Lecture 15

Hypertensive Vascular Disease

An elevated arterial blood pressure is major health problem. A persistent and sustained high blood
pressure has damaging effects on the kidneys (benign and malignant nephrosclerosis), heart (e.g.
hypertensive heart disease,) and brain (e.g. cerebrovascular accident).
Definition and Classification
Arterial or systemic hypertension in a patient is defined clinically as borderline if the systolic blood
pressure is more than 140 Hg, and hypertenslve when the elevation of systolic and diastolic pressure
exceeds 165 and 95 mmHg respectively. The diastolic pressure is often considered more significant.
However, blood pressure varies with many factors such as age of the patient, exercise, emotional
disturbances like fear and anxiety. Therefore, it is important to measure blood pressure on more than one
occasion under least stressful conditions. By means of these criteria, the prevalence of hypertension is
observed in about 25% of population.
Hypertension is generally classified into 2 types:
1. Primary or essential hypertension in which the cause of increase in blood pressure is unknown.
Essential hypertension constitutes about 90-95% patients of hypertension.
2. Secondary hypertension, in which the increase in blood pressure is caused by diseases of the kidneys,
endocrines or some other organs. Secondary hypertension comprises 5-10% cases of hypertension.
According to the clinical course, both essential and secondary hypertension may be benign or
malignant.
Benign hypertension is moderate elevation of blood pressure and the rise is slow as the years pass.
About 90-95% patients of hypertension have benign hypertension.
Malignant hypertension is marked and rapid increase of blood pressure to 200/140 mmHg or more and
the patients have papilloedema, retinal haemorrhages and hypertensive encephalopathy. Less than 5% of
hypertensive patients develop malignant hypertension and life expectancy after diagnosis in these patients
is generally less than 2 years if not treated effectively.
ETIOLOGY AND PATHOGENESIS
The etiology and pathogenesis of secondary hypertension that comprises less than 10% cases has been
better understood, whereas the mechanism of essential hypertension that constitutes about 90% of cases
remains largely obscure. In general, normal blood pressure is regulated by 2 haemodynamic forces
cardiac output and total-peripheral arteriolar resistance. Factors which alter these two factors result in
hypertension. The role of kidney in hypertension, particularly in secondary hypertension, by elaboration
of renin and subsequent formation of angiotensin II, is well established (renin-angiotensin system).
ESSENTIAL (PRIMARY) HYPERTENSION.
By definition, the cause of essential hypertension is unknown.
SECONDARY HYPERTENSION. Mechanisms underlying hypertension with identifiable cause have
been more extensively studied. Based on the etiology, these are described under 3 headings: renal hyper-
tension, endocrine hypertension and hypertension associated with coarctation of aorta.
/. RENAL HYPERTENSION. Hypertension produced by renal diseases is called renal hypertension.
Renal hypertension is subdivided into 2 groups:
i) Renal vascular hypertension e.g. in occlusion of a major renal artery, pre-eclampsia, eclampsia and
polyarteritis nodosa.
ii) Renal parenchymal hypertension e.g. in various types of glomerulonephritis, pyelonephritis, interstitial
nephritis, diabetic nephropathy, amyloidosis and tumours of the kidneys.
In either case, renal hypertension can be produced by one of the 3 inter-related pathogenetic
mechanismsactivation of renin-angiotensin system, sodium and water retention, and release of
vasodepressor materials.
2. ENDOCRINE HYPERTENSION. A number of hormonal secretions may produce secondary hy-
pertension. These are:
i) Adrenal gland-e.g. in primary aldosteronism, Cushing's syndrome, adrenal virilism and
pheochromocytoma.
ii) Parathyroid glande.g. hypercalcaemia in hyperparathyroidism.

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iii) Oral contraceptivesOestrogen component in the oral contraceptives stimulates hepatic synthesis of
renin substrate.
3. COARCTATION OF AORTA. Coarctation of the aorta causes systolic hypertension in the upper part
of the body due to constriction itself. Diastolic hypertension results from changes in circulation.
EFFECTS OF HYPERTENSION
Systemic hypertension causes major effects in 3 main organsheart and its blood vessels, nervous
system, and kidneys. The renal effects are in the form of benign and malignant nephrosclerosis.
