CVSPA01 HYPERTENSION AND ATHROSCLEROSIS

1. DEFINE HYPERTENSION
Hypertension = A sustainable diastolic pressure greater than 90mmHg or a sustainable systolic pressure in excess of 140mmHg is considered to constitute hypertension.
WHO definition: Hypertension is defined a systolic pressure above 160mmHg and/or diastolic pressure above 90mmHg

Medical dictionaries
a. Arterial blood pressure that is higher than the usual range for gender and age. ROBERT SO JR
b. Webster’s : A repeatedly elevated blood pressure exceeding 140 over 90 mmHg. BATCH 15
c. Black’s : High blood pressure (raised pressure of the circulating blood). TAYLORS UNIVERSITY
Pre-hypertension : Systolic 120-139mmHg or diastolic 80-89mmHg
2018/2023
Stage 1 hypertension : Systolic 140-159mmHg or diastolic pressure 90-99mmHg
Stage 2 hypertension : Systolic 160mmHg or higher, diastolic pressure of 100mmHg or higher
2. DISTINGUISH BENIGN FROM MALIGNANT HYPERTENSION BASED ON CLINICAL PRESENTATION AND HISTOPATHOLOGICAL FEATURESS
3. LIST THE COMMON CAUSES FO SECONDARY HYPERTENSION
4. DERIVE THE EFFECTS OF HYPERTENSION ON VARIOUS ORGANS
5. DEFINE ATHEROSCLEROSIS AND EXPLAIN THE ROLE OF ENDOTHELIAL INJURY, INFLAMMATION AND LIPID IN THE PATHOGENESIS OF A PLAQUE
6. DISCUSS MORPHOLOGY, COMPLICATIONS OF A PLAQUE
7. CORRELATE THE CORONARY ARTERY PATHOLOGY WIH THE ISCHAEMIC HEART DISEASE
 Disease/Notes Aetiopathogenesis Clinical features Complications
Hypertension Primary/essential/Idiopathic hypertension ~ 95% Benign Hypertension Vascular effects
Hypertension can cause end-organ damage and is - A complex, multifactorial disease Histologically: Hypertension accelerates atherosclerosis
one of the major risk factor for atherosclerosis - BP is elevated with age - Hypertrophy and thickening of ➢ Causes thickening of the media of muscular
- But with no apparent cause muscular media arteries (especially smaller arteries and
Factors determining BP: Secondary hypertension – identifiable causes - Thickening of elastic lamina arterioles)
Blood pressure- depends on cardiac output and total - Elevated BP due to an identifiable cause - Fibroelastic thickening of intima Normal flow of protein into the vessel wall is
vascular/peripheral resistance. - Hyaline deposition in arteriole walls increased resulting in intramural protein deposition
Cardiac output depends on Pathogenesis (hyaline arteriosclerosis) termed hyaline in benign hypertension and fibrinoid
a. stroke volume (depends on blood volume Essential hypertension: Effects: in malignant hypertension
and influenced by sodium homeostasis) 1. Decreased renal sodium excretion - Reduced size of vessel lumen leads to -Hyaline hypertension: common of ageing small
b. Heart rate (and contractility are regulated • Increase in fluid volume, C.O and peripheral tissue ischaemia arteries, refers to the homogenous appearance of
by alpha and beta adrenergic systems. vasoconstriction - Increased rigidity leads to limited vessel walls due to infiltration by plasma proteins
TPR determined by functional and anatomic changes • Raises BP capacity for expansion and -Fibrinoid deposition: a combination of fibrin
in small arteries and arterioles. constriction infiltration with necrosis of the vessel wall.
Vascular resistance in the arterioles- depends on 2. Raised vascular resistance - Increased fragility of vessels leads to Accelerated atheroma results in an increased
neural and hormonal mechanisms. • Factors/substances that produces an increased risk of haemorrhage incidence of the complications of atheroma in all
vasoconstriction or stimuli that causes structural (especially cerebral) organs affected.
