Cardiovascular pathology
Kim Suvarna
Please note 2 legal issues:
For copyright reasons, I cannot post scanned book images onto the web. The images are derived from Underwood/ Robbins textbooks mainly, although several are previous edition versions. Please use these books if you need pictures.
Also, please note, the images I take from autopsies cannot legally be put onto the web (if they are to be copied) based on the permissions from relatives/ HM Coroner to use them for teaching.
Heart
Normal weight 280-340 g male, 230-280 g female
Two sides, right thinner than left
Two stage electrical generated contraction
Sarcomere proteins
Contraction initiated by depolarisation and changes to calcium concentration
Protein conformational change – contraction
Removal of calcium (energy dependent) for relaxation to occur
Two types of cardiac myocytes
Atrio-ventricular conduction system – slightly faster conduction
General cardiac myocyte
All cells can act as pacemaker
Normal cardiac conduction
Normal coronary circulation
Blood flow through myocardium from aortic root is diastolic
Myocardial hypertrophy and heart failure
Normal systolic ejection fraction 60-65%
Failure to transport blood out of heart = cardiac failure
Cardiogenic shock = severe failure
Frank–Starling mechanism and pericardial sac limitations
Cardiac/volume increases as venous return increases
If you exceed stretch capability of sarcomeres then cardiac contraction force diminishes
Myocardial hypertrophy can be an adaptive/ physiological response ~ athletes/pregnancy
Hypertrophic response triggered by angiotensin 2, ET-1 and insulin-like growth factor 1, TGF-β > These activate mitogen-activated protein kinase
Poor adrenergic sensitisation in cardiac failure
Some loss of cardiac myocytes during life is expected
but significant loss will impair cardiac contraction.
Some evidence for stem cells and cardiac regeneration occurring
but this is usually trivial in terms of effectiveness.
Left sided cardiac failure – pulmonary congestion and then overload of right side.
Right sided cardiac failure with venous hypertension and congestion.
Diastolic cardiac failure ~ Stiffer heart
Hibernating myocardium vacuolated cardiac myocytes following injury (usually hypoxic), may enhance myocyte survival, but poor contraction
Fetal embryogenesis.
The heart comprises a single chamber until the fifth week of gestation, then divided by intra-ventricular and intra-atrial septa from endocardial cushions. The muscular intra-ventricular septum grows upwards from the apex of the heart producing the four chambers and allowing valve development to occur.
Congenital heart disease
> results from faulty embryonic development
> may complicate up to 1% of all live births.
= misplaced structures or arrest of the progression of normal structure development.
VSD 25-30%
ASD10-15%
PDA 10-20%
Fallots 4-10%
PS 5-7%
Coarctation 5-7%
AS 4-6%
TGA 4-10%
Truncus arteriosis 2%
Tricuspid atresia 1%
Multifactorial inheritance.
One child with defect increases probability of second child with another defect.
Single genes associated = trisomy 21 (Downs), Turner Syndrome (XO) and di-George Syndrome.
Homeobox genes particularly associated
Infections – Rubella
Drugs – Thalidomide, alcohol, Phenytoin, amphetamines, lithium, eostrogenic steroids
Diabetes also associated with increased risk of congenital heart disease
Classification reflects
- cyanosis, present or absent
- whether this occurs from birth or whether it develops later.
Initial left – right shunt
VSD, ASD, PDA, truncus arteriosus, anonymous pulmonary venous drainage, hypoplastic left heart syndrome
Right – left shunt
Tetralogy of Fallot, tricuspid atresia
No shunt
Complete transposition of great vessels
Coarctation
Pulmonary stenosis
Aortic stenosis
Coronary artery origin from pulmonary artery
Ebstein malformation
Endocaradial fibroelastosis
Size matters!
Small holes and little significance but big ones allow decompensation.
Initial left – right shunting is fine, albeit inefficient, but progression to Eisenmenger’s complex involves right side > left side shunting associated with right side cardiac failure and right side cardiac hypertrophy.
Patent foramen ovale.
Probe patent 17%
Paradoxical emboli DVT > CNS infarction!
Ostium secundum, 90% variable sized opening = central defect in central septum.
Ostium primum type defect in lower part of septum primum
Other types exist.
Eventually produces cardiac arrhythmias, pulmonary hypertension, right ventricular hypertrophy and cardiac failure. Risk of infective endocarditis.
Persistent/ patent ductus arteriosus (PDA), beyond birth, is unusual, since the vessel usually occludes by fibrotic change after vascular spasm as the neonate starts breathing.
