin
(PGI2, dilator), endothelin (ET, constrictor) and endothelium-derived relaxing factor (EDRF, which
may be at least in part nitric oxide, NO). Impaired endothelial cell-mediated dilatation is an early
feature of atherosclerosis.
Fatty streaks arise from the endothelial penetration of blood-borne monocytes which subsequently
become 'foam-cell' macrophages laden with lipid. Plaque progression leads to the development of the
fibrofatty lesion, which is frequently eccentric and can result in significant luminal stenosis. It
becomes increasingly 'fibrous' and 'complex' with a dense cap of connective tissue and smooth
muscle cells (SMC) overlying a core of lipid and necrotic cells (necrotic core). Matrix and connective
tissue are deposited by SMC, many of which are also 'foam-cells' . Cell proportions in lesions vary,
with more SMC in coronaries and more macrophages in aortae.
24 of 57 16/10/10 10:28 AM
Immunologically active T-lymphocytes, mast cells, immunoglobulins, terminal C5b-9 complement
complex and complement receptors are present in atheroma. Complement activation may follow the
deposition of antibodies to antigens such as native, glycosylated or oxidised lipoproteins, infectious
Fatty streaks arise from the endothelial penetration of blood-borne monocytes which subsequently
become 'foam-cell' macrophages laden with lipid. Plaque progression leads to the development of the
fibrofatty lesion, which is frequently eccentric and can result in significant luminal stenosis. It
becomes increasingly 'fibrous' and 'complex' with a dense cap of connective tissue and smooth
muscle cells (SMC) overlying a core of lipid and necrotic cells (necrotic core). Matrix and connective
tissue are deposited by SMC, many of which are also 'foam-cells' . Cell proportions in lesions vary,
with more SMC in coronaries and more macrophages in aortae.
Immunologically active T-lymphocytes, mast cells, immunoglobulins, terminal C5b-9 complement

complex and complement receptors are present in atheroma. Complement activation may follow the
deposition of antibodies to antigens such as native, glycosylated or oxidised lipoproteins, infectious
agents, or could represent a direct activation of complement by extracellular lipids such as those
present in the necrotic core of atherosclerotic plaque.
Contractile and synthetic SMC phenotypes have been described in plaque. Growth factors such as
platelet derived growth factor (PDGF) can induce the change from contractile to synthetic phenotype
and the subsequent release of cytokines, growth factors, and extracellular matrix from synthetic SMC.
Conversely, components of extracellular matrix (eg heparan sulphate) can inhibit SMC transformation,
proliferation and migration.
Further rapid progression of atherosclerosis leads to plaque instability. Fissuring of an advanced

fibrofatty plaque may develop as a result of collagen rupture. Endothelial cell separation and
denudation permits platelet adhesion to exposed subendothelium and foam cell macrophages with
subsequent development of intraluminal thrombosis. Mild plaque fissuring causing intraplaque
haemorrhage can cause significantly increased coronary stenosis without necessarily causing luminal
thrombosis and occlusion, while deep fissuring is more likely to be associated with vessel occlusion by
thrombosis. A deep fissure is also likely to permit escape of some of the necrotic core as an
atheroembolus which will travel 'downstream' and may occlude distal arterial branches. During
organisation of thrombus, growth factors from adherent platelets promote SMC proliferation.
Regression of atherosclerotic lesions in non-human primates occurs more readily in fatty streaks than
in raised fibrous lesions and is associated with an increase in lesion calcification and collagen
deposition and a decrease in lesion cholesteryl ester content. However, arteries do not return to their
prediseased state. Thus lowering serum cholesterol may preferentially induce regression of
foam-cell-rich fatty streaks and perhaps reduce the cellularity and lipid content of macrophage- and
lipid-rich lesions of advanced plaque, but only produce mild changes in the degree of angiographically
apparent coronary stenosis.
References
Kumar, V., et al., 2005, Robbins and Cotran pathologic basis of disease, 7th ed., Elsevier Saunders,
Philadelphia. [Available as a E-Book] Chapter 11 (Blood Vessels > Atherosclerosis)
Provides an illustrated overview of the morphological features of atherosclerosis.
Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s . Nature 1993; 362(6423):
801-809.
Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the
acute coronary syndromes-part 1. N.Engl.J.Med. 1992; 326(4): 242-250.
Davies MJ, Woolf N. Atherclerosis: what is it and why does it occur? Brit.Heart J. 1993; 69(Suppl.):
3-.11.
For extra detail, the following references give overlapping but complementary views of the
development of atherosclerosis. Reference 1 covers cellular interactions and cytokines in some detail,
reference 2 outlines the potential role of plaque fissuring in lesion progression, and reference 3
outlines the important features of plaque predisposing to plaque rupture and acute coronary
syndromes.
Author: Professor Len Kritharides, Medicine
25 of 57 LEARNING TOPIC - Gross and fine anatomy of blood vessels 16/10/10 10:28 AM
Anatomy of the coronary arteries

syndromes.
Author: Professor Len Kritharides, Medicine
LEARNING TOPIC - Gross and fine anatomy of blood vessels
Anatomy of the coronary arteries
Revise the general structure of the heart from the learning topic Structure of heart and great
vessels . In particular the position of the external sulci.
What is the origin, course and main branches of the left and right coronary arteries?
Which arteries or branches supply the left and right ventricles, the interventricular septum and
the conducting system?
Where do the branches of these two arteries anastomose with each other? What is the
significance of the anastomosis?
Histology
How does the histological structure of elastic and muscular arteries, arterioles and capillaries
vary?
Additional
How is the venous drainage of the heart organised?

Which nerves innervate the coronary arteries and what effect do they have on coronary blood
flow?
References
Moore, K. L., et al., 2006, Clinically oriented anatomy, 5th ed., Lippincott Williams & Wilkins,
Baltimore, MD. Chapter 3 (Pelvis & Perineum)
Drake, R. L., et al., 2005, Gray's anatomy for students, ed., Elsevier/Churchill Livingstone,
Philadelphia. Chapter 3 (Thorax)
Ross, M. H. and W. Pawlina, 2006, Histology : a text and atlas with correlated cell and molecular
biology, 5th ed., Lippincott Wiliams & Wilkins, Baltimore, MD. Chapter 13 (Cardiovascular system)
Author: Dr Richard Ward, Anatomy and Histology
LEARNING TOPIC - History of chronic fatigue syndrome
Chronic Fatigue was first considered a pathological entity in the 1750s.
In the 1800s the syndrome had many different names and there was much debate as to the cause. It
was variably called nervous exhaustion, weak nerves, neurasthenia, autonomic imbalance syndrome
or Da Costa syndrome.
The 20th century has seen this entity linked to many diseases, such as Brucellosis, epidemic
neurasthenia, chronic EBV (Epstein-Barr virus) syndrome, total allergy syndrome, and chronic yeast
infection.
The application of scientific techniques has yet to elucidate a definite cause for this constellation of
symptoms with fatigue as its central symptom.
Chronic fatigue syndrome was in recent history most fully described as Myalgic Encephalomyelitis
(ME). This illness was thought to be related to a coxsackie virus infection and first occurred in
Coventry and then at the Royal Free Hospital in London in 1955.
Since that description of the syndrome Chronic Fatigue System or ME has been in a state of evolution,
and it was in the late 1970s and early 1980s when it reached its peak in the literature. In 1988 the
26 of 57 16/10/10 10:28 AM
Centre for Disease Control in Atlanta published what has become the working definition for chronic
fatigue syndrome.
Debate is still spirited in the literature, with those who believe Chronic Fatigue Syndrome is a physical
symptoms with fatigue as its central symptom.
Chronic fatigue syndrome was in recent history most fully described as Myalgic Encephalomyelitis
(ME). This illness was thought to be related to a coxsackie virus infection and first occurred in
Coventry and then at the Royal Free Hospital in London in 1955.
Since that description of the syndrome Chronic Fatigue System or ME has been in a state of evolution,
and it was in the late 1970s and early 1980s when it reached its peak in the literature. In 1988 the
Centre for Disease Control in Atlanta published what has become the working definition for chronic
fatigue syndrome.
Debate is still spirited in the literature, with those who believe Chronic Fatigue Syndrome is a physical
illness and those who believe it is psychological in nature. Most authorities seem to believe that it is a
combination of both these factors.
As with any chronic illness with no effective treatment of defined aetiology, there is a chronic fatigue
industry offering many unproven cures to the patients with this illness. There are also many support
groups keeping patients informed of the progress of research and raising funds for research into this
illness as is shown in some of the Internet references below.
References
Holmes GP, Kaplan JE, Gantz NM et al. Chronic Fatigue syndrome: a working case definition. Ann. Int.
Med 1988; 108(3): 387-389
Hickie I, Lloyd A, Wakefield D, Parker G. The psychiatric status of patients with chronic fatigue
syndrome. Br. J. Psychiatry 1990; 156: 534-540
Medical Staff of the Royal Free Hospital. An outbreak of encephalomyelitis in the Royal Free Group,
London in 1955. Br Med J 1957, October, 2: 895-904
Internet Sites
(The contents of these sites may not necessarily be based on evidence.)
The American Association for Chronic Fatigue Syndrome (AACFS): http://www.aacfs.org/ .
Chronic Fatigue Syndrome/Myalgic encephalomyelitis Information Page: http://www.cfs-news.org/ .
Author: Dr Ravinay Bhindi, Medicine
LEARNING TOPIC - Immune mechanisms in rheumatic fever
The association of acute pharyngeal infection with beta-haemolytic Group A Streptococci and acute
rheumatic fever (ARF) is the most compelling example of an acute bacterial infection inducing tissue
damage through auto-immune mechanisms. Following untreated clinical pharyngitis with a wide
variety of streptococcal serotypes, about 3% of subjects will develop ARF involving the joints, skin
and the heart. In a minority of patients (10-15%), involvement of the basal ganglia will cause a
pattern of involuntary movements, termed chorea. Many, but not all, serotypes are capable of leading
to ARF, and high attack rates are associated with virulent strains belonging to several M-protein
serotypes.
Anti-cardiac auto-antibodies and molecular mimicry
Patients with ARF develop antibodies which react with cardiac tissue. This led to the concept of
'molecular mimicry', which refers to the sharing of antigenic determinants by the initiating infectious
agent and the host tissues. During the pharyngitis, streptococcal antigens stimulate an antibody
response which cross-reacts with a variety of antigens in cardiac tissue. With successive streptococcal
infections, the titre of antibodies rises and the patient has recurrent episodes of ARF and progressive
cardiac damage. The level of cardiac-reactive antibodies correlates with the clinical activity of the
rheumatic fever. Eventually the damaged cardiac tissue may provide antigens to stimulate the
auto-immune antibody response and perpetuate the cycle of tissue damage.
27 of 57 16/10/10 10:28 AM
There is a wide range of cross reactivity between streptococcal antigens and the heart, including
cardiac myosin and streptococcal M-protein, a surface protein which is the target of opsonic
antibodies
'molecular mimicry', which refers to the sharing of antigenic determinants by the initiating infectious
agent and the host tissues. During the pharyngitis, streptococcal antigens stimulate an antibody
response which cross-reacts with a variety of antigens in cardiac tissue. With successive streptococcal
infections, the titre of antibodies rises and the patient has recurrent episodes of ARF and progressive
cardiac damage. The level of cardiac-reactive antibodies correlates with the clinical activity of the
rheumatic fever. Eventually the damaged cardiac tissue may provide antigens to stimulate the
auto-immune antibody response and perpetuate the cycle of tissue damage.
There is a wide range of cross reactivity between streptococcal antigens and the heart, including
cardiac myosin and streptococcal M-protein, a surface protein which is the target of opsonic
antibodies
myocardial sarcolemma and streptococcal membrane proteins
heart valve glycoprotein and hyaluronate in the capsule of streptococci
Immunopathology and T cell recognition
Immunoglobulin and complement are deposited in the heart during acute carditis, suggesting the
auto-antibodies may contribute to the cardiac damage. However, the characteristic histological
feature of rheumatic carditis is a mononuclear cell infiltrate, predominantly of T cells including both
CD4+ and CD8+ T cells. Lymphocytes from patients with ARF do react with streptococcal membrane
antigens. Further, patients with acute and chronic RF have high titres of high affinity IgG anti-cardiac
antibodies. This type of antibody response requires T cell help (see PBL 1.07, lecture 2), indicating
that T cells also participate in the auto-immune response. This would require shared peptide
determinants between streptococci and cardiac tissue, and recently cross-reactive auto-epitopes
between the M-protein and cardiac myosin have been demonstrated.
Why do a minority of infected individuals develop Rheumatic Fever?
Given the wide-spread crossreactivity between Group A streptococci and the heart, why do so few
people develop ARF? There is clearly an individual susceptibility to develop ARF and this is due in part
to the genetic control of the host immune response. In some subjects this control is influenced by the
HLA genes, as HLA-DR2 and HLA-DR4 are associated with ARF in certain populations, however other
undefined genes must also be involved.
Although the mechanism of chorea is not resolved, this may also be a manifestation of molecular
mimicry leading to auto-immune tissue damage. Sera from patients with active chorea contain IgG
antibodies which react with neuronal antigens in the caudate and subthalamic nuclei, the basal
ganglia involved in chorea.
References
Author: Professor Warwick Britton, Medicine
LEARNING TOPIC - Lifestyle modification in vascular disease
Lifestyle modification of people with vascular disease is an essential component of secondary

prevention.
Cigarette smoking, poor dietary habit and inactivity are the major modifiable lifestyle risk factors.
In diabetes which adversely affects vascular disease, lifestyle modification will aid weight loss and
improve blood sugar control reducing vascular complications.
The doctor's role is to identify, assess, prioritise and initiate appropriate changes of these risk factors
while being mindful of the psychosocial issues that may impede the process.
A number of approaches are available to facilitate lifestyle modification:
Communication skills are important in:
Utilising the doctor-patient relationship.

Distributing and explaining appropriate patient education material including kits, leaflets, tapes,
videos, phone support services provided by Government agencies, the National Heart
Foundation, pharmaceutical firms and support groups.
Enlisting the assistance of family members, carers and significant others, eg educating the wife
28 of 57 if she is the family cook, giving the patient the responsibility to walk the dog. 16/10/10 10:28 AM
Allied health professionals:
Paramedical eg. dietitians, psychologists, physiotherapists.

Communication skills are important in:
Utilising the doctor-patient relationship. http://smp.sydney.edu.au/compass/guide/handbook/block/5

Distributing and explaining appropriate patient education material including kits, leaflets, tapes,
videos, phone support services provided by Government agencies, the National Heart
Foundation, pharmaceutical firms and support groups.
Enlisting the assistance of family members, carers and significant others, eg educating the wife
if she is the family cook, giving the patient the responsibility to walk the dog.
Allied health professionals:
Paramedical eg. dietitians, psychologists, physiotherapists.