Role of kidney: changes in the vessel wall - After many years of benign
When there is a fall in BP, renin is secreted → • Result in an increase in peripheral vascular progression, 5% of such patients enter Heart
cleaves to Ang to AngI → converted to AngII by ACE resistance an accelerated malignant phase LV undergoes hypertrophy
AngII raises BP by increasing both TPR (direct action • Causes primary hypertension - From increased workload
on vascular SM and causes vasoconstriction) and Malignant (Accelerated) Hypertension - Causing increased susceptibility to
Blood volume (by stimulating secretion of 3. Genetic factors Acute, destructive changes in the walls of small spontaneous arrhythmias
aldosterone by the adrenal zona glomerulosa and • Genetic defects may be in the enzymes involved arteries when BP rises suddenly and markedly - IHD due to accelerated atherosclerosis
increased reabsorption of sodium in distal tubules) in aldosterone metabolism, sodium reabsorption • Results in necrosis of the vessel wall (common complication of
and smooth muscle cell growth • Infiltration of necrotic media by fibrin (ie, hypertension)
Kidney also produces vasodilators including PG and • Variation in genes encoding components of the fibrinoid necrosis of vessels) - Eventually ventricle no longer able to
NO which counterbalances the vasoconstriction by renin-angiotensin system Destructive changes result in deal with increased TPR, and left heart
AngII • Polymorphism in both angiotensinogen locus and • Cessation of blood flow through small fails → back pressure on the lungs →
the AngII type I receptor vessels within multiple foci of tissue produces dyspnea on exertion →
Pathological classification of Hypertension necrosis pulmonary oedema develops
Benign hypertension – Stable elevation of BP over 4. Environmental factors • Often with IV thrombosis
many years • Stress • Areas typically affected : retina (high-grade Brain
Process mainly involves small arteries and arterioles, retinopathy) and kidneys (glomerular Intracerebral haemorrhage
• Obesity
evokes spasm, hardening and affects some disease) Small vessel damage within the cerebral
• Smoking
important organs hemispheres results in the development of micro-
• Lack of physical activity
Malignant (accelerated) hypertension – a rare infarcts
• Heavy intake of Na salt
condition characterized by a dramatic elevation of - Which form hypertensive lacunae
BP over a short period of time. - Ie, small areas of destroyed brain filled
Secondary hypertension:
Diastolic pressure often greater than 130mmHg with fluid
1. Mechanism of renovascular hypertension
Kidneys
• Renal artery stenosis → decreased glomerular Arteriolosclerosis leads to progressive ischaemia of
flow and pressure in the afferent arteriole of the nephrons and chronic renal failure.
glomerulus → stimulates renin secretion and
ROBERT SO JR • Termed to be benign hypertensive
production of AngII → vasoconstriction →
nephrosclerosis
BATCH 15 increased TPR
• Common cause of chronic renal failure in
• Renal artery stenosis also increases sodium
TAYLORS UNIVERSITY middle-aged and elderly population
reabsorption → increases blood volume through
2018/2023 Retina
the aldosterone mechanism
Hypertension may produce retinal ischaemia and
2. Primary hyperaldosteronism
infarction
One of the most common cause of
- Visible on fundoscopic examination
secondary hypertension
 Morphological Changes in Hypertension
Large/Medium vessel disease: Atherosclerosis
• Hypertension is one of the major
modifiable risk factors for atherogenesis
• Causes degenerative changes in the walls
of large and medium arteries
• Predisposes to
1. Aortic dissection
2. Cerebro-vascular haemorrhage

