Pathology of Hypertension PDF

PATHOLOGY OF HYPERTENSION OUTLINE INTRODUCTION EPIDEMIOLOGY PATHOGENESIS MORPHOLOGY AUTOPSY FINDINGS REFERENCES INTRODUCTION Hypertension is raised pressure within any vascular bed eg systemic hypertension, pulmonary hypertension, portal hypertension Without qualification,...

PATHOLOGY OF HYPERTENSION OUTLINE INTRODUCTION EPIDEMIOLOGY PATHOGENESIS MORPHOLOGY AUTOPSY FINDINGS REFERENCES INTRODUCTION Hypertension is raised pressure within any vascular bed eg systemic hypertension, pulmonary hypertension, portal hypertension Without qualification, hypertension is usually synonymous with systemic arterial hypertension. Its main clinical importance is as a major risk factor for cardiovascular diseases INTRODUCTION… Systemic and local tissue blood pressures must be maintained within a narrow range to prevent untoward consequences. Low pressures (hypotension) result in inadequate organ perfusion and can lead to dysfunction or tissue death. Conversely, high pressure (hypertension) can cause end organ damage EPIDEMIOLOGY Hypertension is a worldwide epidemic 26% of the world’s population affected Prevalence in the US estimated to be about 34% Primary contributor to heart disease and stroke, the 1st and 3rd leading causes of death worldwide respectively Blacks have the highest rates of hypertension, with an increasing prevalence AETIOLOGY In 95% of cases of hypertension there is no detectable cause; such patients are said to have primary or essential hypertension. In the remaining cases, hypertension is secondary to an underlying condition, often renal disease, alcohol misuse, or, occasionally, an endocrine disorder. AETIOLOGY… Hypertension has been classified into a ‘benign’ form, in which the prognosis is measured in decades, and a ‘malignant’ or accelerated form, which, if untreated, is universally fatal within 2 years. BLOOD PRESSURE REGULATION Blood pressure is determined by vascular resistance and cardiac output. Vascular resistance is regulated at the level of the arterioles, influenced by neural and hormonal inputs. Cardiac output is determined by heart rate and stroke volume, which is strongly influenced by blood volume. Blood volume in turn is regulated mainly by renal sodium excretion or resorption. BLOOD PRESSURE REGULATION… Renin, a major regulator of blood pressure, is secreted by the kidneys in response to decreased blood pressure in afferent arterioles. In turn, renin cleaves angiotensinogen to angiotensin I; subsequent endothelial catabolism produces angiotensin II, Angiotensin II regulates blood pressure by increasing vascular SMC tone and by increasing adrenal aldosterone secretion, thereby increasing renal sodium resorption. PATHOGENESIS The etiology and pathogenesis of secondary hypertension has been better understood, whereas that of essential hypertension remains largely obscure. In general, normal blood pressure is regulated by 2 haemodynamic forces—cardiac output and total peripheral vascular resistance. Factors which alter these two factors result in hypertension. Mechanisms of Essential hypertension 1. Genetic Factors: supported by occurrence of hypertension in twins, epidemiologic data, experimental animal studies and identification of hypertension susceptibility gene (angiotensinogen gene) 2. Environmental factors such as stress, obesity, smoking, physical inactivity, and heavy salt consumption all are implicated in hypertension. Mechanisms of Essential hypertension… 3. Insufficient renal sodium excretion in the presence of normal arterial pressure may be a key initiating event in essential hypertension and, indeed, a final common pathway for the pathogenesis of hypertension. Insufficient sodium excretion leads to an increase in fluid volume, increased cardiac output, and peripheral vasoconstriction, thereby elevating blood pressure. At the higher blood pressure, enough additional sodium is excreted by the kidneys to equal intake and prevent further fluid retention. Thus a new steady state of sodium balance is achieved (“resetting of pressure natriuresis”), but at the expense of an increase in blood pressure. Mechanisms of Secondary Hypertension Renovascular hypertension: causes decreased glomerular flow and pressure in the afferent arteriole of the glomerulus initiating RAAS Primary hyperaldosteronism: one of the most common causes of secondary hypertension. It may be idiopathic or less commonly caused by aldosterone secreting adrenal adenomas Single-gene disorders cause severe but rare forms of hypertension. Mutations affecting proteins that influence sodium reabsorption. PATHOLOGY OF HYPERTENSIVE VASCULAR DISEASE Arteriosclerosis is a general term used