Cardiac Myocytes Part 3 25 - University of Sheffield



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%

← ASD 10-15%

← 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

1. systemic hypertension

2. cigarette smoking

3. diabetes mellitus

4. 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

o Subendocardial/patchy infarction

o 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.

Secondary dilated cardiomyopathy

Causes – alcohol, increasing prevalence. Male bias.

Cobalt toxicity

Catecholamines- these are usually derived from exogenous sources, but occasionally pheochromocytoma/paraganglioma.

Micro-infarction ?

Anthracyclines. - Dose dependant toxicity. 550 mg/m2.

Cyclophosphomide

Cocaine

Pregnancy. This may affect up to 1% of females, with an Afro-Caribbean bias. Many recover spontaneously, but one can be left with permanently damaged and dilated heart.

Hypertrophic cardiomyopathy (HCM)

Many mutations recognised involving β-myosin, myosin binding protein C, troponin T, titin etc.

Proposed mechanism is that HCM is related to defects in force degeneration/ energy usage allowing progressive sarcomeric dysfunction.

Compensatory hypertrophy often occurs.

Some mutations are associated with clinical features

← β-myosin = cardiac hypertrophic and dysrhythmia

← troponin T = risk of sudden death

Asymmetric hypertrophy with distortion of a papillary architecture.

Increased fibrosis in tissues.

Ventricular outflow distortion.

Myocyte disarray.

Variation in small artery substructure.

Many patients have positive family history with cardiac failure and sudden death.

Some present with classic ischaemic heart disease symptoms.

Investigations show high ejection fraction although many apparently are normal. Investigations include echocardiography and other imaging modalities together with investigation of genetics and family history.

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

A degenerative condition with progressive dilatation of the right ventricle with fibrosis, lymphoid infiltrate and fatty tissue replacement.

Particularly common in parts of Italy

? 1% of sudden deaths in UK.

Restrictive cardiomyopathy

This is a group of diseases in which poor dilation of the heart restricts the eventual ability of the heart to take on blood and pass it to the rest of the body.

Amyloid. This can either be amyloid related to the heart (cardiac amyloid) or part of a systemic disorder (amyloidosis AL, AA).

Firm enlarged and heavy heart with diffuse infiltration of the protein into the mycyctes, blood vessels and valves.

Progressive deterioration with right and left side failure.

Classic low voltage ECG.

Endomyocardial disease

= endomyocardial fibrosis, particularly in African settings and Löeffler endocarditis.

This is a temporate region disorder with high grade eosinophilia , rash and progress endocarditis leading to cardiac failure.

Characteristically grey-white layer of fibrous tissue extending of the endocardial surfaces of the ventricular cavities.

Stiff and poorly compliant ventricle.

Storage disease

← Glycogen storage disease – type II, III & IV

← Mucopolysaccharosis-glycosaminoglycans deposition in cells – Hurler syndrome

← Sphingolipidoses – Fabry disease

← Haemochromatosis – multiorgan dysfunction with excess iron deposition in multiple tissues.

Sarcoid. A chronic granulomatous disease with numerous granulomas of non-caseating giant cell type. May involve the heart producing widespread areas of fibrosis and compensatory hypertrophy. It can produce a restrictive disorder. If it involves the conduction system then this may be the prime pathology of the patients with the risk of sudden death.

Channelopathies. Gating currents for Na, K

with association to long QT syndrome, Brugada syndrome etc.

Cardiac myxoma

At least 75% of cardiac tumours with bias towards atria.

Rather jelly like proliferation of myxoid cells with abundant endothelial vascular channels.

Usually produces obstructive symptoms but risk of embolisation.

Rhabdomyoma – paediatric tumour with similarity to fetal cardiac cells

probably a hamartoma

Cardiac sarcomas. These are rare and can show differentiation towards vascular, fibrous and muscle phenotypes. Almost invariably fatal.

Metastatic disease.

Relatively rare clinically, but if adequately sampled at autopsy then tumours of lung, breast, gastro-intestinal tract, melanoma and lymphomas can be found quite regularly.

Pericardial disease.

Serious pericardial effusion – low protein content with few cellular elements.

Sero-sanguinous effusion – following trauma, surgery or resuscitation.