Medical specialist units eg shared care programs, smoking cessation clinics, cardiac
rehabilitation units, obesity clinics.
Community resources eg. National Heart Foundation, Public Health Units, Alcoholics Anonymous,
smoking cessation programs eg Smokescreen.
Commercial enterprises eg. Gutbusters, Weight Watchers, the local gym, various sporting and
activity clubs.
Pharmaceutical agents:
These may be used as an adjunct to lifestyle modification eg
Nicotine replacement therapy

Dexfenfluramine hydrochloride as an appetite suppressant in a small subgroup of obese
patients.
The person with vascular disease is most likely to achieve and maintain lifestyle changes under the
care of a family General Practitioner because of the GP's unique and ongoing relationship with the
patient and the insight he/she has into the patient's biopsychosocial situation. The treating specialist
has an important role in providing positive reinforcement of lifestyle changes, and encouraging
initiation of these at point of contact when a patient is amenable to initiatory lifestyle change.
References
Brownell KD, Cohen LR. Adherence to dietary regimens. 2: Components of effective interventions.
Behavioural Medicine 1995 Winter; 20 (4):155-64.
Oldenburg B, Owen N, Gomel M, Graham-Clarke P. Lifestyle change and cardiovascular disease.

Australian Family Physician Vol. 21 August 1992; 21(8): 1137-1144.
Mendelsohn C. Smokescreen for 1990s: a new approach to cessation. Australian Family Physician.
1994 23(5): 841-848.
New South Wales. Dept. of Health, 1996, Physical activity and health : a special communication from
the Chief Health Officer, 2nd ed., State Health Publication No. (HP) 950129
Exercise for people with heart disease. National Heart Foundation, NSW Division.
National Heart Foundation of Australia, 1995, Exercise for people with heart disease : guidelines for
the prescription and conduct of non-medically supervised, community-based exercise programsed.,
National Heart foundation, [Surry Hills, N.S.W.]
Author: Dr David Lim, Medicine
LEARNING TOPIC - Long term management of childhood cardiac disease
The course of congenital heart disease is influenced largely by its severity (impact on normal
cardiovascular physiology) and the medication and surgical procedures used to treat it when
necessary.
Differentiation of the consequences of these management strategies is important.
The general outcome for unoperated patients with significant left to right shunts and right to left
shunts, should be differentiated from the lesser range of problems for patients with minor,
29 of 57 16/10/10 10:28 AM
haemodynamically unimportant lesions.
When surgery is required issues such as surgical myocardial scar, the fate of the cardiac 'prosthetics',
myocardial or valve dysfunction, and incompletely corrected lesions arise in latter followup.
The course of congenital heart disease is influenced largely by its severity (impact on normal
cardiovascular physiology) and the medication and surgical procedures used to treat it when
necessary.
Differentiation of the consequences of these management strategies is important.
The general outcome for unoperated patients with significant left to right shunts and right to left
shunts, should be differentiated from the lesser range of problems for patients with minor,
haemodynamically unimportant lesions.
When surgery is required issues such as surgical myocardial scar, the fate of the cardiac 'prosthetics',
myocardial or valve dysfunction, and incompletely corrected lesions arise in latter followup.
An approach to primary care management of these patients may need to take this into account.
Consequences of unoperated congenital heart disease

viz: cyanosis, volume load, congestive cardiac failure, paradoxical embolus, polycythaemia,
stroke, brain abscess, ventricular dysfunction, arrhythmia, bacterial endocarditis
prophylaxis.
Consequences of surgical management of congenital heart disease.
Practical advice for patients and families after management of congenital heart disease.
References
Relevant sections of general Paediatric text books will overview these issues and should be read first.
More detailed discussions can be found in:
Jordan, Scott. Heart Disease in Paediatrics. 1989.
Moss, A. J., et al., 2001, Moss and Adams' heart disease in infants, children, and adolescents, including
the fetus and young adult, 6th ed., Lippincott Williams & Wilkins, Philadelphia ; London. [Available as
an E-Book]
Garson, A., 1997, The science and practice of pediatric cardiology, 2nd ed., Williams & Wilkins,
Baltimore
Jacobs, M. L. and W. I. Norwood, 1992, Pediatric cardiac surgery : current issues., Butterworth-
Heinemann, Boston
Jacobs, Norwood. Paediatric Cardiac Surgery - Current Issues. Butterworth-Heineman, 1992.
Wilson, Neutze. Adult congenital heart disease: principal and management guidelines. Aust & NZ J
Med 1993; 23(6): 697-705.
Bethesda Conference. Congenital Heart Disease after Childhood: An expanding patient population.
JACC 1991; 18(2): 311-342.
Kaplan. Bacterial endocarditis prophylaxis - tradition or necessity . Am J Cardiol 1986; 57(6):

478-479.
Awadallah et al. The changing pattern of infective endocarditis in childhood . Am J Cardiol

1991; 68(1): 90-94.
Wilson, W. et al. Prevention of Infective Endocarditis. Guidelines From the American Heart
Association. A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and
Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on
Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and
Outcomes Research Interdisciplinary Working Group. Circulation . 2007 online Apr 19
Author: Clinical Associate Professor Gary Sholler, Paediatrics and Child Health
LEARNING TOPIC - Medicolegal issues in information-giving
Autonomy
"The fundamental principle underlying consent is said to be a right of self-determination: the
30 of 57 principle, or value choice, of autonomy of the person ... It is an ethical principle which is simply 16/10/10 10:28 AM
reflected in legal rules because our law has been developed by judges sensitive to the practical
application of generally held community ethical principles (Kirby, M. (1983) "Informed consent: what
does it mean?" Journal of Medical Ethics 9:69, at page 70).
LEARNING TOPIC - Medicolegal issues in information-giving http://smp.sydney.edu.au/compass/guide/handbook/block/5
Autonomy
"The fundamental principle underlying consent is said to be a right of self-determination: the
principle, or value choice, of autonomy of the person ... It is an ethical principle which is simply
reflected in legal rules because our law has been developed by judges sensitive to the practical
application of generally held community ethical principles (Kirby, M. (1983) "Informed consent: what
does it mean?" Journal of Medical Ethics 9:69, at page 70).
Giving information
The giving of information to patients is an ethical obligation and a legal requirement, and relates to
the concept of autonomy, that is, enabling the individual to control their own life. The term 'informed
consent' clearly specifies that consent to a medical procedure needs to be based on adequate
information.
Valid and Informed consent

Informed consent is not synonymous with valid consent, because the requirement that consent be
informed is only one aspect of a valid consent. The individual should have the legal capacity to give
consent, be in a situation where consent may be given freely, without any duress, force, fraud, deceit
or coercion, and have sufficient information to make an informed and enlightened decision.
Three areas of law are relevant to informed consent - (1) the crime of battery, (2) the tort of trespass
which includes assault and battery, and (3) the tort of negligence. Practically, the issue is raised
usually within the arena of the civil law or torts. Trespass is a general term for several causes of
action, the most relevant here being assault and battery. A battery is an intentional touching of
another person without consent of that person and without lawful excuse; an assault is the
intentional creation in another person of an apprehension of imminent, harmful or offensive contact.
Negligence is relevant where it can be shown that there was an obligation on the part of the
practitioner to provide certain information, and that if the information had been given to the patient
that the patient would not have consented to the procedure being carried out.
The nature of the information

The requirements for the type and amount of information to be disclosed vary with the circumstances.
Ultimately the courts have reserved the right to determine what is reasonable. The patient should be
told the diagnosis, the alternative treatments, and what the practitioner recommends and why. The
information given to the patient must encompass an adequate explanation of the proposed procedure,
and be couched in language that the patient can comprehend. Giving a patient a pamphlet may well be
insufficient, particularly if there is no follow-up to ensure the patient could read and understand the
pamphlet, and had no further questions. Medical jargon should be avoided. Imprecise terminology
which may have different subjective interpretations (such as, 'rare', 'often', and 'not serious') should
be avoided, in favour of precise description of risks and probabilities (where they are available). The
courts have implied that the more invasive the procedure, or the graver the consequences, the greater
should be the level of disclosure. Risks such as risk of death, disability and other serious
consequences should be disclosed, as should information about possible benefits of a procedure.
Other serious consequences such as effect on work, and time required for recuperation, should be
disclosed.
As a rule of thumb, large risks of minor harm and small risks of major harm should be disclosed and
especially if there is anything to indicate that a patient would be very concerned about any particular
outcome.
A valid consent is not required in an emergency, because the courts have presumed that an
unconscious patient in a life-threatening situation would have consented to treatment. Furthermore,
this presumption is in accordance with community values.
If a patient cannot give a valid consent owing to temporary or permanent disability, recourse should
be made to obtaining third party consent, consistent with the provisions of the Guardianship Act 1987
(NSW) (see Learning Topic on Guardianship).
Consent forms
A valid consent form needs to contain details of the actual procedure to be performed. The signed
consent form does not provide proof that the patient consented, but is merely evidence that he or she
signed the particular form. The signature itself does not prove that the patient understood the
information given, or the nature and effect of the procedure. Consent must be operative at the time
the procedure is performed, and it is important for the consent form to be signed as close as possible
to the time the procedure is performed. The patient's ability to give valid consent should not be
31 of 57 16/10/10 10:28 AM
compromised by the effects of pre-operative medication, for example.
It is doubtful whether a patient may waive his/her right to the information necessary to make an
informed and valid decision. If a patient stated that he/she did not want to know what was going to
Consent forms
A valid consent form needs to contain details of the actual procedure to be performed. The signed
consent form does not provide proof that the patient consented, but is merely evidence that he or she
signed the particular form. The signature itself does not prove that the patient understood the
information given, or the nature and effect of the procedure. Consent must be operative at the time
the procedure is performed, and it is important for the consent form to be signed as close as possible
to the time the procedure is performed. The patient's ability to give valid consent should not be
compromised by the effects of pre-operative medication, for example.
It is doubtful whether a patient may waive his/her right to the information necessary to make an
informed and valid decision. If a patient stated that he/she did not want to know what was going to
happen and did not want to make the decision, but preferred the doctor to make the decision, a
practitioner who acted upon this statement would be unwise. Waiving the important and fundamental
right to autonomy in decision making about one's own body is so significant that it would be
preferable for the waiver to be written, and for independent corroboration to be obtained that the
patient prefers a third party to make the decision. If the patient persists in refusing to accept
information or decision-making responsibility, recourse may have to be made to the Guardianship
Tribunal. The medical practitioner cannot assume the right to make decisions on the part of the
patient, except in an emergency.
References
It would be advisable to consult specialist resources on medico-legal issues, particularly those

relating to the Australian legal system. Useful references include:
Bates PW, Dewdney JC, Australian CCH Health and Medical Law Editors, Health and Medical Law
Reporter, CCH Australian Ltd, paragraphs 16-900 to 16-970 (Consent) and 17-000 to 17-420
(Elements of Consent)
See also - http://www.lawlink.nsw.gov.au/lrc.nsf/pages/ip24chp08

NSW Law Reform Commission, 2004, Minors’ consent to medical treatment. Issues paper 24.
Author: Professor Susan Hayes, Medicine
LEARNING TOPIC - Microbiology of endocarditis and rheumatic heart disease
Rheumatic fever and carditis (pericarditis, myocarditis and endocarditis) are sequels to one or more
attacks by certain infectious agents.
Rheumatic fever (RF) is a nonsuppurative acute inflammatory complication of infection due to certain
strains of beta-haemolytic Group A Streptococcus pyogenes. RF is characterised mainly by arthritis,
chorea, or carditis (sometimes followed by residual heart disease), alone or in combination. The skin
(subcutaneous nodules and erythema marginatum) may also be involved.
RF occurs mostly during school age (peak 5-15years). The incidence of RF is 0.1 to 3% of those with
streptococcal infections. The latent period is 1-5 weeks (av 19 days) between streptococcal
pharyngitis and the initial episode of acute RF. The average duration of RF is 3 months or longer.
Carditis is the most significant manifestation of RF. Murmurs are the most frequent clear sign of
carditis when the patient is first seen. After the acute attack many people are left with damaged heart
valves (rheumatic heart disease). Valve involvement characterised by an acute interstitial valvulitis
may cause valvula oedema. Left untreated, valve thickening, fusion, and retraction or other
destruction of leaflets and cusps may occur, leading to stenotic or regurgitant functional changes.
Abnormal or damaged valves are most susceptible to infection and colonisation e.g., by alpha
haemolytic streptococci and cause endocarditis (see below). Recurrent acute attacks of RF frequently
cause more damage to the heart valves.
Antibiotics will not modify an acute RF attack, due to cross-reacting autoimmunity, nor affect the
subsequent development of carditis. However, a recommended regimen of antibiotics is prescribed to
eradicate any remaining group A streptococci. A treatment goal is to suppress inflammation while
32 of 57 avoiding a rebound. Aspirin or another NSAID is the first choice. 16/10/10 10:28 AM
Endocarditis - inflammation of the endocardium (membrane lining the chambers of the heart and
covering the cusps of the various valves) - is caused directly by microbial colonisation of the
Abnormal or damaged valves are most susceptible to infection and colonisation e.g., by alpha
haemolytic streptococci and cause endocarditis (see below). Recurrent acute attacks of RF frequently
cause more damage to the heart valves.
Antibiotics will not modify an acute RF attack, due to cross-reacting autoimmunity, nor affect the
subsequent development of carditis. However, a recommended regimen of antibiotics is prescribed to
eradicate any remaining group A streptococci. A treatment goal is to suppress inflammation while
avoiding a rebound. Aspirin or another NSAID is the first choice.
Endocarditis - inflammation of the endocardium (membrane lining the chambers of the heart and
covering the cusps of the various valves) - is caused directly by microbial colonisation of the
endocardium or indirectly by RF. Infective endocarditis is due to organisms being physically present,
unlike RF, that predisposes to colonisation. The disease can be either acute or chronic. Whilst almost
all bacteria and many fungi can infect/colonise the endocardium the majority of cases (>80%) are
caused by streptococci and staphylococci - many derived from normal flora e.g., from minor trauma to
the oropharynx, gastrointestinal tract and genitourinary tract.
As the bacteria colonise the endocardium, they form 'vegetations' that interfere with valve function.
They break off easily to form arterial emboli. The interval between colonisation of the endocardium
and the onset is 2 weeks. Untreated, death can occur in about 6 weeks. The initial symptoms include
low grade fever, anorexia, fatigue anaemia and splenomegaly.
Blood culture is most important in the laboratory diagnosis.
Treatment includes combination antibiotic therapy for at least 14 days. Antibiotic regimen is based on
species sensitivity and minimum bactericidal concentrations (MBC) in the blood maintained.
Anticoagulation with heparin is contraindicated.
Prevention of endocarditis in patients with heart-valve damage or a heart murmur can be helped by
antibiotics before medical/dental procedures as well as by the maintenance of good oral hygiene.
Author: Dr Vitali Sintchenko, Infectious Diseases
LEARNING TOPIC - Normal ECG
The spread of action potentials through the heart leads to electrical changes on the body surface
which can be recorded as the electrocardiogram. At this stage you need to be familiar with the
appearance of the normal ECG