to include all conditions with thickening and hardening of the arterial walls. It has five morphologic entities i. Senile arteriosclerosis (affects arteries) ii. Hypertensive arteriolosclerosis (affects arterioles) iii. Mönckeberg’s arteriosclerosis iv. Medial calcific sclerosis) (affects arteries) v. Atherosclerosis (affects arteries) PATHOLOGY OF HYPERTENSIVE VASCULAR DISEASE… Hypertensive arteriosclerosis has three common forms: 1) Hyaline arteriolosclerosis, 2) Hyperplastic arteriolosclerosis 3) Necrotising arteriolitis Hyaline Arteriosclerosis Hyaline sclerosis is a common arteriolar lesion that may be seen physiologically due to ageing, or may occur pathologically In benign nephrosclerosis in hypertensives and as a part of microangiopathy in diabetics Exact pathogenesis unknown but thought to be due to: Leakage of component of plasma across the vascular endothelium Immunologic reaction Normal aging process exaggerated in hypertension and Diabetes Morphology Gross: The visceral arterioles are particularly involved. The vascular walls are thickened and the lumina narrowed or even obliterated. Microscopically: The thickened vessel wall shows structureless, eosinophilic, hyaline material in the intima and media Hyaline Arteriosclerosis Thickened arteriolar wall with increased protein deposition and markedly narrowed lumen Hyaline Arteriosclerosis Hyperplastic Arteriosclerosis The hyperplastic or proliferative type of arteriolosclerosis is a characteristic lesion of malignant hypertension; Other causes include haemolytic-uraemic syndrome, scleroderma and toxaemia of pregnancy. The pathogenesis is thought to result from changes following endothelial injury from systemic hypertension, hypoxia or immunologic damage leading to increased permeability. A healing reaction occurs in the form of proliferation of smooth muscle cells with fibrosis. Morphology Gross: Luminal and thickening of the vessel walls especially the intima Hyperplastic Arteriosclerosis… Microscopically: Onion Skin lesion: loosely placed concentric layers of hyperplastic smooth muscle cells, with thickening of the walls and luminal narrowing  Hyperplastic Arteriosclerosis nion-skinning) causing luminal obliteration (arrow) Necrotising Arteriolitis Necrotising arteriolitis occurs in vessels in which there is sudden and great elevation of pressure The changes seen are said to result from direct physical injury to the vessel wall. Morphology of Necrotising Arteriolitis Hyaline sclerosis Fibrinoid necrosis of vessel wall Acute inflammatory infiltrate of neutrophils in the adventitia Oedema and haemorrhages often surround the affected vessels Pathology of Hypertensive Disease in the Brain Hypertension is the risk factor most commonly associated with deep brain parenchymal hemorrhages, It accounts for more than 50% of clinically significant hemorrhages and for roughly 15% of deaths among individuals with chronic hypertension. Hypertensive intraparenchymal hemorrhage may originate in the putamen (50% to 60% of cases), thalamus, pons, cerebellar hemispheres (rarely), and other regions of the brain Pathology of hypertensive Disease in the Brain Hypertension leads to a number of vessel wall abnormalities: accelerated atherosclerosis in larger arteries Hyaline arteriosclerosis in smaller arteries Proliferative changes and frank necrosis of arterioles in severe cases Pathology of hypertensive Disease in the Brain… Arteriolar walls affected by hyaline change are thickened but more vulnerable to rupture than normal vessels Most hypertensives over middle age have microaneurysms in very small cerebral arteries in the brain tissue. Rupture of one of the numerous microaneurysms is believed to be the cause of intracerebral haemorrhage. Morphology of hypertensive Disease in the Brain Acute primary intraparenchymal hemorrhages are characterized by a central core of clotted blood that compresses the adjacent parenchyma This compression leads to secondary infarction of the affected brain tissue, with anoxic neuronal and glial changes as well as edema. Eventually the edema resolves, hemosiderin- and lipid- laden macrophages appear Morphology of hypertensive Disease in the Brain… proliferation of reactive astrocytes is seen at the periphery of the lesion Rarely, blood may rupture through the surface of the brain into the subarachnoid space. Morphology of hypertensive Disease in the Brain… After a few weeks to months, the haematoma undergoes resolution with formation of a slit-like space called apoplectic cyst which contains yellowish fluid. Old hemorrhages show areas of parenchymal cavitary destruction with a rim of brownish discoloration. Massive hypertensive ganglionic hemorrhage rupturing into a lateral ventricle.  