Learning objectives in Cardiovascular disease

What is oedema?
Oedema is swelling of a tissue due to accumulation of fluid in the extravascular
department.

What mechanisms give rise to oedema?

Factors which determine the maintenance of the intravascular volume (Starling’s laws)
determine the presence or absence of oedema.

Important mechanisms are:

* Increased vascular permeability due to e.g. inflammation
* Increased intravascular hydrostatic pressure
* Decreased oncotic pressure (e.g. in hypoalbuminaemia)
* Increased interstitial osmotic pressure (e.g. in the inflammatory exudates)
Pulmonary oedema occurs in left ventricular failure due to increased hydrostatic pressure.

Ankle oedema occurs in congestive (or right) heart failure due to increased hydrostatic
pressure in the systemic venous system.

Accumulation of fluid in the abdomen (ascites) occurs in cirrhosis as a result of increased

hydrostatic pressure (from portal hypertension) and as a result of decreased plasma
oncotic pressure (due to hypoalbuminaemia).

What is the difference between a transudate and an exudate?

In general transudates are low in protein and result from a change in the hydrostatic
pressure. So pulmonary and ankle oedema seen in heart failure are usually transudates.

Exudates tend to occur as part of a more active process and the fluid tends to be rich in
proteins. So in inflammation, protein rich fluid leaves vessels as they become more
permeable.

What is a collection of fluid in the pleura called? What is a collection of fluid in the
peritoneum called?

Collection of fluid in the pleura is known as a pleural effusion

· Collection clear fluid = hydrothorax. Causes include pneumonia, tuberculosis, left
heart failure.
· Collection of blood = haemothorax. Commonest causes is trauma.
· Collection of lymph = chylothorax. Seen in malignant disease.
· Collection of pus = pyothorax (empyema). Seen in purulent inflammatory
processes.

Collection of fluid in the peritoneum is known as ascites

· Seen in cirrhosis of the liver, in peritonitis, in nutritional deficiency and intra-
abdominal malignancies

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Learning objectives in Cardiovascular disease

Define shock.

Shock is defined as circulatory impairment so severe as to impair the normal functioning

of vital organs.

List the different types of shock

* Cardiogenic shock (myocardial infarct, pulmonary embolus etc).

* Septic shock (gram negative septicaemia)
* Anaphylactic shock (as part of a severe allergic reaction)
* Hypovolaemic shock (after extensive blood or fluid loss)
* Neurogenic shock (seen after a variety of severe insults such as spinal injury)

Explain the pathophysiology of shock.

The exact mechanism of shock depends to large extent on which type of shock.

Cardiogenic and hypovolaemic shock are due to impairment of pumping or not having
enough blood to pump.

Septic shock, anaphylactic shock and neurogenic shock are characterized by widespread
vasodilation with a lack of venous return to the heart.

The body has an initial compensatory response by causing vasoconstriction of the skin
and splanchnic circulation which means that blood is preferentially diverted to vital
organs such as the heart and brain. If the shock is uncorrected, the patient enters a
decompensated phase of irreversible shock.

Septic shock is commonly due to endotoxins released by gram-negative organs. A key

molecule in the pathogenesis of septic shock is nitric oxide (NO) which cause a massive
refractory vasodilation.

What are the possible consequences of shock?

The effects of shock are mediated largely by impaired perfusion of vital organs.

In the early stages, vasoconstriction of the skin and kidney vasculature results in cold and
pale skin and a reduced urinary output. The heart pumps faster (tachycardia) and there
may be achange in the consciousness level.

In the later stages, cells become damaged and may necrose. The late stages of shock are
evidenced by the onset of multi-organ failure (kidney, liver, lung, heart, brain).

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Learning objectives in Cardiovascular disease

What is atheroma?

Atheroma is a disease of the intima of arteries characterized by accumulation of lipid-rich

material associated with cellular reactions.

Translated from the Greek derivation it means ‘porridge-like’.

What is its distribution in the body?

