PATHOLOGY OF BLOOD

VESSELS

1.NORMAL VESSELS
3 concentric layer; intima, media &
adventitia
Arteries
Capillaries
Veins

Vascular organization
Large elastic arteries > mediumsized arteries > small arteries
>arterioles > capillaries > postcapillary venules > collecting
venules > veins

2.VASCULAR WALL CELLS AND

THEIR RESPONSE TO INJURY
Endothelial cells;
Elaboration of Anticoagulant, Antithrombotic,
Fibrinolytic Regulators
Elaboration of Prothrombotic Molecules
Extracellular Matrix Production (Collagen,
Proteoglycans)
Modulation of Blood Flow and Vascular
Reactivity
Regulation of Inflammation and Immunity
Regulation of Cell Growth
Oxidation of LDL

Ctd
Vascular Smooth Muscle Cells
proliferate when appropriately stimulated
synthesize ECM collagen, elastin, and
proteoglycans
elaborate growth factors and cytokines
vasoconstriction or vasodilation

Response of Vascular Wall Cells to

Injury
Endothelial injury contributes to a host of
pathologies including thrombosis,
atherosclerosis, and hypertensive vascular
lesions.
Injury to the vessel wall results in a healing
response, involving intimal expansion by
The recruitment and activation of the SMCs in
this process proliferating SMCs and newly
synthesized ECM.involves signals from cells eg
ECs, and mediators derived from coagulation
and complement cascades.
Therefore, intimal thickening is a
stereotyped Response to Vascular Injury

3.CONGENITAL ANOMALIES
Rarely symptomatic;
Developmental (berry) aneurysms occur in
cerebral vessels.
Arteriovenous fistulas are direct connections
between arteries and veins that bypass the
intervening capillaries.
Fibromuscular dysplasia is a focal irregular
thickening of the walls of medium and large
muscular arteries.

4.ARTERIOSCLEROSIS
Arterial wall thickening and loss of
elasticity.
Arteriolosclerosis affects small arteries and
arterioles with two anatomic variants hyaline and
hyperplastic.
Mnckeberg medial calcific sclerosis; calcific
deposits in muscular arteries.
Atherosclerosis.

5.ATHEROSCLEROSIS
General descriptions;
intimal lesions called atheromas (also
called atheromatous or atherosclerotic
plaques), that protrude into vascular
lumina.
plaque consists of a raised lesion with a soft,
yellow, grumous core of cholesterol (esters)
covered by a firm, white fibrous cap.
obstructs blood flow & weaken the
underlying media and rupture, causing
acute catastrophic vessel thrombosis.
causes ischemic heart disease (IHD) .

Epidemiology
Causes more morbidity and mortality
(roughly half of all deaths) in the
Western world than any other disorder.
The mortality rate for IHD in the United
States is among the highest in the
world and is approximately five times
higher than that in Japan.

Major Constitutional Risk Factors

for IHD
Non-modifiable factors;
Age; between ages 40 and 60, the incidence of
myocardial infarction in men increases fivefold.
Gender; premenopausal women are relatively
protected against atherosclerosis and its
consequences compared with age-matched men.
Genetics; well-established familial predisposition
to atherosclerosis and IHD is multifactorial: such
as hypertension or diabetes, familial
hypercholesterolemia, that result in excessively
high blood lipid levels.

 Major Modifiable Factors;

Hyperlipidemia; esp. hypercholesteremia i.e. LDL
cholesterol has an essential physiologic role delivering
cholesterol to peripheral tissues while mobilizes
cholesterol from developing and existing atheromas.
Hypertension; increase the risk of IHD by
approximately 60% in comparison with normotensive
populations.
Cigarette Smoking; Prolonged (years) smoking of one
pack of cigarettes or more daily increases the death
rate from IHD by 200%.
Diabetes Mellitus; induces hypercholesterolemia, the
incidence of myocardial infarction is twice as high in
diabetic as in non-diabetic individuals.

 Additional Factors;
Inflammation as marked by Creactive protein.
Hyperhomocystinemia.
Lipoprotein A.
Factors Affecting Hemostasis.
Other Factors; like lack of exercise;
competitive, stressful lifestyle, and
obesity.

Pathogenesis
Response-to-injury hypothesis;
Atherosclerosis as a chronic inflammatory
response of the arterial wall to
endothelial injury.
Lesion progression occurs through
interactions of modified lipoproteins,
monocyte-derived macrophages, T
lymphocytes, and the normal cellular
constituents of the arterial wall.

