Cardiovascular System: Rheumatic Heart Diseases,

Hypertension& Cardiomyopathy

DR A. O. OLUWASOLA.

Rheumatic heart disease • A sequelae of rheumatic fever, can be acute

or chronic. • Rheumatic fever is an acute immunologically

mediated multi system Inflammatory disease.• It occurs 10 days to 6 weeks after an episode

of groupA (B-hemolytic) streptococcal (pharyngitis) and often involves the heart.

• Diagnosed by Jones Criteria:• Either two of the major manifestations or • One major and two minor manifestations.

Clinical features ctd.

• Evidence of preceding group A• Streptococcal infection (Antistreptolysin-O titre) • Major manifestations include: • Migratory poly-arthritis of the large joints;• Carditis; Subcutaneous nodules; • Erythema marginatum of the skin and; sydenham

chorea- a neurologic disorder with involuntary purposeless rapid movements.

• Minor manifestations• Non specific sign and symptoms which include

fever, Arthralgia or elevated acute phase reactants.

Clinical features ctd.

• Acute rheumatic fever appear most often in children between the ages 5 and 15 years,

• While about 20% of 1st attacks occur in middle to later life.

• Overall the prognosis for the primary attack is generally good and

• Only 1% of patients die from rheumatic fever. • Increased vulnerability to reactivation of the disease

with subsequent pharyngeal infections. • Carditis is likely to worsen with each recurrence and

damage is cumulative.

Pathogenesis

• Acute rheumatic fever is believed to be a hypersensitivity reaction,

• But the exact pathogenesis remains uncertain. • Autoimmune mech. has been proposed• Antibodies directed against the M proteins of certain

strains of streptococci cross-react with tissue glycoproteins in the heart, joints and other tissues.

• The chronic sequelae result from progressive fibrosis of both healing of the acute inflammatory lesion,

• And the turbulence induced by ongoing valvular deformities.

Morphology

• Acute rheumatic heart disease.• Typically occurs as a pancarditis. • Diffuse inflammation and aschoff bodies may be found

in any of the three layers of the heart. • Aschoff bodies are foci of fibrinoid degeneration

surrounded by lymphocytes, • Occasional plasma cells and plump macrophages

called anitschkow cells• pathognomonic for rherumatic fever or caterpillar

cells • + aschoff giant cells - multinucleated cells.

Aschoff body in a patient with acute rheumatic carditis

• Pericardium- fibrinous pericardial exudate

• Bread and butter pericarditis • Generally resolves without sequelae.• Myocardum –• Shows scattered aschoff bodies within

the interstitial connective tissue • often perivascular

Endocardium

• Can be involved along with cardiac valves (usually left sided) in form of fibrinoid necrosis within the cusps and

• Small (1-2mm) irregular vegetations – verrucae – along the lines of closure of the valves.

• Mac callum patch – irregular thickenings due to subendocardial lesions

Acute and chronic rheumatic heart disease

• Clinical features of acute carditis include pericardial friction rubs,

• Weak heart sounds, tachycardia, arrhythmias,

• Cardiac dilatation which may cause functional mitral valve insufficiency or even heart failure.

Chronic rheumatic heart disease

• Characterized by organization of the acute inflammation and subsequent deforming fibrosis and neo-vascularisation.

• 99% of cases of mitral stenosis is due to RHD. Mitral value alone-65 to 70% of the cases.

• Mitral and aortic valve -25% .• -Leaflet thickening and fusion of the tendinous

cords. • Commissural fibrosis + calcification → fish or

button hole stenosis.

Chronic Rheumatic Heart Disease

• Severe mitral stenosis progresses to left atrial hypertrophy and dilatation,

• Mural thrombosis, • Pulmonary congestion,• Pulmonary vascular sclerosis and then right

ventricular hypertrophy. • The left ventricle is normal is isolated pure

mitral stenosis.

• Other complications of chronic RHD include heart failure,

• Arrhythmias particularly AF in case of M.S,• Thrombo embolic complications and infective

endocarditis. • The long term prognosis is highly variable • Rx- Surgical replacement of diseased valves

with prosthetic device .

The pathogenetic sequence and key morphologic features of

acute rheumatic heart disease.

Background• HYPERTENSION – Elevated blood pressure. • A sustained diastolic pressure greater than 90 mmHg

or • A sustained systolic pressure in excess of 140 mmHg • About 1I.2% of Nigs. aged 15 years and above- 1997

national survey 160/95 mmHg• 20% of adult popn- Western industrialised countries• Prevalence increases with age, • Black individuals are affected by hypertension about

twice as often as whites and • Blacks seem more vulnerable to its complications.