Common sites include:

· Coronary arteries · Aorta
· Carotid arteries · Popliteal arteries
· Cerebral arteries · Iliac vessels

What are the risk factors for atheroma?

The risk factors for atheroma (atherosclerosis) are many and may be modifiable or non-
modifiable (constitutional). In addition, there are many ‘soft’ risk factors
Non-modifiable * Hypertension
* Age * Diabetes mellitus
* Sex ‘Soft’ factors
* Family history * Obesity
Modifiable * Stressful lifestyle
* Cigarette smoking * Homocystinuria
* Hyperlipidaemia * Sedentary lifestyle

What are the pathogenic theories for atheroma?

The currently accepted theory is the ‘response to injury’ hypothesis. It proposes that
atheroma is a response to low grade damage to the endothelium.

Damaging events include smoking, haemodynamic stresses (e.g. in hypertension) and

increased LDL. The damage to the endothelium leads to platelet aggregation and
accumulation of macrophages. Platelets secrete PDGF which attracts smooth muscle cells
from the media and these proliferate and secrete collagen.

Fat accumulates in an intracellular form within macrophages and smooth muscle cells
(foam cells) and an extracellular form (cholesterol clefts). The uptake of fat is enhanced
if it is oxidized and can be taken up via ‘scavenger’ receptors.

Other theories include:

* Thrombogenic hypothesis
* Clonal proliferation hypothesis
* Lipid insudation hyopthesis

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Learning objectives in Cardiovascular disease

What are the gross and microscopic features?

The appearances of atheroma change with time.

Grossly, it starts off as fatty streaks (which may resolve) and as the process advances,
lipid plaque and fibrolipid plaques occur.

Microscopically, the plaque shows accumulation of lipid in free and intracellular forms
(cholesterol clefts and foam cells), fibrosis and often a lymphocytic inflammatory
infiltrate. Later dystrophic calcification may develop.

What are the common clinical consequences of atheroma?

There are 3 main consequences

1. Stenosis of arteries with ischaemia and infarction.
2. Superimposed thrombosis and the subsequent risk of thrombo-embolism.
3. Weakening of arterial walls and the development of aneurysms

Know the arterial supply to the heart

2 main arterial trunks –right and left.

In most people, the right coronary artery is ‘dominant’ in that it supplies the posterior
wall/
The left coronary artery starts off as the left main stem and then divides into the left
anterior descending artery and the left circumflex which supply the anterior and lateral
wall of the left ventricle respectively.

What are the causes of coronary artery occlusion?

* Atherosclerosis
* Complications of an atherosclerotic plaque such as fissuring
* Thrombosis or embolism
* Vasculitis with destruction of the wall
* Vasospasm

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Learning objectives in Cardiovascular disease

What are the clinical syndromes caused by ischaemic heart disease?

* Sudden death * Myocardial infarction

* Stable angina * Ischaemic cardiomyopathy with
* Unstable angina heart failure
Stable angina (angina of effort) is causes by low flow through narrowed coronary arteries. Increased
demands such as during exercise cannot be met and angina pectoris occurs. When the demand returns to
normal, the angina resolves.

Unstable angina is angina which comes on suddenly and which increases in frequency and severity. It si
most commonly due to rupture or fissuring of an atherosclerotic plaque. A significant percentage will
develop myocardial infarction if untreated.

Myocardial infarction is mainly due to complete obstruction of vessels from plaque rupture or expansion or
from thrombosis. Rarely, it may occur as a result of vasospasm.

What is an infarct?
An infarct describes an area of necrosis which is due to obstruction of arterial blood
supply (ischaemia). Very rarely, infarction may follow severe and prolonged venous
obstruction.
Most infarcts are characterized by coagulative necrosis (except for the cerebrum which is
characterized by liquefactive necrosis)
What is the difference between transmural and subendocardial infarction?
As the name suggests, transmural infarction is infarction of the full-thickness of the
ventricular wall. It occurs after blockage of a main artery e.g. lateral infarction after
occlusion of the left circumflex artery. Transmural infarcts produce Q waves on an ECG.