Benign Nephrosclerosis
Benign nephrosclerosis is the term used to describe the kidney of benign phase of hypertension. Mild
benign nephrosclerosis is the most common form of renal disease in persons over 60 years of age but its
severity increases in the presence of hypertension and diabetes mellitus.
PATHOLOGIC CHANGES. Grossly, both the kidneys are affected equally and are reduced in size and
weight, often weighing about 100 gm or less. The capsule is often adherent to the cortical surface. The
surface of the kidney is finely granular and shows V-shaped areas of scarring (small contracted kidney).
The cut surface shows firm kidney and narrowed cortex.
Microscopically, there are primarily diffuse vascular changes which produce parenchymal changes sec-
ondarily as a result of ischaemia. The histologic changes are thus described as vascular and parenchymal :
i) Vascular changes: Changes in blood vessels involve arterioles and arteries upto the size of arcuate
arteries. There are 2 types of changes in these blood vessels:
a) Hyaline arteriolosclerosis that results in homogeneous and eosinophilic thickening of the wall of
small blood vessels.
b) Intimal thickening due to proliferation of smooth muscle cells in the intima.
ii) Parenchymal changes: As a consequence of ischaemia, there is variable degree of atrophy of
parenchyma. These include glomerular shrinkage, deposition of collagen in Bowman's space,
periglomerular fibrosis, tubular atrophy and fine interstitial fibrosis.
CLINICAL FEATURES. There is variable elevation of the blood pressure with headache, dizziness,
palpitation and nervousness. Eye ground changes may be found but papilloedema is absent. Renal
function tests and urine examination are normal in early stage. But in long-standing cases, there may be
mild proteinuria with some hyaline or granular casts. Rarely, renal failure and uraemia may occur.
Malignant Nephrosclerosis
Malignant nephrosclerosis is the form of renal disease that occurs in malignant or accelerated hyper-
tension. Malignant nephrosclerosis is uncommon and usually occurs as a superimposed complication in
5% cases of pre-existing benign essential hypertension or in those having secondary hypertension with
identifiable cause such as in chronic renal diseases. However, the pure form of disease also occurs,
particularly at younger age with preponderance in males.
PATHOLOGIC CHANGES. Grossly, the appearance of the kidney varies. In a case of malignant
hypertension superimposed on preexisting benign nephrosclerosis, the kidneys are small in size,
shrunken and reduced in weight and have finely granular surface. However, the kidneys of a patient who
develops malignant hypertension in pure form are enlarged, oedematous and have petechial haemorrhages
on the surface producing so called flea-bitten kidney. Cut surface shows red and yellow mottled
appearance.
Microscopically, most commonly the changes are superimposed on benign nephrosclerosis.
i) Vascular changes: These are more severe and involve the arterioles. The two characteristic vascular
changes seen are as under:
a) Necrotising arteriolitis develops on hyaline arteriolosclerosis. The vessel wall shows fibrinoid necrosis,
a few acute inflammatory cells and small haemorrhages.
b) Hyperplastic intimal sclerosis or onion-skin proliferation is characterised by concentric laminae of
proliferated smooth muscle cells, collagen and basement membranes.
ii) Ischaemic changes: The effects of vascular narrowing on the parenchyma include tubular loss, fine
interstitial fibrosis and foci of infarction necrosis.
CLINICAL FEATURES. The patients of malignant nephrosclerosis have malignant or accelerated
hypertension with blood pressure of 200/140 mmHg or higher. Headache, dizziness and impaired vision
are commonly found. The presence of papilloedema distinguishes malignant from benign phase of hy-
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pertension. The urine frequently shows haematuria and proteinuria. Renal function tests show deterio-
ration during the course of the illness. Azotaemia (high BUN and serum creatinine) and uraemia develop
soon if malignant hypertension is not treated aggressively. Approximately 90% of patients die within one
year from causes such as uraemia, congestive heart failure and cerebrovascular accidents.
HYPERTENSIVE HEART DISEASE
Hypertensive heart disease or hypertensive cardiomyopaty is the disease of the heart resulting from
systemic hypertension of prolonged duration and manifesting by left ventricular hypertrophy. Even mild
hypertension (blood pressure higher than 140/90 mmHg) of sufficient duration may induce hypertensive
heart disease. It is the second most common form of heart disease after IHD. Therefore, most patients of
hypertensive heart diseasae have advanced coronary atherosclerosis and may develop progressive IHD.
