COMMONWEALTH OF AUSTRALIA
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SYSTEMIC HYPERTENSION
Dr A. Barbour, Discipline of Pathology.
Copyright: University of Adelaide. 2010.
To understand the pathology of systemic hypertension you need a background understanding of
• The normal histological structure and function of arteries and arterioles
• The physiology of blood pressure regulation, including the role of baroreceptors, kidneys, adrenal glands (cortex and
medulla), regulatory centres in the medulla, and sympathetic and parasympathetic nervous systems
• Atherosclerosis, thrombosis, embolism, ischaemia and infarction
• Age related changes in the walls of blood vessels including hyaline arteriolosclerosis
• Cardiac physiology including the Frank Starling mechanism
• Cardiac failure
• Concentric and eccentric myocardial hypertrophy
• Ischaemic heart disease
Physiology:
Blood pressure must be closely regulated:
• High enough to enure sufficient driving pressure for propelling blood to the tissues
• Not so high that it creates extra work for the heart and causes vessel damage
Mean Arterial Pressure is influenced by Cardiac Output (CO) and Peripheral Resistance (PR)
Cardiac output is influenced by
• Cardiac factors: heart rate, stroke volume: both increased by sympathetic stimulation (humoral and neural); heart rate
reduced by parasympathetic stimulation
• Blood volume: influenced by renal sodium and water excretion which are influenced by renal blood flow, aldosterone,
antidiuretic hormone, atrial natriuretic peptide
Peripheral resistance is determined by the tone of arterioles which is influenced by
• Humoral factors: constrictors (e.g. circulating angiotensin II, catecholamines), dilators
• Local factors: autoregulation, hypoxia, pH
• Neural factors: sympathetic stimulation -> constriction
Changes in blood pressure are detected by baroreceptors, and changes in blood volume and flow by left atrial volume receptors
and the kidney.
Regulation of BP is a complex process involving a variety of systems (heart, vascular tone, renal, endocrine) interacting in a
complex fashion.
Age related vascular changes: arteriosclerosis and arteriolosclerosis
• Aorta:
• Media: fragmentation of elastin and increase in collagen -> loss of distensibility and elasticity (aorta becomes stiffer)
• Intima: intimal fibrosis and thickening
• Diameter increases slightly and aorta may become tortuous
• Small and medium arteries: mild medial and intimal fibrosis, elastic fibre fragmentation. Sometimes medial calcification (medium ar
• Arterioles: haemodynamic stress leads to increased endothelial permeability with deposition of plasma proteins in wall,
increased extracellular matrix production and smooth muscle atrophy. The arteriole wall becomes thickened by homogenous
eosinophilic glassy material (‘hyaline’) and the lumen narrowed: arteriolar hyalinosis/hyaline arteriolosclerosis.
These changes may cause a slight increase in BP with age.
Systemic hypertension: Blood pressure is a continuous variable, with progressively increasing BP associated with a
progressively increasing risk of complications.
No rigidly defined threshold for BP above which a person is at risk for complications but a sustained rise in diastolic pressure
above 90 mmHg and/or systolic pressure above 140 mmHg is a guide. Affected persons also often have other risk factors for
cardiovascular disease.
Systemic hypertension is common. It affects approx. 30% of Australian adults, approx one half of these are undiagnosed.
There are primary/essential (90%) and secondary (10%) forms and ‘benign’ and ‘malignant’ forms.
High blood pressure itself generally causes no symptoms. Its complications are largely mediated by its effects on arteries and
arterioles.
The risk of vascular complications increases progressively with BP. Both the diastolic and systolic pressures are important,
though recent evidence suggests that the systolic pressure more accurately reflects cardiovascular risk.