Haemopericardium – direct bleeding from vasculature wall through the ventricular wall following MI

Cardiac tamponade – compression of the heart leading to acute cardiac failure following bleeding in to the pericardial space.

Acute pericarditis – often follows viral infection with acute/chronic inflammation of the pericardial surface.

Variably fibrinous, purulent or haemorrhagic.

Can if severe progress to fibrosis and a restrictive process.

NB. Uremia can produce fibrinous pericarditis.

NB. Bacterial infection – purulent pericarditis.

Blood vessels

← Surfaced by endothelial cells that maintain vascular integrity.

← Adhesion to self.

← Adhesion to underlying strata.

← Leukocyte adhesion molecules. (PSGL-1, VCAM-1, ICAM-1, VLA-4, LFA-1)

← Production of vaso active factors (NO, ET1)

← Production of prostocyclin and adenine metabolites

← Production of factor VIIIa

← Production thrombomodulin

← Production tissue plasminogen activator and urokanase-like factor

← Production of tissue factor, plasminogen activator/inhibitor and factor V

← Production of interleukin-1

← Receptors for factor IX and X and low density life of proteins. Growth factor – heparin

Elastic arteries – two elastic laminae.

Tunica interna, tunica media, tunica adventitia

Vasa vasorum.

Muscular arteries have media with smooth muscle.

Arterioles Endothelial lining with one or two layers of muscle cells but no elastic tissues.

Capillaries – drain to venules – veins (one elastic lamina) no muscle

Gas, fluid and nutrients/waste product exchange at capillary level.

Blood coagulation occurs when fibrinogen is converted to fibrin.

Balance between coagulation and anti-coagulation.

← Otherwise we would completely clot!

Injury activates platelets and increases their adhesiveness to each other and tissue components.

Clot lysis involves plasminogen being converted to plasmin which then acts on fibrin to produce fibrin degredation products (FDP’s). The process can be inhibited by both plasminogen activator inhibitors and alpha-2 antiplasmin.

Atheroma and atherosclerosis

A degenerative condition of arteries characterised often by a fibrous and lipid rich plaque with variable inflammation, calcification and a tendency to thrombosis.

Associated with ischaemic heart disease, myocardial infarction, stroke, peripheral vascular disease etc.

Theories

← Insudation. This held the view that lipid derived from plasma lipoproteins (+)

← Encrustation. In effect the material derived from blood products (platelets etc) (–)

← Injury. Injury drives local cell proliferation as part of the recovery process with proliferation of endothelial cells, macrophages and smooth muscle cells. Evidence of PDGF and other mitogens (+).

← Monoclonal hypothesis. Local tumour proliferation as smooth muscles usually monoclonal. (–)

Unifying hypothesis.

Initiation. Endothelial dysfunction and injury around sites of sheer and damage with subsequent lipid accumulation at sites of impaired endothelial barrier.

Local cellular proliferation and incorporation of oxidised lipoproteins occurs.

Mural thrombi on surface with subsequent healing and repeat of cycle.

Adaptation. As plaque progresses to 50% of vascular lumen size the vessel can no longer compensate by re-modelling and becomes narrowed. This drives variable cell turnover within the plaque with new matrix surfaces and degradation of matrix. May progress to unstable plaque.

Clinical stage. The plaque continues to encroach upon the lumen and runs the risk of haemorrhage of exposure of tissue HLA-DR antigens which may stimulate T cell accumulation. This drives an inflammatory reaction against part of the plaque contents. Complications develop including ulceration, fissuring, calcification and aneurysm change.

Pathological stages

← Fatty streak. These show macrophages filled with abundant lipid but also smooth muscle cells with fat.

← Intimal cell mass. These are collections of muscle cells and connective tissue without lipid – “cushions”.

← The atheromatous plaque

Characterised by distorted endothelial surface containing lymphocytes, macrophages, smooth muscle cells and a varibly complete endothelial surface. There is local necrotic and fatty matter with scattered lipid rich macrophages. Evidence of local haemorrhage may be seen with iron deposition and calcification.

