Download HYPERTENSIVE VASCULAR DISEASE

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 (20-100m)
Note- Arterioles are the principal points of physiologic resistance to blood
flow.
• Capillaries(7-8m) 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 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 - 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.