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Hypertensive vascular disease By: Dr. S.Homathy Normal vessels • Main components of vascular walls are • Intima – endothelial cells • Media – smooth muscle cells (SMC) • Adventitia – extra cellular matrix (ECM) + vasavasorum + nerve fibres. Vascular system • Arterial system • Venous system • Lymphatic system Large arteries Large veins Medium arteries Medium veins Small arteries Small veins Arterioles Collecting venules Post capillary venules Capillaries Types of arteries Based on their size and structural features • Large / Elastic arteries • Aorta and its large branches ( subclavian, common carotid, iliac) • Medium / Muscular arteries • Coronary arteries • Renal arteries • Small arteries (<2mm), arterioles (20-100m) Note- Arterioles are the principal points of physiologic resistance to blood flow. • Capillaries(7-8m) have one cell thick wall and large cross sectional area – useful in exchange of diffusible substances Features of veins – Large diameter - 2/3 of systemic blood is in venous system – Large Lumina – Thinner and less organized walls – Valves to prevent reverse flow Veins are predisposed to – Irregular dilation – Compression – Easy penetration by tumors Lymphatics – Thin walled endothelium lined channels – Serve as a drainage system for retaining interstitial tissue fluid to blood – Important pathway for disease dissemination – bacteria, tumour cells Functions of endothelial cells – Maintenance of permeability barrier – Elaboration of anticoagulant and antithrombotic molecules – Elaboration of prethrombotic molecules – Extra cellular matrix production – Modulation of blood flow and vascular reactivity – Regulation of inflammation and immunity – Regulation of cell growth – Oxidation of LDL Functions of SMCs – Vasoconstriction/dilation in response to normal/pharmacologic stimuli – Synthesize collagen, elastin and proteoglycans – Elaborate growth factors and cytokines – Migrate to the intima and proliferate after injury Vascular disorders Vascular abnormalities cause clinical disease by two mechanisms – Narrowing or completely obstructing the Lumina Progressively- atherosclerosis Precipitously – thrombosis or embolism – Weakening of the walls-leading to dilation or rupture Vascular disease • Congenital anomalies Arteriovenous fistula – some times causes high-out put cardiac failure • Arteriosclerosis Atherosclerosis Monckeberg medial calcific sclerosis Arteriolosclerosis • Hypertensive vascular disease • Aneurysms and dissections • Inflammatory vascular disease. Hypertensive vascular diseases • Hypertension - Elevated blood pressure – DBP >90mmHg – SBP >140mmHg • Affect both the function and structure of blood vessels • HT is a risk factor for atherosclerosis (AS) Coronary heart disease Cerebrovascular accident • Also cause cardiac hypertrophy and Heart failure (hypertensive heart disease) Aortic dissection Renal failure Will discuss about – Normal blood pressure control – Possible mechanisms of hypertension – Pathologic changes in small blood vessels Normal blood pressure control BP = Cardiac out put × Peripheral resistance Blood volume Sodium Mineralocorticoids ANP Constrictors Humoral factors Ang II Catecholamine Thromboxane LT3 Dilators PG Kinins NO Peripheral resistance Local factors Autoregulations Ionic(pH, hypoxia Neural factors Constrictors Dilators Physiological mechanisms to maintain normal blood pressure 1. 2. 3. 4. Autonomic nervous system response Hormonal responses Capillary shift mechanism Kidney and fluid balance mechanisms • Peripheral resistance is regulated predominantly at the level of the arterioles. • It is influenced by neural and hormonal inputs Autonomic nervous system – Most rapidly responding regulator of blood pressure – Control BP by changing blood distribution in the body and by changing blood vessel diameter – Sympathetic and parasympathetic activity will affects veins, arteries and heart – Receives continuous information from the baroreceptors in carotid sinus and the aortic arch – This information is relayed to the brainstem to the vasomotor centre – Vasomotor centre is a cluster of sympathetic neurons found in medulla – It sends efferent motor fibers that innervate smooth muscles of blood vessels – A decrease in blood pressure causes activation of the sympathetic nervous system resulting in increased contractility of the heart and vasoconstriction Hormonal mechanisms – They act in various ways including Vasoconstriction vasodilatation alteration of blood volume • Kidneys and adrenals are central plyers in blood pressure regulation • They interact with each other to modify vessel tone and blood vessel through vrious ways. – The principal hormones raising blood pressure are adrenaline and noradrenaline secreted from the adrenal medulla in response to sympathetic nervous system stimulation »They increase cardiac output and cause vasoconstriction Renin and angiotensin production is increased in the kidney when stimulated by hypotension Capillary fluid shift mechanism – Exchange of fluid that occurs across the capillary membrane between the blood and the interstitial fluid – Low blood pressure results in fluid moving from the interstitial space into the circulation helping to restore blood volume and blood pressure. Kidney and fluid balance mechanism – Regulate the blood pressure by increasing or decreasing the blood volume - changing the GFR leading to increase or decrease