 Central tenets of the hypothesis;

Chronic endothelial injury, with resultant endothelial
dysfunction, causing (among other things) increased
permeability, leukocyte adhesion, and thrombosis.
Accumulation of lipoproteins (mainly LDL and its
oxidized forms) in the vessel wall.
Monocyte adhesion to the endothelium, followed by
migration into the intima and transformation into
macrophages and foam cells.
Platelet Adhesion Factor release from activated
platelets, macrophages, and vascular wall cells, inducing
SMC recruitment, either from the media or from
circulating precursors.
SMC proliferation and ECM production.
Lipid accumulation both extracellularly and within cells
(macrophages and SMCs).

Morphology
Fatty Streaks; composed of lipid-filled foam cells
but are not significantly raised, begin as multiple
minute yellow, flat spots that can coalesce into
elongated streaks,
Atherosclerotic Plaque; a.k.a fibrous or
fibrofatty plaques impinge on the lumen of the
artery and grossly appear white to yellow;
thrombosis superimposed over the surface of
ulcerated plaques is red-brown in color.
Atherosclerotic plaques have three principal
components: (1) cells, including SMCs,
macrophages, and T cells; (2) ECM, including
collagen, elastic fibers, and proteoglycans;
and (3) intracellular and extracellular lipid.

Parts of the plaque (on crosssection):

Superficial fibrous cap is composed of SMCs and relatively

dense collagen.
Shoulder- beneath and to the side of the cap = more cellular
area containing macrophages, T cells, and SMCs.
Necrotic core; deep to the fibrous cap, containing cholesterol
(esters), debris from dead cells, foam cells (lipid-laden
macrophages and SMCs), fibrin, variably organized thrombus,
and other plasma proteins; the cholesterol content is frequently
present as crystalline aggregates that are washed out during
routine tissue processing and leave behind only empty "clefts.
Neovascularization at the periphery of the lesions,

 Plaque changes;
Rupture, ulceration, or erosion; exposes the
bloodstream to highly thrombogenic substances and
induces thrombus formation and occlude the lumen
and lead to downstream ischemia.
Hemorrhage into a plaque
Atheroembolism; plaque rupture can discharge
debris into the bloodstream, producing microemboli
composed of plaque contents.
Aneurysm formation; Atherosclerosis-induced
pressure or ischemic atrophy of the underlying
media, with loss of elastic tissue, causes weakness
of the vessel wall and development of aneurysms
that may rupture

Natural History of
Atherosclerosis
Preclinical and clinical phase.

Prevention of Atherosclerotic
Vascular Disease
Primary prevention programs; cessation of
cigarette smoking, control of hypertension,
weight loss, exercise, and lowering total and
LDL blood cholesterol levels while increasing
HDL (e.g., by diet or through statins)
Secondary prevention programs; use of
aspirin (anti-platelet agent), statins, and beta
blockers (to limit cardiac demand), as well as
surgical interventions (e.g., coronary artery
bypass surgery, carotid endarterectomy).
These can successfully reduce recurrent
myocardial or cerebral events.

6.HYPERTENSIVE VASCULAR
DISEASE
General description;
Elevated blood pressure is called
hypertension.
Remains asymptomatic until late in its
course.
Contributes to the pathogenesis of coronary
heart disease and cerebrovascular
accidents, causes cardiac hypertrophy and
heart failure, aortic dissection, and renal
failure.

Regulation of Blood Pressure

BP= CO X PR
RAA System
Vasodilators
Adrenal aldosterone
ANP

Pathogenesis of
Hypertension
90% to 95% of hypertension is idiopathic (essential
hypertension), which is compatible with long life,
unless a myocardial infarction, cerebrovascular
accident, or other complication supervenes.
Most of the remainder of "benign hypertension" is
secondary to renal disease or, less often, to
narrowing of the renal artery, usually by an
atheromatous plaque (renovascular hypertension).
Accelerated or malignant hypertension, the clinical
syndrome is characterized by severe hypertension
(diastolic pressure over 120mmHg), renal failure,
and retinal hemorrhages and exudates, with or
without papilledema

 Essential Hypertension;
alterations in renal sodium homeostasis and/or vessel wall
tone or structure underlie essential hypertension.
interplay of multiple genetic and environmental factors
affecting cardiac output and/or peripheral resistance.

