Hypertensive vascular disease By: Dr. S.Homathy. Normal vessels Main components of vascular walls are Intima – endothelial cells Media – smooth muscle.

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 diseaseCerebrovascular accident

• Also cause cardiac hypertrophy and Heart failure

(hypertensive heart disease)Aortic dissectionRenal failure

Will discuss about – Normal blood pressure control– Possible mechanisms of hypertension– Pathologic changes in small blood vessels

Normal blood pressure controlBP = Cardiac out put × Peripheral resistance

Blood volume SodiumMineralocorticoidsANP

Peripheral resistanceHumoral factorsConstrictors

Ang IICatecholamineThromboxane

LT3DilatorsPG

KininsNOLocal factors

AutoregulationsIonic(pH, hypoxia

Neural factors

Constrictors

Dilators

Physiological mechanisms to maintain normal blood

pressure

1. Autonomic nervous system response

2. Hormonal responses

3. Capillary shift mechanism

4. 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 areadrenaline 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 hypertensionUsually asymptomaticMost cases discovered when pressure is

measured at a routine medical examinationAffects 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 HTDBP >120mmHg + renal failure + retinal

hemorrhages and exudates with or without papilledema

– It also causes Cardiac failureCVAHypertensive 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

Environmental factors Genetic 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 homeostasisInadequate sodium excretionSalt and water retensionIncrease plasma and ECF volumeIncreased 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 HTMetabolic 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 byfibrinoid 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

LVH, CHD, CHF

Chronic kidney diseaseRetinopathyPeripheral

arterialdisease

Transient ischemic attack, stroke

Hypertensive heart diseaseLVF sustained pressure load on LV myocardium• Metabolic requirement of hypertrophic myocardium

increased• Hypertrophic myocardium become stiff

increasing wall tensionSimultaneous 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 patternConcentric hypertrophy

• Some times involve the septal area- mimicking hypertrophic cardiomyopathy

• Size of the chamberNormal in the early stageDilation is common in long – standing

• As LV failure progresses-RV 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 - commonLung diseases

COPD Chronic interstitial fibrosing diseaseChronic hypoxia with destruction of vascular bedHigh altitude hypoxiaExtra parenchymal restrictive lung disease

Cardiac diseasesLeft to right shunt

Inflammatory vascular diseasesRecurrent 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 vasoconstrictionReduced surface area of the pulmonary vascular

bedIncreased 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 a multichanneledoutpouching of the pulmonary arterial wall

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.

Thank you