Biology of Disease CH0576

1. Biology of Disease CH0576 Disordered Cardiovascular Physiology CH0576

2. 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 CH0576

3. 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. CH0576

4. 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) CH0576

5. 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. CH0576

6. 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. CH0576

7. Angiotensin II • Effects blood pressure by increasing a) peripheral resistance and b) circulating blood volume  elevates arterial blood pressure. CH0576

8. 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. CH0576

9. 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. CH0576

10. 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. CH0576

11. 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. CH0576

12. 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. CH0576

13. 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. CH0576

14. 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. CH0576

15. 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. CH0576

16. 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. CH0576

17. 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. CH0576

18. 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. CH0576

19. 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. CH0576

20. 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. CH0576

21. 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. CH0576

22. 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. CH0576

23. 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. CH0576

24. 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. CH0576

25. 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. CH0576

26. 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. CH0576

27. 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. CH0576

28. 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. CH0576

29. 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. CH0576

30. 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. CH0576