reabsorption of Na through renin-angiotensin system –influences both peripheral resistance and sodium homeostasis Secretion of vasodepressor or antihypertensive substances (prostaglandins and nitric oxide) Risk factors of hypertension • Genetic factors • Environmental factors – Diet – excessive salt consumption – Lifestyle – stressful, physical inactivity – Weight – obesity – Alcohol – increased intake – Oral contraceptives Classification of hypertension • Benign hypertension • Malignant hypertension Based on severity Diastolic HT systolic HT Based on type. Primary Secondary Based on aetiology • Benign hypertension Usually asymptomatic Most cases discovered when pressure is measured at a routine medical examination Affects heart and arteries of all sizes – It causes • • • • • IHD Heart failure CVA acceleration of renal disease Malignant HT • Malignant hypertension Develop in previously normotensive persons often superimposed in preexisting benign HT DBP >120mmHg + renal failure + retinal hemorrhages and exudates with or without papilledema – It also causes Cardiac failure CVA Hypertensive encephalopathy Etiological classification of hypertension • Essential hypertension – 95%, idiopathic, combine with long life unless complications develops • Secondary hypertension – 5-10% Renovascular disease/ renal parenchymal disease AGN CRF Renal artery stenosis Polycystic kidney disease Renin producing tumors Endocrine • Adrenocorticalhyperfunction –Cushing’s syndrome –Primary aldosteronism –Congenital adrenal hyperplasia • Exogenous hormones –Oestrogens –OCP »Drug activate renin – angiotesin – aldosterone system –Glucocorticoids –Mineralocorticoids –Sympathomimetics •Phaeochromocytoma •Acromegaly •Hypothyroidism / Hyperthyroidism •DM Cardiovascular • Coarctation of aorta • Rigidity of the aorta • Increased cardiac output Neurogenic • Increased intracranial pressure • Acute stress • Psycogenic Essential hypertension HT occurs when the relationship between blood volume and total peripheral resistance is altered. • Pathogenesis is uncertain • Multifactorial etiology + Genetic factors Environmental factors • Genetic factors Blood pressure tends to run in families children of hypertensive parents tend to have higher BP than age matched children of people with normal BP. • Fetal factors – Low birth weight is associated with subsequent high BP – May be due to fetal adaptation to intrauterine undernutrition with long term changes in blood vessel structure • Insulin resistance – An association between diabetes and hypertension has long been recognized. Genetic factors Defects in the renal sodium homeostasis Inadequate sodium excretion Salt and water retension Increase plasma and ECF volume Increased cardiac output and peripheral vasoconstriction Increased blood pressure. Functional vasoconstriction Defects in the vascular smooth muscle growth and structure. • Environmental factors – – – – Diet – excessive salt consumption Lifestyle – stressful, physical inactivity Weight – obesity Alcohol – increased intake • Environmental factors affect the variables that control BP in the genetically predisposed individuals • In essential HT both increased blood volume and increased peripheral resistance contribute to increased BP. • Humoral mechanism The autonomic nervous system, renin – angiotensin naturetic peptides o play a role in the physiological regulation of short term changes in blood pressure o & have been implicated in the pathogenesis of essential hypertension. – However there is no convincing evidence that the above systems are directly involved in the maintenance of hypertension. Currently favored hypothesis is that high dietary intake of sodium in a genetically predisposed individuals. Failure of excretion by kidney in the face of prolonged high sodium level Increase in naturetic factors One of this factor inhibits Na+-K+-ATP ase Intracellular Ca2+ concentration increases Vasoconstriction in vascular SMC Secondary hypertension • Renal diseases – Account for over 80% of the cases – Common causes are • • • • diabetic nephropathy, chronic glomerulo nephritis, adult polycystic kidney disease renovascular diseases – HT can itself causes or worsen renal disease – Mechanism of BP elevation is primarily due to sodium and water retention, – although there can be inappropriate elevation of plasma renin level. Clinical symptoms of HT • Mild hypertensive patients are usually asymptomatic • High levels of BP may be associated with – Headache – Epistaxis – Nocturia • Malignant HT may be present with – Severe headache – Visual disturbances – Fits – Transient loss of consciousness • Breathlessness may be present owing to LVH or cardiac failure • Patients may present with the symptoms of complications of hypertension. • Attacks of – Sweating – Headache – Palpitation Vascular pathology in hypertension • Accelerates atherogenesis • Degenerative changes in large and medium arteries leads to – aortic dissection – cerebrovascularhaemorrhages • Small vessel changes – Hyaline arteriolosclerosis – Hyperplasticartriolosclerosis Hyaline arteriolosclerosis High BP • leakage of plasma components across vascular endothelium • excessive ECM production by SMCs secondary to chronic hemodynamic stress of HT Metabolic stress in DM • Accentuates EC injury Morphology • Homogenous, pink, hyaline thickening of the walls of arteriole with loss of underlying structural detail narrowing of the lumen. • Major morphologic