Small vessel diseases

1. Hyaline arteriolosclerosis
Seen in arterioles in patients with benign
hypertension
a. Microscopy : Demonstrated by PAS stain
- Thickening of wall due to
homogenous, pink hyaline material
- narrowing of lumen
b. Mechanism: chronic haemodynamic stress
produced by hypertension → produces
leakage of protein into vessel wall →
increase synthesis of ECM (extracellular
matrix) by smooth muscle cell →
hyalinization of the wall of arteriole
c. Consequence
Arteriolar narrowing → impaired blood
supply to kidney → produces ischaemia
and glomerular scarring. Kidney changes in
benign hypertension are called benign
nephrosclerosis
d. Causes of hyaline arteriosclerosis
- Benign hypertension
- Diabetic microangiopathy
- Old age (either normo- or
hypertensive)

2. Hyperplastic arteriolosclerosis
Proliferation of smooth muscle cells in the vessel
walls
Seen in severe (malignant) hypertension
a. Microscopy
- Blood vessel shows ‘onion-skin’,
concentric, laminated thickening of
the arteriolar wall
ROBERT SO JR
- Narrowing of the arteriolar lumen
BATCH 15 - Fibrinoid deposits
TAYLORS UNIVERSITY - Necrosis of the vessel walls
2018/2023 (necrotizing arteriolitis) particularly in
the kidney
 Atherosclerosis PATHOGENESIS MORPHOLOGY COMPLICATION
Arteriosclerosis =/= Atherosclerosis A. Insudation hypothesis 1. Rupture, ulceration or erosion
Atheroma = Atheromatosis = Atherosclerosis Focal accumulation of lipid in a vessel wall is due to Plaque protrudes into the lumen and can disturb the
insudation (transport) of plasma lipoproteins across blood flow → resulting in turbulent flow of blood →
Dr Imam definition: Atherosclerosis is a pathological an intact endothelium which can damage the endothelium → cause
process in which there is deposition of lipid (fat) and B. Encrustation hypothesis rupture, ulceration or erosion of the intimal surface
fibrous tissue in the arterial walls. Small mural thrombi are formed at the site of of plaques
endothelial damage and these thrombi become
The most important effects of atheroma are IHD, organized and form plaque. 2. Haemorrhage into the plaque
peripheral vascular disease and cerebrovascular C. Monoclonal hypothesis May occur due to rupture of the fibrous cap of the
disease. Single clone (monoclonal) of smooth muscle migrate plaque or of the thin-walled vessels formed due to
from the underlying media into the intima and then neovascularization
Arteriosclerosis = Hardening of arteries, proliferate. The stimulus for monoclonal proliferation
characterized by arterial wall thickening caused by may be metabolites of cholesterol 3. Thrombosis and embolism
a. Arteriolosclerosis: affecting small arteries D. Response-to-injury hypothesis Ulceration/erosion/rupture of endothelial surface
and arterioles Currently favoured hypothesis! Fatty streaks (type II lesions) : Earliest or precursor →exposes the blood to highly thrombogenic
b. Monckeberg medial sclerosis: Atherosclerosis develops as a chronic (inflammatory lesions of atherosclerosis, found in young children subendothelial collagen → favors thrombus
characterized by deposition of calcium in and healing) response of the arterial wall due to (older than 10yr) as well as in adults. formation → can partially or completely occlude the
muscular arteries seen in old age endothelial injury a. Gross: Multiple, small, flat, yellow lesions in lumen (depending on the size of the lumen) → lead
c. Atherosclerosis: most frequent and the intima which may coalesce to form long to ischaemia. The thrombus may become organized
important disease of intima. streaks 1cm or more in length or fragment to form thromboemboli
b. Microscopy: Consists of lipid-filled foamy
Atherosclerosis= is primarily a progressive disease macrophages in the intima
of intima involving large and medium-sized elastic
and muscular arteries, characterized by focal lipid- Atherosclerotic plaque
rich intimal lesions called atheroma (atheromatous Gross
or atherosclerotic plaques) a. Sites: Major vessels involved in
atherosclerosis in descending order
RISK FACTORS - Lower abdominal aorta
(insert table here) - Coronary arteries
1. Endothelial injury and dysfunction - Popliteal arteries
Causes: Endothelial injury/dysfunction 4. Atheroembolism
Modifiable risk factors in Ischaemic Heart Disease - Internal carotid arteries
➢ Haemodynamic disturbances: Plaques Plaque rupture → discharged of atherosclerotic
also - Vessels of the circle of Willis
develop in regions having disturbed blood debris into the bloodstream → results in
1. Hyperlipidaemia b. Colour: White to yellow. If superimposed
flow such as origin or ostia of vessels, atheroemboli
Increase in serum lipids mainly cholesterol by thrombus → red-brown
branching points of vessel and along the c. Size: 0.3-1.5cm diameter. Can coalesce to
(hypercholesterolaemia) is a major modifiable risk 5. Aneurysm formation
posterior wall of the abdominal aorta form larger mass. Advanced lesions are
factor. Atherosclerosis even though an intimal disease may