Amongst the causes of death in hypertensive patients, cardiac decompensation leading to CHF accounts
for about one-third of the patients; other causes of death are IHD, cerebrovascular stroke, renal failure
following arteriolar nephrosclerosis, and dissecting aneurysm of the aorta.
PATHOGENESIS.
Stimulus to hypertrophy of the left ventricle is pressure overload in systemic hypertension. The stress
of pressure on the ventricular wall causes increased production of myofilaments, myofibrils, other cell
organelles and nuclear enlargement. Since the adult myocardial fibres do not divide, the fibres are
hypertrophied. However, the sarcomeres may divide to increase the cell width.
PATHOLOGIC CHANGES. Grossly, the most significant finding is marked hypertrophy of the heart,
chiefly of the left ventricle. The weight of the heart increases to 500 gm or more (normal weight about
300 gm). The weight of the heart is directly related to the severity of hypertension but there is no
correlation between the weight of the heart and duration of hypertension. The thickness of the left
ventricular wall increases from its normal 13 to 15 mm upto 20 mm or more. The papillary muscles and
trabeculae carnea are rounded and prominent. Initially, there is concentric hypertrophy of the left ventricle
(without dilatation). But when decompensation and cardiac failure supervene, there is eccentric hypertro-
phy (with dilatation) with thinning of the ventricular wall and there may be dilatation and hypertrophy of
right heart as well.
Microscopically, the features are not as prominent as macroscopic appearance. The changes include
enlargement and degeneration of myocardial fibres with focal areas of myocardial fibrosis. In advanced
cases, there may be myocardial oedema and foci of necrosis in the myocardium.
CEREBROVASCULAR DISEASES
Cerebrovascular diseases are all those diseases in which one or more of the blood vessels of the brain are
involved in the pathologic processes. These processes can result in 2 main types of parenchymal diseases
of the brain:
1. Ischaemic brain damage (hypoxic encephalopathy and cerebral infarction); and
2. intracranial haemorrhage (intracerebral and subarachnoid haemorrhage).
The stroke syndrome is the cardinal feature of cerebrovascular disease. The term stroke is used for sudden
and dramatic development of focal neurologic deficit, varying from trivial neurologic disorder to
hemiplegia and coma.
ISCHAEMIC BRAIN DAMAGE Ischaemic necrosis in the brain results from ischaemia caused by
considerable reduction or complete interruption of blood supply to neural tissue which is insufficient to
meet its metabolic needs. In all these different forms of anoxia, the end-result is ischaemic brain damage
which may have one of the following two patterns:
1. Ischaemic (hypoxic) encephalopathy, resulting from generalised cerebral hypoperfusion.
2. Cerebral infarction, resulting from severe localised reduction or cessation of blood supply. Ischaemic
(Hypoxic) Encephalopathy
The pathologic appearance of the brain in hypoxic encephalopathy varies depending upon the duration
and severity of hypoxic episode and the length of survival.
Survival for a few hours: No pathologic changes are visible.
Survival 12-24 hours: No macroscopic change is discernible but microscopic examination reveals early
neuronal damage in the form of eosinophilic cytoplasm and pyknotic nuclei, so called red neurons. After
2-7 days: Grossly, there is focal softening. The area supplied by distal branches of the cerebral arteries
suffers from the most severe ischaemic damage and may develop border zone or watershed infarcts in the
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junctional zones between the territories supplied by major arteries. Particularly vulnerable is the border
zone of the cerebral cortex between the anterior and middle cerebral arteries, producing para-sagittal
infarction. Microscopically, the nerve cells die and disappear and are replaced by reactive fibrillary
gliosis. There are minor variations in the distribution of neuronal damage to the cortex; the loss of
pyramidal cell layer is more severe than that of granular cell layer producing laminar necrosis.
Cerebral Infarction
Cerebral infarction is a localised area of tissue necrosis caused by local vascular occlusionarterial or
venous. Occasionally, it may be the result of non-occlusive causes such as compression on the cerebral
arteries from outside and from hypoxic encephalopathy.
