Systemic Pathology

Disease of Blood Vessels

Diseases of blood vessels:
Vascular pathology results in disease via two principal mechanisms:

(1) Narrowing (stenosis) or complete obstruction of vessel lumens,

either progressively (e.g. by atherosclerosis) or precipitously (e.g. by
thrombosis or embolism); and

(2) Weakening of vessel walls, leading to dilation or rupture.

Vascular Structure and Function

• All vessels except capillaries share a three-layered architecture consisting of an

endothelium lined intima, a surrounding smooth muscle media, and supportive
adventitia, admixed with extracellular matrix.

• The intima normally consists of a single layer of endothelial cells sitting on a

basement membrane which is demarcated from the media by the internal
elastic lamina.

• The adventitia lies external to the media and in many arteries is separated
from the media by a well-defined external elastic lamina.
CONT.
• Capillaries are approximately the diameter of a red cell (7 to 8 μm); they have
an endothelial cell lining but no media, although variable numbers of pericytes,
cells that resemble smooth muscle cells, typically lie just deep to the the
endothelium.

• Arteries are divided into three types based on their size and structural features:
(1) Large or elastic arteries, including the aorta, the major branches of the aorta
(the innominate, subclavian, common carotid, and iliac arteries), and the
pulmonary arteries;
(2) Medium sized or muscular arteries, comprising smaller branches of the aorta
(e.g., the coronary and renal arteries); and
(3) Small arteries (2 mm in diameter) and arterioles (20 to 100 um in diameter),
within tissues and organs.
Hypertension
According to the National Heart, Lung, and Blood Institute of the
U.S.A, "A sustained diastolic pressure greater than 89 mm Hg, or a
sustained systolic pressure in excess of 139 mm Hg is considered to
constitute clinically significant hypertension.
Pheochromocytoma:
It is a catecholamine-secreting tumour of adrenal medulla. So, it
results in excessive formation of adrenaline and nor-adrenaline which
causes increased blood pressure.

Malignant hypertension: Accelerated or malignant hypertension is a

clinical syndrome characterized by severe hypertension (i.e. systolic
pressure more than 200 mm Hg, diastolic pressure more than 120 mm
Hg), if untreated, leads to death within 1 to 2 years.
Complications of Hypertension:

• Left ventricular hypertrophy and heart failure (hypertensive heart

failure)
• Aortic dissection
• Renal failure
• Cerebral hemorrhage (stroke)
• Hypertensive retinopathy
Atherosclerosis:
Atherosclerosis is a pattern of vascular disease which is characterized by
atheromas (also called atheromatous or atherosclerotic plaques) that
obstruct vascular lumen and weaken the underlying tunica media.
Common sites of formation of atheromas / atherosclerotic plaques:
1. Proximal portions of the coronary arteries
2. Internal carotid arteries
3. The circle of Willis
4. Large vessels of the lower extremities
5. Renal arteries &
6. Mesenteric arteries.
Pathology/Morphology of an
atheromatous plaque:
The key processes in atherosclerosis are intimal thickening and lipid
accumulation, which together form plaques.
A) Macroscopic:
• Colour: White-yellow and encroach on the lumen of the artery;
superimposed thrombus over
• ulcerated plaques is red-brown.
• Size: Plaques vary in size but can coalesce to form larger masses.
• Shape: On cross-section, atherosclerotic lesions are patchy &
"eccentric". (usually involving only a portion of any given arterial wall
and are rarely circumferential).
CONT.
• Cut section: A. The plaques have a central (necrotic) core covered by
a subendothelial fibrous cap:
1. Superficial fibrous cap: Composed of smooth muscle cells,
macrophages, T cells, and dense collagen.
2. Necrotic core (deep to the fibrous cap): Containing lipid (primarily
cholesterol & cholesterol esters), debris from dead cells, lipid-laden
macrophages, or foam cells, fibrin, variably organized thrombus, and
other plasma proteins.
• Periphery of the lesions: Neovascularization (proliferating small
blood vessels) present.
CONT.
• B. Atherosclerotic plaques have three principal components in
varying proportion

1. Cells (including smooth muscle cells, macrophages, and T cells)

2. Extracellular matrix (including collagen, elastic fibres &
proteoglycans); and
3. Intracellular & extracellular lipid (mostly cholesterol & cholesterol
ester)
 Difference between arteriosclerosis
and atherosclerosis
Difference between arteriosclerosis and atherosclerosis:
Arteriosclerosis (literally means "hardening of the arteries") is a
generic term for thickening and loss of elasticity of arterial wall.

On the other hand, atherosclerosis is the most frequent and clinically

important variety of arteriosclerosis which is characterizedby by
formation of intimal lesions called atheromas or atherosclerotic
plaques.
Risk factors for atherosclerosis:
CONT.
1. Age: Incidence increases with age.