characteristic of benign nephrosclerosis. Hyperplastic arteriolosclerosis • Related to more acute or sever elevations of blood pressure • Characteristic of but not limited to malignant hypertension. Morphology LM • Onion skin, concentric, laminated thickening of the walls of arterioles with progressive narrowing of the lumina. In electron microscope • laminations are seen to consist of SMCs and thickened and reduplicate basement membrane Fibrinoid necrosis • In malignant HT hyperplastic changes are accompanied by fibrinoid deposits Acute necrosis of the vessel wall Known as Necrotizing arteriolitisparticularly in the kidney. Complications of hypertension Hypertensive retinopathy – Grade I – thickening of artrioles – Grade II – arteriolar spasm – Grade III – haemorrhages – Grade IV - papilloedema Subarachnoid haemorrhage Cerebral haemorrhage • Transient ischemic attack, stroke Hypertension Transient ischemic attack, stroke LVH, CHD, CHF Retinopathy Peripheral arterial disease Chronic kidney disease Hypertensive heart disease LVF sustained pressure load on LV myocardium • Metabolic requirement of hypertrophic myocardium increased • Hypertrophic myocardium become stiff increasing wall tension Simultaneous decrease diastolic filling and stroke volume • • • • No increase in number of capillaries Unable to meet metabolic demand . Chronic HT also predispose to AS Hypertrophic myocardium undergo ischaemic injury • Congestive heart failure • MI • Arrhythmias LVH- morphology •The left ventricle is markedly thickened in this patient with severe hypertension that was untreated for many years. •The myocardial fibres have undergone hypertrophy Gross • Weight of the heart usually increased • Hypertrophy typically involved the ventricular wall in a symmetric ,circumferential pattern Concentric hypertrophy • Some times involve the septal area- mimicking hypertrophic cardiomyopathy • Size of the chamber Normal in the early stage Dilation is common in long – standing • As LV failure progressesRV hypertrophy and dilation Microscopic appearence • Cardiac myocytes are enlarged • Contain large, hyperchromatic, rectangular “box-car “ shaped nuclei. • Superimposed ischaemic changes In the normal heart, • thin layers of perimysium and endomysium surround myocardial bundles and myocytes, respectively. • The walls of the blood vessels also contain adventitial fibroblasts that create an endomysial network. In HHD, • there is hypertrophy of cardiomyocytes and transition of fibroblasts to myofibroblasts. • These changes are associated in early disease with increases in ECM manifest by perivascular fibrosis and fibrosis of the endomysium and perimysium. Pulmonary hypertension(PHT) • Mean pulmonary artery pressure >25mmHg at rest or >30mmHg during exercise • Often caused by – decrease in the cross sectional area of the pulmonary vascular bed – but it may result from increased pulmonary vascular blood flow also Causes of PHT – Primary / idiopathic PHT - less frequent • Secondary PHT - common Lung diseases COPD Chronic interstitial fibrosing disease Chronic hypoxia with destruction of vascular bed High altitude hypoxia Extra parenchymal restrictive lung disease Cardiac diseases Left to right shunt Inflammatory vascular diseases Recurrent thromboembolism Primary PHT • Primary PHT is diagnosed when the cause of PHT to be unknown and all other causative conditions have been excluded. • Male: female= 1:3 Chronic vasoconstriction resulting from vascular hyperactivity PHT Endothelial dysfunction Reduced production of prostacyclin and nitric oxide and increased production of endothelin Promote vasoconstriction + growth factors produced by endothelial cells (endothelin, angiotensin II, thromboxane A2) induce migration and proliferation of SMCs responsible for vascular thickening Secondary PHT • Mechanism of secondary PHT depend on the cause Hypoxic vasoconstriction Reduced surface area of the pulmonary vascular bed Increased right ventricular volume or pressure Clinical features of PHT • Secondary pulmonary vascular sclerosis may develop at any age • C/F reflect underlying disease • Primary pul. Vascular sclerosis almost in young persons • Marked by Fatigue, Syncope and Dyspnoea on exertion and Chest pain • Death usually result from R side heart failure within a few years of the diagnosis. Vascular pathology in PHT All forms of arterial sclerosis involve the entire arterial tree include • Main elastic arteries – atheromas • Medium muscular arteries – proliferation of myointimal cells and SMCs, causing thickness of the intima and media with narrowing of the lumina • Small arteries and arterioles – thickening, medial hypertrophy and reduplication of the internal and external elastic membranes • In severe longstanding HT, additional changes take the form of plexiform lesions, necrotisingarteritis with fibrinoid necrosis and thrombosis The plexiform lesions consist of multichanneledoutpouching of pulmonary arterial wall a the Complications of PHT • Corpulmonale / pulmonary heart diseaes - disease of the R sided cardiac chambers • (Read the causes / disorders predispose to corpulmonale) Morphology Acute corpulmonale • Right Ventricle is usually dilated • After massive pulmonary embolism Ht may be normal size Chronic corpulmonale • R ventricular and atrialhypertophy • In extreme cases thickness of the RV wall may exceed that of LV • Pul. Arteries often contain artheromatous plaques and other lesions of PHT.