Fibrosis and thickening of the arteriolar walls in the basal ganglia and subcortical white matter PATHOLOGY OF HYPERTENSION IN THE EYE Normally, the thin walls of retinal arterioles permit a direct visualization of the circulating blood by ophthalmoscopy. There is thickening of the arteriolar walls changing the ophthalmic perception of the circulating blood The vessels may appear narrowed, and the color of the blood column may change from bright red to copper and to silver depending on the degree of vascular wall thickness PATHOLOGY OF HYPERTENSION IN THE EYE… Retinal arterioles and veins share a common adventitial sheath. Therefore, in pronounced retinal arteriolosclerosis the arteriole may compress the vein at points where both vessels cross Venous stasis distal to arteriolar-venous crossing may precipitate occlusions of the retinal vein branches. PATHOLOGY OF HYPERTENSION IN THE EYE… In malignant hypertension, vessels in the retina and choroid may be damaged with morphologic features characterised by necrotising arteriolitis and fibrinoid necrosis of retinal arterioles. Damage to choroidal vessels may produce focal choroidal infarcts, seen clinically as Elschnig spots The ophthalmoscopic finding of a macular star—a spoke-like arrangement of exudate in the macula in malignant hypertension—results from exudate accumulating in the outer plexiform layer of the macula that is oriented obliquely instead of perpendicular to the retinal surface. PATHOLOGY OF HYPERTENSION IN THE EYE… Occlusion of retinal arterioles may produce infarcts of the nerve fiber layer of the retina Axoplasmic transport in the nerve fiber layer is interrupted at the point of axonal damage, and accumulation of mitochondria at the swollen ends of damaged axons creates the histologic illusion of cells (cytoid bodies). Collections of cytoid bodies populate the nerve fiber layer infarct, seen ophthalmoscopically as “cotton-wool spots” The wall of the retinal arteriole (arrow) is thick. There is an exudate (e) in the retinal outer plexiform layer The diameter of the arterioles is reduced, and the color of the blood column appears to be less saturated (copper wire– like) the vein is compressed where the sclerotic arteriole crosses over it PATHOLOGY OF HYPERTENSIVE HEART DISEASE (HHD) Hypertensive heart disease is the 2 nd most common form of heart disease after Ischemic heart disease (IHD) Manifest as left ventricular hypertrophy (LVH) Stimulus to LVH is pressure overload in systemic hypertension. Both genetic and haemodynamic factors contribute to LVH. The stress of pressure on the ventricular wall causes increased production of myofilaments, myofibrils, other cell organelles and nuclear enlargement. PATHOLOGY OF HYPERTENSIVE HEART DISEASE… Since the adult cardiac fibres do not divide, the fibres are hypertrophied. However, the sarcomeres may divide to increase the cell width. The minimal pathologic criteria for the diagnosis of systemic HHD are the following: (1) left ventricular hypertrophy (usually concentric) in the absence of other cardiovascular pathology (2) a clinical history or pathologic evidence of hypertension in other organs (e.g., kidney). Morphology of Hypertensive Heart Disease Gross: Hypertension induces left ventricular pressure overload hypertrophy, initially without ventricular dilation. As a result, the left ventricular wall thickening increases the weight of the heart disproportionately to the increase in overall cardiac size The heart weight may exceed 500 g, and the left ventricular wall thickness may exceed 2.0 cm. Over time, the increased thickness of the left ventricular wall, associated with increased interstitial connective tissue, imparts a stiffness that impairs diastolic filling, often leading to left atrial enlargement. Morphology of HHD… Microscopically: the earliest change of systemic HHD is an increase in the transverse diameter of myocytes, which may be difficult to appreciate on routine microscopy. At a more advanced stage, variable degrees of cellular and nuclear enlargement become apparent, often accompanied by perivascular and interstitial fibrosis. There is marked concentric thickening of the left ventricular wall causing reduction in lumen size. PULMONARY HYPERTENSION Pulmonary hypertension is defined as a mean pulmonary artery pressure greater than or equal to 25mm at rest. Varied causes Morphology of Pulmonary Hypertension Medial hypertrophy of the pulmonary muscular and elastic arteries Right ventricular hypertrophy Plexiform lesions (a tuft of capillary formations in dilated thin walled arterial branches ) is seen in advanced cases A) Atheroma