➢ Risk factors: hyperlipidaemia, oval and range from 8-12cm diameter.
LDL (low density lipoprotein) = bad cholesterol cause pressure or ischaemic atrophy of the
hypertension, toxins from cigarette smoke d. Shape: Irregular with well-defined borders.
• High levels associated with increased risk underlying media. It may also damage the elastic
➢ Others: homocysteine, immunocomplexes e. Distribution: Patchy (focal) and usually
of atherosclerosis tissue and cause weakening of the wall → results in
and infectious agents involve only a portion of the involved
• LDL delivers cholesterol to peripheral aneurysmal dilatation → which may rupture.
Effects: arterial wall. On cross-section → appears as
tissues
➢ Leukocytes (mainly monocyte) adhesion to an eccentric lesion
HDL (high density lipoprotein) = good cholesterol 6. Calcification
endothelium f. Composition: Soft, yellow, grumous core of
• Low levels associated with decreased risk May occur in the central necrotic area of the plaque
➢ Increased vascular permeability lipid covered by a while fibrous cap.
of atherosclerosis (dystrophic calcification)
➢ Platelet adhesion and thrombosis Microscopy
• HDL mobilizes cholesterol from periphery ➢ Movement of LDLs across the endothelium Three main components in varying proportions in
(including atheromatous plaque) and into the intima. ROBERT SO JR
different lesions:
excretes it through bile in liver.
• Exercise and moderate consumption of
a. Cells: Smooth muscle cells, macrophage, T- BATCH 15
2. Migration of monocytes into the intima cells
ethanol raise HDL levels, whereas obesity Leukocytes which adhere at the site of endothelial
TAYLORS UNIVERSITY
b. ECM: Collagen, elastic fibers, proteoglycans
and smoking lowers it injury, are mainly monocytes and T lymphocytes. 2018/2023
c. Lipid: both intracellular and extracellular
• Increase in VLDL leads to reduced HDL
lipids.
Disorders associated with hypercholesterolaemia ➢ Accumulation of leukocytes initiates the These components occur in three regions:
a. Nephrotic syndrome atheroma formation a. Superficial fibrous cap: composed of
ROBERT SO JR
b. Alcoholism ➢ Locally produced chemokines allows smooth muscle cells and collagen
c. Hypothyroidism BATCH 15 penetration of the endothelial layer by b. Necrotic core: Seen deep to the fibrous cap
d. Diabetes mellitus TAYLORS UNIVERSITY monocytes and lymphocytes. Monocytes and contains:
migrate into the intima where they are - Lipid: mainly cholesterol and
2018/2023
2. Hypertension transformed into macrophages. cholesterol esters.
Incidence of atherosclerosis increases as BP rises, - Debris from dead cells
and this excess risk is related to both systolic and - Foam cells (lipid-laden macrophages
diastolic levels of BP and smooth muscle cells)
- Control of hypertension with 3. Lipid accumulation in the intima - Others: fibrin, organized thrombus
antihypertensive therapies reduces Endothelial dysfunction also allows penetration of and plasma proteins
the risk of MI and stroke endothelium by lipoproteins (mainly LDLs) from blood c. Shoulder: Peripheral region beneath and to
→ LDLs accumulate within the intima of the vessel the side of the cap. It is more cellular and
3. Cigarette smoking ➢ LDLs is oxidized by the action of oxygen free contains macrophages, smooth muscle
Most important avoidable cause of atherosclerosis radicals produced locally by cells and T-cells.
monocytes/macrophages and dysfunctional
4. Diabetes mellitus endothelial cells. Neovascularization: Proliferating small blood vessels,
Potent risk factor for atherosclerosis may be seen at the periphery of the lesions near the
Diabetes is associated with hypercholesterolaemia 4. Formation of foam cells and activation of shoulder.
→ increases the risk of atherosclerosis. The macrophages
incidence of MI and other atherosclerotic vascular Macrophage engulfs lipoproteins and oxidized LDLs Major clinical consequences of atherosclerosis
diseases (strokes, gangrene of lower extremities) is ➢ From extracellular space in the intima 1. Myocardial infarction
more in diabetic patients than in non-diabetic ➢ Their cytoplasm becomes foamy and these 2. Cerebral infarction (stroke)
cells are called foam cells 3. Aortic aneurysm
Non-modifiable/Constitutional Risk Factors Note- foam cells in atherosclerosis; 4. Peripheral vascular diseases (gangrene of
(S.A.F.E) a. Smooth muscle cells foot)
1. Genetic abnormalities /Ethnicity b. Tissue macrophages
Most common inherited modifiable risk factors c. Blood monocytes Clinicopathologic manifestations of Atherosclerosis
(hypertension, hyperlipidaemia and DM) are ➢ Some foam cells undergo apoptosis → 1. Atherosclerosis stenosis (luminal
polygenic. releases lipids → form lipid-rich center, narrowing)
Mendelian disorders, ie, familial often called the necrotic core in the ➢ Reduces the lumen size of the involved
hypercholesterolaemia are associated with atheromatous plaques. vessel → lead to tissue ischaemia and this
