HYPERTENSION

Solomon E Quayson
 LECTURE FORMAT
 DEFINITION
 CLASSIFICATION
 CAUSES AND PATHOGENESIS
• ESSENTIAL HYPERTENSION
• SECONDARY HYPERTENSION
 CLINICAL FEATURES AND VASCULAR
PATHOLOGY
• BENIGN HYPERTENSION
• MALIGNANT HYPERTENSION
 LECTURE OBJECTIVES
 At the end of the lecture, each student will be able to
 Define and explain hypertension
 State and explain the various types of hypertension
 Discuss the aetiologic factors involved in the
different types of hypertension
 Discuss/explain the pathogenetic mechanisms
involved in the development of hypertension
 Describe the morphologic changes brought about by
hypertension
 Describe the clinical features of hypertension
explaining how they arise
 DEFINITION
 “Hypertension",used without qualification, means
systemic arterial hypertension.
 Generally hypertension means raised pressure in a
vascular bed.
 BP
 Rises gradually throughout life
 Has a distribution curve, which is skewed to the right

 Therefore any dividing line between normotension and

hypertension is arbitrary
 HPT is considered one extreme of this distribution rather
than a distinct disease
 HPT therefore defined as a disorder in which the
level of sustained arterial pressure is higher than
expected for the age, sex and race of the
individual under consideration.
 Normal variations preclude a precise numerical
definition as no level separates risk from safety but
harmful effects of BP increase continuously as the
pressure rises
 A person with a sustained resting diastolic BP > 90
mm Hg or a systolic BP > 140 mm Hg would be at
risk of developing the complications of hypertension
 WHO has made working definitions as follows:
• Hypertension: systolic pressure 160 mm Hg
and/or diastolic pressure  95 mm Hg.
• Borderline hypertension: systolic pressure
between 140 and 160 mm Hg and/or diastolic
pressure 90-95 mm Hg.
 When there is elevation of systolic pressure alone
this is called isolated systolic hypertension
 When there is elevation of both systolic and
diastolic pressures this is called diastolic
hypertension.
 Of the two types, diastolic hypertension is more
dangerous
 The height of the diastolic pressure is used to further
categorise hypertension as follows:
 mild diastolic pressure between 95 and 104mm
Hg
 moderate at 105 to 114 mm Hg

 severe at pressures above 115 mm Hg

 Normal blood pressure is increased by stimuli such
as exercise, exposure to cold, emotion and change in
position from supine to standing.
 Individuals in whom such a rise is excessive are said
to have "labile hypertension".
 Diagnosis of an individual as hypertensive can be
difficult.
 Single blood pressure readings can be spuriously
high. Several measurements may be necessary and
great care must also be taken to ensure that the
blood pressure is taken with a cuff of appropriate
size and shape.
 CLASSIFICATION
 In 90 to 95% of cases of hypertension, no apparent
cause can be found - idiopathic, primary or
essential.
 The remaining 5 to 10% result from other
underlying conditions - secondary.
 Further classified according to the clinico-
pathological consequences of the blood pressure
level:
 Benign hypertension: indolent, progressing over many
years with a moderately raised blood pressure,
asymptomatic and compatible with long life. 95% of
cases
 Malignant hypertension: rapidly rising blood pressure,
which, if untreated,  to organ damage & death in a year
or 2. 5% of cases
 AETIOLOGY AND PATHOGENESIS
ESSENTIAL HYPERTENSION:
AETIOLOGY: Although the cause of essential
hypertension is unknown, several factors are related to its
development.
• The absence of any sharp separation between normal, mild
hypertension and severe hypertension is an indication that a
mosaic of factors causes hypertension.
• These include
• genetic and racial factors,

• environmental factors such as stress, smoking, physical

inactivity, obesity and diet,
• cell membrane abnormalities and electrolyte control,
nervous system reactivity, arterial reactivity and
circulating vasoactive agents
 Genetic and Racial Factors:
 Indicated by a strong family history of essential
hypertension
• Children whose parents are hypertensive have increased
risk of developing hypertension.
• Unimodal distribution of blood pressure suggest that
inheritance is polygenic
 the excessively high incidence in black populations
• Rates are much higher in black Africans with 40-45% of
adults being affected
• Incidence in black Americans about twice that of white
Americans
• The disease appears to behave differently between blacks
and whites; more severe complications more common in
blacks than in whites
 Single gene disorders that cause rare, severe forms
of hypertension
 Defects in aldosterone metabolising enzymes –