like changes usually limited to large vessels B) Marked medial hypertrophy Pulmonary Hypertensive Heart Disease Cor pulmonale or pulmonary heart disease is the disease of right side of the heart resulting from disorders of the lungs. It may be acute or chronic; the latter is more common. Chronic lung diseases as well as diseases of the pulmonary vessels cause increased pulmonary vascular resistance. The most common underlying mechanism causing pulmonary hypertension is by pulmonary vasoconstriction, activation of coagulation pathway and obliteration of pulmonary arterial vessels. Pulmonary Hypertensive Heart Disease… Pulmonary hypertension causes pressure overload on the right ventricle and hence right ventricular enlargement. Initially, there is right ventricular hypertrophy, but as cardiac decompensation sets in and right heart failure ensues, dilatation of right ventricle occurs. it should also be remembered that pulmonary hypertension most commonly occurs as a complication of left-sided heart disease. Morphology of Pulmonary Hypertensive Heart Disease In acute cor pulmonale there is marked dilation of the right ventricle without hypertrophy. On cross-section, the normal crescent shape of the right ventricle chamber is transformed to a dilated ovoid. In chronic cor pulmonale, the right ventricular wall thickens, sometimes up to 1.0 cm or more Sometimes, the hypertrophied right ventricle compresses the left ventricular chamber or leads to regurgitation and fibrous thickening of the tricuspid valve. The right ventricle is markedly dilated and has a thickened free wall and hypertrophied trabeculae The shape of the left ventricle (to the right) has been distorted by the enlarged right ventricle. PATHOLOGY OF HYPERTENSION IN THE KIDNEYS Hypertension is intimately linked with the Kidneys because renal diseases can be both a cause and a consequence of hypertension Lesions associated with hypertension include nephrosclerosis and renal artery stenosis Nephrosclerosis Nephrosclerosis is the term used for the renal pathology associated with sclerosis of renal arterioles and small arteries It is strongly associated with hypertension Nephrosclerosis at autopsy is associated with advanced age, is more frequent in blacks than in whites It may be seen in the absence of hypertension. Nephrosclerosis… Two processes participate in the arterial lesions: Medial and intimal thickening; a response to hemodynamic changes, aging, genetic defects, or some combination of these Hyalinization of arteriolar walls, caused by extravasation of plasma proteins through injured endothelium and by increased deposition of basement membrane matrix Nephrosclerosis… The narrow lumen of the vessels caused by the thickened walls lead to focal parenchymal ischemia Ischemia leads to glomerulosclerosis and chronic tubulointerstitial injury, and it produces a reduction in functional renal mass. Morphology of Nephrosclerosis Gross: The kidneys are either normal or moderately reduced in size, with average weights between 110 and 130 g. The cortical surfaces have a fine, even granularity that resembles grain leather The loss of mass is due mainly to cortical scarring and shrinking. Morphology of Nephrosclerosis… On histologic examination, there is narrowing of the lumens of arterioles and small arteries, caused by thickening and hyalinization of the walls (hyaline arteriolosclerosis) Intimal thickening due to proliferation of smooth muscle cells in the intima. Atrophy of the parenchyma Close-up of the gross appearance of the cortical surface in benign nephrosclerosis illustrating the fine, leathery granularity of the surface. Hyaline arteriolosclerosis. High-power view of two arterioles with hyaline deposition, marked thickening of the walls, and a narrowed lumen. Malignant Nephrosclerosis Malignant nephrosclerosis is the form of renal disease that occurs in malignant or accelerated hypertension. Malignant nephrosclerosis is uncommon and usually occurs as a superimposed complication in 5% cases of pre-existing benign essential hypertension It can also occur in those having secondary hypertension with identifiable cause such as in chronic renal diseases. However, the pure form of disease also occurs, particularly at younger age with preponderance in males. Morphology of Malignant Nephrosclerosis Gross: In a case of malignant hyper tension superimposed on pre-existing benign nephrosclerosis, the kidneys are small in size, shrunken and reduced in weight with a fine granular surface However, the kidneys of a patient who develops malignant hypertension in pure form are enlarged, oedematous and have petechial haemorrhages (‘flea- bitten kidney’).