the nomenclature of the ECG
understanding how electrical activity spreads through the heart
the concept of the electrical axis
the nomenclature of the 12 leads used for clinical ECGs
how the electrical axis is determined from a 12 lead ECG and why it is useful.
Electrical activity normally arises in the sinoatrial node (SAN) and then spreads radially out from the
SAN across both atria. When part of the atria is polarised at the resting potential (-80 mV) and
another part is depolarised to the peak of the action potential (+ 30 mV), the resulting voltage
gradients cause current flow.
An important principle is that all current flow at one time can be represented by a single current
with a certain magnitude and direction (the vector sum of currents) and the angle between this
current and an agreed system of axes is called the electrical axis at that moment.
A second principle is that electrode pairs along the line of that axis will see the largest voltage
change while those perpendicular to the axis will record no voltage difference. Thus by having a
series of electrode pairs arranged around the vertical plane (the limb leads) one can determine
the electrical axis in the vertical plane. Similarly the chest leads are arranged around a
horizontal plane and determine the direction of the electrical axis in that plane (called rotation).
These considerations determine the size of the P wave produced by atrial depolarisation and the leads
in which it is most prominent. Similar but more complex considerations can explain the form of
ventricular depolarisation (the QRS wave) and ventricular repolarisation causes the T wave.
The PQ interval represents the time taken for conduction from the SAN (i) across the atria, (ii)
through the atrioventricular node, and (iii) through the fast conduction system of the ventricles to the
ventricular muscle. When this time is elongated or irregular it suggests some defect in normal
conduction. The QT interval represents the duration of the ventricular action potential and should get
33 of 57 16/10/10 10:28 AM
shorter during exercise.
Value of the electrical axis. A simple example is left ventricular hypertrophy (enlargement) which
occurs in systemic hypertension as the left side of the heart increases to deal with an increased work
in which it is most prominent. Similar but more complex considerations can explain the form of
ventricular depolarisation (the QRS wave) and ventricular repolarisation causes the T wave.
The PQ interval represents the time taken for conduction from the SAN (i) across the atria, (ii)
through the atrioventricular node, and (iii) through the fast conduction system of the ventricles to the
ventricular muscle. When this time is elongated or irregular it suggests some defect in normal
conduction. The QT interval represents the duration of the ventricular action potential and should get
shorter during exercise.
Value of the electrical axis. A simple example is left ventricular hypertrophy (enlargement) which
occurs in systemic hypertension as the left side of the heart increases to deal with an increased work
load. Because the left side of the heart is bigger, the net current flow to the left is bigger and this
shifts the electrical axis in the vertical plane to the left (anti-clockwise).
You also need to be familiar with all the events of the cardiac cycle and understand the timing of the
atrial and ventricular contraction, the opening and closing of the valves and the way each of these
relates to the ECG.
Clinically the main value of the ECG is in the diagnosis of arrhythmias, ischaemic heart disease and
infarcts. Many other cardiac conditions also have identified ECG abnormalities.
References
LEARNING TOPIC - Oedema
Oedema is a common symptom and sign with many disparate causes. It means accumulation of fluid
in the interstitial space, and to understand how it occurs it is necessary to understand the balance of
forces across the capillary wall. The interstitial space is the part of the extracellular space which is
outside the capillaries and between the cells.
To distinguish oedema from other cause of tissue swelling, eg fat, tumours, chronic inflammation and
fibrosis, the classic test is that oedema 'pits', ie firm pressure with a finger leaves a dent which takes
a minute or so to obliterate. The distribution of the oedema is often diagnostic and can involve the
ankles, legs, sacrum, scrotum, peritoneum, pleural cavities, the lung tissue (pulmonary oedema is
particularly serious), the face, lips, glottis and vocal cords (may cause asphyxiation in severe food
allergies), the brain etc. The distribution of oedema is affected by the patients position, eg bedridden
patients tend to have sacral oedema.
The forces tending to cause fluid to cross the capillary wall (from plasma to interstitial space) were
first described by Starling (who also discovered Starling's Law of the Heart and the first hormone,
secretin). One factor which favours movement of fluid out of the capillary is the hydrostatic pressure
within the capillary, and this is offset by the hydrostatic pressure of the interstitial space itself (often
close to zero). While the mean pressure in the capillaries is around 25 mmHg, it is higher at the
arterial end and lower at the venous end. Because molecules with very large molecular weights do not
easily move through the capillary wall, these are retained in the capillary and exert a colloid osmotic
pressure which tends to attract fluid into the capillary. It is a useful exercise in physical chemistry to
convert the known amounts of impermeable proteins in blood into their molar concentration and then
into the osmotic pressure they exert (using the gas laws). The answer is that the plasma proteins
(chiefly albumin) exert a colloid osmotic pressure of about 20 mmHg which attracts fluid into the
capillary. This is offset by the colloid osmotic pressure of any proteins within the interstitial space.
The rate at which fluid crosses the capillary wall is then the sum of these four pressures multiplied by
the capillary permeability. Finally, excess fluid in the interstitial space can often be removed by the
lymphatics.
Any of the above factors can be disturbed. Hydrostatic pressure in the capillary (and all other blood
compartments) is increased when Na and H 2 0 are retained, as in heart failure and steroid overdose,
and can cause massive oedema over the ankles, legs and sacrum. An important distinction is that
L-sided heart failure tends to cause pulmonary oedema, whereas R-sided heart failure tends to cause
systemic oedema. Reduced serum albumin is another large category causing generalised oedema and
can be caused by malnutrition (kwashiorkor) or malabsorption of proteins, loss of proteins as in renal
failure or nephrotic syndrome or failure to synthesis albumin which occurs in liver disease. Increased
capillary permeability occurs in many allergic reactions and is probably caused by histamine release
34 of 57 16/10/10 10:28 AM
eg bee stings, food allergies and these can cause dangerous but short lived oedemas. Finally,
blockage of lymphatic channels by infection (filariasis leading to elephantiasis) or by tumour, surgery
or radiation damage can also result in oedema.
compartments) is increased when Na and H 2 0 are retained, as in heart failure and steroid overdose,
and can cause massive oedema over the ankles, legs and sacrum. An important distinction is that
L-sided heart failure tends to cause pulmonary oedema, whereas R-sided heart failure tends to cause
systemic oedema. Reduced serum albumin is another large category causing generalised oedema and
can be caused by malnutrition (kwashiorkor) or malabsorption of proteins, loss of proteins as in renal
failure or nephrotic syndrome or failure to synthesis albumin which occurs in liver disease. Increased
capillary permeability occurs in many allergic reactions and is probably caused by histamine release
eg bee stings, food allergies and these can cause dangerous but short lived oedemas. Finally,
blockage of lymphatic channels by infection (filariasis leading to elephantiasis) or by tumour, surgery
or radiation damage can also result in oedema.
References
LEARNING TOPIC - Overview of cardiovascular function
The cardiovascular system consists of a pump and a complex series of tubes. Its function is to supply
ever cell of the body with its needs (O , glucose, amino acids, lipids, vitamins, hormones, heat,
2
inorganic ions, H O, .. etc.) and to remove waste products (CO ,H O, lactate, protons, urea, heat,
2 2 2
.. etc. The supply to each cell should be in accordance with its needs.
14
There are ~10 cells in the body so supplying each with its needs, which are different for each cell
type and change with cell activity, is a formidable task. While this complex task generally continues
successfully without any conscious activity on our part, inevitably there are conflicts from time to
time and priorities have been set (by evolution) which determine which cells are highest priority and
have a protected circulation during times of stress.
If the blood supply to the brain ceases for > 10s we lose consciousness (potentially a disaster in
evolutionary terms). Consequently supplying blood to the brain is the highest priority and, because
blood supply to the brain requires the heart, blood supply to the heart is equally high priority. If blood
supply to the brain ceases for more than ~ 10 min there is likely to be permanent brain damage even
if flow is restored.
To understand the circulation some understanding of the underlying physical principles is valuable.
Two processes are central; diffusion and flow through tubes. Diffusion is the process by which
molecules move down their concentration gradient powered by the random thermal motion of
molecules. Thus if a cell uses O , the concentration of O in the cell decreases, and the increasing
2 2
inward concentration gradient causes additional O to diffuse into the cell. In general the rate of
2
diffusion is proportional to the concentration gradient, to the area involved and to the diffusion
coefficient of the molecule and inversely proportional to the square of the distance involved. Although
the mathematics of diffusion are complex a very simple rule of thumb is that diffusion over a distance
3
of 1 m is near complete in 1 ms. Because of the inverse square law, diffusion over 1 mm (10 ! m)
3 2 12
takes (10 ) ms or 1000s or 15 min. Diffusion over 1 m takes 10 ms or 30 years. These physical
principles dominate the design of cells and the need for a circulation to supply any region greater than
10-100 !m. Thus single cells do not require a circulation (diffusion is sufficient) whereas all large
multicellular organs require a circulation.
The second process, flow in pipes, is dealt with extensively in physiology texts. Flow through a tube is
4
proportional to the pressure gradient across the region of interest and to the (radius) and inversely
proportional to the length of the pipe and the viscosity of the solution. Again these physical factors
are critical to the design of a series of pipes which transport blood sufficiently close to every cell to
enable diffusion to carry molecules to (and from) the cell. The regulation of flow to the region of a
small group of cells is determined by the radius of the pipe carrying blood to the region and this
radius is regulated by a series of mechanism which will be explored in the Blood flow to tissues
lecture.
2
2 2 2
35 of 57 16/10/10 10:28 AM
14
lecture.
2
2 2 2
14
time and priorities have been set (by evolution) which determine which cells are highest priority and
have a protected circulation during times of stress.
If the blood supply to the brain ceases for > 10s we lose consciousness (potentially a disaster in
evolutionary terms). Consequently supplying blood to the brain is the highest priority and, because
blood supply to the brain requires the heart, blood supply to the heart is equally high priority. If blood
supply to the brain ceases for more than ~ 10 min there is likely to be permanent brain damage even
if flow is restored.
To understand the circulation some understanding of the underlying physical principles is valuable.
Two processes are central; diffusion and flow through tubes. Diffusion is the process by which
molecules move down their concentration gradient powered by the random thermal motion of
molecules. Thus if a cell uses O , the concentration of O in the cell decreases, and the increasing
2 2
inward concentration gradient causes additional O to diffuse into the cell. In general the rate of
2
diffusion is proportional to the concentration gradient, to the area involved and to the diffusion
coefficient of the molecule and inversely proportional to the square of the distance involved. Although
the mathematics of diffusion are complex a very simple rule of thumb is that diffusion over a distance
3
of 1 m is near complete in 1 ms. Because of the inverse square law, diffusion over 1 mm (10 ! m)
3 2 12
takes (10 ) ms or 1000s or 15 min. Diffusion over 1 m takes 10 ms or 30 years. These physical
principles dominate the design of cells and the need for a circulation to supply any region greater than
10-100 !m. Thus single cells do not require a circulation (diffusion is sufficient) whereas all large
multicellular organs require a circulation.
The second process, flow in pipes, is dealt with extensively in physiology texts. Flow through a tube is
4
proportional to the pressure gradient across the region of interest and to the (radius) and inversely
proportional to the length of the pipe and the viscosity of the solution. Again these physical factors
are critical to the design of a series of pipes which transport blood sufficiently close to every cell to
enable diffusion to carry molecules to (and from) the cell. The regulation of flow to the region of a
small group of cells is determined by the radius of the pipe carrying blood to the region and this
lecture.
Generally in the circulation evolutionary design has ensured that diffusion is sufficient for the supply
of molecules to cells and, with a few exceptions, it is not under physiological control. In contrast
supply of blood to the tissues changes continuously to meet the "supply to each cell according to its
needs" constraint and is central to understanding the regulation of the blood supply. To a good
approximation the pressure in the collection vessels (venules and veins) is atmospheric (called zero)
while the pressure in the distribution vessels (arteries and arterioles) is maintained at a more or less
constant level (the arterial pressure). This means that the flow to the exchange vessels (the
capillaries from which diffusion then carries molecules to the cells) depends only on the radius of the
10 4
vessel supplying them. Roughly there are 10 capillaries so the 10 cells supplied by each capillary
all receive a similar blood supply though they can vary their supply by diffusion.
One of the many complications to this system is the effects of hydrostatic pressures on the human
circulation and particularly the changes associated with posture. The properties of the pump are
unaffected by postural changes and by good fortune arterial pressure is generally measured in the
upper arm which is almost exactly at the level of heart. When we become upright, ~1.3 m of blood (~
100 mm Hg) is added to the arterial pressure in the foot. Exactly the same happens to venous
pressure, so the gradient of pressure across the tissues of the foot is unaffected and, simplistically,
blood flow to the foot is unaffected. But vessels also dilate when the pressure inside them increases
and these lead to accumulation of blood particularly in the more compliant vessels which are the
veins.
You should also revise the physics of measuring blood pressure using a sphygmomanometer and cuff.
The elementary anatomy of the cardiovascular system, names and distributions of the major arteries
36 of 57 and veins and chambers of the heart, are essential background. 16/10/10 10:28 AM
References
Berne, R. M., 2004, Physiology, 5th ed., Mosby, St. Louis. Chapters 14 (Overview of the heart and
blood flow to the foot is unaffected. But vessels also dilate when the pressure inside them increases
and these lead to accumulation of blood particularly in the more compliant vessels which are the
veins.
You should also revise the physics of measuring blood pressure using a sphygmomanometer and cuff.
The elementary anatomy of the cardiovascular system, names and distributions of the major arteries
and veins and chambers of the heart, are essential background.
References
Berne, R. M., 2004, Physiology, 5th ed., Mosby, St. Louis. Chapters 14 (Overview of the heart and
blood vessels) and 18 (Haemodynamics) and 20 (Microcirculation and Lymphatics) provide an
excellent coverage of these issues.
LEARNING TOPIC - Overview of congenital heart disease
Congenital Heart Disease is one of the most common forms of serious congenital abnormality. Its
range, however, is wide and many patients may have minor abnormalities not likely to produce either
overt or occult damage to the patient.
Congenital heart lesions are quite unlike the pathology seen in the adult.
The wide range of congenital heart abnormalities can be divided into broad subcategories of acyanotic
and cyanotic heart disease. Alternate approaches may consider physiology of left to right shunts, and
obstructive lesions. These may occur independently or in combination (such as in this case).
The problems of differentiating congenital cardiac pathology from the normal heart arises often in
young children and babies since a cardiac murmur, commonly seen arising from the normal heart of a
child, may raise suspicions when its character is unusual.
Early and appropriate management can be life saving or avoid the long term damaging sequelae of
unrecognised abnormality. This management will usually be delivered by a paediatric cardiologist and
paediatric cardiac surgeon, but initial recognition will depend on the primary care physician in many
cases.
Heart and Great Vessel Anatomy
An understanding of normal cardiac anatomy will prepare the student to appreciate the variety of
structural lesions possible, without needing to be familiar with each one. Each area of the heart
(alone or in combination) may be affected by maldevelopment.
Physiology of cardiac shunts and vascular resistance
These lesions will often have associated septal defects allowing blood to cross between the
pulmonary and systemic circulations. This movement of blood, or 'shunt', will be dictated by a number
of factors including the size of the defect and the 'downstream' resistance to flow. In many important
lesions resistance may be either at a structural level or at the level of vascular resistance (especially
in the pulmonary circulation). The issue of PVR is particularly important to understanding the clinical
presentation and course of young infants with ventricular septal defect and other types of 'left to right
shunt' lesions.
Incidence and range of congenital heart disease and congestive cardiac failure in infants
Once these concepts are recognised the incidence and range of congenital heart abnormalities can be
better appreciated, and the causes of congestive heart failure in babies, and its time of presentation,
be understood.
References
Relevant sections of general Paediatric text books will often overview these issues.
37 of 57 More detailed discussions can be found in: 16/10/10 10:28 AM

