Pathology of

cardiovascular system
Dr. Wangari
Wambugu
Outline
 Blood vessels and lymphatics
 Diseases of arteries
 Diseases of veins and lymphatics
 Tumors
 Heart:
 Heart failure
 Congenital heart dse
 Ischaemic heart disease
 Hypertensive heart dse
 Valvular heart dse
 Cardiomyopathies
 Myocarditis
 Shock & other haemodynamic d/o
Pathology of blood vessels and
lymphatics
Pathology of blood and lymphatic
vessels

The main cellular components of the walls

of vessels are:

1) endothelial cells

2) smooth muscle cells

3) pericytes (the cells normally arranged

along capillaries and venules)
 Pathology of blood and lymphatic
vessels

1) Endothelial cells:
a) serve as a semipermeable membrane,
b) regulate thrombosis, thrombolysis and platelet adherence,
c) influence vascular tone and blood flow,
d) metabolize hormones,
e) regulate immune and inflammatory reactions,
f) modify lipoptoteins in the artery wall,
g) regulate the growth of other cell types, including smooth muscle cells.
Pathology of blood and lymphatic
vessels

Endothelial injury
is critical to the formation of thrombi, to the
initiation of atherosclerosis and the vascular
effects of hypertension and other disorders !!
Pathology of blood and lymphatic
vessels

Endothelial dysfunction

Endothelial activation
Pathology of blood and lymphatic
vessels

The term endothelial dysfunction is often used to describe

several types of potentially reversible changes in the
functional state of endothelial cells that occur in response
to environmental stimuli.
 Pathology of blood and lymphatic
vessels
• The term endothelial activation reflects alterations in gene expression and
protein synthesis.
• Inducers of endothelial activation include
• cytokines and bacterial products (which cause inflammatory injury and
septic shock),
• hemodynamic stress and lipid products (involved in pathogenesis of
atherosclerosis),
• advanced glycosylation of end products (involved in pathogenesis of
diabetes),
• viruses,
• complement components and
• hypoxia.
Pathology of blood and lymphatic
vessels

• Activated endothelial cells also elaborate adhesion

molecules, other cytokines and chemokines,
growth factors, molecules of the major
histocompatibility complex (MHC), procoagulant or
anticoagulant factors and vasoactive molecules
that are involved either in vasoconstriction or in
vasodilatation.
Pathology of blood and lymphatic
vessels

2) Smooth muscle cells :

a) mediate vasoconstriction,
b) mediate vasodilatation,
c) synthesize the collagen, elastin, and proteoglycans,
d) elaborate the growth factors and cytokines,
e) proliferate, and
f) migrate to the intima.

3) Pericytes have role as supportive and connective elements.

Pathology of blood and lymphatic
vessels

The final result of vascular injury is intimal

thickening !!
 Diseases of arteries

A)Congenital anomalies
B) Atherosclerosis
C) Hypertensive vascular disease
D) Inflammatory disease – Arteritides
(Vasculitides)
E) Raynaud disease
F) Aneurysms and dissections
 Diseases of arteries

A. Congenital Anomalies
Aberrations of the usual anatomic pattern of branching, shape and
anastomosing.
Of Importance are:
Berry aneurysms -developmental aneurysms involving cerebral vessels
Arteriovenous fistulas or aneurysms- abnormal communications between
arteries and veins usually arised as developmental defect, from rupture of
an arterial aneurysm into adjacent vein, or from injury, or from inflammatory
necrosis of adjacent vessels.
Their clinical significance depends on short-circuit blood from the arterial to
the venous side, causing the heart to pump additional volume, sometimes
inducing cardiac failure.
Diseases of arteries

B. Arteriosclerosis
It is a generic term for three patterns of vascular disease that have in
common thickening and loss of elasticity of arterial walls:
1) Atherosclerosis – characterized by the formation of intimal
fibrous plaques that often have a central core rich in lipid
(fibrofatty plaques).
2) Mönckeberg medial calcific sclerosis – characterized by
calcific deposits in medium-sized muscular arteries in persons
older than 50 years. These medial lesions forming irregular
medial plates or discrete transverse rings have much less clinical
importance.
3) Arteriolosclerosis – the hyaline and hyperplastic thickening of
small arteries and arterioles which causes luminal narrowing and
down stream ischemic injury.
Diseases of arteries
B. Atherosclerosis
Introduction