The left – right side shunting eventually means the lung circulation is overloaded with pulmonary hypertension and right side cardiac failure subsequently.
Risk of infective endocarditis.
Can be closed surgically, by catheters or by prostaglandin inhibitors (Indomethacin).
Tetralogy of Fallot
Four main features
Pulmonary stenosis
Ventricular septal defect
Dextraposition/over-riding ventricular septal defect
Right ventricle hypertrophy
Characteristic boot-shape on radiology and macroscopically.
Often associated with other cardiac abnormalities.
As a result of the pulmonary stenosis, right ventricle blood is shunted into the left heart producing cyanosis from birth. Surgical correction usually is performed during the first two years of life, as progressive cardiac debility and risk of cerebral thrombosis increases.
Complete transposition of the great arteries (TGA)
This involves the aorta coming off the right ventricle and the pulmonary trunk off the left ventricle.
Male bias, and particular associated with diabetes. Survival is only possible if there is communication between the circuits and virtually all have an atrial septal defect allowing blood mixing.
Treatment = arterial switch with less than 10% overall mortality.
Coarctation of the aorta.
This is secondary to an excessive sclerosing/obliterating process that normally closes the ductus arteriosus, extending into the aortic wall.
The net result is a narrowing of the aorta just after the arch, with excessive blood flow being diverted through the carotid and subclavian vessels into systemic vascular shunts to supply the rest of the body.
Particularly associated with Turner’s syndrome, and with an association with Berry aneurysms of the brain.
Persistence of the posterior shelf.
Discrepant blood pressures in upper and lower part of the body.
Complications of cardiac failure, rupture of dissecting aneurysm, infective endarteritis, cerebral haemorrhage, stenosis of bicuspid aortic valve (associated).
Treatment = ablatation of stenosed segment.
Endocardial fibroelastosis.
Secondary endocardial fibroelastosis = a frequent complication of congenital aortic stenosis and coarctation. Profound dense collagen and elastic tissues deposited on endocardial aspect of the left ventricle produces progressive stiffening of the heart and cardiac failure. Similar changes may affect the valves.
Primary endocardial fibroelastosis, may follow a familial pattern.
Both are relatively rare.
Dextrocardia.
The normal anatomy of the heart is versed with rightward orientation of the access. It can occur without abnormal positioning of the visceral organs but is usually associated with severe cardiovascular abnormalities.
It is more often associated with other organ isomerism.
Ischaemic heart disease
- Angina (standard, Prinzmetal/unstable, accelerated/crescendo)
- Myocardial infarction
- Chronic congestive cardiac failure ~ 75% of these patients with dilated/failing hearts reflect ischaemic heart disease
- Sudden death
Risk factors
- systemic hypertension
- cigarette smoking
- diabetes mellitus
- elevated cholesterol
Also ....obesity, increasing age, male sex, family history, oral contraceptive pill, sedentary life habit, personality features etc
Reasons for imperfect blood supply to the heart
Atherosclerosis
Thrombosis
Thromboemboli
Artery spasm
Collateral blood vessels
Blood pressure/cardiac output/heart rate
Arteritis
Also anaemia, altered oxygen dissociation curve, carbon monoxide, cyanide
Increased demand from hypertension, valvular heart disease, hyperthyroidism, fever, thiamin (B1) deficiency, catecholamine stress....
Healthy individual has coronary reserve 4-8 times of resting blood flow
Coronary arteries have no resistence in practical terms
Constriction/dilation of small intramyocardial branches, < 400 µm diameter.
For relatively limited foci of stenosis up to 75% of cross section coronary artery architecture can be lost without impairment of blood flow.
At 90% limited blood supply during exercise/demand may be significant.
Other conditions that limit coronary flow.
Coronary arteritis
Dissecting aneurysm of aorta
Syphilitic aortitis, congenital abnormality of coronary artery origin
Myocardial bridge
Pattern of infarction
- Subendocardial/patchy infarction
- Transmural infarction
Complications of infarcts differ according to which territory has compromised.
Dating of myocardial infarction
Reperfusion of ischaemic myocardium – followed the development of clot-busting agents and angioplasty techniques. Reperfusion of completely infarcted tissue can produce significant haemorrhage. The reperfusion allows oxygen delivery and a further degree of injury as a result of generation of superoxide radicals etc.
Contraction band necrosis
Pathological complications of ischaemic damage –
Arrhythmias (supraventricular and ventricular)
Left ventricular failure – cardiogenic shock.