Subendocardial infarcts involve the inner 1/3 of the myocardium. It is most commonly
seen after an epiusode of hypotension in patients with significant coronary artery
stenosis. The subendocardial zone is at the end of the arterial perfusion zone.

What are the gross and microscopic features of a myocardial infarct with specific
reference to their timing?

0-12 hours The myocardium looks normal grossly and microscopically. Specialised
enzyme tests can detect early changes.
12-24 hours The myocardium becomes pale and the muscle cells become bright pink
(hyepreosinophilic)
24-72 hours The myocardium becomes softened. Muscle cells die and neutrophils are
seen.
3-10 days A hyperaemic border develops around the infarct. Macrophages and
granulation tissue cone in to clear away the debris and begin the
the process of healing.
Weeks Scarring occurs. Myocardial cells cannot regenerate

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Learning objectives in Cardiovascular disease

What are the complications of myocardial infarction?

The complications of myocardial infarction are many. They may be divided into early
and late (occurring in the days or weeks following the infarct)
Early
* Cardiogenic shock
* Arryhtmias (asystole, ventricular fibrillation etc.)
Late
* Further episodes of arryhtmias
* Left ventricular failure
* Rupture of muscle (depends on where the rupture occurs)
o Rupture of free wall of ventricle leads to haemopericardium and cardiac
tamonade.
o Rupture of the intraventricular septum leads to a ventricular septal defect.
o Rupture of papillary muscle leads to valvular incompetence
* Mural thrombosis
* Dilatation of scarred myocardium leading to a ventricular aneurysm
* Dressler’s syndrome. This occurs in a proportion of patients 2-10 months after the
infarct and is characterized by pericarditis and a raised ESR.
* Recurrent myocardial infarction.

Review Starling’s curves.

Starling’s curves describe the adaptive changes in the myocardial cells in response to a
change in the workload expected on it.

The greater the pre-load (end-diastolic volume), the greater the force of contraction of the
cardiac myocyte. This allows all the blood to be expelled and the end-systolic volume to
approach zero. The capacity of the myocyte to increase contraction is finite and
eventually this system fails.

In healthy individuals, it takes along time before ‘decompensation’ occurs but in patients
with heart disease, this point is reached early and they suffer heart failure.

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Learning objectives in Cardiovascular disease

What are the causes of left heart failure? What are the clinical features?

* Ischaemic heart disease

* Valvular heart disease (mitral stenosis, aortic stenosis etc.)
* Hypertension with left ventricular hypertrophy
* Myocarditis
* Cardiomyopathy

The clinical features of left heart failure are due to engorgment of the pulmonary
capillary bed and impairment of drainage of the pulmonary veins into the left atrium.
Fetaures include dyspneoa, orthopnoea, paroxysmal nocturnal dyspnoea, haemoptysis.
Examination of the chest reveals pulmonary oedema.

What are the causes of right heart failure? What are the clinical features?

* Cor pulmonale
* Secondary to left ventricular failure (congestive cardiac failue)
* Due to right-side valve disease (e.g tricuspid regurgitation or pulmonary stenosis)

Clinical features include dyspnoea, raised jugular venous pressure, ankle oedema and
hepatomegaly. Patients may also have dyspeptic symptoms due to congestion of the veins
of the stomach.

What is cor pulmonale?

Cor pulmonale is failure of the right ventricle which occurs secondary to lung disease.
The lung disease causes pulmonary hypertension with right ventricular hypertrophy and
then failure.

What are the major types of cyanotic and non-cyanotic congenital heart disease?

Cyanotic heart disease is usually associated with right to left shunts. The major type of
cyanotic congenital heart disease is Fallot’s tetralogy. It comprises:
· VSD
· Over-riding aorta
· Pulmonary stenosis
· Right ventricular hypertrophy.