11-hydroxylase and 17α-hydroxylase – result in

↑mineralocorticoid activity
 Defects in proteins involved in sodium
reabsorption – Epithelial Na+ Channel – results in
↑distal tubular reabsorption of Na+
 Genetic variations (polymorphisms) in the genes
encoding angiotensinogen, ACE and receptors for
angiotensin II
 These polymorphisms may explain racial

differences in BP regulation
 Through renin, the kidney forms angiotensin I,
which is converted to angiotensin II by ACE
 Angiotensin II alters BP by
  PR by direct action on vascular smooth muscle to
cause vasoconstriction
  blood volume by stimulating aldosterone secretion,
which in turn  distal tubular reabsorption of Na and
water.
 Some patients with essential HPT respond to
treatment with ACE inhibitors
 In essential hypertension plasma renin levels are
normal in 60% of patients,  in 15% and  in 25%
 Recently, variations or mutations in the genes
coding for angiotensinogen, ACE and some of the
receptors for angiotensin II have been linked with
HPT
 Stress:
 Higher incidence of HPT in urban than rural
populations; rise in incidence in rural populations
migrating to urban areas.
 Diet:
 Populations with  Na intake have prevalence of
HPT than those with ↓ intake
 Studies of restriction of salt intake have shown
beneficial effect on BP in HPT
 A study in Ghana has shown that some
hypertensives have a  threshold taste for salt and so
tend to consume more salt than the general
population
 However, there is a wide variation in susceptibility
to salt, which is genetically determined
 Nervous System Reactivity and Circulating
Vasoactive Agents :
 Resting vascular tone is controlled by the
sympathetic nervous system.
 When compared with controls, patients with
essential HPT have higher BPs at any given level of
circulating catecholamines
 Young hypertensives tend to have higher resting
plasma noradrenalin levels than age-matched,
normotensive controls.
 Chronic or repeated vasonconstriction may → ↑
vascular thickening and ↑ PR
PATHOGENESIS:
 BP depends on the product of cardiac output and
total PR.
 The cause of HPT therefore must be related to:
 A primary  in CO or

 An  in PR or
 Both.

 in cardiac output may arise from:

d Na+ excretion (↑Na+ reabsorption) or
Excessive salt intake.
 The d blood volume will lead to d CO and tissue
overperfusion.
 Auto-regulation, in which d blood flow through resistance
vessels leads to vasoconstriction, occurs to prevent
overperfussion.
 Vasoconstriction in turn  PR and, concomitantly,
BP.
 At the higher pressure, enough additional sodium
can be excreted to prevent fluid retention.
 Thus a new altered but steady state of sodium
excretion is attained but at a higher blood pressure.
Alternatively vasoconstrictive influences may be the
cause of HPT
 Increased PR resulting in sustained high blood
pressure may be caused by:
• Increased sympathetic tone: increased release of renin
and generation of angiotensin II; presence of other
vasoconstrictive substances in the blood such as
catecholamines and endothelin, and excessive
responsiveness to behavioural or neurogenic factors of
vascular smooth muscle
 • Structural thickening in the wall of resistant vessels
caused by chronic or repeated vasoconstriction
 Thus in a given individual HPT may be attributable
to a combination of factors affecting the
haemodynamic variables.
 Disturbances in any of the factors controlling normal
blood pressure acting in genetically predisposed
individuals may lead to essential hypertension.
 In summary:
 Although single gene defects can cause essential
HPT, this occurrence is uncommon.
 More likely that combined effect of mutations or
polymorphisms at several gene loci that control BP
interacting with a host of environmental factors →
HPT.
 Thus essential HPT is a complex, multifactorial
disorder.
SECONDARY HYPERTENSION
AETIOLOGY:
Hypertension may result from many underlying
conditions:
• Renal disease
• Endocrine disease
• Drug induced
• Other diseases such as pre-eclampsia and coarctation of
the aorta.
 Renal causes by far the commonest accounting for
over 80% of cases
 May be due to:
• Renovascular disorders
• Parenchymal disease.
 Renovascular Hypertension
 Reduction in renal blood above 50%  activation of
the renin-angiotensin system with plasma renin
and angiotensin II levels.
 Juxtaglomerular hyperplasia develops and HPT
results from the excessiely high levels of renin and
angiotensin.
 Important causes of obstruction to renal arterial flow
include:
• Stenosis from atheroma near the renal artery
ostium
• Fibromuscular dysplasia of the renal artery