Secondary Hypertension;
Renal: acute glomerulonephritis, chronic renal disease,
polycystic disease, renal artery stenosis, renal vasculitis, reninproducing tumors.
Endocrine: Adrenocortical hyperfunction, Exogenous hormones,
Pheochromocytoma, Acromegaly, Hypo/hyperthyroidism,
Pregnancy-induced.
Cardiovascular: Coarctation of aorta , polyarteritis nodosa
increased intravascular volume , increased cardiac output ,
rigidity of the aorta.
Neurologic: psychogenic , increased intracranial pressure ,
sleep apnea, acute stress (surgery).

Vascular Pathology in
Hypertension
Accelerating atherogenesis
Potentiate both aortic dissection and
cerebrovascular hemorrhage
Two forms of small blood vessel disease
Hyaline Arteriolosclerosis: a homogeneous pink
hyaline thickening of the walls of arterioles with loss of
underlying structural detail and with narrowing of the
lumen
Hyperplastic Arteriolosclerosis. Related to acute
or severe elevations of blood pressure, characteristic
of malignant hypertension , associated with "onionskin," concentric, laminated thickening of the walls of
arterioles with luminal narrowing ,the laminations
consist of SMCs and thickened, duplicated basement
membrane.

7.ANEURYSMS AND
DISSECTIONS
General description;
aneurysm is a localized abnormal dilation of a blood
vessel or the heart
"true" aneurysm.
false aneurysm (pseudoaneurysm): pulsating hematoma.

arterial dissection arises when blood enters the wall of

the artery, as a hematoma dissecting between its
layers.
Causes; atherosclerosis and cystic medial degeneration
of the arterial media, wall-weakening factors like include
trauma, congenital defects (e.g., berry aneurysms),
infections (mycotic aneurysms), or syphilis, and
vasculitis.
Mycotic aneurysms can originate (1) from embolization
of a septic thrombus, usually as a complication of
infective endocarditis; (2) as an extension of an adjacent
suppurative process; or (3) by circulating organisms
directly infecting the arterial wall.

Abdominal Aortic Aneurysm

Definition
Out pouching of the aorta, most
commonly in abdominal aorta,
following
atherosclerotic destruction of the
aortic media, leading to vessel wall
weakness

 Morphology
Big fusiform or sacular bulge out the side of the
abdominal aorta of varying width and length
below the renal arteries and above the bifurcation
of the aorta.
Often contains atheromatous ulcers with
thrombi (source of atherothrombotic origin)
May be so large that it compresses nearby vessels
or the thrombus causes occlusion syndromes
Special Variants
Inflammatory AAA = Macrophages, Giant Cells,
Lymphocytes, Plasma cells, AAA
Mycotic AAA = Supuritic lesions with organisms
hiding inside (salmonella)

 Pathogenesis
Atherosclerosis is number 1 cause
Cystic Medial Degeneration = Collagen.
Aneurysms come from abnormal
collagen
(Marfans) or an abnormality of collagen
remodeling (increased degradation decreased
synthesis caused by an immune reaction)
resulting in an inherently weakened aortic
wall

 Clinical Course
Rupture is often fatal.
Hemorrhage occurs into the peritoneum.
size = risk
Obstruction of a vessel (mesenteric, renal,
vertebral) leading to ischemic injury
Direct Compression of the ureter or of the
vertebrae (casing vertebral erosion)
Embolism from the thrombus thats sitting inside
Tumor = AAA is a palpable mass that may

Syphilitic Aneurysm
Cause
obliterative endarteritis characteristic of the
tertiary stage of syphilis can involve small
vessels in any part of the body.
Syphilis (stage 3) has a vascular predilection
for small vessels, especially of the aorta
Infection with subsequent Inflammation of
the vasa vasorum leads to obstruction,
inducing ischemia and obliterative
endarteritis of the aorta, causing death of
muscle and elastic tissue, called syphilitic
aortitis

 Morphology

Starts in the adventitia with vessels with

inflammation reactions in adventitia.
syphilitic aortitis.
Muscle that dies is replaced with fibrous
scar tissue in the media, contraction
of which causes the treebarking
appearance
Effects thoracic aorta with possible
dilation of aortic valve leading to
insufficiency