Generally reflects >40% muscle damage
Extension of infarction, rupture of the myocardium (into pericardial space, between chambers, across papillary muscle insertion)
Aneurysm.
This is a dilation of part of the myocardial wall, usually associated with fibrosis and atrophy of myocytes.
Variable fatty tissue replacement may also occur.
The dilatation of the thin walled sac allows blood stasis and thrombosis.
Risk of subsequent embolism of such material.
Pericarditis (Dressler syndrome).
This is a delayed pericarditic reaction following infarction (2-10 weeks).
All therapeutic models aim to improve blood supply along the coronary vessels affected, and to restore blood to ischaemic parts of the myocardium.
Thrombolytic enzymes
Percutaneous translumenal coronary angioplasty (PTCA)
Coronary bypass grafting
Other techniques (laser – drill)
Stents
(transplantation)
Chronic ischaemic heart disease.
The effects of established infarcted tissue on overall myocardial function cannot be underestimated.
Progression along cardiac dysrhythmias – progressive cardiac failure/dilatation
Hypertension.
WHO classification >140/90 mm Hg. Hypertensive heart disease – reflects cardiac enlargement due to hypertension, and in the absence of other cause.
Compensatory hypertrophy of the heart initially with increased myocyte size, squaring of the nuclei and slight increase of the interstitial fibrous tissue.
Initially able to handle the increased workload, eventually the hypertrophy no longer compensates.
Falling amount of oxygen delivery to cardiac myocytes produces further fibrosis and progressive contractile dysfunction.
Often associated with coronary atheroma and ischaemic heart disease – aggravating situation.
Particularly associated with fatal intracerebral haemorrhage.
Cor pulmonale.
= Right ventricular hypertrophy and dilatation due to pulmonary hypertension.
May reflect an acute event.
Embolisation of material into the pulmonary circuit, but is more common chronically reflecting a variety of lung disorders.
Chronic bronchitis and emphysema
Pulmonary fibrosis
Cystic fibrosis
Recurrent emboli
Primary pulmonary hypertension
Peripheral pulmonary stenosis
Intravenous drug abuse
High altitude
Schistosomiasis
Abnormal movement of the thoracic cage (Pickwickian syndrome, kyphoscoliosis, neuromuscular disorders etc).
Classically disproportionate right ventricular hypertrophy as compared with the left.
Progressive features of right side cardiac failure with venous overload, peripheral oedema and progressive hepatic congestion.
Acute rheumatic fever
Group A β-haemolytic streptococcus infection
usually upper respiratory tract
Remains a major factor with regard to heart disease in the developing world.
Peak age of pathology 9-11 years, but can occur in adults.
Development of immunity against the streptococcal pharyngitis produces antibodies that cross react with cardiac myocytes and valvular glycoproteins.
This produces localised inflammation and subsequent scarring.
Clinical features include carditis
(cardiomegaly, murmurs, pericarditis and cardiac failure) polyarthritis, chorea, erythema marginatum and subcutaneous nodules.
Minor criteria for diagnosis include
previous history of rheumatic fever, arthralgia, raised CRP, ESR and white cell count.
Antibodies against group A streptococcal antigens, anti-streptolysin O, anti-DNAse B and anti-hyaluronidase.
Symptoms and features diminish after 3-6 months.
Some patients die acutely and are shown to have granulomatous foci of inflammation (Aschoff body, Anitchkov cells and some giant cells). There may be pericarditis and endocarditis.
Chronically scarring and deformity produces contracture of the valve and chordae tendinae. These may subsequently calcify and distort blood flow allowing localised thrombosis. They also provide ideal settling sites for bacteria within the blood stream, and the development of infective endocarditis.
> Progressive cardiac dysfunction as a result of the slowly distorting valvular function.
Other disorders affecting cardiac valves include
SLE, rheumatoid arthritis, ankylosing spondylitis and other connective tissue disorders.
Infective endocarditis.
This is an infective process involving the cardiac valves.
Previously subdivided in to acute and subacute forms, both are characterised by high rates of morbidity and mortality.
Falling rheumatic fever rates have now meant that the commonest cause in children is congenital heart disease.
In adults causes include rheumatic valvular heart, mitral valve prolapse, intravenous drug abuse, prosthetic valves, diabetes, the elderly and pregnancy.
Characteristic organisms include streptococci and staphylococci although fungi and atypical bacteria are also recognised.
Infection produces rapidly increasing cardiac valve distortion and disruption with acute cardiac dysfunction.
Apart from the sudden development of cardiac failure and septic problems there are other consequences including generation of infected thromboemboli and damage to the kidneys (focal segmental glomerulonephritis FSGS).