Non-cyanotic heart disease is usually associated with left to right shunts. Examples
include:
· Ventricular septal defect (VSD)
· Atrial septal defect (ASD)
· Patent ductus arteriosus (PDA
· Aortic coarctation

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Learning objectives in Cardiovascular disease

What is Eisenmenger’s syndrome?

This describes the onset of cyanosis in patients with congenital heart disease which are
characterized by left to right shunts initially. The right to left shunt causes pulmonary
hypertension and this eventually results in a reversal of the shunt with mixing of
unoxygenated blood from the right heart with oxygenated blood from the left heart.
What is rheumatic fever? What is the cause? What are the clinical features? What
are the long-term complications?
Rheumatic fever is an immune disease that follows infection in childhood, usually
streptococcal pharyngitis. Group A ß-haemolytic streptococcus is the principal subgroup
responsible. Certain individuals produce antibodies to antigenic components of the
bacteria; these antibodies cross-react with host cardiac antigens.
All layers of the heart may be involved (myocarditis, pericarditis and valvulitis).
The diagnosis is made by examining clinical and laboratory criteria (Jones’ criteria).
Clinical criteria include skin rash, arthralgia, carditis and chorea. Laboratory criteria
include positive culture for Group A ß-haemolytic streptococcus, positive ASO titre and
a raised ESR
The key microscopic feature is the Aschoff nodule which is an area of degenrate collagen
surrounded by macrophages. These macrophages secrete fibroblastic factors which cause
scarring.
The principal long-term complication of rheumatic fever is scarring of the cardiac valves
(rheumatic valve disease). The mitral valve is most commonly involved and mixed
stenosis-incompetence commonly results.
What are the risk factors for infective endocarditis?

* Pre-existing abnormality of the valves

o Congenital abnormality such as bicuspid aortic valve.
o Rhuematic valve disease
o Prosthetic valves

* Bacteraemia
o After instrumentations such as cystocopy or dental procedures

* Immunodeficiency

A combination of these risk factors may be present in any individual patient.

Identification of at-risk individuals (i.e. with pre-existing valve abnormalities) should be
given prophylactic antibiotics if undergoing dental surgery etc.

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Learning objectives in Cardiovascular disease

What are the differences between the subacute and the acute form of this disease?

Acute endocarditis is usually due to a virulent organism such as staphylococcus aureus.

The disease is rapidly progressive with valve destruction and death is frequent. Acute
endocarditis frequently arises on normal valves and is seen in intravenous drug users (in
whom involvement of right sided valves may be seen).

Subacute endocarditis is the commonest type and occurs on structurally abnormal valves.
The organsisms are usually of low virulence (e.g. Streptococcus viridans). Valve
destruction occurs more slowly and there is time for the development of other
complications:
· Embolism of valvular vegetations
· Para-immune phenomena caused by the formation of immune complexes which are
trapped within blood vessels. These may result in splinter haemorrhages and
glomerulonephritis.
· Cytokine release leads to fever, malaise and anaemia etc. Splenomegaly may also
be seen.

Vegetation seen in infective endocarditis are made up of fibrin, platelets and bacterial
colonies.

Name the other conditions which give rise to vegetations on valves

All these examples are characterized by sterile vegetations

* Libmann-Sacks endocarditis seen in SLE
* Marantic endocarditis seen in patients with disseminated cancer or in
hypercoagulable states
* Rheumatic vegetations seen in acute rheumatic fever.

What is myocarditis? What are common causes?

Myocarditis is a rare disease in which diffuse inflammation of the myocardium occurs. It

may result in arrythmias, heart failure or a dilated cardiomyopathy.

It may be seen after a viral infection (such as influenza and Coxsackie viruses) or after
exposure to toxins such as diphteria.

Immune myocarditis is part of rheumatic fever. Iatrogenic myocarditis is seen as part of

the rejection process after cardiac transplantation.

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Learning objectives in Cardiovascular disease

What is a cardiomyopathy? Name the different types and causes?

Cardiomyopathy are diseases which primarily affect the heart muscle.