• Emboli involving the artery or its intrarenal

branches
 Renal Parenchymal Disease
 Many chronic parenchymal renal diseases may
result in hypertension.
• Chronic pyelonephritis,
• Chronic glomerulonephritis,
• Polycystic kidneys,
• Diabetic nephropathy,
• Chronic interstitial nephritis and
• Hydronephrosis.
 In some diseases such as glomerulonephritis
hypertension may occur in the early stages.
 The mechanisms of hypertension induction by
parenchymal disease are:
• Sodium and water retention due to chronic renal failure
• Renin-angiotensin-aldosterone
 In many chronic renal disease endarteritis obliterans
of the interlobular arteries and arteriolar intimal
hyperplasia occur and aggravate the hypertension
 Endocrine Causes
 Diseases of the adrenal gland:
• Phaeochromocytoma - cause hypertension by secreting
catecholamines. In 50% of cases the hypertension is
episodic and is often severe.
• Conn's syndrome (primary hyperaldosteronism) - raised
aldosterone levels causes mild HPT due to Na and water
retention.
• Cushing's syndrome - both glucocorticoids and
mineralocorticoids contribute to the hypertension.
• Congenital adrenal hyperplasia - Sodium-retaining
intermediate products of steroid synthesis cause HPT
 The mechanisms of hypertension in acromegaly,
thyrotoxicosis and hypothyroidism are not fully
understood.
 Renin secretion by renal tumours - renal cell carcinoma,
nephroblastoma and tumours of the juxtaglomerular
apparatus - and ectopic renin secretion by bronchial
carcinoma are rare causes of hypertension.
 Drugs
 Many have been shown to cause or aggravate HPT
• Oral contraceptive pill
• Steroids

• Carbenoxolone

• Patients on MAO inhibitors who eat tyramine-containing

foods may develop paroxysms of severe HPT
 Other Causes
• Secondary hypertension occurs in pre-eclampsia and
alcohol abuse. The mechanims are uncertain.
 CLINICAL FEATURES AND
VASCULAR PATHOLOGY
Benign Hypertension
 In most cases blood pressure rises to moderately
high levels and remains fairly stable over years to
decades.
 Rise nearly always starts between the ages of 45 and
55 years.
 Benign course is most characteristic but may also be
seen with the secondary form
 Usually symptomless but symptoms may develop
and include
• palpitations,
• audible pulsation in the head
 • headaches,
• attacks of dizziness especially on stooping,
• easy fatigability.
• Breathlessness on exertion, dyspnoea at rest and
paroxysmal nocturnal dyspnoea, all due to pulmonary
oedema, occur as cardiac failure develops.
 Increased peripheral resistance and cardiac workload
associated with hypertension causes left ventricular
hypertrophy.
• During life this can be detected with the ECG and also
seen in a chest x-ray.
• At autopsy there is often considerable, concentric
thickening of the left ventricular wall.
• The hypertrophy can be obscured by left ventricular
dilatation when congestive cardiac failure supervenes.
CONCENTRIC HYPERTROPHY
DILATED HYPERTROPHIED LEFT
VENTRICLE
Morphologic Changes
 Hypertension causes changes in arteries of all sizes.
 The changes in large and medium-sized arteries are
the same in all types of hypertension,
 Different processes occur in the smaller arteries (1
mm diam. or less) and arterioles in benign (chronic)
and malignant (accelerated) hypertension.
 Large and medium-sized arteries:
• In the early stages consist mainly of medial hypertrophy
resulting from increased smooth muscle mass and elastic
fibres. Classical hypertensive arterial change seen in young
hypertensive persons.
• The intima thickened by increased numbers of
longitudinally oriented smooth muscle fibres
• With time, hyperplastic and hypertrophic changes are
replaced by collagen, other matrix proteins and proteo-
glycans, the thickened artery becoming rigid and less
compliant which contributes to an increase in systolic
blood pressure.
• The lumen is dilated and the vessels are often elongated
and tortuous
• In medium-sized arteries there is reduplication of the
internal elastic lamina.
• Changes are termed hypertensive arteriosclerosis.
• Marked increase in proteoglycans in the media of large

arteries results in cystic medial degeneration.