Protean symptoms
Fever, anorexia, fatigue
Progressive splenomegaly, petechiae, clubbing
Neurological dysfunction due to mitotic emboli and aneurysms
NB Still has 30-40% mortality rate despite antibiotics.
Non-bacterial thrombotic endocarditis/marantic endocarditis
sterile thrombotic matter deposit on valves with variable degrees of valve dysfunction.
Characteristic in neoplastic conditions.
Degenerative valve disease
Calcific aortic stenosis.
May reflect rheumatic aortic valve disease or degenerative processes (senile type).
Accelerated in bicuspid aortic valves.
Associated with coronary artery disease. Classically 65-80 years age.
Nodular calcific deposits in cusps with progressive distortion of valves opening/closure.
Obstruction to left ventricle outflow produces pressure overload and cardiac hypertrophy.
Risk of sudden cardiac death.
Myocardial infarction risk.
Increased propensity for infective endocarditis.
Mitral valve disease
Calcification of the mitral valve annulus is usually asymptomatic and of no significance. It does not usually affect the mobile leaflets.
However, calcification of the valves, following rheumatic valvular disease or previous inflammation/valvitis, is of significance with either mitral stenosis or regurgitant pathology.
Mitral valve prolapse describes degeneration of the mitral valves such that the inner fibrosa layer becomes more loose and fragmentary with accumulation of mucopolysaccharide material.
The valve cusp bow upwards and may not close adequately producing incompetence/regurgitation.
There is an association with sudden cardiac death and a risk of infective endocarditis.
Strong association with underlying connective tissue disorders, and Marfan’s syndrome, myotonic dystrophy and other conditions are known to be associated.
S3 sound on auscultation – caused by the snap of redundant leaflets as they prolapse into the left atria.
~ 6% of female population, but clearly not all have symptoms.
Myocarditis
Reflects inflammation of the myocardium usually associated with muscle cell necrosis and degeneration.
Multiple aetiologies although viral myocarditis is the commonest.
Direct viral toxicity with associated cell mediated immunity aggravating cell damage. Healing with scarring, but high risk of sudden death.
Causes
Viruses – Coxsackie, Adeno-, Echo, Influenza
Rickettsia – typhus
Bacteria –diphtheria, staphylococcal, streptococcal, borrelia, leptospira
Fungi and Protozoa parasites – toxoplasmosis, cryptococcus
Metazoa - echinococcus
Non-infectious causes
Hypersensitivity/immune related diseases – rheumatic fever, SLE, scleroderma, drug reaction, rheumatoid arthritis
Radiation
Miscellaneous – sarcoid, uraemia
Macroscopically dilated with poor muscle movement on specialist investigations.
Acute phase shows predominantly lymphocyte infiltrate cutting throughout the myocardium and destroying muscle fibres.
Healing phase shows patchy fibrosis with no specific features
Symptoms vary from palpitations through to latitude, often in association with an upper respiratory tract infection preceding.
Drug reactions
This often causes an inflammatory infiltrate particularly around blood vessels within the myocardium. There may be a predominance of eosinophils.
Giant cell myocarditis
A very rare highly aggressive form of cardiac disease with areas of muscle cell death due to macrophage giant cells. Often fatal.
Early treatment is transplantation but disease can often recur.
Metabolic diseases
Hyperthryoidism, hypothyroidism
Thiamin deficiency (vitamin B1/thiamin)
Particularly association with poor diet
~ poor vegetable intake, alcoholics and those with self neglect
Cardiomyopathy
Various types ~ primary cardiac disease with contractile dysfunction and atypical morphology
DCM
HCM
ARVC
secondary
rare forms
Dilated cardiomyopathy (DCM)
One third familial, but possibly more
Most autosomal dominant (AD)
but some recessive and X-linked.
(Mitochondrial myopathy also recognised)
Mutations in several genes are recognised –
dystrophin, δ-sarcoglycan, troponin T, β myosin heavy chain, actin, lamin A/C, desmin etc
Theory = poorly generated contractile force leads to progressive dilation of heart with some diffuse interstitial fibrosis.
May also follow a viral myocarditis or an inflammatory myocarditis/toxic myocarditis
Pathologically – enlarged, heavy and dilated heart, possibly cardiac weight up to 900 g.
Histology shows variable atrophy and hypertrophy
increased interstitial tissue
occasional inflammatory cells
Clinical progression slowly deteriorating cardiac failure, dysrrhythmias and ultimately death.