Classification

• I. 10 or 20

• II. Systemic or Pulmonary

1. Primary & Systemic. About 90 to 95% - idiopathic /primary (essential HT).

2. Remaining 5-10% most are secondary to renal disease (renovascular HT).

• Categories: mild 95-104, mod 105-114, severe >115.

Mechanisms of Hypertension

• The BP level in any individual is a complex trait• Determined by the interaction of multiple genetic,

environmental and demographic factors, hence,• Multiple mechanism play a role in hypertension

• These mechanisms constitute aberrations of the normal physiologic regulation of blood pressure.

• The magnitude of arterial pressure depends on two fundamental hemodynamic variables: cardiac output and total peripheral resistance.

• The kidney by influencing both peripheral resistance and sodium homeostasis, plays an important role in blood pressure regulation.

The critical roles of cardiac output and peripheral resistance in blood

pressure regulation.

Mechanisms of Essential Hypertension

• Interaction of genetic and environmental factors

1. Genetic factors e.g. Liddle syndrome, 17αhydroxylase deficiency e.t.c.

2. Environmental factors e.g. 1. Stress, 2. Obesity, 3. Smoking,4. Physical inactivity5. Heavy consumption of salt

Hypothetical scheme for the pathogenesis of essential

hypertension

Causes of Secondary Hypertension Renal

Acute glomerulonephritis

Chronic renal disease

Polycystic disease

Renal artery stenosis

Renal artery fibromuscular dysplasia

Renal vasculitis

Renin-producing tumors

Endocrine

Adrenocortical hyperfunction (Cushing syndrome, primary aldosteronism, congenital adrenal hyperplasia)

Exogenous hormones (glucocorticoids, estrogen [including pregnancy-induced and oral contraceptives], sympathomimetics

Pheochromocytoma

Acromegaly

Hypothyroidism (myxedema)

Hyperthyroidism (thyrotoxicosis)

Pregnancy-induced

Causes of Secondary Hypertension ctd

Cardiovascular

Coarctation of aorta

Polyarteritis nodosa (or other vasculitis)

Increased intravascular volume

Increased cardiac output

Rigidity of the aorta

Neurologic

Psychogenic

Increased intracranial pressure

Sleep apnea

Acute stress, including surgery

Accelerated/malignant HT

• –Seen in about 5% of hypertensives – rapidly rising BP, • Usually super imposed on preexisting HT.• The clinical syndrome is characterized by:• Severe hypertension (i.e., systolic pressure over 200 mm

Hg, diastolic pressure over 120 mm Hg) • If untreated leads to death in 1 or 2 years. • Causes renal failure and • Retinopathy: Retinal haemorrhages and exudates +

papilloedema, • Brain – Charcot Bouchard microaneurysms,

Intraparenchymal haemorrhages, hypertensive encephalopathy.

Vascular pathology

• Affects both small & large vessels:• Two main forms of small blood vessels diseases:1. Hyaline arteriolosclerosis: • Encountered generally in elderly and diabetics but more

generalized and more severe in hypertensives.• Vascular lesions consists of homogenous pink, hyaline

thickening of the walls of arterioles and with narrowing of the lumen.

• Presumably the chronic hemodynamic stress of HT accentuates endothelial injury → leakage of plasma proteins and hyaline deposition with narrowing and

• Consequent ischaemia and organ shrinkage as in benign nephrosclerosis.

Hyaline arteriolosclerosis

2-Hyperplastic Arteriosclerosis

• Related to more acute and severe elevations of BP, • Therefore xristic of malignant HT (diastolic press > 110

mmHg) • Manifests as onion –skin concentric laminated

thickening of the walls of arterioles with progressive narrowing of lumina

• Often accompanied by deposits of fibrinoid material (fibrinoid necrosis) and

• Acute necrosis of the vessels walls – necrotizing arterolitis.

• All tissues throughout the body may be affected but the favoured site is the kidney.

Hyperplastic arteriolosclerosis (onionskinning)

Atherosclerosis

HEART

• Hypertensive heart disease: • Systemic= left sided; pulmonary= right- sided • Systemic: diagnostic criteria – • (i) LVH – usually concentric in the absence of any

cardiovascular pathology that might have induced it and

• (ii) A history or pathologic evidence of hypertension. • This hypertrophy is an adaptive response to pressure

over load which can lead to myocardial dysfunction, cardiac dilation, congestive heart failure and sudden death.