atherosclerosis ➢ Oxidized LDL is cytotoxic to endothelial cells lesion is called critical stenosis
and smooth muscle and can cause ➢ In small arteries: ischaemic injury
2. Family history endothelial dysfunction ➢ Ie, Coronary artery: chest pain with
Atherosclerotic disease often runs in families. ➢ Oxidized LDL causes activated macrophages exertion (stable angina)
Familial predisposition is usually multifactorial, due which produces ➢ Other sites: ischaemia of bowel
to genetic, environmental and lifestyle factors. a. Cytokines (TNF) – increases leukocyte (mesenteric occlusion), sudden cardiac
adhesion death, chronic ischaemic heart disease,
3. Increasing age b. Chemokine (monocyte chemotactic ischaemic encephalopathy, intermittent
Clinical manifestations of atherosclerosis is usually protein 1) – accumulation of claudication (diminished perfusion of
observed after middle age and the lesions monocytes extremities)
progressively rise with each decade. c. ROS – aggravate oxidation of LDL
d. Growth factors – stimulate smooth
4. Gender/Sex muscle cell proliferation and ECM
Premenopausal women have lower incidence of synthesis
atherosclerosis-related diseases compared to males
of the same age group. 5. Migration of smooth muscle cells into the
After menopause, this gender differences intima
disappears- this may be due to protective role of Growth factor (ie, platelet-derived growth factor)
oestrogen. However, hormone replacement therapy from activated platelets, macrophages, and
has no role in the prevention of coronary heart endothelial cells causes migration of smooth muscle 2. Acute plaque change (sudden change
disease. cells either from the arterial media or form circulating occurring in an atheromatous plaque) in
precursors. which the composition of plaque is
Achilles tendon xanthoma: Pathognomic of familial dynamic and it decides the risk of rupture.
hypercholesterolaemia. 6. Smooth muscle cell proliferation in the Vulnerable plaques – more likely to rupture
intima and ECM production - One necrotic centre with large areas
Additional Risk Factors : Smooth muscle cells proliferate and produce ECM of foam cells and extracellular lipids
1. Inflammation (mainly collagen and proteoglycans). Many growth - Thin fibrous caps or contains few
2. C-reactive protein levels factors can cause smooth muscle cell proliferation. smooth muscle cells
Marker for systemic inflammation and predicts risk These includes PDGF, fibroblast growth factor and - Have clusters of inflammatory cells
of atherosclerosis related diseases. transforming growth factor-alpha (TGF-alpha) Stable plaque
3. Hyperhomocysteinaemia ➢ Smooth muscle cells may also engulf - Thick, densely collagenized fibrous cap
Rare autosomal recessive inborn error oxidized LDL and form foam cells - Minimal inflammation
Elevated circulating homocysteine → premature and - Negligible lipid core
severe atherosclerosis 7. Lipid accumulation Mechanical strength and stability of plaque: depends
4. Metabolic syndrome Occurs both intracellularly (within macrophages and mainly on the collagen in the fibrous cap. The
Associated with central obesity, insulin resistance smooth muscle cells) and extracellularly. balance between synthesis against its degradation of
and is known risk factors for atherosclerosis ➢ Extracellular lipid s derived from insudation collagen decides the integrity of fibrous cap.
5. Increased lipoprotein (a) levels from the vessel lumen (mainly in the - Collagen synthesis: by SMC
An altered form of LDL and structurally similar to presence of hypercholesterolaemia) and - Collagen degradation: by
plasminogen. It competes with plasminogen in clots also from necrotic foam cells. inflammatory cells in the plaque
and decreases the ability to form and clear clots. ➢ Cholesterol in the plaque is also due to an Extrinsic factors: also contribute to plaque changes
Increased Lp(a) levels are associated with higher risk imbalance between influx and efflux. HDL ➢ Adrenergic stimulation raises systemic BP
of atherosclerosis, independent of total cholesterol probably transfers cholesterol from these or induce local vasoconstriction and
or LDL levels. lesions and leas to its excretion by the liver. increase the physical stresses on a given
6. Raised procoagulant levels plaque.
Ie, thrombin, platelet activation and raised ➢ Emotional stress can also contribute to
fibrinogen → increased risk plaque disruption
7. Inadequate physical activity
8. Stressful lifestyle 3. Thrombosis (causes luminal occlusion)
9. Obesity Partial or total thrombosis over a disrupted plaque is
10. Alcohol consumption observed in acute coronary syndromes. Mural
thrombi in a coronary artery can undergo
embolization.
This will often result in infarction of the part served.
An example is MI due to thrombosis of a coronary
artery.
 4. Vasoconstriction
Vasoconstriction reduces the size of arterial lumen
and increases the local mechanical forces. This cause
disruption of plaque.