2. Gender: Atherosclerosis is more common in men in all age groups,

although the incidence increases in postmenopausal women.

3. Genetics: Family history is the most important independent risk

factor for atherosclerosis. Certain Mendelian disorders are strongly
associated with atherosclerosis (c.g. familial hypercholesterolemia),
but these account for only a small percentage of cases.
 CONT.
4. Hyperlipidemia:
Hyperlipidemia and more specifically hypercholesterolemia- is a major
risk factor for atherosclerosis; even in the absence of other risk factors,
hypercholesterolemia is sufficient to initiate lesion development.
Atherosclerosis is directly proportional to increase LDL, also known as
"bad" cholesterol and decrease HDL, also known as "good" cholesterol.

5. Hypertension: It is a major risk factor, and is associated with,

premature atherosclerosis. It increases the risk of IHD by
approximately 60%.
CONT.
• 6.Diabetes mellitus:
It induces hypercholesterolemia and markedly associated with
premature atherosclerosis. Atherosclerotic peripheral vascular
occlusive disease, often leading to gangrene of the lower extremities, is
common in diabetic patients.

7. High carbohydrate intake: High carbohydrate intake Atherosclerosis.

CHO converted to fat.
Additional risk factors:
1. Inflammation & C-reactive protein (CRP)
2. Metabolic syndrome
3. Factors affecting hemostasis (e.g. thrombin, platelet-derived factors
etc.)
Other factors
• Obesity
• Lack of exercise/physical inactivity
• High carbohydrate intake
• "Type A" personality with stress factors in lifestyle.
Metabolic syndrome
Metabolic syndrome is characterized by insulin resistance,
hypertension, dyslipidemia (elevated LDL and depressed HDL),
hypercoagulability, and a proinflammatory state.
Pathogenesis of atherosclerosis:
Atherosclerosis progresses in the following sequence:
1. Endothelial injury and dysfunction, causing increased vascular
permeability

2. Accumulation of lipoproteins (mainly LDL and its oxidized forms) in

the Tunica Intima.

3. Monocyte adhesion to the endothelium, followed by migration

into the intima and transformation into macrophages
CONT.
4.Macrophage engulf oxidized LDL and become Foam cell

5.Growth Factor release from activated macrophages which causes

Smooth muscles cell migration and proliferation, extracellular matrix
production

6.Progressive development of atherosclerotic plaque

Effects/complications of
atherosclerosis
1. Rupture of the surface of atheromatous plaques exposes highly
thrombogenic substances and leads to thrombus formation at the site
of the plaque, producing obstructive disease.
2. Hemorrhage into the atheromatous plaque
3. Ischemia: Thrombosis can partially or completely occlude the
lumen and lead to down stream ischemia.
4. Atheroembolism: Plaque rupture can discharge atherosclerotic
debris into the bloodstream, producing microemboli.
5. Aneurysm formation: Atherosclerosis-induced pressure causes
weakness resulting in aneurysmal dilation and potential rupture.
Aorta: Aortic aneurysms
CONT.
6. Calcification: Atheromas often undergo calcification.

7. Infarction: Ischemia induced infarction results in various organs due

to atherosclerotic plaque. So, atherosclerosis related infarctions in
various organs are:
• Heart: Myocardial infarction (Heart attack)
• Brain: Cerebral infarction (stroke)
• Peripheral vessels: Peripheral vascular disease (gangrene of the legs)
CONT.
8. Complication due to atherosclerotic stenosis (Gradual occlusion of
vessel lumen):
• Mesenteric occlusion & bowel ischemia
• Sudden cardiac death
• Chronic ischemic heart disease (CHD)
• Ischemic encephalopathy
• Intermittent claudication (diminished perfusion of the extremities).
Blood vessels frequently involved by
atherosclerosis with their possible
clinical consequences:
1. Coronary arteries: Ischemic heart disease and myocardial infarction (heart
attack).
2. Larger branches of the carotid arteries & the circle of Willis: Stroke from cerebral
ischemia & infarction.
3. Large vessels of the lower extremities (e.g. popliteal arteries): Peripheral
vascular occlusive disease with findings varying from claudication to ischemic
necrosis and gangrene.
4. Aorta: Aortic aneurysms.
5. Renal arteries: Renal arterial ischemia with secondary hypertension.
6. Mesenteric arteries: Ischemic bowel disease.
Prevention of atherosclerosis:
..Cessation of cigarette smoking
• Control of hypertension
• Weight reduction
• Increase exercise
• Moderation of alcohol consumption
• Lowering total and LDL blood cholesterol levels while increasing
HDL.
Aneurysm
An aneurysm is a localized abnormal dilation of a blood vessel or the heart
that may be congenital or acquired. When it involves the aorta, it is called
aortic aneurysm.
• True aneurysm: When an aneurysm involves an attenuated but intact
arterial wall or thinned ventricular wall of the heart, it is called a "true"
aneurysm. Atherosclerotic and congenital vascular aneurysms, as well as
ventricular aneurysms that follow transmural myocardial infarctions.