Jordan, Scott. Heart Disease in Paediatrics. London: Butterworths, 1989.
Moss, A. J., H. D. Allen, et al., 2001, Moss and Adams' heart disease in infants, children, and
Relevant sections of general Paediatric text books will often overview these issues.
More detailed discussions can be found in:
Jordan, Scott. Heart Disease in Paediatrics. London: Butterworths, 1989.
Moss, A. J., H. D. Allen, et al., 2001, Moss and Adams' heart disease in infants, children, and
adolescents, including the fetus and young adult, 6th ed., Lippincott Williams & Wilkins, Philadelphia ;
London. [Available as an E-Book]
Garson, A., 1997, The science and practice of pediatric cardiology, 2nd ed., Williams & Wilkins,
Baltimore
Anderson, R. H., 2002, Paediatric cardiology, 2nd ed., Churchill Livingstone, London
LEARNING TOPIC - Pathogenesis of hypertension
Hypertension is divided into primary or essential hypertension and secondary forms of hypertension.
It is still not clear whether it is a single disorder, or a disorder with several subsets of patients having
varying 'causes' of hypertension. Factors in the pathogenesis of hypertension relate to (a) those
important in regulating normal blood pressure such as the heart, the kidneys, vascular diameter and
the venous system and (b) how these systems are influenced by the autonomic nervous system,
various circulating hormones (such as catecholamines, ANP, renin, aldosterone and other steroids)
and numerous local hormones or autacoids (eg. prostaglandins, nitric oxide and endothelin). (c)
Various lifestyle and dietary factors, including exercise, ethanol intake and dietary sodium level.
Even though blood pressure is chiefly determined by both peripheral resistance and cardiac output,
the division of hypertension into volume or constrictor subsets has been unrewarding, as all patients
tend eventually to have elevation of peripheral resistance and normal cardiac output. Thus in
hypertension, the increase in blood pressure results from constriction of small arteries and arterioles.
This leads to an increased resistance to flow. The increased peripheral resistance may result from
either the presence of increased stimuli leading to excess vasoconstriction (increased vascular
reactivity) or from intrinsic abnormalities within the resistance vessels that cause an increased
response to normal stimuli, or from a combination of the two mechanisms.
Abnormalities relating to sympathetic nerve endings (pre and postsynaptic) have been described in
animal models of hypertension but there is still considerable debate as to their importance in human
hypertension. Similarly, catecholamines have been clearly implicated only in the genesis of
hypertension with phaeochromocytoma. The renin-angiotensin-aldosterone system (RAAS) has been
extensively studied. Hypertension associated with severe unilateral renal artery stenosis,
aldosterone-secreting tumours of the adrenal cortex, renin secreting tumours, oral contraceptive pill
use or some dialysis-dependent chronic renal failure patients, is commonly due to aberrations in the
RAAS.
The kidney deserves special attention, it is both a victim and culprit in the hypertensive process.
Recent evidence implicates defective renal sodium excretion as a pivotal hypertensive mechanism.
+ +
Hypotheses to explain this include inhibitors of tubular and vascular smooth muscle Na K ATPase
(and a consequent elevation of intracellular calcium leading to vasoconstriction), congenitally reduced
nephron numbers (or filtration surface areas) and also heterogeneity within the nephron population.
A rare autosomal, dominantly-inherited form of human hypertension, Liddle's Disease (which is also
characterized by hypokalaemia, suppressed aldosterone, response to inhibitors of distal tubular
sodium transport but not to mineralocorticoid antagonists) has thrown new light on other yet to be
explored pathogenetic hypertensive mechanisms. Mutations of the aldosterone-regulated and
+
amiloride-sensitive epithelial Na channel (ENaC) gene, lead to the constitutive activation of ENaC
and cause Liddle's syndrome. The consequent excessive reabsorption of sodium in the distal nephron
causes severe hypertension. Molecular techniques increasingly are uncovering other new mechanisms
of hypertension such as that concerning ACE gene polymorphism and 11"-hydroxysteroid
dehydrogenase type-2 gene mutations.
38 of 57 16/10/10 10:28 AM
References

sodium transport but not to mineralocorticoid antagonists) has thrown new light on other yet to be
explored pathogenetic hypertensive mechanisms. Mutations of the aldosterone-regulated and
+
amiloride-sensitive epithelial Na channel (ENaC) gene, leadhttp://smp.sydney.edu.au/compass/guide/handbook/block/5
to the constitutive activation of ENaC
and cause Liddle's syndrome. The consequent excessive reabsorption of sodium in the distal nephron
causes severe hypertension. Molecular techniques increasingly are uncovering other new mechanisms
of hypertension such as that concerning ACE gene polymorphism and 11"-hydroxysteroid
dehydrogenase type-2 gene mutations.
References
Zanchetti A, Tarazi RC, eds. Pathophysiology of Hypertension: Volume 8. Handbook of Hypertension.

Amsterdam: Elsevier, 1986.
Sherwood, L., 2007, Human physiology : from cells to systems, 6th ed., Thomson/Brooks/Cole,
Australia
Author: Clinical Associate Professor Adrian Gillin, Medicine
LEARNING TOPIC - Pathophysiology of hypertension
Normal blood pressure regulation is dependent upon total peripheral vascular (arteriolar) resistance
and cardiac output. It appears likely that in systemic hypertension, the persistent elevation of blood
pressure at rest may be due to factors involving an increase in either or both of these haemodynamic
variables. For example a boost in cardiac output may be achieved by fluid retention (as outlined
below) or as a response to defective pressure "natriuresis" with sodium retention.
The majority of patients with systemic hypertension (~90%) have no clear underlying cause
demonstrable after investigation. Such patients are referred to as having essential hypertension. It is
probable that most of the pathophysiological mechanisms of hypertension in this group will have been
referred to in Independent Learning Topic 3 "Pathogenesis of Hypertension". Accordingly, in this
Learning Topic there will be emphasis on the pathophysiology of hypertension in those patients in
whom an underlying and sometimes remediable cause is demonstrable. i.e. those patients with
secondary hypertension.
Chronic renal disease
A number of renal diseases of diverse origin can lead to the development of hypertension. These
diseases include:
Renal ischaemia frequently due to renal artery atherosclerosis, either at its orifice or in its stem.
('renovascular hypertension')
Chronic renal parenchymal damage following for example, immunological glomerular injury
(glomerulonephritis) or recurrent bacterial infections.
In such patients, the alterations in renal perfusion with blood will tend to activate the renin-
angiotensin system whereby the enzyme renin released from the juxtaglomerular apparatus converts
the plasma protein, angiotensinogen (from the liver) to angiotensin:
This is further processed by angiotensin-converting enzyme (ACE) and ACE-peptidases in the

endothelial cell membrane to the biologically active vasoconstrictor agent angiotensin II.
This mechanism will tend to lead to an increase in the patient's blood pressure and to boost
renal perfusion.
Essential hypertension itself, either when mild to moderate (benign) but especially when very severe
(malignant) may lead to structural and functional alterations in the kidney which may activate the
renin-angiotensin system.
Adrenal lesions
The adrenal cortex produces hormones such as glucocorticoids and mineralocorticoids which have
effects on blood pressure. The mineralocorticoid, aldosterone for example affects blood pressure
levels by its effect on salt and water metabolism.
In functional lesions of the adrenal cortex such as adenoma, hyperplasia and carcinoma, the increased
39 of 57 16/10/10 10:28 AM
production of such hormones tends to lead to secondary hypertension. Aldosterone stimulation is also
involved during activation of the renin-angiotensin system.
Another adrenal lesion capable of producing secondary hypertension is a functional tumour of the
Adrenal lesions
The adrenal cortex produces hormones such as glucocorticoids and mineralocorticoids which have
effects on blood pressure. The mineralocorticoid, aldosterone for example affects blood pressure
levels by its effect on salt and water metabolism.
In functional lesions of the adrenal cortex such as adenoma, hyperplasia and carcinoma, the increased
production of such hormones tends to lead to secondary hypertension. Aldosterone stimulation is also
involved during activation of the renin-angiotensin system.
Another adrenal lesion capable of producing secondary hypertension is a functional tumour of the
adrenal medulla referred to as phaeochromocytoma. This tumour may produce an excessive amount
of noradrenaline, a vasoconstrictor compound.
The various lesions referred to above are firmly associated with secondary hypertension. It is
probable that the mechanisms by which they lead to increased peripheral resistance may also
contribute toward the increased vascular resistance in patients with essential hypertension.
Evidence for renal involvement in essential hypertension includes elevation of plasma renin in some
patients with this disorder and production by the kidney of vasodepressor substances such as
prostaglandins and the endothelial relaxant, nitric oxide which may counterbalance the effects of the
renin-angiotensin system.
References
The text-book by Kumar et al provides coverage of fundamental concepts in Pathology. Cotran et al is

similar in its provision of fundamentals but is a more comprehensive text. The text by Rubin and
Farber is comparable with Cotran et al.
All these texts provide basic correlation of fundamental disease processes and the clinical
abnormalities with which they are associated.
Kumar, V. and S. L. Robbins, 2007, Robbins basic pathology, 8th ed., Saunders/Elsevier, Philadelphia,
PA
Kumar, V., A. K. Abbas, et al., 2005, Robbins and Cotran pathologic basis of disease, 7th ed.,
Elsevier Saunders, Philadelphia.[Available as a E-Book]
Author: Professor Roger Dampney, Physiology
LEARNING TOPIC - Pathophysiology of ischaemia
Myocardial ischaemia is a pathological condition which occurs when there is insufficient blood flow to
meet the metabolic demands of the beating heart (ischein = to suppress, haemia = blood). Under
normal circumstances blood flow to the myocardium is well matched to the demands of the heart for
O and nutrients. As myocardial O demand increases, it must be parallelled by an increase in
2 2
myocardial blood flow, because coronary arteriovenous O extraction is near maximal at rest.
2
The major determinants of myocardial O consumption are: 1) Heart rate 2) Left ventricular (LV) wall
2
stress (this is dependent on LV volume, and LV afterload or systolic blood pressure) 3) Contractility.
Exercise and emotional stress increase all of the determinants of O consumption, and in the normal
2
heart, coronary blood flow increases up to five fold to meet this demand. When there is an
atherosclerotic stenosis in an epicardial coronary artery, it may limit the ability of the coronary
circulation to increase flow. The haemodynamics of stenoses are such that flow limitation during
exercise occurs when 70% of the lumen diameter is obstructed, while a stenosis of 90% will limit
flow at rest. Stenoses of <50% lumen diameter do not usually limit flow during exercise.
Ischaemia can therefore result from either a significant fall in coronary blood flow (supply ischaemia),
or an increase in myocardial O demand in excess of the diseased coronary circulation ' s ability to
2
increase flow due to the presence of obstructive coronary artery disease (demand ischaemia). Thus
demand ischaemia typically occurs during exercise in patients with a coronary stenosis of 70% or
40 of 57 16/10/10
greater and is quickly relieved by rest. Supply ischaemia occurs at rest when an artery occludes or
10:28 AM
suddenly develops a stenosis of 90% or greater. This usually results from coronary thrombosis which
may be complete or subtotal, although vasoconstriction or spasm are alternative mechanisms. If
obstruction occurs more gradually, collaterals may develop and reduce or even prevent ischaemia.
exercise occurs when 70% of the lumen diameter is obstructed, while a stenosis of 90% will limit
flow at rest. Stenoses of <50% lumen diameter do not usually limit flow during exercise.
Ischaemia can therefore result from either a significant fall in coronary blood flow (supply ischaemia),
or an increase in myocardial O demand in excess of the diseased coronary circulation ' s ability to
2
increase flow due to the presence of obstructive coronary artery disease (demand ischaemia). Thus
demand ischaemia typically occurs during exercise in patients with a coronary stenosis of 70% or
greater and is quickly relieved by rest. Supply ischaemia occurs at rest when an artery occludes or
suddenly develops a stenosis of 90% or greater. This usually results from coronary thrombosis which
may be complete or subtotal, although vasoconstriction or spasm are alternative mechanisms. If
obstruction occurs more gradually, collaterals may develop and reduce or even prevent ischaemia.
Severe supply ischaemia with complete occlusion of an epicardial coronary artery for longer than 30
minutes will result in myocardial infarction (myocardial cell death).
Within a few seconds of ischaemia, there are profound metabolic and physiological changes in the
affected region of myocardium. Metabolism switches from aerobic utilisation of fatty acids to
anaerobic glycolysis with production of lactic acid. High energy phosphate production falls, and this
causes failure of both contraction and active relaxation, which can result in elevation of LV
+ +
end-diastolic pressure and breathlessness. Because less energy is available for membrane Na /K
+
pump, K leaks out of cells, raising resting membrane potential and reducing action potential size
and duration. This produces characteristic ECG changes: ST segment depression with subendocardial
ischaemia and ST segment elevation with transmural ischaemia. Elevation and depression of ST
segments are relative to the isoelectric segments in the TP and PQ periods.
A late event in myocardial ischaemia is the generation of chest pain (angina pectoris). The pain
producing stimulus is probably adenosine, and the sensation is carried by sympathetic afferents which
synapse between spinal segments C8 and T4 producing referred pain in the retrosternal area, typically
radiating to the left arm or neck. Many attacks of ischaemia, however, are not accompanied by anginal
pain (silent ischaemia).
Author: Professor Ben Freedman, Medicine
LEARNING TOPIC - Personality and coronary heart disease
Linkages between personality and disease

Increasing evidence supports the view that personality is related to the development of disease and
influences disease outcomes. Although the research is promising, the methodological issues are
complex, and there may be multiple causal linkages which can vary across the lifespan and be related
to individual differences. Many research projects are limited by the factors of time, the disease under
study, emphasis on treatment rather than prevention of disease, the possibility that disease may
cause personality changes rather than the other way around, and a research focus upon ill individuals
rather than long-term examination of population samples.
Personality
Personality refers to the patterns of cognitive, affective, and behavioural dispositions that
characterise individuals. Personality patterns are thought to be relatively stable across time and
context. For an overview of the main approaches to describing personality and theories of personality
development, it will be useful to read the relevant sections of your text books. There is now fairly
broad consensus that broad classifications of personality can be made on the basis of the 'Big Five'
traits: (see the learning topic on Personality and Addiction). Research is also attempting to identify
more specific personality factors that contribute to effectiveness and adaptiveness, influencing
sickness and health.
Personality and CHD (coronary heart disease)