Dr. Imam slides:

The fatty Streak (Type II lesion)

• Comprises a slightly elevated zone on the

arterial wall caused by accumulation of a
small number of lipid laden macrophages,
with minimal free lipid
• They occur in all societies, even those
without high prevalence of atheroma, but
are thought to be the origin of atheroma,
as they occur at the same site

The fibrous plaque (Type V lesion)

ROBERT SO JR
BATCH 15
TAYLORS UNIVERSITY ROBERT SO JR
2018/2023 BATCH 15
TAYLORS UNIVERSITY
2018/2023
 • Lipid accumulates, free and in foamy
histiocytes
• SMC migrate from the media and
proliferate
• Fibrosis develops around the lipid, and
forms a cap over the lesion

The complicated plaque (Type VI lesion)

• Ulcers and fissures of the fibrous cap reveal

plaque contents, resulting in thrombosis
• The plaque may undergo calcification,
visible on X-ray
• Inflammation associated with the plaque
destroys the media which undergoes
fibrosis and is weakened

Note; Maximum atheroma occurs at the sites of

haemodynamic stress ie, bifurcation

Effects of Atheroma on Blood vessels

Effects on blood on Effects on
vessels organs/parts served
Luminal narrowing Ischaemia
Luminal occlusion Infarction
Embolism Ischaemia and
infarction
Weakened wall Aneurysm