Normal Heart

Hypertensive Heart Disease

Morphology of Heart• Circumferential hypertrophy without dilatation of the

ventricle • Increase LV wall thickness • Cardiomegally with increased hrt wt. → impaired

diastolic filling → • Left atrial enlargement + AF, • Microscopically: ↑myocyte diameter, • later irregular with interstitial fibrosis. No hyperplasia.• Other possible complications include: • IHD from the potentiating effect of HT on coronary

artherosclerosis, Cong.hrt. failure and sudden cardiac death as above.

Pulmonary HT• Pulmonary vasculature

1. Primary pulmonary hypertension2. Secondary causes:

• Chronic obstructive pulm. disease,• Pneumoconiosis; • Recurrent pulm. thrombo-embolism;• Marked obesity and • Chronic altitude sickness.

• It can be acute or chronic: • Acute-massive pulm. thromboembolism → marked Rt vent dilation

without hypertrophy; • Chronic – right vent. Hypertrophy, dilatation and potentially

failure (Cor pulmonale) + pulmonary vascular sclerosis

Pulmonary Hypertension

Renal Changes

• Benign Nephrosclerosis: Sclerosis of renal arterioles and small arteries with resultant parenchymal ischaemia.

• Morphology – Hyaline arteriolosclerosis & fibroelastic hyperplasia.

• (N) or shrunken kidneys + fine granularity. • Malignant nephrosclerosis – occurs in 1-5% of

hypertensives. Morphology – 1. “flea bitten” appearance.2. Fibrinoid necrosis of arterioles; 3. Hyperplastic arteriolitis4. Necrotizing glomerulitis • BP usually >130 mmHg diastolic →

Benign Nephrosclerosis.

Malignant Nephrosclerosis

Fibrinoid Necrosis

BRAIN

• The most important effects of hypertension on the brain include:

1. Massive hypertensive intracerebral hemorrhage,- +berry aneurysms

2. Lacunar infarcts and slit hemorrhages,

3. Hypertensive encephalopathy. Atherosclerosis and diabetes are frequently associated diseases

Massive hypertensive hemorrhage

• The cerebral vessels develop arteriolar sclerosis and may become occluded; - TIA

• Ischaemic strokes 75-80%; hmgic-15%; SAH-5%; 5%

• Development of single or multiple, small, cavitary infarcts-lacunes, or lacunar state (état lacunaire)

• Lacunes can either be clinically silent or cause severe neurologic impairment.

• Widening of the perivascular spaces around affected vessels - (état criblé).

BRAIN-2

Lacunar infarcts in the caudate and putamen.

• Slit Hemorrhages • Rupture of the small-caliber penetrating vessels and the

development of small hemorrhages. Which resorbs, slitlike cavity (slit hemorrhage) surrounded by brownish discoloration;

• Hypertensive Encephalopathy • Clinicopathologic syndrome arising in a hypertensive

patient characterized by diffuse cerebral dysfunction, including headaches, confusion, vomiting, and convulsions, sometimes leading to coma.

• Edematous brain with or without transtentorial or tonsillar herniation. Petechiae and fibrinoid necrosis of arterioles in the gray and white matter may be seen microscopically.

BRAIN-3

Hypertensive Enchephalopathy

• Vascular (multi-infarct) dementia –• Multiple, bilateral, gray matter (cortex, thalamus, basal

ganglia) and white matter (centrum semiovale) infarcts caused by multifocal vascular disease, consisting largely of

• (1) cerebral atherosclerosis, • (2) vessel thrombosis or embolization from carotid vessels

or from the heart, or • (3) cerebral arteriolar sclerosis from chronic hypertension. • Binswanger disease • Pattern of injury preferentially involves large areas of the

subcortical white matter with myelin and axon loss,

BRAIN-4

Multi infarct dementia

EYE• RETINAL VASCULAR DISEASE• A- ‘Non Malignant’ Hypertensive retinopathy1. Thickened arteriolar wall -generalized arteriolar narrowing2. Copper & Silver wiring. Vessels may appear narrowed, and the

color of the blood column may change from bright red to copper and to silver depending on the degree of vascular wall thickness

3. A – V nipping Retinal arterioles and veins share a common adventitial sheath.

Therefore, in pronounced retinal arteriolosclerosis, the arteriole may compress the vein at points where both vessels cross

4. Venous stasis distal to arteriolar-venous crossing may precipitate occlusions of the retinal vein branches.

EYE-2• B Malignant Hypertensive Retinopathy, • Vessels in the retina and choroid may be damaged. –

Hmges, hard exudates• + Optic disc oedema• Elschnig's spots -Damage to choroidal vessels may

produce focal choroidal infarcts, • Retinal detachment -Damage to the choriocapillaris, the

internal layer of the choroidal vasculature, may, in turn, damage the overlying retinal pigment epithelium and permit exudate to accumulate in the potential space between the neurosensory retina and the retinal pigment epithelium.