Atherosclerosis significantly contributes to

serious morbidity and mortality –
approximately half or more of all deaths.
It primarily affects elastic arteries (e.g., aorta,
carotid and iliac arteries) and large and
medium sized muscular arteries (e.g., coronary
and popliteal arteries).
The disease often begins in childhood, but
symptoms are not usually evident until middle
age.
Symptomatic atherosclerotic disease is most
often localized to the arteries supplying the
heart, brain, kidneys, lower extremities, and
small intestine.
Diseases of arteries

Consequences:

Myocardial infarction (heart attack)

Cerebral infarction (stroke)
Aortic aneurysms
Gangrene of the legs
Mesenteric occlusions
Sudden cardiac death
Chronic ischemic heart disease
Ischemic encephalopathy
Diseases of arteries

B. Atherosclerosis

Epidemiology
Atherosclerosis is virtually ubiquitous among the populations of North
America, Europe, Australia, New Zealend, Russia. In contrast, it is
much less prevalent in Central and South America, Africa, and Asia.
Many evidences exist that it depends on the life style and dietary
customs.
 Diseases of arteries
B. Atherosclerosis
 Risk Factors
 Non-modifiable factors:
 Age (advanced age),
 sex (male, postmenopausal women, the protective
effect of estrogens is ↓),
 genetics (polygenic familiar predisposition,
 genetic abberrations in lipoprotein metabolism resulting
in excessively high blood lipid levels
 Diseases of arteries
B. Atherosclerosis

 Potentially modifiable factors

Hyperlipidemia,
Hypertension,
Smoking,
Diabetes mellitus,
 Diseases of arteries
B. Atherosclerosis

 Other factors:
Elevated plasma homocysteine,
Factors affecting hemostasis and thrombosis
diet, life style, personal habits.
Diseases of arteries
B. Atherosclerosis

 Hyperlipidemia:
 A major risk factor.
 Hypercholesterolemia more significant than
hypertrigyceridaemia
 Main cholesterol being LDL-C

 HDL-C-good cholesterol-mobilizes lipids frm atheroma to

the liver
Diseases of arteries

B. Atherosclerosis

Hypertension: It is a stronger risk factor than hypercholesterolemia after age

45 years.
Men whose blood pressure exceeds 169/90 mm Hg have a more than 5-fold
greater risk of ischemic heart disease than those with blood pressures of
140/90 mm Hg or lower.
Smoking: When one or more packs of cigarettes are smoked per day for
several years, the death rate from ischemic heart disease increases twice.
Diabetes mellitus: DM induces hypercholesterolemia and markedly increases
predisposition to atherosclerosis.
The incidence of myocardial infarction is twice as high, the incidence of
strokes is 4-fold greater, and the incidence of gangrene of the lower
extremities 100-fold greater.
Diseases of arteries

B. Atherosclerosis

Elevated Plasma Homocysteine: Recent clinical and epidemiologic

studies have indeed shown a more general relationship between total
serum homocysteine levels and coronary artery disease, peripheral
vascular disease, stroke, or venous thrombosis. There is evidence
that homocysteine may cause endothelial dysfunction, through
formation of reactive oxygen species. It also interferes with with the
vasodilator and antithrombotic functions of nitric oxide.
Factors Affecting Hemostasis and Thrombosis: Several other markers
of hemostatic and thrombotic function are potent predictors of risk for
major atherosclerotic events (plasminogen activator inhibitor-1 level,
plasma fibrinogen level, C-reactive protein level).
Diseases of arteries
B. Atherosclerosis

Pathogenesis of atherosclerosis

The contemporary view of the pathogenesis: Atherosclerosis is a

chronic inflammatory response of arterial wall initiated by some
form of endothelial injury!!