• False aneurysm: A false aneurysm (also called pseudo-aneurysm) is a

defect in the vascular wall leading to an extravascular hematoma that
freely communicates with the intravascular space ("pulsating hematoma").
Causes of aneurysm:
1. Atherosclerosis
2. Hypertension
3. Trauma
4. vasculitis
5. Congenital defects (e.g. berry aneurysms)
6. Tertiary syphilis (rare cause).
Haemangioma
Haemangioma is the benign neoplasm of the blood vessel.
Types:
1. Capillary hemangiomas
2. Juvenile hemangiomas (so-called "strawberry type" hemangiomas)
3. Cavernous hemangioma
4. Pyogenic granulomas.

Angiosarcoma:
Angiosarcoma is the malignant neoplasm of the blood vessel.
Capillary hemangioma:
They are the most common type that occur in the skin, subcutaneous
tissues, and mucous membranes of the oral cavities and lips, as well
as in the liver, spleen, and kidneys.

• Morphology:
• ⚫Bright red to blue
• • Few millimeters to several centimeters in diameter. At level with
the surface of the skin or slightly elevated. Intact overlying
epithelium
Continue
Vasculitis:
Vasculitis is defined as inflammation of vessel walls.

• It is frequently associated with systemic manifestations (including

fever, malaise, myalgias, and arthralgias) and organ dysfunction that
depends on the pattern of vascular involvement.
• Vessels of any type (large, medium & small) in virtually any organ
can be affected, but most vasculitis affect small vessels ranging in
size from arterioles to capillaries to venules.
Pathogenesis of vasculitis:
• Infectious vasculitis: Direct invasion of vascular walls by infectious
pathogens

• Non-infectious vasculitis: Immune-mediated inflammation (due to

local or systemic immune response, including immune complex
deposition, formation of anti-neutrophil cytoplasmic antibodies
(ANCA), or T cell responses to vascular wall antigens}
• Giant cell (temporal) arteritis: It is a chronic inflammatory disorder of
• large to small-sized arteries that principally affects arteries in the head
• especially the temporal arteries but also the vertebral and ophthalmic
arteries. Persistant severe head pain (usually temple area)

• Takayasu arteritis:This is a granulomatous vasculitis of medium and

larger arteries characterized principally by ocular disturbances and
marked weakening of the pulses in the upper extremities (pulseless
dis)
• Takayasu arteritis classically involves the aortic arch. In a third of
patients, it also affect it’s branches (coronary and renal arteries) &
pulmonary artery
 PAN
• Polyarteritis nodosa (PAN): It is a systemic vasculitis of small or
• medium-sized muscular arteries, typically involving renal and
• visceral vessels but sparing the pulmonary circulation. Vessels of the
• kidneys, heart, liver, and gastrointestinal tract are involved in descending
• order of frequency. Clinical manifestations result from ischemia and
infarction of affected tissues and organs.

• Kawasaki disease: It is an acute febrile, usually self-limited illness of

• infancy and childhood (80% of patients are 4 years old or younger); it is
• associated with an arteritis affecting large to medium-sized, and even
• small vessels.(high fever,swollen red tongue and lips)
Raynaud phenomenon:
• Raynaud phenomenon refers to paroxysmal pallor or cyanosis
resulting from exaggerated vasoconstriction of arteries and
arterioles in the extremities, particularly the fingers and toes, but
also occasionally the nose, earlobes, or lips.

• The involved digits classically show "white and blue" color changes
from most proximal to most distal.
Types:
• Raynaud phenomenon can be a primary entity or secondary to other
disorders.

1. Primary Raynaud phenomenon (previously called Raynaud

disease): In response to cold or emotional stresses.
2. Secondary Raynaud phenomenon: Caused by other diseases like
SLE, scleroderma, Buerger disease,certain drugs or even
atherosclerosis.
Raynauds
Buerger disease:
• Thromboangiitis obliterans (Buerger disease) is characterized by segmental,
thrombosing, acute and chronic inflammation of medium-sized and small
arteries, principally the tibial and radial arteries, with occasional secondary
extension into the veins and nerves of the extremities.
• It is a distinctive disease that often leads to vascular insufficiency, typically of
the extremities. It occurs almost exclusively in heavy cigarette smokers,
usually before age 35.

• Clinical features:
• Cold induced Raynaud phenomenon
• Leg pain induced by exercise that is relieved on rest (intermittent claudication)
• Chronic ulcerations of the toes, feet or fingers
• Gangrene later on.
Varicose Veins
Varicose veins are abnormally dilated, tortuous veins produced by
prolonged, increased intraluminal pressure leading to vessel dilation
and incompetence of the venous valves.

• The superficial veins of the upper and lower legs are commonly
involved.