The linkages between heart disease and 'Type A personality behaviour' have been studied extensively.
The key features of the Type A behaviour pattern are: insecurity, hostility, time urgency, impatience
and competitiveness. Friedman and Rosenman first described Type A behaviour on the basis of
structured interviews in which they observed tense facial and body musculature, rapid body
movements, explosive conversational speech, and hand or teeth clenching. Since then more
convenient methods, such as self-report questionnaires, have been used though it seems that they do
not measure precisely the same construct. A meta-analysis of prospective studies of Type A
personality, hostility and coronary heart disease (CHD) found no association between Type A
personality and CHD; the only significant association was in healthy adult studies where angina was
included as an outcome (Myrtek, 2001). Type A personality does not appear to be a robust predictor
41 of 57 of CHD across different cultures and socio-economic groups. 16/10/10 10:28 AM
Given the inability of measurements of Type A behaviour to predict risk of morbid events following the
initial incidence of CHD, investigative focus has shifted toward identifying those elements of the
structured interviews in which they observed tense facial and body musculature, rapid body
movements, explosive conversational speech, and hand or teeth clenching. Since then more
convenient methods, such as self-report questionnaires, have been used though it seems that they do
not measure precisely the same construct. A meta-analysis of prospective studies of Type A
personality, hostility and coronary heart disease (CHD) found no association between Type A
personality and CHD; the only significant association was in healthy adult studies where angina was
included as an outcome (Myrtek, 2001). Type A personality does not appear to be a robust predictor
of CHD across different cultures and socio-economic groups.
Given the inability of measurements of Type A behaviour to predict risk of morbid events following the
initial incidence of CHD, investigative focus has shifted toward identifying those elements of the
construct most strongly associated with CHD. With more conventional risk factors statistically
controlled (e.g. heredity, obesity, diet and smoking) research has indicated that expressive hostility,
particularly antagonistic interactions with others (anger-out), appears most strongly associated with
CHD (Myrtek, 2001). Other hostility related constructs, including cynical mistrust, potential for
hostility, and suppressed resentment (anger-in) have also been found to predict CHD mortality and
morbidity. Other clusters of psychological variables that are currently being investigated with respect
to multiple disease outcomes are emotional suppression, depressive symptoms, and the adoption of a
pessimistic or fatalistic attitude to life and health.
The term 'Type D' (distressed personality) has entered the literature recently, describing the
combination of negative affectivity and social inhibition – Type D personality is a vulnerability
characteristic related to cardiovascular morbidity and mortality (Steptoe and Molloy, 2007). The Type
D personality is distinct from other psychological characteristics that may predict prognosis in heart
disease, such as social isolation of depression (Kupper and Denollet, 2007). Several methods of
assessing Type D personality have been developed.
A long-term study over eight decades has found that conscientiousness in both childhood and
adulthood is associated with longevity, partly because high levels of conscientiousness are related to
low levels of risk behaviour including cigarette smoking, poor diet and activity levels, excessive use of
alcohol or drugs, violence, risky sexual behaviour, risky driving and suicide (Bogg and Roberts, 2004)
Psychological hardiness and resiliance

There is evidence that certain personality constellations may be associated with positive health
outcomes. Kobasa introduced the notion of psychological hardiness made up of three characteristics:
sense of control, commitment, and the viewing of change as exciting challenge rather than threat. A
related concept is psychological resilience, the ability to bounce back from negative events by using
positive emotions to cope.
The role of personality characteristics in predisposing patients to CHD is an evolving field of study.
There are implications for psychotherapeutic interventions with CHD patients and their families.
References
Bogg, T., and Roberts, B.W., 2004, Conscientiousness and health-related behaviors: a meta-analysis of
the leading behavioural contributors to disease. Psychological Bulletin; 130: 887-919.
Kupper, N. and Denollet, J., 2007, Type D personality as a prognostic factor in heart disease:
assessment and mediating mechanisms. Journal of Personality Assessment; 89(3): 265-276.
Myrtek, M., 2001, Meta-analyses of prospective studies on coronary heart disease, type A personality,
and hostility. International Journal of Cardiology; 79(2-3): 245-251.
Steptoe, A. and Molloy, G.J. 2007, Personality and heart disease. Editorial. Heart; 93(7): 783-784; see
also other articles in this edition.
Alder, B., 2004, Psychology and sociology applied to medicine : an illustrated colour text, 2nd ed.,
Churchill Livingstone, Edinburgh ; London ; New York
Stevens, V.M., 2007, Behavioral science, 2nd ed., Mosby/Elsevier, Philadelphia

42 of 57 16/10/10 10:28 AM
These text books provide a brief introduction to the main approaches to personality and personality
measurement. For those unfamiliar with the topic it can provide a quick overview.
Available in Medical Library: see Library Catalogue http://smp.sydney.edu.au/compass/guide/handbook/block/5
Alder, B., 2004, Psychology and sociology applied to medicine : an illustrated colour text, 2nd ed.,
Churchill Livingstone, Edinburgh ; London ; New York
Stevens, V.M., 2007, Behavioral science, 2nd ed., Mosby/Elsevier, Philadelphia
These text books provide a brief introduction to the main approaches to personality and personality
measurement. For those unfamiliar with the topic it can provide a quick overview.
For further information, the following has additional value.
Friedman, H.S., 2008, The multiple linkages of personality and disease. Brain, Behavior, and
Immunity; 22: 668-675.
LEARNING TOPIC - Pregnancy and cardiovascular system
Pregnancy is associated with a marked change in cardiovascular function of the mother which is
aimed at ensuring that the fetus is well served with nutrients, the mother can adequately dispose of
waste products from her own increased metabolism and that of the fetus, the breasts can be
developed for breast feeding, and the mother can be protected from blood loss at the time of delivery.
The changes in the cardiovascular system
occur early in pregnancy and proceed the fetal demand

exceed fetal demand
are all completely reversed after delivery
The changes that involve the cardiovascular system specifically are
the formation of a low resistance vascular network in the uterus which contains approximately 1
litre of blood at term
progesterone induced vasodilatation in the body causing a marked increase in regional blood
flow
kidney flow increases by 60% to improve excretion
skin flow increases by 50% to improve heat loss
liver flow increases by 50% to improve hepatic function
increase in gut flow improves nutrient absorption
increase in blood flow to the breast is approximately 200% over non pregnant levels to
ensure that the breasts are developed ready for feeding the infant.
uterine flow increases from 30mls/min in the non-pregnant woman to 600mls/min at term
7
the only organ not to have increased blood flow is the brain
Women are prone to fainting in pregnancy due to low BP caused by the vasodilatation associated with
progesterone. The maximum of vasodilatation occurs in the middle trimester and blood pressure is
lowest at that time.
Plasma volume increases by 40%. This increase is related to fetus size and is induced by
increased Aldosterone which results from increased renin excretion both at the kidney and
uterus.
Red cell mass increases by 18-20%. This increase is smaller than that of the plasma volume and
a physiological anaemia therefore results with the normal haemoglobin level being between a
105-140 grams/litre at term.
The vasodilatation due to the progesterone and the large uterine blood flow could potentially
cause a massive fall in blood pressure. This, however, does not occur due to the increase in
blood volume as outlined above and because cardiac output is increased. Cardiac output
increases mainly because of an increase in the heart rate. There is also a small increase in
stroke volume. This increase in cardiac output is sufficient to ensure good supplies of oxygen
delivered to the fetus and other tissues in the body. The increases in plasma volume, heart rate
and stroke volume result in a decrease in cardiac reserve (the ability to increase cardiac output
above the normal level). This means that pregnant women are prone to congestive heart failure
43 of 57 if they have an abnomal heart or if they are treated with drugs or fluids that speed up the 16/10/10
heart 10:28 AM
rate, drop the blood pressure, or increase circulating volume.
The increase in the uterine size causes an upward pressure on the diaphragm. This upward
pressure on the diaphragm causes a change in the cardiac axis in the electrocardiogram, with
cause a massive fall in blood pressure. This, however, does not occur due to the increase in
blood volume as outlined above and because cardiac output is increased. Cardiac output
increases mainly because of an increase in the heart rate. There is also a small increase in
stroke volume. This increase in cardiac output is sufficient to ensure good supplies of oxygen
delivered to the fetus and other tissues in the body. The increases in plasma volume, heart rate
and stroke volume result in a decrease in cardiac reserve (the ability to increase cardiac output
above the normal level). This means that pregnant women are prone to congestive heart failure
if they have an abnomal heart or if they are treated with drugs or fluids that speed up the heart
rate, drop the blood pressure, or increase circulating volume.
The increase in the uterine size causes an upward pressure on the diaphragm. This upward
pressure on the diaphragm causes a change in the cardiac axis in the electrocardiogram, with
the axis being rotated to the right as compared to the non-pregnant woman.
The jugular venous pressure (a measure of pressure to the right side of the heart) is increased
in pregnancy due to the increased intravascular volume. The jugular venous pressure is
therefore raised in pregnancy and is an unreliable measure of right sided heart pressures in
women from 20 weeks of pregnancy onwards.
References
Fetal cardiovascular physiology, in, Creasy, R.K., Resnik, R., Iams, J.D.,(eds.), 2004, Maternal-fetal
medicine : principles and practice, 5th edn., W.B. Saunders Co., Philadelphia.
Author: Dr Henry Murray, Obstetrics and Gynaecology
LEARNING TOPIC - Prenatal Diagnosis and Down Syndrome
The population frequency of Down Syndrome is approximately one in six hundred and sixty in NSW.
During the 1950s several epidemiologic studies of Down syndrome showed a strong correlation in
incidence of Down syndrome and maternal age. The incidence of Down syndrome rising from one in
four hundred and seventy four at maternal age 20-24 to one in twenty eight at maternal age 45 (See
fact sheets 15 and 27 at http://www.genetics.com.au/factsheet/default.htm).
This observation became the cornerstone of interventions requested by couples to reduce the risk of
having a baby with Down syndrome.
Fetal Diagnosis of Chromosome Anomalies

Fetal diagnosis of chromosome aneuploidy, specifically Down syndrome became feasible in the early
1970s when it became technically feasible to karyotype dividing fetal cells from amniotic fluid. Other
technical advances permitted highly accurate diagnosis from analyses of chorionic villus cells. Initially
fetal diagnosis was offered where the risk of Down syndrome approximated the risk of the procedure
(procedure related pregnancy loss of 1 %).
Fetal Screening for Chromosome Anomalies

Fetal screening which at best provides a risk estimate is based on combinations of:
Maternal serum parameters of fetal well-being (e.g. Alpha Fetoprotein, Unconjugated Estriol,
Human Chorionic Gonadotrophin, Inhibin A)
Fetal measurement (e.g. nuchal fold translucency, femoral length, length of nasal spine).
Considerations to be taken into account in counselling families and also evaluating the public health
efficacy of screening interventions include:
the sensitivity, specificity, risks and negative consequences associated with the various
screening methods (e.g. Triple test, Nuchal Fold Translucency) that are available for
prenatal prediction of Down syndrome;
the need for and benefits of genetic counselling and informed consent to screening or
diagnostic testing;
the dilemmas encountered by prospective parents faced with the possibility of the birth
and subsequent parenting and care of a child with Down syndrome; and how factors such
as the prospective mother’s age, whether the prospective parents already have children
and whether they already have a child with Down syndrome affect the dilemmas;
44 of 57 the legal and ethical issues associated with decisions about the abortion of a fetus with
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Down syndrome.
References
prenatal prediction of Down syndrome;
the need for and benefits of genetic counselling and informed consent to screening or
diagnostic testing; http://smp.sydney.edu.au/compass/guide/handbook/block/5
the dilemmas encountered by prospective parents faced with the possibility of the birth
and subsequent parenting and care of a child with Down syndrome; and how factors such
as the prospective mother’s age, whether the prospective parents already have children
and whether they already have a child with Down syndrome affect the dilemmas;
the legal and ethical issues associated with decisions about the abortion of a fetus with
Down syndrome.
References
Patterson D, Costa AC. Down syndrome and genetics - a case of linked histories. Nature Reviews
Genetics 2005 Feb;6(2):137-47.
Marteau TM, Croyle RT. Psychological responses to genetic testing . BMJ 1998; 316(7132):693-6.
New South Wales Genetic Services Advisory Committee. Prenatal Testing/Screening for Down
Syndrome & Other Chromosomal Abnormalities Website
Gibert RE, Augood C, Ades AE et al. Screening for Down's syndrome: effects, safety, and cost
effectiveness of first and second trimester strategies . BMJ 2001; 323(7310):423-426.
Hall S, Bobrow M, Marteau TM. Psychological consequences for parents of false negative results on
prenatal screening for Down's syndrome: retrospective interview study . BMJ 2000;
320(7232):407-412.
Wellesley D, Boyle T, Barber J, Howe DT. Retrospective audit of different antenatal screening policies
for Down syndrome in eight district general hospital in one health region. BMJ
2002; 325(7354):15-18.
Raeburn S. Evidence based screening for Down syndrome . BMJ 2000; 320(7235):592-593.
Howe DT, Gornall R, Wellesley D, Boyle T, Barber J. Six year survey of screening for Down syndrome
by maternal age and mid-trimester ultrasound scans . BMJ 2000; 320(7235):606-610.
LEARNING TOPIC - Regulation of cerebral blood flow
The cerebral blood flow remains relatively constant over a wide range of perfusion pressure. This
appears to be a consequence primarily of a tight coupling between neural (metabolic) activity and the
resistance of cerebral blood vessels.
The brain relies almost exclusively on glucose as its substrate for energy metabolism. Therefore,
because it is unable to store energy, the brain requires a constant supply of oxygenated blood
containing an adequate concentration of glucose. In humans at rest the cerebral blood flow is 15-20%
of the total cardiac output, and the oxygen consumption of the brain is about 20% of the oxygen
consumption for the whole body.
Anatomical features of the cerebral circulation

There is a high degree of collateralization of cerebral arteries. In particular, there is considerable
communication between the basal cerebral arteries at the circle of Willis, between the branches of the
external carotid artery and the intracerebral circulation, and between cerebral arteries on the surface
of the brain. This collateralization reduced the risk that occlusion of one artery will lead to inadequate
blood flow (ischaemia) to the brain region normally supplied by that artery, because in that situation
collateral vessels can supply adequate blood flow. There are, however, regions of the brain that are
supplied by arteries which do not communicate with other arteries, and such regions regions are
therefore more vulnerable to ischaemic damage in the event of occlusion of the arteries that supply
them.
Autoregulation of cerebral blood flow

As in any region, the blood flow to the brain (cerebral blood flow, CBF) depends upon the perfusion
45 of 57 pressure (i.e. the difference between the pressure in the cerebral arteries and the cerebral veins) and
16/10/10 10:28 AM
the vascular resistance in the brain (cerebrovascular resistance). The mean pressure in the cerebral
arteries is essentially the same as in all systemic arteries (i.e. the mean arterial pressure), while the
cerebral venous pressure is usually low (~ 10 mmHg or less). Thus, the perfusion pressure depends
collateral vessels can supply adequate blood flow. There are, however, regions of the brain that are
supplied by arteries which do not communicate with other arteries, and such regions regions are
therefore more vulnerable to ischaemic damage in the event http://smp.sydney.edu.au/compass/guide/handbook/block/5
of occlusion of the arteries that supply
them.
Autoregulation of cerebral blood flow