There are described the following steps:

a) chronic endothelial injury,
b) insudation of lipoproteins (mainly LDL and VLDL) into the vessel wall,
c) modification of such lipoproteins by oxidation,
d) adhesion of blood monocytes to the endothelium,
Diseases of arteries
B. Atherosclerosis

Pathogenesis of atherosclerosis-cont’d
e)migration of monocytes into the intima and their transformation into
macrophages and foam cells,
f) adhesion of platelets to focal areas of denudation or to adherent leukocytes

g) release of factors from activated platelets, macrophages or vascular cells,

h) migration of smooth muscle cells from media into intima
i) proliferation of smooth muscle cells in the intima and elaboration of
extracellular matrix,
j) accumulation of collagen anf proteoglycans,
k) enhanced accumulation of lipids within macrophages, smooth muscle cells
and extracellularly.
Diseases of arteries

B. Atherosclerosis

Morphology
The key processes are intimal thickening and lipid accumulation,
producing the characteristic atheromatous plaques (AP). Their
precursors are fatty dots (FD) and streaks (FS).
Diseases of arteries

B. Atherosclerosis

Fatty streaks present nearly universally in children. They do not cause

any disturbance in blood flow, however, they may be precursors of AP.
FSs begin as multiple yellow flat spots – fatty dots (FD) which are less
than 1 mm in diameter. Subsequently they merge into elongated (1
cm long and longer) FSs. They are composed of lipid-filled foam cells
with T-lymphocytes and extracellular lipids.
Diseases of arterias

B. Atherosclerosis
Atheromatous plaques are the basic lesions within the intima, having
a core of lipid (mainly cholesterol and cholesterol esters) and
a covering fibrous cap. APs are also called fibrous, fibrofatty, lipid, or
fibrolipid plaques which have white to whitish yellow colour and rise
intima slightly into the lumen of the artery. The centers of larger
plaques may contain a yellow debris, hence the term atheroma. Their
distribution in humans is characteristic. The abdominal aorta is usually
much more involved than thoracic aorta, and aortic lesions tend to be
much more prominent around the origins (ostia) of its major vessel
branches.
Diseases of arteries

B. Atherosclerosis

Atheromatous plaques have 3 principal components:

1) cells, including smooth muscle calls, macrophages, and other
leukocytes,
2) connective tissue extracellular matrix, including collagen, elastic
fibers, and proteoglycans, and
3) intracellular and extracellular lipid deposits. In advanced
atherosclerosis, the fatty atheroma may be converted to a fibrous
scar.
Natural history
Diseases of arterias

B. Atherosclerosis

The complicated lesions are defined by:

a) patchy or massive calcification,
b) focal rupture or gross ulceration,
c) thrombus formation (thrombosis) producing emboli,
d) hemorrhage into a plaque,
e) aneurysmal dilatation of large vessels.
Diseases of arteries
C. Hypertensive Vascular Disease

 One of the most important risk factors in both coronary

heart disease and cerebrovascular accidents.
 It may also lead to cardiac hypertrophy with heart
failure, aortic dissectin, and renal failure.
 About 90-95% of hypertension is idiopathic and
apparenly primary – essential hypertension.
 Of the remaining, 5-10% is secondary to renal disease
or, less often, to narrowing of the renal artery (usually by
an atheromatous plaque) – renovascular hypertension.
Diseases of arteries
C. Hypertensive Vascular Disease

 Infrequently, secondary hypertension is the result

of diseases related to the adrenal gland (such as
primary aldosteronism, Cushing syndrome,
pheochromocytoma etc.).
 About 5% of hypertensive persons show a
rapidly rising blood pressure, which, if untreated,
leads to death within 1 or 2 years – malignant
hypertension.
Diseases of arteries
C. Hypertensive Vascular Disease

Morphology
•Hypertension accelerates atherogenesis and causes changes in the
structure of the wall of blood vessels that potentiate both aortic dissection
and cerebrovascular hemorrhage.
•Hypertension is associated with 2 forms of small blood vessel disease
•hyaline arteriolosclerosis -in elderly patients, more severe in patients with
hypertesion and diabetes, a homogenous, pink, hyaline thickening of the
walls of arterioles with narrowing of the lumen
•hyperplastic arteriolosclerosis -in patients with more severe elevation of
blood pressure, there is typical onion-skin, concentric thickening of the walls
of arterioles with progressive narrowing of the lumens
Diseases of arteries
D. Inflammatory Disease – Arteritides, Vasculitides

Infectious Vasculitides: bacterial- Neisserial, Rickettsial, Spirochetal, fungal,

viral,

Non-Infectious Vasculitides: so-called systemic necrotizing vasculitides

(affecting aorta, medium-sized vessels) and small vessel vasculitides
(affecting arterioles, venules and capillaries). Pathogenesis involves immune
compexes, antineutrophil cytoplasmic antibodies (ANCA) and antibodies to
endothelial cells.