Theory of causation of primary or essential hypertension (no specific cause)
Multifactorial
• Genetic influences are important and multiple genes are involved. Blacks especially are more susceptible and more at risk
of complications. Genetic factors may influence for example
• Sympathetic responses
• Transport of ions across cell membranes in vessels or kidney
• Arteriolar responses to local regulatory factors
• Activity of the renin angiotensin aldosterone system
• High and low renin and ‘non-modulating’ subsets: probable genetic influence
• Lifestyle
• Amount of salt in diet
• Alcohol intake
• Levels of physical activity
• Weight
• Hyperinsulinaemia/insulin resistance (this can influence e.g. renal sodium retention, increased sympathetic activity,
smooth muscle hypertrophy, ion transport across cell membranes)
• Eating an appropriate diet, reducing weight, reducing amount of salt in diet, limiting alcohol intake and increasing
physical exercise can help to control high blood pressure.
• Age and gender: the prevalence of hypertension in premenopausal females is lower than in age-matched males or
postmenopausal women.
Metabolic/insulin resistance syndrome
Characterised by
• Central/visceral obesity
• Atherogenic dyslipidemia (mainly high triglycerides and low HDL cholesterol)
• Insulin resistance
• Raised blood pressure
• Other
Genetic factors and obesity predispose persons to insulin resistance.
The pathogenesis is complex and involves an interaction of genetic factors and metabolic factors related to obesity e.g.
secretion of substances including hormones and cytokines from adipose tissue into blood that can contribute to raised blood
pressure and insulin resistance
Metabolic syndrome is common, affecting a quarter to a third of adults, and its prevalence is rising as obesity and the mean age
of the population increase
Persons are at increased risk of
• Atherosclerosis and related complications contributed to by
• Factors released from adipose tissue may contribute to endothelial dysfunction
• Dyslipidemia
• Hypertension
• Developing type 2 diabetes mellitus
• Complications related to hypertension
• Steatohepatitis, which may lead to cirrhosis of the liver and liver failure
Causes of secondary hypertension (identifiable cause, in many cases treatable)
Systolic hypertension with wide pulse pressure
• Decreased compliance of aorta (arteriosclerosis). Age related medial and intimal changes with additional extracellular
matrix deposition and elastin fragmentation in large arteries including aorta. Arteries are hardened and less elastic
(and dilate slightly) -> elevation of the systolic pressure and widening of the pulse pressure. If excessive -> isolated
systolic hypertension.
• Increased stroke volume e.g. aortic regurgitation, hyperthyroidism, fever
Systolic and diastolic hypertension
• Renal e.g. diabetic glomerulosclerosis, chronic pyelonephritis, certain glomerulonephritides, polycystic renal disease,
chronic renal failure (many causes)
• Endocrine e.g. adrenocortical adenoma producing cortisol or aldosterone, phaeochromocytoma, pituitary adenoma
producing ACTH
• Vascular e.g. coarctation of aorta, renal artery stenosis
• Medications e.g. corticosteroids, oral contraceptives
• Neurogenic/cerebral e.g. raised intracranial pressure
• Other e.g. hypercalcemia, toxaemia of pregnancy, sleep apnoea
Benign hypertension
Common, usually essential (primary), usually develops following young adulthood.
Slow moderate rise in BP. 5% of cases may enter a malignant phase.
Effects:
• Arteries:
• Predisposes to atherosclerosis
• Predisposes to aortic dissection
• Intimal tear -> blood dissects in outer media
• Most commonly arises in ascending aorta
• Complications include aortic rupture; extension of dissection around aortic branches e.g. carotids,
coronaries -> ischaemia/infarction; dissection proximally into pericardial cavity -> haemopericardium and
tamponade. In some cases the blood in the dissection re-enters the aorta.
• Worsens hardening or sclerosis of small, medium and large arteries (occurs to some extent with age anyway):
increased extracellular matrix and elastic fibre fragmentation in intima and media
• Worsens hyaline arteriolosclerosis/arteriolar hyalinosis (also occurs with age): haemodynamic stress leads to
increased endothelial permeability with deposition of plasma proteins in wall, increased extracellular matrix
production and smooth muscle atrophy. Wall becomes thickened by homogenous eosinophilic material
(‘hyaline’) and lumen becomes narrowed.