Retinal Detachment

EYE-3• Occlusion of retinal arterioles may produce

infarcts of the nerve fiber layer of the retina. • “Cotton-wool spots".• Accumulation of mitochondria at the swollen ends

of damaged axons creates the histologic illusion of cells (cytoid bodies).

• Collections of cytoid bodies populate the nerve fiber layer infarct, seen ophthalmoscopically as "cotton-wool spots".

Nerve fiber layer infarct

CARDIOMYOPATHY, • Heart disease resulting from a primary

abnormality in the myocardium. • There are main 3 recognized types:• Dilated, hypertrophic and restrictive based on

clinical functional and pathologic considerations.• Arrythmogenic Right ventricular

Cardiomyopathy.• Dilated (DCM) – Most common; xrised by

progressive cardiac hypertrophy, dilatation and contractile (systolic) dysfunction.

The three distinctive and predominant forms of

cardiomyopathies.

Pathways of dilated and hypertrophic cardiomyopathy

Causes of Dilated Cardiomyopathy

• Idiopathic,• myocarditis (viral),• Alcohol abuse,• Doxorubicin, • Peripartum,• Genetic 30-40%–(dystrophin gene)• Morphology-• Heart is usually heavy and enlarged and flabby

with dilation of all chambers,•

• Mural thrombi are common + thrombo-embolism

• + functional regurgitation • microscopy – non specific changes hypertrophic

fibres enlarged nuclei and stretched/thin:• Interstitial fibrosis; • Commoner between ages 20-60 presenting with

slowly progressive congestive hrt failure,• Death occurs within 2years usually attributable

to hrt failure or arrhythmia.

Dilated cardiomyopathy

Hypertrophic HCM/Idiopathic hypertrophic sub-aortic stenosis

• -Xrised by myocardial hypertrophy,

• Abnormal diastolic filling and in about one third of cases intermittent left ventricular out flow obstruction.

• The heart is heavy,

• Muscular and hypercontracting.

Hypertrophic Cardiomyopathy

Myofibre Disarray

Morphology

• - There is disproportionate thickening of the ventricular septum as compared with the free wall of the L.V.

• Asymmetric septal hypertrophy;• (1/3 = symmetric)• Micro: • Hypertrophic fibers;• Myofibre disarray and interstitial fibrosis.

Pathogenesis

• : 5% of cases are familial. • AD inheritance• - Mostly any of 4 genes coding myocardial contratile

elements may be affected,• B-myosin heavy chain most frequently affected,• Others are troponin T,• Tropomyosin,• Myosin binding protein C.• Clinically – there is reduced stroke volume,• Anginal pain from myocardial ischemia.

• However major problems are atrial fibrillation,

• Mural thrombosis + embolization infective endocarditis on mitral valve,

• Intractable cardiac failure and ventricular arrhythmias and sudden death.

Restrictive cardiomyopathy

• – A disorder xrized by a primary decrease in ventricular filling during diastole;

• It can be idiopathic or associated with distinct disease that affects the myocardium principally radiation fibrosis,

• Amyloidosis, candidiasis, metastatic tumour or metabolic disorders.

• Morphology – in idiopathic – bilaterial,• Dilatation common with patchy or diffuse,• Fibrosis and normal or slightly enlarged ventricle.

Endomyocardial fibrosis

• – A disease of children and young adults in African and other tropical areas,

• Xrised by fibrosis of the ventricular endocardium and sub endocardium that extends from the apex toward and often involving the tricuspid mostly,& the mitral valve.

• It → reduced ventricular compliance and diastolic filling + ventricular mural thrombi.

• Cause is unknown.

Epidemiology

• – Affects people of lower socio-economic group.

• Disease has been linked to filariasis,

• Eosinophil leucocytosis,

• Consumption of plantain and immunological factors.