As in any region, the blood flow to the brain (cerebral blood flow, CBF) depends upon the perfusion
pressure (i.e. the difference between the pressure in the cerebral arteries and the cerebral veins) and
the vascular resistance in the brain (cerebrovascular resistance). The mean pressure in the cerebral
arteries is essentially the same as in all systemic arteries (i.e. the mean arterial pressure), while the
cerebral venous pressure is usually low (~ 10 mmHg or less). Thus, the perfusion pressure depends
primarily on the systemic arterial pressure. The cerebrovascular resistance depends mainly on the
internal diameters of the small intracranial arteries and arterioles, which are the main resistance
vessels. This is described by the following equation:
CBF = cerebral perfusion pressure/cerebrovascular resistance.
A remarkable feature of the cerebral circulation is the fact that the CBF remains relatively constant
over a wide range of mean arterial pressure (approximately 60-150 mmHg). This implies that, within
this pressure range, a decrease in arterial pressure is accompanied by a decrease in cerebrovascular
resistance (i.e. vasodilation), while an increase in arterial pressure is accompanied by an increase in
cerebrovascular resistance (i.e. vasoconstriction). The effect of this is to ensure that within this range
of arterial pressure the CBF is appropriate for the metabolic demands of the brain. When the arterial
pressure decreases below the lower limit of cerebral autoregulation, the CBF falls significantly, but
this is partly compensated for by an increase in oxygen extraction. Once this compensatory increase
in oxygen extraction has reached its limit, however, a further decrease in arterial pressure will lead to
ischaemia. For example, an acute and precipitous decrease in arterial pressure that occurs during the
vaso-vagal response may cause transient ischaemia of the cerebral cortex and loss of consciousness
(syncope). Conversely, when the arterial pressure increases above the upper limit of cerebral
autoregulation, oedema may occur.
The upper and lower limits of autoregulation are increased in people with chronic hypertension. While
this has a protective effect when arterial pressure is elevated, a decrease in arterial pressure in
hypertensive patients can result in brain ischaemia at levels of pressure which, in normotenive
people, would not be associated with ischaemia. In addition, the upper and lower limits of
autoregulation are also increased as a result of stimulation of sympathetic nerves supplying the
cerebral blood vessels. Thus, in conditions where sympathetic activity increases acutely (e.g. during
exercise or stress) the increase in the autoregulatory range tends to match the acute increase in
arterial pressure that occurs under these conditions.
Factors controlling cerebrovascular resistance

Although cerebral blood vessels are innervated by sympathetic nerves, their function appears to be
primarily to vary the autoregulatory range, as discussed above. The main factor regulating the
resistance of cerebral arterioles is local metabolic activity. An increase in the neuronal activity in a
particular brain region leads to an increase in the production of metabolites such as H+ ions or
adenosine. This in turn results in vasodilation in that region. It is possible that nitric oxide (NO) also
plays a key role, mediating the vasodilation that is triggered by the increased concentration of
metabolites. It is likely that this tight coupling between changes in metabolic activity and
cerebrovascular resistance is the principal mechanism underlying cerebral autoregulation. For
example, a decrease in arterial pressure would initially cause a reduction in cerebral blood flow,
leading to a mismatch between the rate of production of metabolites and their removal, so that an
increase in the concentration of metabolites would occur, leading to vasodilation which in turn would
restore CBF, despite the reduction in arterial pressure.
The CBF is also very sensitive to changes in the concentration of CO in the arterial blood. This is
2
largely mediated via the resultant changes in the concentration of H+ ions in the extracellular fluid
surrounding cerebral arterioles, but may also in part be mediated indirectly, via pH-dependent release
of other vasoactive factors, such as prostaglandins or NO. One potential serious consequence of the
sensitivity of CBF to changes in blood CO levels is that hyperventilation can result in a large
2
decrease in CBF, even leading to unconsciousness. This is explained by the fact that hyperventilation
van greatly reduce the blood CO level, resulting in cerebral vasoconstriction and hence reduced CBF.
2
Recent studies have also indicated that glial cells (astrocytes) in the brain also may play an important
role in the coupling between neuronal activity (metabolic activity) and CBF. According to this
2+
hypothesis, neurotransmitters released by neurons cause a change in the intracellular Ca
concentration of nearby astrocytes, which then in turn release vasodilating compounds (e.g.
prostaglandins). Consistent with this hypothesis, astrocytic processes are closely associated with
both synapses and cerebral blood vessels. Further studies are required, however, before the
46 of 57 importance of this neuron-astrocyte-blood vessel pathway in the regulation of CBF can be fully 16/10/10 10:28 AM
evaluated.
References
Recent studies have also indicated that glial cells (astrocytes) in the brain also may play an important
role in the coupling between neuronal activity (metabolic activity) and CBF. According to this
2+
hypothesis, neurotransmitters released by neurons cause a change in the intracellular Ca
concentration of nearby astrocytes, which then in turn release vasodilating compounds (e.g.
prostaglandins). Consistent with this hypothesis, astrocytic processes are closely associated with
both synapses and cerebral blood vessels. Further studies are required, however, before the
importance of this neuron-astrocyte-blood vessel pathway in the regulation of CBF can be fully
evaluated.
References
Markus, H.S. Cerebral perfusion and stroke . Journal of Neurology, Neurosurgery and Psychiatry.
2004, March, 75: 353-361.
For those interested in current ideas ideas the role of astrocytes in regulating CBF, see:
Anderson, C.M. and Nedergaard, M. Astrocyte-mediated control of cerebral microcirculation . Trends

in Neurosciences 2003, 26(7): 340-345.
LEARNING TOPIC - Short term regulation of blood pressure
Disturbances in arterial blood pressure that occur over the short term (seconds or minutes) are
compensated for by rapidly-acting control systems, of which the single most important is the arterial
baroreceptor reflex.
Arterial pressure is regulated by several interrelated systems, which have different time-courses of
action. These can be divided into short-term, intermediate term and long-term mechanisms. The
short-term mechanisms are neural reflexes, the intermediate mechanisms are hormonal, and the
long-term mechanisms consists mainly of the renal system which relates blood volume and hence
arterial pressure. This learning topic will focus on the short-term mechanisms.
Arterial baroreceptor reflex

In the short term (ie seconds or minutes), the main mechanism regulating blood pressure is the
arterial baroreceptor reflex. The arterial baroreceptors are spray-type nerve endings lying in the walls
of the carotid sinus and aortic arch. They are stretch receptors, but signal pressure by responding to
changes in the pressure-induced stretch of the arterial wall. The primary afferent fibres originating
from the carotid sinus and aortic arch baroreceptors (which run in the glossopharyngeal and vagal
cranial nerves, respectively) terminate in the nucleus of the solitary tract (NTS), within the medulla
oblongata. From the NTS, baroreceptor afferent signals are transmitted over central pathways to the
vagal preganglionic neurons (located in the medulla oblongata) and sympathetic preganglionic
neurons (in the thoracic and upper lumbar segments of the spinal cord) that regulate the
cardiovascular system.
The baroreceptors are tonically active at normal levels of arterial pressure, and are able to signal
changes in pressure within the range from approximately 50 mmHg (threshold) to 160 mmHg
(saturation level). A change in the firing rate of baroreceptors, in response to a change in pressure,
reflexly alters the activity of sympathetic nerves innervating the heart and blood vessels, and vagal
nerves innervating the heart, via the central pathways referred to above. In this way, a transient
change in arterial pressure (eg as a consequence of a change in posture) is rapidly compensated for,
so that the arterial pressure is restored back close to its previous level.
The baroreceptor control system is of little or no importance in long-term regulation of arterial

pressure, simply because the baroreceptors adapt (within 1-2 days) to whatever pressure level they
are exposed to. Thus, dysfunction of the baroreceptor reflex cannot be the cause of maintained high
arterial pressure (hypertension). Instead, the main importance of the baroreceptor reflex is in
buffering disturbances to the cardiovascular system, as may arise from changes in posture, metabolic
activity or external threats triggering sympathetic reactions.
Short-term control of arterial pressure by other reflexes

Apart from the baroreceptors, other groups of receptors can also reflexly alter the activity of
47 of 57 autonomic nerves innervating the cardiovascular system. These include the arterial chemoreceptors 16/10/10 10:28 AM
(located in the carotid body and aortic arch) and receptors in the low-pressure part of the circulation
(particularly the left and right atria). Primary afferent fibres originating from these receptors, like the
arterial baroreceptors, run in the glossopharyngeal or vagal nerves and terminate in the NTS.
are exposed to. Thus, dysfunction of the baroreceptor reflex cannot be the cause of maintained high
arterial pressure (hypertension). Instead, the main importance of the baroreceptor reflex is in
buffering disturbances to the cardiovascular system, as may arise from changes in posture, metabolic
activity or external threats triggering sympathetic reactions.
Short-term control of arterial pressure by other reflexes

Apart from the baroreceptors, other groups of receptors can also reflexly alter the activity of
autonomic nerves innervating the cardiovascular system. These include the arterial chemoreceptors
(located in the carotid body and aortic arch) and receptors in the low-pressure part of the circulation
(particularly the left and right atria). Primary afferent fibres originating from these receptors, like the
arterial baroreceptors, run in the glossopharyngeal or vagal nerves and terminate in the NTS.
The arterial chemoreceptors are stimulated primarily by a decrease in the pO level of the arterial
2
blood, but can also be stimulated by a large fall in arterial pressure, as may occur during severe
haemorrhage. Stimulation of the chemoreceptors results in a reflex vasoconstriction, which helps to
raise arterial pressure. Receptors in the atria respond primarily to changes in blood volume, which
affects the pressure within the atria and central veins. A decrease in atrial pressure (eg as a
consequence of a haemorrhage) results in a reflex increase in the activity of sympathetic vasomotor
nerves, particularly those innervating the kidney. In addition, signals from atrial receptors also reach
the hypothalamus and cause an increase in the release of antidiuretic hormone (vasopressin) from
the pituitary gland. In summary, then, a decrease in atrial pressure triggers reflex sympathetic and
hormonal changes that increase vascular resistance and reduce urine production. Conversely, an
increase in atrial pressure has the opposite effect, producing a reflex vasodilatation and rise in urine
production. The atrial reflex plays an important role in the cardiovascular adjustments to a change in
posture, and to haemorrhage.
References
Guyton, A. C. and J. E. Hall, 2006, Textbook of medical physiology, 11th ed., Elsevier Saunders,
Philadelphia. Chapter 18 (Nervous Regulation of the Circulation, and Rapid Control of Arterial Pressure
)
For more specialised reading, the following are useful references:
Agewall S et al. Reflexogenic neuronal and humoral responses to selective stimulation of low-pressure
cardiopulmonary receptors in man. J. Intern. Med. 1991; 229(2): 151-158.
Coleridge HM, Coleridge JCG. Cardiovascular afferents involved in regulation of peripheral vessels .
Annu. Rev. Physiol 1980; 42(1): 413-427.
Hainsworth R. Reflexes from the heart . Physiol. Rev. 1991; 71(3): 617-658.
LEARNING TOPIC - Social roles: responses to health and illness
Role theory is a sociological approach which conceives of most social situations having characteristic
behaviour patterns or roles. When individuals are placed in certain social positions, there are
expectations of their own behaviours and those of others with whom they are interacting. People play
many roles in their lives; roles are learned, culturally-related and sometimes influenced by gender.
The role of the doctor involves performing actions, having aims, addressing problems and interacting
with others (patients, patients’ families, other health professionals) in ways which are relatively
common to all doctors. By abstracting the common features of the role it is possible to clarify
interactions and purposes and gain insight and understanding of various roles in the health care
system.
The Sick Role

A person with an illness has a relatively well defined role in most societies, as being sick is associated
with a set of obligations and responsibilities which were first described by sociologist Talcott Parsons
(1951). The four main expectations for the sick role are: (a) a right to exemption from normal social
role responsibilities, eg work; (b) a right not to be held accountable for the illness; (c) a duty to
experience illness as undesirable and not to resign themselves to the illness; (d) a duty to seek out
48 of 57 16/10/10 10:28 AM
expert assistance and to cooperate with recommended treatment in attempting to get well. Medical
practitioners are empowered to allow patients to enter this role, and as such, become social
regulators. One implication of the sick role is that some illnesses are viewed as legitimate, and others
which might be interpreted as being the 'fault' of the patient (such as substance abuse related
system.
The Sick Role

A person with an illness has a relatively well defined role in most societies, as being sick is associated
with a set of obligations and responsibilities which were first described by sociologist Talcott Parsons
(1951). The four main expectations for the sick role are: (a) a right to exemption from normal social
role responsibilities, eg work; (b) a right not to be held accountable for the illness; (c) a duty to
experience illness as undesirable and not to resign themselves to the illness; (d) a duty to seek out
expert assistance and to cooperate with recommended treatment in attempting to get well. Medical
practitioners are empowered to allow patients to enter this role, and as such, become social
regulators. One implication of the sick role is that some illnesses are viewed as legitimate, and others
which might be interpreted as being the 'fault' of the patient (such as substance abuse related
illnesses), are viewed as illegitimate. Conversely, some illness sufferers push to have their illness
recognised as a medical condition, this medicalisation supposedly changing society's view of the
sufferer from 'bad' to 'ill' (as has happened in the past with mental illness). Parson's sick role has
been criticised as: (1) more appropriate to acute disorders, not chronic illness where the patient may
in fact be encouraged to continue normal social role obligations; (2) medicalising some disorders and
removing patient's responsibilities for behavioural choices; and (3) culture- and class-related.
Labelling
Friedson (1970) comments on the unequal nature of the doctor-patient relationship, and the power of
the doctor to label illness. The process of labelling is two-pronged; on one hand it may assist the
patient by allowing understanding of their condition and relief from social role obligations, whereas
on the other hand it may cause the patient to enter the sick role unnecessarily (eg male patients who
defined themselves as sick, when it was found that they had asymptomatic high blood pressure), and
may stigmatise the patient (as with mental illness).
Illness Behaviour
Mechanic introduced the term 'illness behaviour' to describe activities undertaken by a person who
has symptoms in order to define the state of their health and discover a suitable remedy. Associated
with this is the premise that the experience of illness may be used to achieve social and personal
goals unrelated to alterations in biological systems or the pathogenesis of disease, that is, secondary
gain. Particular groups of individuals have been found to be under-utilisers of medical services and to
be more likely to tolerate symptoms of disease, have a different definition of symptoms from the
medical profession, be likely to consult friends or family or alternative healers, be frightened or wary
about going to the doctor, feel that little could be done about their condition and be unable to 'make
time' to go to the doctor. These intervening variables mediating between the presence of symptoms
and the act of consulting a doctor are often patterned according to social and cultural factors,
including the ability to tolerate pain, the social and cultural meaning of symptoms, and the social
network of the individual.
Abnormal Illness Behaviour

In Mechanic's formulation of illness behaviour, the term 'abnormal illness behaviour' is
non-evaluative and describes no more than statistical variation from a norm. Pilowsky, however, has
developed an extension of this usage to cover a range of disease-associated behaviours often labelled
hypochondriacal, hysterical, malingering, and so on. He defines abnormal illness behaviour as 'the
persistence of an inappropriate or maladaptive mode of perceiving, evaluating and acting in relation
to one's own state of health, despite the fact that a doctor (or other appropriate social agent) has
offered a reasonably lucid explanation of the nature of the illness and the appropriate course of
management to be followed'. A number of contemporary issues now mean that illness behaviours are
currently important to governments, the medical profession and the wider community. These issues
include the rising number of people with chronic illness, widening definitions of health and illness,
re-thinking acceptable quality of life, wider use of services, the increasing availability and use of
alternative and complementary therapies, easier public access to information on illness and
treatment, and greater emphasis on patient empowerment and involvement in decision making.
References
Broome, A. and S. P. Llewelyn, 1995, Health psychology : process and applications, 2nd ed., Chapman
& Hall, Melbourne.
George, J. and A. Davis, 1998, States of health : health and illness in Australia, 3rd ed., Addison
Wesley Longman, Melbourne.
Pilowsky, I., 1997, Abnormal illness behaviour. Wiley.