Classification on the basis of the size of the involved blood vessels, the
anatomic site, clinical manifestation and histological characteristics of the
lesion: Large, medium and small vessel vasculitis
Diseases of arterias
F. Aneurysms and Dissection

•Aneurysm – localized abnormal dilatation of blood vessel that occurs

most commonly in the aorta or the heart.
•It can be true (complete but often attenuated arterial wall
components) or false (extravascular hematoma that communicates
with the intravascular space).
•Causes of true aortic (or any vessel) aneurysms are:
• Atherosclerosis
• Cystic medial degeneration.
• Syphilitic aneurysm (tertiary stage of syphilis).
Diseases of arteries
F. Aneurysms and Dissection

•Aortic Dissection (Dissecting Hematoma) – is characterized by

dissection of wall and penetration of blood in between and along the
laminar planes of the media, with the formation of a blood-filled channel
within the aortic wall – a dissecting intramural hematoma (aneurysm). It
can rupture outside, causing massive hemorrhage
•Causes:
• Hypertension
• Systemic or localised defect of collagen e.g marfan syndrome
• Iatrogenic e,g during arterial canulation
• Marked atherosclerosis
• Syphilis
• unknown
 Diseases of veins and lymphatics

A) Varicose Veins
B) Thrombophlebitis and
Phlebothrombosis
C) Syndrome of vena cava superior
D) Syndrome of vena cava inferior
E) Lymphangitis and Lymphedema
Diseases of veins and lymphatics

A) Varicose Veins
Abnormally dilated, tortuous veins produced by prolonged,
increased intraluminal pressure and/or by loss of support of the
vessel wall. Usually the superficial veins of the leg are involved.
There is marked variation in the thickness of the wall. Intraluminal
thrombosis and valvular deformities are frequently found. Despite
thrombosis of superficial varicose veins, embolism is rare (sharp
contrast to the relatively frequent thrombembolism that arises from
thrombosed deep veins).
Diseases of veins and lymphatics

•Important sites of varicose formation:

•Esophageal varices- in patients who have cirrhosis of the liver and
portal hypertension
•anorectal junction-varicose dilation of the hemorrhoidal plexus of
veins called hemorrhoids resulting of prolonged pelvic congestion,
source of bleeding and site of thrombosis
Diseases of veins and lymphatics

B) Thrombophlebitis and Phlebothrombosis

•Inflammation/venous thrombosis
•Deep leg veins a/c for > 90% of cases
•Some important risk factors incl:cardiac failure
•Malignancy
•Pregnancy
•Obesity
•Post-op
•Prolonged bed rest/immobilization
•Genetic hypercoagulable states
Diseases of veins and lymphatics

C) Syndrome of vena cava superior

Usually caused by neoplasms (occasionally by other lesions such as

aortic aneurysm) that compress or invade the v. cava superior
(primary bronchogenic carcinoma, mediastinal lymphoma). The
consequent obstruction produces a distinctive clinical complex
(dusky cyanosis, marked dilation of the veins of the head, neck, and
arms. Commonly the pulmonary vessels are also compressed, and
consequently resipartory distress may develop.
Diseases of veins and lymphatics

D) Syndrome of vena cava inferior

This syndrome may be caused by the similar processes
(hepatocellular carcinoma, renal cell carcinoma, thrombus).
Obstruction induces marked edema of the legs, distention of the
superficial collateral veins of the lower abdomen, and, when the
renal veins are involved, massive proteinuria.
Diseases of veins and lymphatics

E) Lymphangitis and Lymphedema

Primary diseases – extremely uncommon.
Secondary processes – develop in association with inflammation or
cancer.
Lymphangitis: bacterial infections spreading into and through the
lymphatics.
Obstructive lymphedema: Occlusions of lymphatic drainage by
tumor, by postradiation fibrosis, by filariasis, trauma or by
inflammatory thrombosis which is accompanied by abnormal
accumulation of interstitial fluid in the affected part.
 Tumors

A) Benign tumors and tumor-like lesions

B) Bordeline tumors
C) Malignant tumors
Tumors

A) Benign tumors and tumor-like lesions

Hemangioma
Lymphangioma
Glomus tumor
Tumors

B) Low grade malignant/intermediate grade/Borderline tumors

Kaposi
Hemangioendothelioma
Tumors
 Malignant:
 Angiosarcoma
 Hemangiopericytoma