PATHOLOGIC CHANGES. Cerebral infarcts may be anaemic or haemorrhagic.
Grossly, an anaemic infarct becomes evident 6-12 hours after its occurrence. The affected area is soft and
swollen and there is blurring of junction between grey and white matter. Within 2-3 days, the infarct
undegoes softening and disintegration. Eventually, there is central liquefaction with peripheral firm glial
reaction and thickened leptomeninges, forming a cystic infarct. A haemorrhagic infarct is red and
superficially resembles a haematoma. It is usually the result of fragmentation of occlusive arterial emboli
or venous thrombosis.
Histologically, the sequential changes are as under:
1. Initially, there is eosinophilic neuronal necrosis and lipid vacuolisation produced by breakdown of
myelin. Simultaneously, the infarcted area is infiltrated by neutrophils.
2. After the first 2-3 days, there is progressive invasion by macrophages and there is astrocytic and
vascular proliferation.
3. In the following weeks to months, the macrophages clear away the necrotic debris by phagocytosis
followed by reactive astrocytosis, often with little fine fibrosis. A haemorrhagic infarct has some
phogocytes containing haemosiderin.
4. Ultimately, after 3-4 months an old cystic infarct is formed which shows a cyst traversed by small
blood vessels and has peripheral fibrillary gliosis. Small cavitary infarcts are called lacunar infarcts and
are commonly found as a complication of systemic hypertension.
INTRACRANIAL HAEMORRHAGE
Haemorrhage into the brain may be traumatic, non-traumatic, or spontaneous. There are two main types
of spontaneous intracranial haemorrhage:
1. Intracerebral haemorrhage, which is usually of hypertensive origin.
2. Subarachnoid haemorrhage, which is commonly aneurysmal in origin.
Intracerebral Haemorrhage
Spontaneous intracerebral haemorrhage occurs mostly in patients of hypertension. The common sites of
hypertensive intracerebral haemorrhage are the region of the basal ganglia (particularly the putamen and
the internal capsule), pons and the cerebellar cortex. Clinically the onset is usually sudden with headache
and loss of consciousness. Depending upon the location of the lesion, haemispheric, brain stem or
cerebellar signs will be present. About 40% of patients die during the first 3-4 days of haemorrhage,
mostly from haemorrhage into the ventricles. The survivors tend to have haematoma that separates the
tissue planes which is followed by resolution and development of an apoplectic cyst accompanied by loss
of function.
PATHOLOGIC CHANGES. Grossly and microscopically, the haemorrhage consists of dark mass of
clotted blood replacing brain parenchyma. The borders of the lesion are sharply-defined and have a
narrow rim of partially necrotic parenchyma. Small ring haemorrhages in the Virchow-Robin space in the
border zone are commonly present. Ipsilateral ventricles are distorted and compressed and may contain
blood in their lumina. Rarely, blood may rupture through the surface of the brain into the subarachnoid
space. After a few weeks to months, the haematoma undergoes resolution with formation of a slit-like
space called apoplectic cyst and containing yellowish fluid. Its margins are yellow-brown and contain
haemosiderin-laden macrophages and a reactive zone of fibrillary astrocytosis.
Subarchnoid Haemorrhage
Haemorrhage into the subarachnoid space is most commonly caused by rupture of an aneurysm, and
rarely, rupture of a vascular malformation.

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In more than 85% cases of subarachnoid haemorrhage, the cause is massive and sudden bleeding from a
berry aneurysm on or near the circle of Willis.
Clinically, berry aneurysms remain asymptomatic prior to rupture. On rupture, they produce severe
generalised headache of sudden onset which is frequently followed by unconsciousness and neurologic
defects. Initial mortality from first rupture is about 20-25%. Survivors recover completly but frequently
suffer from recurrent episodes of fresh bleeding.
PATHOLOGIC CHANGES. Rupture of a berry aneurysm frequently spreads haemorrhage throughout
the subarachnoid space with rise in intracranial pressure and characteristic blood-stained CSF. An
intracerebral haematoma may develop if the blood tracks into the brain parenchyma. The region of the
brain supplied by the affected artery frequently shows infarction, partly attributed to vasospasm.