There are 3 main categories
* Dilated cardiomyopathy which produces a flabby and poorly contractile heart.
Commonly seen after myocarditis or after treatment with certain drigs such as
adriamycin.
* Restrictive cardiomyopathy in which the heart becomes stiffen and can neither fill
properly of contract properly. Examples include haemochromatosis, amyloid and
subendocardial fibroelastosis.
* Hypertrophic cardiomyopathy which is characterized by excessive thickening of the
heart. Examples include HOCM.

What is HOCM? What is the genetics of the disorder? What are the clinical
features?

HOCM stands for hypertrophic cardiomyopathy. It is an important causes of sudden

death in young people. The ventricular walls are massively thickened and the
interventricular septum is often excessively thickened. Microscopically, the myocytes are
arranged in a haphazard manner (myofibre disarray) and fibrous tissue is increased.

Many cases of HOCM have a family history with an autosomal dominant pattern of
inheritance. Relatives of an affected member should be screened with echocardiography
and genetic testing if available. The main genetic mutation appears to be in the gene
coding for the heavy chain of the myosin molecule.

The thickened interventricular septum may obstruct outflow throught he aortic valve and
patients may present with episodes of syncope or heart failure or sudden death.

The abnormal arrangement of the myocytes and the fibrosis predispose to arryhtmias.

What is pericarditis? Name some causes. What are the clinical features?

Pericarditis is inflammation of the pericardium which are meothelial lined tissues which
line the heart (visceral pericardium) and which make up the pericardial sac (parietal
pericardium). Pericarditis often produces a pericardial effusion.

The commonest causes are:

· After a myocardial infarction · Uraemic (seen in chronic renal
· After a viral illness failure)
· Post-operatively · Bacterial and tuberculous
pericarditis
Most cases of pericarditis are asymptomatic or produce only mild symptoms. Patients
may be dyspnoeic and show evidence of the causative disease (e.g. infection, MI).
Auscultation of the chest reveals a pericardial friction rub. If an effusion develops, the
rub often disappears.

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Learning objectives in Cardiovascular disease

What is the clinical significance of a pericardial effusion?

Pericardial effusions are most commonly due to pericarditis. A bloody effusion may be
due to rupture of the ventricular wall after a myocardial infarct.

Since the pericardial cavity is an enclosed space, fluid that enters has no direct way of
escaping (it will eventually resorb). If large amounts of fluid accumulate, it may
compress the heart and impair the pumping capacity of the heart. This is known as
cardiac tamponade and must be treated by drainage.

Define an aneurysm

An aneurysm is an abnormal focal dilatation of an artery. It may be saccular or fusiform

in shape.

It should be distinguished from a pseudoaneurysm in which the wall of tha aneurysm is

not made up of arterial wall e.g. after a knife wound to an artery a pseudoaneurysm made
up of extravascular haematoma develops.

List the causes of aneurysm formation. Name the commonly involved sites

* Atherosclerotic anueryms in the abdominal aorta. This is a common type and if it

becomes very large is at risk of rupture.
* Berry aneurysm in the arteries of the circle of Willis. These are due to congenital
defects in the elastic lamina. They predispose to subarachnoid haemorrhage.
* Syphilitic aneurysm in the aortic arch. These are due to inflammatory destruction of
the media and occlusion of the vasa vasorum.
* ‘Dissecting aneurysm’ in the thoracic aorta in which a split occurs between the inner
2/3 and outer 1/3 of the aorta and blood enters. The blood may track forward to involve
the aortic arch vessels or backwards to involve the coronary arteries of pericardium.
Predisposed to be hypertension and degenerative changes in the media (Marfan’s
syndrome, Ehler_Danlos syndrome).
* Mycotic or infective aneurysm. Destrustion of wall by bacteria in an infected
thrombus or embolus. Seen in the aortic arch after infective endocarditis

What is a varix?

A varix is an abnormal dilatation of a vein. It usually is more extensive than an aneurysm.

The most common predisposing factors are venous obstruction e.g. the post-phlebitic
limb and insufficiency of the valves within the veins.