49 of 57 16/10/10 10:28 AM
Rogers, T., 2001. Barriers to the doctor as patient role: a cultural construct. Royal Australian College
of General Practitioners.
http://www.racgp.org.au/gphealth/doctorsaspatients
Broome, A. and S. P. Llewelyn, 1995, Health psychology : process and applications, 2nd ed., Chapman
& Hall, Melbourne.
George, J. and A. Davis, 1998, States of health : health and illness in Australia, 3rd ed., Addison
Wesley Longman, Melbourne.
Pilowsky, I., 1997, Abnormal illness behaviour. Wiley.
Rogers, T., 2001. Barriers to the doctor as patient role: a cultural construct. Royal Australian College
of General Practitioners.
http://www.racgp.org.au/gphealth/doctorsaspatients
LEARNING TOPIC - Structure of heart and great vessels
Structure of the pericardium and heart
Revise the structure and relationships of the pericardium.

How is the external surface of the heart described?
What are the major structures and their locations within the four chambers of the heart?
Review briefly the organisation of the conducting system of the heart.
Surface anatomy of the heart
How is the middle mediastinum defined?

What are the surface markings of the heart and its valves as projected onto the anterior chest
wall?
What components of the heart make up the four borders of the heart when it is viewed from
anteriorly?
The great vessels
Briefly review the position, relationships and branches or tributaries of the aorta, superior and
inferior vena cava and the pulmonary arteries and veins. In particular note their connections
with the heart and their relationships as they leave or enter the heart.
References
Resources material associated with this Learning Topic.
Moore, K. L., et al., 2006, Clinically oriented anatomy, 5th ed., Lippincott Williams & Wilkins,
Baltimore, MD. Chapter 3 (Pelvis and Perineum)
Drake, R. L., et al., 2005, Gray's anatomy for students, ed., Elsevier/Churchill Livingstone,
Philadelphia. Chapter 3 (Thorax)
Ross, M. H. and W. Pawlina, 2006, Histology : a text and atlas with correlated cell and molecular
biology, 5th ed., Lippincott Wiliams & Wilkins, Baltimore, MD. Chapter 13 (Cardiovascular system)
Author: Dr Richard Ward, Anatomy and Histology
LEARNING TOPIC - Support for carers
A carer is someone who provides care and support for a parent, partner, child, relative or friend who
has a disability, is frail and aged, or who has a chronic mental or physical illness. It is a fact that many
of us will provide and/or receive such care at some stage during our lives.
Down syndrome is one of many conditions where an individual may be, or may become, reliant upon
their partners, family members or other people to provide continuing care at home. Other examples of
50 of 57 conditions where care may also be required include people with HIV, arthritis, cancer, cardiac disease,
16/10/10 10:28 AM
cerebral palsy, dementia, diabetes, emphysema and other respiratory conditions, head injury, other
intellectual disabilities, mental illness, motor neurone disease, multiple sclerosis, muscular dystrophy,
Parkinson's disease, spinal cord injury and stroke, as well as frail aged people and people receiving
A carer is someone who provides care and support for a parent, partner, child, relative or friend who
has a disability, is frail and aged, or who has a chronic mental or physical illness. It is a fact that many
of us will provide and/or receive such care at some stage during our lives.
Down syndrome is one of many conditions where an individual may be, or may become, reliant upon
their partners, family members or other people to provide continuing care at home. Other examples of
conditions where care may also be required include people with HIV, arthritis, cancer, cardiac disease,
cerebral palsy, dementia, diabetes, emphysema and other respiratory conditions, head injury, other
intellectual disabilities, mental illness, motor neurone disease, multiple sclerosis, muscular dystrophy,
Parkinson's disease, spinal cord injury and stroke, as well as frail aged people and people receiving
palliative care at home at the end of life.
Increasing awareness has been given in recent years to the provision of support and assistance for
carers. Many families have found that they have had to provide homecare for family members with
significant disability particularly since the closure of residential facilities for people with intellectual
disability and the lack of availability of suitable institutional care for people with many chronic
conditions. There is no doubt that many people with chronic conditions and their families prefer
homecare however there are many challenges.
One of the important roles of the doctor providing medical care for a person with a chronic condition
is to ensure that the well being of their carers is also being addressed. After all if the carers are
unable to cope, then the care of the individual may be in jeopardy. The needs of all family members
should be addressed; this is particularly important for other children, in the case of a child with a
disability, and for the primary care giver in any situation. Often, but not always, the burden of care
falls upon the women in the family. It is important that the family and other carers are involved in
medical discussions and decision making, with the consent of the individual patient. It is important to
ask carers about how they are coping and to pick up early signs of stress and to provide assistance
and support.
Home visits are an essential component of Australian general practice. This is particularly the case for
people with chronic disabling conditions or the terminally ill. Seeing the person in their home
environment can help uncover concerns and allow the doctor to more clearly appreciate some of the
difficulties which face carers. A wise family doctor will listen to concerns expressed by carers. After all
the carers are looking after the individual 24 hours a day and have the opportunity to observe and
detect problems early on.
Support networks are important. These may exist both within the family and from outside and may
include the family's general practitioner and visiting nursing professionals. Such networks can
engender security and assist in alleviating or preventing stressful circumstances.
It is important that carers are aware of available support services. The Carers Australia provides
information, education, counselling, advocacy and other ongoing supports for carers through
branches in all states and territories of Australia. This can be a useful first point of contact for carers
and clinicians looking for suitable resources. See: www.carersaustralia.com.au The website also
include resources including information for carers on financial support and pensions, guidelines on
how to provide safe care at home, advice on looking after yourself and respite care. It is available in
13 languages.
References
Students can find additional useful background material on the role of carers of people with chronic
illness in Australia from the following references:
Bridges-Webb C, Giles B, Speechly C, Zurynski Y, Hiramanek N. Patients with dementia and their
carers in general practice. Australian Family Physician 2006;35:923-4. www.racgp.org.au/afp/200611
/12571
Brodaty H, Green A. Who cares for the carer? The often forgotten patient. Australian Family Physician
2002, 31(9):833-836.
Bulsara CE, Fynn N. An exploratory study of GP awareness of carer emotional needs in Western
Australia. BMC Family Practice 2006, May, 7:33.
Students can find additional information on support for carers in Australia from the following
organisations:
51 of 57 16/10/10 10:28 AM
Carers Australia www.carersaustralia.com.au
NSW Council for Intellectual Disability. www.nswcid.org.au/

2002, 31(9):833-836.
Bulsara CE, Fynn N. An exploratory study of GP awareness ofhttp://smp.sydney.edu.au/compass/guide/handbook/block/5

carer emotional needs in Western
Australia. BMC Family Practice 2006, May, 7:33.
Students can find additional information on support for carers in Australia from the following
organisations:
Carers Australia www.carersaustralia.com.au
NSW Council for Intellectual Disability. www.nswcid.org.au/
Author: Professor Simon Willcock, General Practice
LEARNING TOPIC - Syncope
Syncope (or fainting) is triggered by an abrupt decrease in arterial blood pressure, which in turn may
result from a variety of causes. The most common cause (vasovagal syndrome) is associated with
changes in sympathetic and cardiac vagal activity.
Definition
Syncope is defined as a disturbance or loss of consciousness as a result of an abrupt reduction of
blood flow to the brain, which is typically of short duration (seconds to minutes).
Causes of syncope
Normally, blood flow to the brain is regulated by an intrinsic autoregulatory mechanism, which
maintains blood flow at a level sufficient to meet the metabolic demands of the brain, even if there
are transient decreases in mean arterial blood pressure. However, if there is a large fall in mean
arterial pressure (i.e. to a level < 45-50 mmHg), the autoregulatory mechanism is insufficient to
maintain a level of cerebral blood flow that is sufficient to meet the metabolic demands of the brain,
resulting in a loss of consciousness.
Arterial blood pressure is normally regulated by the baroreceptor reflex, so that a large decrease in
blood pressure (hypotension) can only occur if the factor causing the hypotension is so great that it
cannot be compensated for by the baroreceptor reflex, or if the baroreceptor reflex itself is impaired.
There are four main factors that can cause abrupt and large decreases in blood pressure, leading to
syncope:
Obstruction to the circulation. Any factor which obstructs the outflow from the left or right
ventricles, or which impairs the pumping capacity of the ventricles, may cause a fall in cardiac
output which, if severe enough, will lead to a large fall in arterial pressure. Such factors include
aortic stenosis (which narrows the aorta), hypertrophic cardiomyopathy (in which the
contractility of the cardiac muscle is impaired), pulmonary stenosis (which narrows the
pulmonary artery), or pulmonary embolism (in which the outflow resistance of the right
ventricle is greatly increased).
Transient arrhythmias. A rapid increase in the rate of ventricular contractions (ventricular
tachycardia) may result in a very short filling time and hence greatly reduced stroke volume,
leading to a reduced cardiac output despite the increased heart rate. The ventricular tachycardia
may occur as a result of abnormalities of the cardiac pacemaker (sino-atrial node) or in the
conduction of action potentials through the heart. Conversely, other abnormalities of the
pacemaker or cardiac conduction pathways may lead to a slowing of the heart rate
(bradycardia), which if severe enough will also lead to a greatly reduced cardiac output. The
decrease in cardiac output in turn will result in a decrease in arterial blood pressure.
Neurological disorders . A variety of neurological disorders can result in dysfunction of the vagal
parasympathetic nerves innervating the heart, or sympathetic vasoconstrictor nerves
innervating the blood vessels, leading to an impairment of the normal baroreceptor reflex
control of blood pressure. A feature of these conditions is a reduction in blood pressure when
the subjects stand up (postural hypotension).
Vasovagal syndrome. This is the most common cause of syncope, and is so named because it is
characterised by a combination of vagally mediated cardiac slowing (bradycardia) and
peripheral vasodilation. The result is that both cardiac output and total peripheral resistance is
reduced, so that arterial pressure falls sharply, to the point where transient cerebral ischaemia
and loss of consciousness occurs. It is the vasodilation that is the most important factor,
because blockade of the vagally-mediated bradycardia (by injection of atropine) does not
prevent the syncope. Attacks are usually initiated by emotional stimuli (e.g. fainting at the sight
52 of 57 of blood, or on receiving very bad news). Vasovagal syncope occurs infrequently in healthy 16/10/10 10:28 AM
people, but in some people occurs frequently and in the absence of any obvious stimulus - in
these cases the term 'malignant vasovagal syndrome' is used.
Vasovagal syndrome. This is the most common cause of syncope, and is so named because it is
characterised by a combination of vagally mediated cardiac slowing (bradycardia) and
peripheral vasodilation. The result is that both cardiac output and total peripheral resistance is
reduced, so that arterial pressure falls sharply, to the point where transient cerebral ischaemia
and loss of consciousness occurs. It is the vasodilation that is the most important factor,
because blockade of the vagally-mediated bradycardia (by injection of atropine) does not
prevent the syncope. Attacks are usually initiated by emotional stimuli (e.g. fainting at the sight
of blood, or on receiving very bad news). Vasovagal syncope occurs infrequently in healthy
people, but in some people occurs frequently and in the absence of any obvious stimulus - in
these cases the term 'malignant vasovagal syndrome' is used.
Studies in humans have demonstrated that the vasodilation associated with vasovagal syncope is due
to an inhibition (usually complete abolition) of sympathetic vasoconstrictor nerve activity. This
finding indicates that the baroreceptor reflex is suppressed during a vasovagal attack, because the
fall in arterial pressure would normally trigger a reflex increase in sympathetic vasoconstrictor
activity. It is thought that the sympathoinhibition and cardiac vagal activation is a stereotyped
autonomic response, triggered by centers in the forebrain that receive inputs activated by emotional
stimuli. The survival value of the vasovagal syncope is unclear; it is conceivable, however, that it is
the human equivalent of the 'playing dead' reaction displayed by some animals when confronted with
a predator from which they cannot escape.
References
Lip, G. Y. H., S. P. Singh, et al., 1998, Key topics in cardiovascular medicineed., BIOS Scientific
Publishing, Oxford, UK. pp. 181-184
LEARNING TOPIC - The foetal circulation
The adult circulation contains two separate pumps in series. The right ventricle pumps blood through
the lungs where it is oxygenated. The left ventricle pumps blood through the body where oxygen is
consumed. In the foetus the circulation differs markedly from the adult since the placenta replaces
the lungs as the source of oxygen while the fetal lungs have no gas exchange function. Furthermore
at birth, after tying and cutting the umbilical cord and the expansion of the lungs with the first breath,
the fetal circulation changes rapidly to one approximating to the adult.
The main features of the fetal circulation are as follows.
Two large umbilical arteries leave the iliac artery and carry about 50% of the cardiac output to
the placenta.
A single umbilical vein carries oxygenated blood back from the placenta and joins the inferior
vena cava, bypassing the liver.
Of the blood returning to the right atrium about half crosses through the foramen ovale, which
connects the R and L atria, and enters the left atrium.
Of the blood pumped out of the right ventricle into the pulmonary artery, about half, instead of
entering the lungs, passes through the ductus arteriosus which connects the pulmonary artery
and the aorta, and enters the systemic circulation.
These differences between fetal and adult circulation occur both because of the anatomical
connections present in the foetus but also because the uninflated fetal lung has a very high resistance
to blood flow and the fetal systemic circulation has a low resistance because of the placenta.
Consequently the pressures on the right side of the heart are higher than on the left (in contrast to
the adult) and blood flows from R to L atrium through the foramen ovale and from the pulmonary
artery to the aorta through the ductus arteriosus.
At birth three main changes occur. The cord is tied and systemic peripheral resistance doubles
increasing pressure in the L heart and aorta. At the first respiratory inflation the resistance to
pulmonary blood flow falls dramatically, pressure in the R heart drops and flow through the foramen
ovale and ductus arteriosus falls or reverses. In the next day or so the ductus arteriosus, which
contains smooth muscle in its wall, normally constricts and is no longer patent. The foramen ovale
acts as a valve so that once L atrial pressure is greater than R it normally prevents flow.
53 of 57 16/10/10 10:28 AM
An understanding of these pressure changes is essential to understanding the direction of abnormal
flow if any of the normal fetal connections remain patent or other abnormal anatomical connections
are present in the heart. If right to left shunts occur in the adult then deoxygenated venous blood
artery to the aorta through the ductus arteriosus.
At birth three main changes occur. The cord is tied and systemic peripheral resistance doubles
increasing pressure in the L heart and aorta. At the first respiratory inflation the resistance to
pulmonary blood flow falls dramatically, pressure in the R heart drops and flow through the foramen
ovale and ductus arteriosus falls or reverses. In the next day or so the ductus arteriosus, which
contains smooth muscle in its wall, normally constricts and is no longer patent. The foramen ovale
acts as a valve so that once L atrial pressure is greater than R it normally prevents flow.
An understanding of these pressure changes is essential to understanding the direction of abnormal

