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Biology of Disease CH0576

Disordered Cardiovascular Physiology

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Disordered Physiology of CVS

• A potentially vast field.• Necessary to concentrate on a few

specific areas.• The first topic is an aspect which can

be both an underlying cause of further cardiovascular pathology and a disease state in its own right.– HYPERTENSION

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Hypertension

• ‘A sustained elevation of arterial blood pressure’

• It is an enormous health problem for a number of reasons:-

• It is very common• Its effects are often fatal or at least far reaching.• It can be asymptommatic until late in its course.• It increases the risk of development of coronary

heart disease, stroke and peripheral vascular disease.

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Hypertension

– Hence hypertension is closely associated with the commonest causes of death in the elderly in the U.K.

• Coronary Heart Disease (CHD)• Cerebral Vascular Accidents (CVA’s)

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Control of Arterial Blood Pressure

• This variable is dependent upon the interaction of two parameters:-

a) Cardiac Output (HR x SV) b) Peripheral Resistance• An increase in either, or both, of

these parameters will cause an elevation of arterial blood pressure.

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Revision of Blood Pressure Control

• The kidneys and the Cardiovascular Centres of the brain play some very important roles in the regulation and control of arterial blood pressure:-

a) The baroreceptor reflex. b) Renin-Angiotensin system.

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Angiotensin II

• Effects blood pressure by increasinga) peripheral resistance andb) circulating blood volume elevates arterial blood pressure.

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Angiotensin II

• Increasing Peripheral Resistance:– Vasoconstriction (direct effect on

vascular smooth muscle)– Stimulation of vasomotor centres in

brain.– Promotes catecholamine release from

the adrenal medulla.• Adrenaline and noradrenaline increase heart

rate and vigour of contraction.

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Angiotensin II

• Increasing Blood volume:– Stimulates the adrenal cortex to secrete

aldostrone. Increases uptake of Na+ from the DCT of

the kidney tubules. Na+ uptake is accompanied by an

increased uptake of water, hence serving to expand blood volume.

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Angiotensin II

– Angiotensin II also has an effect on the ‘thirst centres’ of the brain.

– The individual is impelled to take in fluids and consume salty food if any is available.

– Once activated this complex homeostatic mechanism is normally regulated by a negative feedback system.

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Hypertension

• An arbitrary level of arterial blood pressure was set at 140/90 mmHg.

• Any sustained elevation above this level was considered as hypertensive.

• The elevation in the diastolic pressure is seen as the most critical.– The heart is relaxed and the elevation is

due to an peripheral resistance to flow.

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Hypertension

• Using this criterion, around 38% of the population were deemed to be hypertensive!

• The arbritary level was then altered-–> 160 mm Hg systolic– and/or > 95 mm Hg diastolic.– The new criterion means that about 18%

of the population are hypertensive.

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Classification

• Hypertension is divided into two classes:-

• Primary (or Essential) - a state in which no specific underlying cause can be identified.– About 90% of cases fall into this

category.–Most often in patients > 40 years.

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Classification

• Primary hypertension is the result of interactions between numerous risk factors:-– Genetic predisposition– obesity– smoking– level of physical activity– alcohol consumption– numerous as yet unidentified factors.

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Classification

• Secondary: Secondary hypertension is associated with a specific underlying disease state, which results in arterial blood pressure being raised.

• Commonest cause of 2° is a reduced blood flow through the kidneys.– triggering the renin-angiotensin

mechanism, elevating blood pressure.

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Hypertension

• Regardless of the cause, most cases of hypertension are ultimately fatal, unless some form of intervention is given.

• Hypertension (of both 1° & 2° types) seems to follow either of two possible clinical courses.

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Clinical Courses• In most cases the progression of

the elevated blood pressure is very slow, and is termed ‘benign’ hypertension.

• In up to 5% of cases the progressive elevation is extremely rapid - this is referred to as ‘accelerated’ or ‘malignant’ hypertension.– Usually following kidney damage

arising from previously benign hypertension.

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Malignant/Accelerated• The rapid increase in blood

pressure causes endothelial damage, which promotes the formation of small thrombi.

• This restricts blood flow and causes red cell destruction.

• Further angiotensin is generated and a vicious circle of elevating blood pressure ensues.

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Pathological Consequences

• The pathological consequences of hypertension are seen in a number of tissues and organ systems:-– Heart– Brain– kidney– Aorta and peripheral vascular system– Eyes.

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Consequences: Heart• Increased pressure within the

vascular system leaves the heart attempting to pump blood against an increasing resistance. stress on heart and vessels heart undergoes hypertrophy LVH is a very poor prognostic indicator Appropriate anti-hypertensive therapy may cause regression of the state.

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Consequences : Brain

• Hypertensives are particularly prone to developing large intracerebral haemorrhages due to the rupture of intracerebral blood vessels.

• The vessels of the brain do not possess the same level of tissue support of other organs of the body. they are particularly susceptible to

rupture by high pressures.

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Consequences : Kidney

• Arteriosclerosis leads to progressive ischaemia (reduction in blood flow) of the nephron.

• There is eventual destruction of the glomeruli and consequent atrophy of the associated renal tubules.

• The patient gradually develops slowly progressive chronic renal failure.

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Consequences : Aorta/Vessels

• Hypertension predisposes to the development of:-– severe atheroma– abdominal aortic aneurysms– peripheral vascular disease caused by

atherosclerosis, is evident by a delayed or absent peripheral pulses.

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Consequences: Eyes

• Hypertension can cause retinal haemorrhage or exudate, potentially leading to blindness.

• Again, the fine vessels of the retina are particularly fragile and lack the structural support of vessels in other tissues.

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Detection

• Despite its seriousness, hypertension is often asymptommatic and is detected by routine measurement of blood pressure.

• It may be detected by the damage it has caused to target organs:– changes in heart sounds, protein in

urine, abnormal peripheral pulses, retinal change on routine eye examination.

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Management of hypertension

• Non-pharmacological : Assessment of hypertension best performed by several measurements of blood pressure in a seated individual on several occasions.

• Some form of intervention is indicated if diastolic pressure is consistently > 100 mm Hg.

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Management of hypertension

• Non-pharmacological management may be enough to control mild HPT.

• In patients requiring pharmacological intervention, some other concomitant measures can help produce better control at lower drug doses.

• Alterations in life style factors are appropriate for reducing blood pressure.

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Management of hypertension

• Life style factors:-– Stopping smoking.– Achieving ideal body weight by

reducing total calorie intake and taking appropriate exercise.

– Avoiding excessive alcohol intake.– Reducing dietary intake of salt.

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Management of hypertension

• Blood pressure can be lowered by 1.5 mm Hg for each kg of body weight lost.

• A reduction or cessation of alcohol intake can decrease blood pressure by 5 - 10 mm Hg.

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Pharmacological Intervention

• Main drugs used in the treatment of hypertension are:– Diuretics– Beta - blockers– Angiotensin Converting Enzyme

inhibitors (ACE inhibitors)– Calcium channel blockers– Alpha - blockers.