Complicated plaques = Calcification, mural thrombus, vulnerable plaque

Complications of plaque rupture

➢ Acute occlusion due to thrombus

➢ Chronic narrowing of vessel lumen with healing of the local thrombus

➢ Aneurysm change

➢ Embolism of thrombus +/- plaque lipid content

Risk factors

Hypertension

Serum cholesterol level

Tobacco smoking

Diabetes

Increasing age

Male > female

Inactive and stressful life patterns

Homocysteine level

CRP

(? Infection – Chlamydia, Helicobacter, Herpes )

Hypertensive vascular disease

Approximately 20-25% of the population will suffer from this.

Racial bias – Afro-Caribbean

Increased risk of aortic aneurysm, stroke, myocardial infarction/rupture

Essential hypertension.

Altered renin-angiotensin system elevates blood pressure by impairing sympathetic output increasing mineralocorticoid secretion and direct vaso-constriction.

It is balanced by atrial natriuretic factor.

In effect the changes to auto-regulation produce an increase in peripheral resistance, that in normality would allow increased blood pressure, diuresis and restoration of normal pressure and volume.

Hypertension, irrespective of the cause, alters blood vessel walls whereby the lumen size is decreased as the wall thickness increases.

Since resistance ~ 1/(4

=> a progressive increase in vascular resistance in hypertensives.

Acquired causes of hypertension

Chronic vascular disease – diabetes, primary elevation of aldosterone, Cushing syndrome, pheochromocytoma, hyperthyroidism, coarctation of the aorta and rennin secreting tumours.

Exogenous (drugs) agents may also be relevant.

Arteriosclerosis.

Hyaline arterosclerosis shows a deposition of basement membrane-like material and accumulation of plasma proteins within the vessel wall.

May reflect ageing but it is accelerated in diabetic and hypertensive individuals.

Malignant or accelerated hypertension

>160/110 mmHg

Fibrinoid necrosis of the vessel with local inflammation and focal smooth muscle cell proliferation.

Other artery disorders

← Mönckeberg medial sclerosis – degenerative calcification of large and medium sized arteries. Usually clinically of no significance.

← Raynaud’s phenomenon. Intermittent bilateral ischaemia of digits/extremities precipitated by motional cold temperature. Accelerated in cases of scleroderma and SLE. May produce distal atrophy and ulceration.

← Fibromuscular dysplasia. = Abnormal architecture for the arteries producing variable lumen narrowing and distal poverty of circulation. Particular importance in the renal arteries which produce renal vascular insufficiency and progressive hypertension due to renin-angiotensin stimulation.

Vasculitis

An inflammatory and variably necrotic process centred on the blood vessels that may involve arteries, veins or capillaries.

Immune background

➢ Deposition of immune complexes

➢ Direct attack on vessels by antibodies

➢ Cell mediated immunity

➢ Viral infection

➢ Serum sickness = model

Viral antigens can be found in human vasculitis cases.

– HSV, CMV, Parvovirus

Small vessel vasculitis is associated with anti-neutrophil cytoplasmic antibodies (ANCA) (perinuclear pANCA, cytoplasmic cANCA).

p ANCA ~ myeloperoxidase

c ANCA ~ proteinase 3

Polyarteritis nodosa (PAN) affects medium and small muscular arteries

Male>female

Patchy necrotising arteritis with neutrophils, lymphocytes, plasma cells and macrophages. p ANCA+

May thrombose and have distal infarction, or heal with subsequent aneurysms.

May involve widespread damage to kidneys, cerebrocirculation, cardiac tissue.

Without treatment may prove rapidly fatal.

Hypersensitivity angiitis

Leucocytoclastic vasculitis, cutaneous vasculitis, cutaneous necrotising venulitis, systemic hypersensitive angiitis/microscopic polyarteritis

Affects the smallest arteries and arterioles

Precipitants = drugs (aspirin, penicillin, etc)

Infections (streptococci/staphylococci/viral hepatitis, TB, bacterial endocarditis)

c/o Palpable purpura

Microscopically fibrinoid necrosis and inflammation around small vessels.

May also be a feature of collagen vascular disease (lupus/rheumatoid/Sjogren syndrome), Henoch-Schoenlein purpura, dysproteinaemia

Some cases reflect neoplasia.

60% p ANCA, 40% c ANCA

Churg-Strauss syndrome

Allergic granulomatosis and angiitis

Strong association with asthma

Two thirds positive c/p ANCA

Necrotising lesions of small medium arteries, arterioles and veins affecting lungs/spleen/kidney/heart/liver/CAN etc.