flow if any of the normal fetal connections remain patent or other abnormal anatomical connections
are present in the heart. If right to left shunts occur in the adult then deoxygenated venous blood
becomes mixed with arterialised blood and cyanosis is possible.
References
Guyton, A. C. and J. E. Hall, 2006, Textbook of medical physiology, 11th ed., Elsevier Saunders,
Philadelphia Chapter 83 has a clear account of the fetal circulation and its transition at birth.
LEARNING TOPIC - Treatments for hypertension
Background
We know from population studies that stroke, coronary heart disease (CHD), cardiac failure and
progressive impairment of renal function occur more often and at an earlier age in people with above-
average levels of blood pressure (BP). Furthermore, from interventional studies in which patients
with high BP were randomly assigned to antihypertensive therapy or placebo, there is good evidence
that pharmacological intervention reduces the risk of stroke by about 40% and the risk of CHD by
about 15%. The benefits of drug treatment have been demonstrated even in mild hypertension
(BP>140/90 mmHg), and in patients with isolated systolic hypertension (especially the elderly). A
variety of antihypertensive drugs is available, affecting one or more components of the equation:
mean BP = cardiac output (CO) x total peripheral resistance (TPR)
(CO = Heart rate x Stroke volume)
BP targets
In general, the target for well treated hypertension is resting BP <140/90 mmHg in uncomplicated
hypertension, and <130/80 mmHg in those with concomitant diabetes, renal disease or arterial
disease. In practice, combination therapy with two or more of the drugs described below is often
required to meet these targets.
Non-pharmacological therapy
When a diagnosis of hypertension is made, secondary causes must be sought and treated, and
end-organ damage sought and other vascular risk factors measured (eg lipids, weight, blood sugar).
The first step in treating hypertension is instituting lifestyle measures including sensible diet, weight
loss where appropriate, salt restriction and a regular exercise program. Where these measures fail or
are insufficient to meet BP targets (as above), drug therapy should be considered.
Drug therapy
First line agents
1. Calcium Antagonists
This family of drugs, all of which block calcium channels, can be broadly divided into the
dihydropyridines (eg nifedipine, felodipine, amlodipine) and the non-dihydropyridines (eg
verapamil and diltiazem). Nifedipine-like drugs act exclusively on vascular smooth muscle,
lowering BP by vasodilation, whereas verapamil and diltiazem have additional effects on the
heart, reducing AV nodal conduction and myocardial contractility. Dihydropyridines induce reflex
sympathetic activation, which often gives rise to the typical side effects of tachycardia, flushing
and headache, whereas the fall in BP with verapamil or diltiazem is associated with a reduction
(or little change) in heart rate. Dihydropyridines are particularly suitable for combination with a
54 of 57 16/10/10 10:28 AM
beta blocker, but verapamil and diltiazem are contraindicated in combination with beta blockers
because of the risks of profound bradycardia and heart failure. All the calcium antagonists
(except amlodipine) have an intrinsically short half-life, so they are often formulated in a
Slow-Release system to facilitate fewer daily doses.
dihydropyridines (eg nifedipine, felodipine, amlodipine) and the non-dihydropyridines (eg
verapamil and diltiazem). Nifedipine-like drugs act exclusively on vascular smooth muscle,
lowering BP by vasodilation, whereas verapamil and diltiazem have additional effects on the
heart, reducing AV nodal conduction and myocardial contractility. Dihydropyridines induce reflex
sympathetic activation, which often gives rise to the typical side effects of tachycardia, flushing
and headache, whereas the fall in BP with verapamil or diltiazem is associated with a reduction
(or little change) in heart rate. Dihydropyridines are particularly suitable for combination with a
beta blocker, but verapamil and diltiazem are contraindicated in combination with beta blockers
because of the risks of profound bradycardia and heart failure. All the calcium antagonists
(except amlodipine) have an intrinsically short half-life, so they are often formulated in a
Slow-Release system to facilitate fewer daily doses.
2. Angiotensin Converting Enzyme (ACE) Inhibitors
This family of drugs are all broadly similar in terms of their antihypertensive profile, eg
captopril, enalapril, and perindopril. They block the enzymatic conversion of angiotensin I to
angiotensin II (ANG II) which is a potent vasoconstrictor hormone produced not only in the
circulation but also in many organs. Thus, inhibition of both circulating and tissue-based ACE
contributes to the antihypertensive effect. All ACE inhibitors except captopril and lisinopril are
prodrugs, requiring conversion in the liver to the active diacid metabolite, eg enalaprilat, and the
reduction in BP following ACE inhibition is not accompanied by any reflex tachycardia. 15-20%
of patients complain of a dry cough, and renal function may deteriorate, especially in patients
with renovascular hypertension. ACE inhibitors have useful ancillary properties, eg reducing LVH
and improving arterial compliance. Their antihypertensive effects are enhanced by
co-administration of a diuretic.
3. Angiotensin receptor-antagonists
This is a relatively new group of antihypertensive agents that competitively block the AT1
subtype of angiotensin II receptors on vascular smooth muscle. Examples include Iosartan and
irbesartan. These drugs appear to have similar efficacy to ACE inhibitors but are associated with
less cough. Like ACE inhibitors, they appear to have particular renoprotective effects in subjects
with diabetes.
4. Diuretics
Thiazide diuretics are effective antihypertensive agents, eg hydrochlorothiazide, indapamide and
bendrofluazide. They are particularly useful in the elderly. Thiazides have a tendency to cause
undesirable metabolic side effects, eg hypokalaemia, hyperglycaemia and hyperuricaemia, but
such problems are usually of little clinical significance when the drugs are used in low doses.
+
Nevertheless, they are best avoided in patients with diabetes or gout. Use of K supplements
+ +
and/or K - sparing diuretics is usually unnecessary, but serum K should be monitored. The
fall in BP is due, at least in part, to natriuresis and diuresis, but thiazides probably also have
direct vasodilator effects that contribute to their antihypertensive mechanism. They are cheap,
as effective and well tolerated as newer types of antihypertensive, and there is strong evidence
to support their benefits in reducing mortality from hypertensive complications.
5. Beta-Adrenoceptor Antagonists
All beta blockers are broadly similar in terms of their antihypertensive efficacy, although
pharmacologically some are more selective for b1-receptors (eg atenolol and metoprolol), some
are more lipid soluble (eg propranolol) and some have intrinsic sympathomimetic activity (ie
partial agonists eg oxprenolol). Beta blockers primarily lower BP by reducing heart rate and
cardiac output, but other mechanisms may also contribute, eg inhibition of renin release. These
drugs are useful either as monotherapy or in combination with other agents, eg diuretics or
dihydropyridine calcium antagonists. All beta blockers are contraindicated in patients with
reversible obstructive airways disease (eg asthma) or peripheral vascular disease, and they are
often avoided in patients with diabetes. Typical side effects of beta blocker therapy (in 15-20%
of patients) include tiredness, impotence, exercise limitation, excessive bradycardia or heart
block, and sleep disturbance.
Second line agents
1. Other Drugs
Other drugs used occasionally include alpha-1 adrenoceptor antagonists (eg prazosin,
terazosin), which are vasodilators; centrally-acting drugs (eg clonidine and methyldopa) which
decrease sympathetic outflow; and hydralazine, which is a direct relaxant of vascular smooth
muscle.
Author: Professor David Celermajer, Medicine
LEARNING TOPIC - Ventricular arrhythmias

55 of 57 16/10/10 10:28 AM
Ventricular arrhythmias are disturbances of the electrical excitation of the ventricular myocardium
that affect the rate and coordination of contraction. Disturbed rate or coordination may severely
muscle.
Author: Professor David Celermajer, Medicine
LEARNING TOPIC - Ventricular arrhythmias
Ventricular arrhythmias are disturbances of the electrical excitation of the ventricular myocardium
that affect the rate and coordination of contraction. Disturbed rate or coordination may severely
reduce the heart's overall pumping efficiency.
Pumping efficiency is most affected by mean ventricular rate, the optimal rate varying with the state
of the peripheral circulation and venous return, e.g. rest v exercise. Pumping efficiency is also
affected by the timing of atrial contraction prior to ventricular contraction. This is particularly
important when the ventricles are scarred of thickened and do not relax properly in diastole ('diastolic
dysfunction'). Pumping efficiency is also affected slightly by disturbed His-Purkinje conduction so that
the QRS duration is prolonged and the ventricular wall does not contract synchronously, but this is
usually important only when the heart has reduced reserves of pumping power for other reasons.
Very rapid ventricular rates shorten diastole and reduce coronary blood flow, leading to myocardial
ischaemia. At the extremes the heart may have no cardiac output ('cardiac arrest') with no electrical
activity ('asystole'), or because the beating is very rapid (300/min, 'ventricular flutter') or totally
un-coordinated and chaotic ('ventricular fibrillation').
Ventricular arrhythmias are classified into bradycardias (slow) or tachycardias (fast). Ventricular
Bradycardia is the result of failure of conduction of the normal electrical impulses from the sinus or
atrioventricular node to the ventricles. With complete failure of conduction, the normal His-Purkinje
system depolarises spontaneously at about 40/min (escape rhythm) but may be slower or display no
automaticity at all if diseased. Treatment is by artificial electronic pacemaker, which may pace the
right ventricle only, both the atria and ventricles ('dual chamber') to relate atrial and ventricular
contraction times appropriately, and both the right and left ventricles simultaneously ('bi-ventricular')
to ensure that the left ventricle contraction is synchronous. Emergency treatment for bradycardia with
loss of conciousness prior to instituting electrical pacing is a beta1 adrenergic stimulant, e.g.
isopropyl nor-adrenaline ('Isuprel' ~5 mcg/ min I.V. infusion), just sufficient to prevent syncope and
oliguria.
Ventricular tachycardia is due to electrical depolarisations arising within the ventricles themselves.
Because ventricular depolarisation is abnormal and not usually via the His Purkinje system the QRS
complexes in the ECG are larger, abnormal in shape and of longer duration than normal. The atria may
continue to beat normally, unrelated to the ventricles, or may be entrained by backward (retrograde)
conduction through the atrioventricular node.
Ventricular tachycardia occurrs most frequently as a result of an electrical depolarisation wave

following a constant circular course in the ventricular myocardium ('re-entrant tachycardia') and
exciting the ventricles repeatedly. The refractory period of the ventricular myocardium normally
prevents this arrhythmia. If conduction through the myocardium is slowed, e.g. by bands of scar
tissue or ischaemic myocardium, or the ventricles are enlarged or hypertrophied so that longer
pathways and conduction times are possible this arrhythmia may occur. It can be precipitated by
premature ventricular ectopic beats, or by programmed ventricular electrical stimulation in the
electrophysiology laboratory. The re-entry electrical wave may follow a constant anatomical path
('ventricular tachycardia') or break up into multiple uncoordinated re-entry loops ('ventricular
fibrillation'). Spontaneous cessation will occur if the electrical waves cannot propogate the electrical
wavefront to any adjacent excitable myocardium.
Treatment is by modifying sympathetic tone with beta1 adrenergic blockade, by modifying the
conduction time and refractory period of the myocardium with other 'anti-arrhythmic' drugs, by
interrupting the re-entry loops by rapid electrical pacing, electrically depolarising all the ventricular
myocardium at once (bi-phasic defibrillation), or by destroying localised potential re-entry pathways
by electro-cautery or surgery.
A rarer cause of abnormal rapid ventricular tachyarrhythmias is abnormality in myocardial cell

membrane electrical properties leading to repetitive action potentials. These are likely in acute
myocardial ischaemia, some drug intoxications (e.g. digoxin), and genetic abnormalities in myocardial
cell membrane ion channels, sometimes associated with long QT interval in the resting ECG or
congenital deafness due to the same ion channel defects being expressed in the hair cells of the
cochlear.
56 of 57 16/10/10 10:28 AM
References
A rarer cause of abnormal rapid ventricular tachyarrhythmias is abnormality in myocardial cell
membrane electrical properties leading to repetitive action potentials. These are likely in acute
myocardial ischaemia, some drug intoxications (e.g. digoxin), and genetic abnormalities in myocardial
cell membrane ion channels, sometimes associated with long QT interval in the resting ECG or
congenital deafness due to the same ion channel defects being expressed in the hair cells of the
cochlear.
References
Berne, R. M., 2004, Physiology, 5th ed., Mosby, St. Louis
Elsevier/Churchill Livingstone, Edinburgh ; New York
Zipes, D. P. and E. Braunwald, 2005, Braunwald's heart disease : a textbook of cardiovascular

medicine, 7th ed., W.B. Saunders, Philadelphia, Pa.[Available as a E-Book]
Author: Emeritus Professor John Uther, Cardiology, Western Clinical School
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LEARNING TOPICS - BLOCK 5

1. Activation of the heart

LEARNING TOPIC - Activation of the heart

Activation of the heart includes

The spread of electrical activity

the appearance of a typical ventricular action potential

Use the textbooks in your Tutorial Room

Berne, R. M., 2004, Physiology, 5th ed., Mosby, St. Louis.

Author: Professor David G Allen, Physiology

LEARNING TOPIC - Assessing peripheral vascular disease

LEARNING TOPIC - Assessing peripheral vascular disease

Use the textbooks in your Tutorial Room

Author: Associate Professor Peter Thursby, Surgery

LEARNING TOPIC - Atrial fibrillation

AV Nodal Ablation and Implantation of Pacemaker

Use the textbooks in your Tutorial Room

Author: Clinical Associate Professor Mark Mcguire, Medicine

LEARNING TOPIC - Causes of heart failure

Use the textbooks in your Tutorial Room

Author: Professor Richmond Jeremy, Medicine

LEARNING TOPIC - Causes of tiredness

Use the textbooks in your Tutorial Room

Murtagh J. Fatigue : a general diagnostic approach. Australian Family Physician 2003;32(11):873-876.

Author: Professor Simon Willcock, General Practice

LEARNING TOPIC - Chromosomal abnormalities and early development in Down syndrome

Cytogenetic Mechanisms Responsible for Down Syndrome

Cytogenetic Mechanisms Responsible for Down Syndrome

What are the Mechanisms which Produce Trisomy 21

Use the textbooks in your Tutorial Room

Use the textbooks in your Tutorial Room

Author: Professor David Sillence, Genetic Medicine

LEARNING TOPIC - Chronic viral infections

Chronic viral infections may

cause apparently acute illness, particularly by reactivation

Use the textbooks in your Tutorial Room

Author: Professor Peter McMinn, Infectious Diseases

LEARNING TOPIC - Clinical and laboratory assessment in heart failure

Use the textbooks in your Tutorial Room

Author: Professor Richmond Jeremy, Medicine

Author: Professor Richmond Jeremy, Medicine

LEARNING TOPIC - Complications of ischaemic heart disease

Left ventricular dysfunction:

Rupture of the myocardium:

Author: Dr Suchitra Chandar, Cardiology

LEARNING TOPIC - Complications of rheumatic heart disease

Use the textbooks in your Tutorial Room

Use the textbooks in your Tutorial Room

Additional detail on acute rheumatic fever

Author: Clinical Associate Professor David Richmond, Medicine

LEARNING TOPIC - Cyanosis: causes and consequences

Use the textbooks in your Tutorial Room

Author: Clinical Professor Iven Young, Medicine

LEARNING TOPIC - Detecting alcohol abuse

Medical Presentations of Alcohol Related Problems

• Possible Early Problems

• Later Stage Problems - In addition to the above -

Assessment of an alcohol problem

Pathology Tests and Biochemical Markers

Questionnaires as Screening Instruments

Use the textbooks in your Tutorial Room

Use the textbooks in your Tutorial Room

Australian Alcohol Guidelines