• Kidneys: hyaline arteriolosclerosis -> chronic glomerular, tubular and interstitial ischaemia -> tiny foci of atrophy of
tubules and glomeruli (-> obsolescence or sclerosis of glomeruli), interstitial fibrosis -> ‘benign
nephrosclerosis’/arteriolar nephrosclerosis/arterionephrosclerosis (kidney smaller with narrowed cortex and
granular surface), sometimes with mild proteinuria. When severe -> impaired renal function and occasionally
chronic renal failure.
• Heart:
• Increased afterload on the left ventricle -> concentric left ventricular hypertrophy (LVH)
• Increased stiffness of LV -> impaired LV diastolic filling -> CCF
• Increased oxygen demand of hypertrophied myocardium may not be met and increased LV diastolic
pressure reduces coronary perfusion pressure gradient -> acute and/or chronic ischaemia -> angina,
subendocardial infarction, LVF and CCF, sudden death from fatal arrhythmia
• Subcellular changes may ultimately contribute to impaired myocyte functioning
• Ischaemic heart disease (IHD) from coronary atherosclerosis
• Brain:
• Hyaline arteriolosclerosis (lipohyalinosis) +/- Charcot-Bouchard microaneurysm formation in small penetrating
arteries/arterioles -> intracerebral haemorrhage. Common sites include basal ganglia/thalamus/internal capsule
(commonest), pons and cerebellum. Hypertensive cerebral vascular damage tends to occur where very small
arteries come directly off medium sized arteries (e.g. lenticulostriate or deep penetrating arteries come directly
off the middle cerebral arteries) and are exposed to unusually high pressures for vessels of their size.
• Cerebral infarction and transient ischaemic attacks (TIA) related to atherosclerosis
• Lacunar infarction: small infarcts (1-15mm), typically in the basal ganglia or brainstem, may be multiple. Arise
due to hypertensive arteriolosclerotic narrowing of small arteries, embolic occlusion or atherosclerotic narrowing
+/- thrombosis of small intracerebral arteries. (In hypertensive and diabetic patients, atherosclerosis may extend
distally into small arteries about 2mm diameter.)
• Role in pathogenesis and rupture of berry aneurysms -> subarachnoid haemorrhage
• Retina: hyaline arteriolosclerosis -> exudates, haemorrhages, microinfarcts, arteriovenous nipping, silver and copper
wiring -> visual disturbance. Changes can be graded,
Progression: Long course but potentially serious side effects. Death may occur due to e.g.
• Congestive cardiac failure
• IHD: Sudden cardiac death or complications of MI
• Intracerebral haemorrhage or cerebral infarction
• Chronic renal failure
• Complications of aortic dissection
Malignant hypertension
Some cases arise de novo, others after a benign phase (more common), more often with secondary HT
Uncommon.
More rapidly progressive rise in BP and BP higher than benign.
Abrupt rise in BP. BP often very high. Diastolic pressure 140+ mmHg
Effects:
• Arterioles: hyperplastic arteriolosclerosis ("onion skin" endarteritis), fibrinoid necrosis, thrombosis of small arteries and
arterioles
• Kidneys: small artery and arteriolar changes as above -> acute glomerular ischaemia and necrosis -> acute renal failure.
Fibrinoid necrosis may extend into the glomeruli, which may also undergo proliferative changes, or total necrosis.
• Heart: acute cardiac failure: acutely increased systemic resistance significantly increases the load on the LV, increasing
oxygen demand and potentially leading to ischaemia with failure and/or pulmonary oedema
• Brain: hypertensive encephalopathy: mechanism uncertain but possibly involves vasodilatation of cerebral arterioles
with altered cerebral blood flow and fibrinoid necrosis of small arteries/arterioles -> disturbance of the blood brain
barrier and cerebral oedema -> raised ICP -> seizures, altered conscious state, herniation
• Retina: papilloedema from raised intracranial pressure, also retinal haemorrhages, exudates, microinfarcts
Progression: Rapid progression over weeks/months. Full-blown syndrome is a medical emergency.
Death may occur due to e.g.:
• Acute renal failure
• Hypertensive encephalopathy
• Acute heart failure