 Presentation
All causes by the encroachment on
mediastinal tissues
Crush the lungs = Dyspnea Pain
from rib and vertebral erosions
Death from rupture
Crush the esophagus =
Dysphagia, Cardiac Disease from
valve involvement Aortic
Regurgitation

Aortic Dissection
Definition
blood splays apart the laminar planes of the media
to form a blood-filled channel within the aortic wall
ruptures through the adventitia and into various
spaces, where it causes either massive
hemorrhage or cardiac tamponade (hemorrhage
into the pericardial sac).
men aged 40 to 60 years, with antecedent
hypertension (> 90% of cases ), and younger
patients with systemic or localized abnormalities of
connective tissue affecting the aorta ( Marfans )

 Morphology
A single intimal tear cuts into but not through
the media of the ascending aorta creating a
blood filled pocket within the aorta, between
layers
Dissection can continue in both direction
(towards the heart and towards the femoral)
Usually rupture outwards, but can rupture back
inwards
Outward = hemorrhage = fatal
Inward = second intimal tear back into the normal lumen,
forming a new vascular channel (doublebarrel Aorta)
which can, over time, endothelize and become a
permanent vessel.

No distinguishing histology except for

warning signs = elastic tissue
fragmentation and medial
degeneration

 Pathogenesis
HTN is primary causative agent, if you see
HTN pick Dissecting Hematoma
Medial weakening is not required for
dissection, but cystic medial necrosis
from
Marfans or Ehlers Danlos (weak elastic
layer) predisposes dissection
If you have a dissection, pick HTN. If HTN
isnt there, pick Marfans
Once dissection has happened, arterial blood
pressure favors hematoma

 Clinical Course
If the dissection is Proximal
subclavian/carotid (type A = bad), if
distal (type B = better)
Pain in the chest radiating to the back
is a tell tale sign
Death usually results from rupture
If dissection involves aortic root, you can get
valve problems (regurgitation, murmur

Classification of dissections

8.VASCULITIS
General description;
Inflammation of vessel walls.
2 mechanisms: immune-mediated
inflammation and direct invasion of
vascular walls by infectious pathogens.
Noninfectious Vasculitis.
Infectious Vasculitis.
Vasculitis Associated with Other Disorders .

Non-infectious Vasculitis
N

Classification;
Large-Vessel Vasculitis
Giant-cell (temporal) arteritis
Takayasu arteritis

Medium-Vessel Vasculitis
Polyarteritis nodosa
Kawasaki disease

Small-Vessel Vasculitis
Wegener granulomatosis
Churg-Strauss syndrome
Microscopic polyangiitis

 Pathogenesis;
immune complex deposition; Antibody and
complement are typically detected in vasculitic
lesions, DNA-anti-DNA complexes(SLE) and drug
hypersensitivity.Can be 2ndary to viral infections.
antineutrophil cytoplasmic antibodies (ANCAs);
circulating antibodies that react with neutrophil
cytoplasmic antigens. Cytoplasmic localization (cANCA) >>proteinase-3 (PR3) and Perinuclear
localization (p-ANCA) >>myeloperoxidase (MPO).
anti-endothelial cell antibodies; Antibodies to ECs
may predispose to certain vasculitides, for example
Kawasaki disease.

 Giant-Cell (Temporal) Arteritis

Most common form of Vasculitis, especially in Elderly
Women
affects the arteries in the head-esp. the temporal
arteries-but also the vertebral and ophthalmic arteries
& the aorta (giant-cell aortitis).
T cell-mediated immune response to an unknown
vessel wall antigen.
nodular intimal thickening with reduction of the
lumen and occasional thrombosis.
granulomatous inflammation within the inner media
centered on the internal elastic membrane.
fragmentation of the internal elastic lamina
Head pain, vision disturbances /blindness(ophthalmic
artery involved)
Responds well to steroids.

