Hypertension & Pathological Consequences PDF

32 Hypertension and its pathological consequences ILOs By the end of this lecture, students will be able to  Understand the definition of hypertension.  Discuss mechanisms, causes and types of hypertension.  Understand the pathological consequences of raised arterial pressure Definitions There is...

32 Hypertension and its pathological consequences ILOs By the end of this lecture, students will be able to  Understand the definition of hypertension.  Discuss mechanisms, causes and types of hypertension.  Understand the pathological consequences of raised arterial pressure Definitions There is a continuous spectrum of arterial blood pressures within the population. It is not a bimodal distribution with one group in whom blood pressure is ‘ normal ’ and a clear dividing line to the ‘ abnormal ’ pressure group. There is disagreement as to whether systolic pressure or diastolic pressure is the most important indicator for a decision to initiate treatment for hypertension There is also no clear internationally agreed definition as to what constitutes hypertension. The pragmatic definition of hypertension advanced in 1971 by Professor Geoffrey Rose is still appropriate, i.e. ‘ That level of blood pressure above which investigation and treatment do more good than harm. Nevertheless, sustained diastolic pressures greater than 90 mm Hg or sustained systolic pressures in excess of 140 mm Hg are reliably associated with an increased risk for atherosclerosis and are therefore used as cutoffs in diagnosing hypertension in clinical practice. Nevertheless, sustained diastolic pressures greater than 90 mm Hg or sustained systolic pressures in excess of 140 mm Hg are reliably associated with an increased risk for atherosclerosis and are therefore used as cutoffs in diagnosing hypertension in clinical practice. (Mild / Benign hypertension): In people with systolic pressures between 140 and 159 mm Hg or diastolic pressures between 90 and 99 mm Hg other factors must be part of the decision to treat. 1 Malignant or accelerated hypertension: patients may present with uncontrolled hypertension and blood pressures perhaps in excess of 220/120 mm Hg. It is vitally important to initiate treatment immediately in this group. Mechanisms of hypertension Mean arterial blood pressure = Cardiac output X Total peripheral resistance All forms of established hypertension are primarily associated with an increase in the resistance to blood flow. There may be changes in cardiac output in the early stages of the development of some forms of hypertension but, fundamentally, raised resistance in the arterioles is the basic mechanism for established hypertension. o Causes of hypertension 1. Essential (90-95%) Idiopathic hypertension. o In this group there is no single definable mechanism but there have been a large number of factors: o Several genetic polymorphisms o Environmental factors (e.g stress) o Reduced renal sodium excretion. o Increased vascular resistance. 2. Secondary (5-10%) a physiologically definable cause o Renal disease commonest cause of 2ry HT (linked to increased activity of the reninangiotensin system) 2 o Phaeochromocytoma (linked to raised adrenal medulla catecholamine secretion) o Conn’s syndrome (linked to raised adrenal cortex aldosterone secretion). o Pathological consequences of raised arterial pressure, 1. Hypertension is a risk factor for the development of atherosclerosis and will accelerate its development in large arterial blood vessels. However, the structure of the lesions produced is the same as in normotensive subjects. In addition there are changes in the vascular wall which are selective responses to hypertension. These include thickening of the media layer of muscular arteries as a result of smooth muscle hyperplasia and collagen deposition. The latter changes occur in small arteries and arterioles rather than the large vessels affected by atherosclerosis 2. Hyaline arteriolosclerosis, is associated with benign hypertension.  It is marked by homogeneous, pink hyaline thickening of the arteriolar walls, with loss of underlying structural detail, and luminal narrowing.  The lesions stem from leakage of plasma components across injured ECs into vessel walls, and increased ECM production by SMCs in response to chronic hemodynamic stress. 3. 4. 5.  In the kidneys, the arteriolar narrowing caused by hyaline arteriosclerosis leads to diffuse vascular compromise and nephrosclerosis (glomerular scarring). These pathological changes lead to --------nephron loss and the ultimate development of chronic renal failure. The nephron loss leads to--- exacerbation of the hypertension, a vicious circle Hyperplastic arteriolosclerosis Is more typical of severe hypertension. Vessels exhibit “onion skin,” concentric, laminated thickening of arteriolar walls and luminal narrowing. The laminations consist of SMCs and thickened, reduplicated basement membrane. In malignant hypertension, these changes are accompanied by fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitis), which are particularly prominent in the kidney. Other vascular disorders associated with hypertension include – Intracerebral haemorrhage, – Dissecting aneurysm of the aorta and – Subarachnoid haemorrhage due to the rupture of berry aneurysms. Data suggest that about 62% of cerebrovascular disease and 49% of ischaemic heart disease can be attributed to inadequate management of hypertension. Hypertensive heart disease: is a consequence of the increased demands placed on the heart by hypertension, causing pressure overload and ventricular hypertrophy. Myocyte hypertrophy is an adaptive response to pressure overload in which sarcomeres are added in parallel to the original sarcomeres (remodeling), there are limits to myocardial 3 adaptive capacity, however, and persistent hypertension eventually can culminate in dysfunction, cardiac dilation, CHF, and even sudden death. A. Systemic (left-sided) hypertensive heart disease; There is marked concentric thickening of the left ventricular wall causing reduction in lumen size. Note also the left atrial dilation due to stiffening of the left ventricle and impaired diastolic relaxation, leading to atrial volume overload. Left ventricular hypertrophy in the absence of other cardiovascular pathology (e.g., valvular stenosis), History or pathologic evidence of hypertension.  The heart weight can exceed 500 g (normal for a 60- to 70-kg individual is 320 to 360 g), and the left ventricular wall thickness can exceed 2.0 cm (normal is 1.2 to 1.4 cm).  With time, the increased left ventricular wall thickness imparts a stiffness that impairs diastolic filling and can result in left atrial dilation.  In long-standing systemic hypertensive heart disease leading to congestive failure, the hypertrophic left ventricle typically is dilated. B. Chronic cor pulmonale; The right ventricle is markedly dilated and hypertrophied with a thickened free wall and hypertrophied trabeculae 4