* Cut surface will show red and yellow mottled appearance Morphology of Malignant Nephrosclerosis… Microscopically: The changes are usually superimposed on benign nephrosclerosis. Hyperplastic intimal sclerosis or onionskin proliferation characterised by concentric laminae of proliferated smooth muscle cells, collagen and basement membranes. Necrotising arteriolitis develops on hyaline arteriolosclerosis. The vessel wall shows fibrinoid necrosis, a few acute inflammatory cells and small haemorrhages. Tubular loss, fine interstitial fibrosis and foci of infarction necrosis. Renal Artery Stenosis Unilateral renal artery stenosis is responsible for 2% to 5% of hypertension cases Hypertension secondary to renal artery stenosis is caused by increased production of renin from the ischemic kidney. Morphology of Renal Artery Stenosis The most common cause of renal artery stenosis (70% of cases) is narrowing at the origin of the renal artery by an atheromatous plaque. This occurs more frequently in men, and the incidence increases with advancing age. The plaque is usually concentrically placed, and superimposed thrombosis often occurs. Morphology of Fibromuscular Dysplasia The second most frequent cause of stenosis is fibromuscular dysplasia of the renal artery. This heterogeneous entity is characterized by fibrous or fibromuscular thickening that may involve the intima, the media, or the adventitia of the artery The ischemic kidney is reduced in size and shows signs of diffuse ischemic atrophy Morphology of Fibromuscular Dysplasia… The arterioles in the ischemic kidney are usually protected from the effects of high pressure, thus showing only mild arteriolosclerosis. In contrast, the contralateral nonischemic kidney may show more severe arteriolosclerosis, depending on the severity of the hypertension. Fibromuscular dysplasia of the renal artery, medial type, showing marked fibrous thickening, and the lumen is stenotic. (Elastic Van Gieson Stain) PORTAL HYPERTENSION Increase in pressure in the portal system usually follows obstruction to the portal blood flow anywhere along its course. Portal veins have no valves and thus obstruction anywhere in the portal system raises pressure in all the veins proximal to the obstruction. Normal portal blood pressure is 5-10mmHg The pathophysiology of portal hypertension is complex and involves resistance to portal flow at the level of sinusoids and an increase in portal flow caused by hyperdynamic circulation Portal Hypertension.. Cirrhosis is by far the commonest cause of portal hypertension Cirrhosis is a diffuse liver disease characterised by effacement of normal lobular architecture, formation of nodules separated by fibrous septa and alternate areas of hepatocellular necrosis and regenerative nodules. Major Clinical Consequences of Portal Hypertension Morphology of Liver Cirrhosis Cirrhosis is marked by the presence of parenchymal nodules surrounded by dense bands of fibrosis throughout the liver, converting the normally smooth liver capsule into a bumpy surface with depressed areas of scarring and bulging regenerative nodules The size of the nodules, pattern of scarring, the degree of parenchymal collapse and the extent of vascular thrombosis all vary between diseases and to an extent between individuals with the same disease. Cirrhosis from chronic viral hepatitis Bulging regenerative nodules can be seen on the liver surface AUTOPSY FINDINGS History : Middle aged to elderly adult May be a known hypertensive General exam: obese Facial deviation Leg swelling Abdominal swelling AUTOPSY FINDINGS… Brain: Intracerebral haematoma, subarachnoid bleeding or intraventricular bleeding Older lesions usually undergo organization to leave a cystic gliotic cavity Hyaline arteriosclerosis AUTOPSY FINDINGS… Heart: Enlarged Weight >350g Left ventricular wall thickness >1.5cm Papillary muscles may be hypertrophied Right ventricular wall is thickened with trabeculations especially in those with longstanding pulmonary hypertension Valvular dimensions usually deranged AUTOPSY FINDINGS… Lungs Lungs are heavy if there was pulmonary oedema Cut surface may show oozing frothy fluid Medial hypertrophy of the arteries AUTOPSY FINDINGS… Kidneys: Size may be normal or reduced Fine granularity and scarring of the cortical surfaces Medial and intimal thickening Hyalinization Onion skin lesions in malignant hypertension Liver: Scarring and bulging regenerative cirrhotic nodules REFERENCES Textbook of Pathology by Harsh Mohan Underwood General and Systemic Pathology Muir’s Textbook of Pathology, 15th edition Robbins Basic Pathology Robbins and Cotran, 10th edition Robbins and Cotran Atlas of Pathology THANK YOU