Examples of varices are varicose veins, haemorrhoids, varicocoele in the scrotum and
oesophageal varices (seen in portal hypertension).

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Learning objectives in Cardiovascular disease

What is vasculitis? Give some examples

Vasculitis is inflammation and destruction of blood vessels. It may affect any group of
vessels (venules, capillaries, arteries etc.).
There are 3 main groups of vasculitides:-
· Hypersensitivity vasculitis which is most commonly caused by a drug reaction and
causes a skin rash. Henoch-Schonlein purpura is another example.
· As part of a multiorgan auto-immune disease such as SLE or rheumatoid disease.
· Systemic vasculitides in which vessel involvement is the predominant problem e.g.
polyarteritis nodosa.
Here is a list of common vasculitides
* Hypersensitivity
* Polyarteritis nodosa
* Wegener’s granulomatosis
* Churg-Strauss syndrome (asthma, eosinophilic infiltrate)
* Kawasaki’s disease
* Takayasu’s disease (aortic arch and branches)
* Buerger’s disease (lower limb vessels, smokers)
* Connective tissue disease such as SLE.
Know something about:- temporal arteritis, polyarteritis nodosa, Wegener’s and
Henoch-Schonlein purpura)
Temporal arteritis
* aka. giant cell arteritis, cranial arteritis
* common in the elderly
* presents with headache and tenderness of the temporal scalp.
* ESR raised above 100 mm/hr
* Needs urgent treatment with steroids to offset risk of central retinal artery occlusion
and blindness
* Rarely affects extracranial arteries and may be associated with polymyalgia
rheumatica.
* Granulomatous and giant cell destruction of the elastic lamina
Polyarteritis nodosa
* Systemic disease which involves small to medium sized arteries.
* Severe disease with a significant mortality
* Involvement of kidney, gut, heart and brain common
* There is an association with chronic hepatitis B infection
Wegener’s granulomatosis
* Acute inflammation and granulomatous inflammation
* Nasal, lung and renal involvement
Henoch-Schonlein purpura
* The inflammation is neutrophilic with fragments of nuclear dust (leucocytoclastic
vasculitis)
* Involvement of skin, kidney, alimentary tract and joints seen.

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Learning objectives in Cardiovascular disease

What is systemic hypertension?

Elevated systemic blood pressure. There are varying degrees (mild, moderate etc.). The
minimum diagnostic level is 90mmHg diastolic pressure.

Malignant hypertension may occur de-novo but more commonly occurs on a background
of benign hypertension (accelerated phase). It must be recognized and treated as the
morbidity and mortality associated is high.

Classify hypertension with regard to aetiology.

There are 2 types of hypertension with regard to aetiology:-

1. Primary (essential) hypertension is the commonest (90%). The exact cause is

unknown but probably involves an interplay between genetic factors and environmental
factors such as salt intake.
2. Secondary hypertension is due to an identifiable cause, most commonly renal disease
with imbalance of the renin-angiotensin-aldosterone system. Causes include:
* Renal artery stenosis
* Chronic glomerulonephritis and pyelonephritis
* Phaeochromocytoma
* Coarctation of the aorta
* Hyperthyroidism
* Adrenal disease such as Cushing’s and Conn’ syndromes
* Paraneoplastic e.g. renin production by renal cell carcinoma

Know the complications of hypertension.

The major consequences of hypertension are on 4 main organs:

* Heart – left ventricular hypertrophy and hypertensive heart disease
* Brain – intracerebral haemorrhage from Charcot-Bouchard aneurysms
* Kidney – nephrosclerosis and chronic renal failure
* Arteries – atherosclerosis and aneurysm formation. Aorta, coronary and retinal
arteries are importantly involved

Compare the microscopy of benign and malignant (accelerated) hypertension.

Benign hypertension

* Thickening of the muscular media

* Hyaline arteriosclerosis

Malignant hypertension

* Fibrinoid necrosis
* Fibrointimal proliferation

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