Granulomatous inflammation with intense eosinophilic infiltrates.

Variable fibrinoid necrosis and thrombosis may progress to aneurysm change.

Use to have poor prognosis but steroids have improved disease.

Giant cell arteritis

(temporal arteritis/granulomatous arteritis)

Commonest type of vasculitis.

Focal, chronic and granulomatous inflammation of temporal arteries mostly.

Association with polymyalgia rheumatica.

Can involve large arteries (aortic aneurysm/dissection).

Average age 70+. Female bias.

Genetic background with familial history sometimes.

➢ Thickened blood vessel, often palpable.

➢ Granulomatous inflammation involving the full thickness of the wall with macrophages, lymphocytes, plasma cells, neutrophils and occasionally eosinophils.

➢ Giant cells tend to congregate around IEL. Variable necrosis.

➢ Old areas of inflammation show up as focal scars with fragmentation of elastic laminae. Thrombosis may occur.

Tends to be benign and self limited but if affects the ocular artery will result in blindness.

Can affect systemic arteries elsewhere with atypical presentation.

Wegener’s granulomatosis

This is a vasculitis of the respiratory tract and kidney.

It has a male bias, principally around the fifth-sixth decades.

90% ANCA positive, mainly c ANCA.

Parenchymal necrosis, vasculitis and granulomatous inflammation with neutrophils, lymphocytes, plasma cell, macrophages and eosinophils.

May involve the small arteries and veins.

Particularly affects the respiratory tract, kidney and spleen.

Lungs = bilaterial pneumonitis with nodular infiltrates that undergo cavitation.

Mimic TB. Chronic sinusitis and ulcers of the nasal tissues are common.

Kidney = focal necrotising glomerulonephritis which progresses to cresentric glomerulonephritis.

Rather protean symptoms initially with pneumonitis/sinusitis.

Haematuria and proteinuria are common.

May have skin rash, joint pains and neurological changes.

Takayasu’s arteritis/aortitis

mainly female (90%) classically involves artery of aorta. Asian bias.

Kawasaki disease

Mucocutaneous lymph node syndrome

Arteritis principally affecting the coronary arteries.

May progress to death due to thrombosis with acute myocardial infarction.

Associated with Parvovirus B19 and Coronavirus.

Also some cases with staphylococci, streptococci and Chlamydial infection.

Generation of antigens that bind to the MHC class II receptors.

Buerger disease.

An inflammatory disease of medium and small arteries affecting the distal limbs.

Strong association with tobacco smoking.

Cell mediated hypersensitivity to collagen II and III with impaired endothelium – dependant vasodilatation function.

Neutrophilic infiltrate involving the vessels with subsequent thrombosis and micro- abscess change.

Distal ischaemic symptoms and necrosis.

Smoking cessation may lead to remission.

Aneurysms.

These are dilated areas of vasculature suggesting either congenital or required weakness of the wall of the vessels. The incidence rises with age and they are common findings at autopsy and investigations for other pathology.

Described as fusiform, saccular, dissecting and arterio-venous.

Abdominal aortic aneurysm.

>50% dilatation of aortic diameter

prevalence rises with age

strong association with atheromatous disease

familial clustering suggests a genetic component

local inflammatory changes can be profound and involve ureters and local nerves.

Majority below renal arteries.

Vascular thrombosis (lines of Zahn)

Clinically abdominal dilatation is initially silent.

Fragmentation of the lumenal thrombus leads to distal embolisation and ischaemic damage.

Major problem is the risk of aneurysm rupture.

Those greater than 5-6 cm diameter increased risk.

Prophylactic replacement with Dacron graft or endolumenal prosthesis carries a lower morbidity/mortality risk than waiting for point of rupture.

Berry aneurysm this rounded berry-like vascular dilatation is particularly common in the cerebral circulation.

~ consequence of longstanding hypertension and/or focal area of weakness within the arterial substructure.

Particularly ~ Circle of Willis. >>> Subarachnoid haemorrhage >>> sudden death.

Dissecting aneurysm.

This is a haematoma within the arterial wall with blood entering under pressure from the lumenal surface and dissecting along the length of the media.