• Atheroma is more severe in persons with chronic

hypertension.
 Small arteries and arterioles:
• Longstanding hypertention produces generalized
disease of arterioles and small arteries.
• Medial thickening of small arteries
• Intimal thickening is more marked resulting in luminal
narrowing (hypertensive or hyperplastic
arteriolosclerosis)
• The major change is hyaline arteriolosclerosis
• Starts as patchy deposits of hyaline material, initially
beneath the endothelium and then involving the full
thickness of the wall
• Gradually extends to involve the whole circumference of
the wall, and when severe replaces all the parts of the
wall except the endothelium.
• Arteriolar wall shows a subendothelial, homogeneous,
glassy pink material due in part to plasmatic vasculosis –
deposition of plasma derived proteins in the vessel wall
HYPERPLASTIC ARTERIOLOSCLEROSIS
HYALINE ARTERIOLOSCLEROSIS
HYALINE ARTERIOLOSCLEROSIS
• These vascular changes are most easily appreciated
in the spleen and kidney.
• Medium sized renal arteries and arterioles show marked
intimal proliferation and hyalinization of the
muscular media
• Causes focal areas of ischaemia with periglomerular
fibrosis and glomerulosclerosis, loss of tubules and
scarring.
• Results in finely granular cortical surfaces and thinned
cortex.
• Renal failure is uncommon but does occur in the few
who progress to malignant hypertension.
• Uncommon in arterioles of the brain, pituitary,
thyroid, heart, GIT, skin and skeletal muscles.
• Seen in diabetes mellitus and in old age in the
absence of hypertension.
HYPERTENSIVE NEPHROPATHY
• Hypertension accelerates or precipitates several
disorders including:
• Atherosclerosis, especially coronary arterial
atherosclerosis with consequent ischaemic heart disease
• Spontaneous intracerebral haemorrhage
• Dissection of the aorta – due to cystic medial
degeneration
• Subarachnoid haemorrhage due to rupture of berry
aneurysm
• Malignant hypertension supervenes in a small
proportion of cases of benign essential hypertension
(less than 10% of patients).
• In such cases renal failure develops.
PONTINE HAEMORRHAGE
PONTINE HAEMORRHAGE
SUBARACHNOID HAEMORRHAGE
 Malignant Hypertension
• A clinico-pathological syndrome characterized by:
• rapidly rising blood pressure with diastolic
pressure usually over 120 mm Hg,
• rapidly progressive renal injury resulting in
uraemia, and
• retinal haemorrhages, infarcts and exudates with
or without papilloedema.
• Rarely, hypertensive encephalopathy with by
epileptiform fits and transient paralysis caused by
cerebral oedema resulting from failure of the
resistance vessels of the brain to withstand the
increased pressure
• Most cases occur in patients with previous benign
hypertension either essential or more often
secondary to renal disease - this is called accelerated
hypertension.
• In many cases, malignant hypertension arises
apparently de novo and typically occurs in black
males in their third or fourth decade
• The consequences of malignant hypertension are:
• acute left ventricular failure with left ventricular
hypertrophy with or without dilatation
• blurred vision due to papilloedema and retinal
haemorrhages
• haematuria and renal failure due to renal arteriolar
fibrinoid necrosis
• severe headache and cerebral haemorrhage
 Morphologic Changes:
 Small arteries and arterioles:
• There is intimal thickening with consequent
luminal narrowing due to hyperplastic
(proliferative) arteriosclerosis (endarteritis) also
called "onion-skin" lesion - found mainly in the
renal interlobular arteries and consists of loosely
arranged layers of modified smooth muscle cells.
• Damage to blood vessels may be accompanied by
intravascular coagulation which worsens the
endothelial cell damage.
• Passage of blood at high pressure through these
vessels causes red cell fragmentation – micro-
angiopathic haemolytic anaemia.
• Hallmark is fibrinoid necrosis (necrotizing
arteriolitis) of small arteries and arterioles
manifested by:
• focal area of pyknosis
• polymorph infiltration
• intramural extravassation of red cells
• fibrin thrombosis of the lumen which may cause small
infarcts.
• Kidney is the most affected organ
• Vessels involved are the afferent glomerular arterioles
and distal interlobular arteries
• May extend into the glomerulus and rupture of
capillaries produces visible petechial haemorrhages on
the cortical surface of the kidney giving it a "flea
bitten" appearance on gross examination.
HYPERPLASTIC ARTERIOSCLEROSIS
HYPERPLASTIC ARTERIOSCLEROSIS
FIBRINOID NECROSIS
MALIGNANT NEPHROSCLEROSIS