Often h/o hypertension

?? cystic medial degeneration (Erdheim = age-related)

? Marfan’s syndrome and other connective tissue disorders.

Majority occur just above aortic ring

← prunes of the large arteries supplying the head

← may rupture into local soft tissues, may rupture into pericardium.

Double-barrelled aorta if blood re-enters circulation.

Syphilis – inflammatory disease affecting the vasa vasorum. May produce degeneration of the media and subsequent aneurismal change.

Wrinkled bark intima ~ ascending aorta.

Varicose veins.

A varicose vein is an enlarged and torturous vein, principally affecting the superficial leg veins.

Risk factors – age, female (pregnancy related), hereditary, posture, obesity

Progressive incompetence of valves with further back pressure on venous circuit.

Thinning and dilatation of vascular wall in places with patchy calcification.

May produce stasis dermatitis with trophic changes to the skin.

nb. Other varicose veins – haemorrhoids, oesophageal varices, varicocele

Lymphatic vessel obstruction

Elephantiasis – filiarsis.

Infestation of the lymph nodes and lymphatic vasculature by tropical parasites.

Tumour obstruction

Surgical clearance (particularly breast surgery).

Inherited lymphoedema – Milroy disease

Vascular tumours.

Haemangioma.

This is a benign proliferation of blood vessel tissue, which varies in name and substructure depending on the site and age of the patient.

➢ Capillary haemangioma – birth marks, ruby spots

➢ Juvenile haemangioma – strawberry haemangioma

➢ Cavernous haemangioma – port wine stains

Glomus tumour.

A benign neoplasm involving the glomus body

Composed of vascular channels with proliferation of the glomus cells (neuromyoarterial receptors) mainly affect the hands.

Painful!

Haemangioendothelioma

A vascular tumour of endothelial cells of low grade malignancy.

May metastasise to other sites around the body.

Angiosarcoma.

This is a highly aggressive malignant neoplasm of endothelial cells.

Commonly skin, soft tissue, breast, bone, live and spleen.

Rapidly enlarging haemorrhagic tumour with rapid dissemination to other organs.

Environmental carcinogens – arsenic and vinyl chloride.

Kaposi’s sarcoma

Linked to HIV disease and AIDS

Associated with human herpes virus 8 (HHV8)

Painful purple/brown nodule between 1 and 10 mm diameter.

Often on the skin. May progress and disseminate.

Deep vein thrombosis.

Risk factors –

➢ Venous flow stasis from any cause (eg. cardiac failure, chronic venous insufficiency, post operative immobilisation, prolonged bed rest)

➢ Injury (trauma, surgery, child birth)

➢ Hypercoaguability (OCP), pregnancy, cancer, inherited thrombophilic disorders)

➢ Advanced age

➢ Sickle cell disease

It is not clear what the true prevalence of deep vein thrombosis actually is within general population or hospital population.

However, a variety of features may occur following formation

← Lysis

← Organisation

← Provocation

← Embolisation

Painful/tender calves may reflect deep vein thrombosis (Homan sign).

Treatment = anticoagulants. +/- ? Filter

Embolism

= the passage of material through the venous or arterial circulations.

Commonest process is thrombo-embolus from a deep vein thrombosis.

Post operative deep vein thrombosis occurs often following surgery or immobilisation following illness.

They are commonly found to embolise in patients beyond the age of 40 years.

May be asymptomatic and small.

May produce transient dyspnoea for relatively small emboli.

May produce focal pulmonary infarction with chest pain, haemoptysis and secondary effusion.

Can produce cardiovascular collapse and sudden death (saddle embolus).

Paradoxical embolism – embolus that travels through the venous circuit then across from the right to the left side of the heart through a patent foramen ovale.

Systemic arterial embolism usually causes infarction of the tissue as the material impacts in the nutrients/oxygen supplying vasculature.

Sources

← Atherosclerotic plaques, mural thrombus in heart or vasculature

← Infective endocarditis

← Sites particularly vulnerable – brain, intestine, distal limbs, kidneys and coronary circulation

Other types of embolism –

← Air embolism

← Acute decompression sickness

← Amniotic fluid embolism

← Fat embolism

← Bone marrow embolism

← Talc/cotton/other material from intravascular injection.

The end !

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download