 Takayasu Arteritis
"pulseless disease
transmural fibrous thickening of the
aorta-particularly the aortic arch and
great vessels.
severe luminal narrowing of the
major branch vessels- loss of pulse.
in women younger than 40 years of
age(Japanese population)
intimal hyperplasia and irregular
thickening of the vessel wall

adventitial mononuclear infiltrates >>

mononuclear inflammation in the media
>> granulomatous inflammation(giant
cells and patchy medial necrosis)
reduced blood pressure and weaker
pulses in the upper extremities with
coldness or numbness of the fingers;
ocular disturbances, and neurologic
deficits. Claudication of the
legs(distal aorta involved); pulmonary
hypertension(PA involved). Narrowing
of the coronary ostia >>MI, systemic
hypertension(renal arteries involved)

Polyarteritis Nodosa
Involves renal and visceral vessels but not the
pulmonary circulation.
segmental transmural necrotizing inflammation
of small to medium-sized arteries
part of the vessel circumference involved,
with a predilection for branch points.
weakens the arterial wall >>aneurysms or
even rupture.
Impaired perfusion >>in the distribution of
affected vessels
transmural inflammation >>fibrinoid
necrosis >>fibrous /nodular thickening of the
vessel wall that can extend into the
adventitia(which may coexist)

Kawasaki Disease
self-limited illness of infancy and childhood (80% of
patients are younger than 4 years)
coronary arteritis >>aneurysms that rupture or
thrombose, causing AMI.
leading cause of acquired heart disease in
children.
delayed-type hypersensitivity -T cells to
uncharacterized vascular antigen.
pronounced inflammation affecting the entire
thickness of the vessel wall.
Clinical Course: mucocutaneous lymph node
syndrome with conjunctival & oral erythema and
erosion, edema of the hands and feet, erythema of
the palms and soles, a desquamative rash, and
cervical lymph node enlargement

Microscopic Polyangiitis
necrotizing vasculitis that affects capillaries , arterioles
and venules.
hypersensitivity vasculitis or leukocytoclastic
vasculitis.
necrotizing glomerulonephritis (90% of patients) and
pulmonary capillaritis present.
an antibody response to antigens such as drugs (e.g.,
penicillin), microorganisms (e.g., streptococci),
heterologous proteins, or tumor proteins.
segmental fibrinoid necrosis of the media- with focal
transmural necrotizing lesions
granulomatous inflammation is absent.
infiltrating and fragmenting neutrophils- in postcapillary
venules.
little or no immunoglobulin can be seen in most
lesions (so-called "pauci-immune" injury).

Wegener Granulomatosis
Triad
Acute necrotizing granulomas of the upper respiratory tract
Necrotizing or granulomatous vasculitis
Renal disease in the form of focal necrotizing, often
crescentic, glomerulonephritis.

cell-mediated hypersensitivity response,

possibly to an inhaled infectious or other
environmental agent.
The upper respiratory tract lesions range from
inflammatory sinusitis with mucosal
granulomas to ulcerative lesions of the nose,
palate, or pharynx, rimmed by granulomas
with geographic patterns of central necrosis
and accompanying vasculitis
renal lesions

Clinical Features
persistent pneumonitis with bilateral nodular and
cavitary infiltrates
chronic sinusitis (90%),
mucosal ulcerations of the nasopharynx (75%), and
evidence of renal disease (80%).
Other features include rashes, muscle pains, articular
involvement, mononeuritis or polyneuritis, and
fever
Allergic granulomatosis and angiitis (Churg-Strauss
syndrome) has association with allergic rhinitis,
bronchial asthma, and peripheral eosinophilia; pANCAs are present in roughly half the patients.

Thromboangiitis Obliterans
Buerger Disease
segmental, thrombosing acute and chronic
inflammation(tibial and radial arteries)
exclusively in heavy smokers of cigarettes, usually
beginning before age 35.
direct toxicity to endothelium by some tobacco
products, or an idiosyncratic immune response to
the same agents
sharply segmental acute and chronic vasculitis of
medium-sized and small arteries, predominantly of the
extremities.
superficial nodular phlebitis, cold sensitivity of the
Raynaud type in the hands, and instep claudication.

Vasculitis Associated with Other

Disorders
Disorders; rheumatoid arthritis, SLE,
malignancy, or systemic illnesses
such as mixed cryoglobulinemia,
antiphospholipid antibody
syndrome and Henoch-Schnlein
purpura
Rheumatoid vasculitis
Lupus vasculitis

Infectious Vasculitis
Direct invasion of infectious agents;
Aspergillus and Mucor species
mycotic aneurysms
can induce thrombosis and infarction.

9.RAYNAUD PHENOMENON
Results from an exaggerated
vasoconstriction of digital arteries and
arterioles
Two types;
Primary Raynaud phenomenon; exaggeration
of central and local vasomotor responses to cold
or emotion(common in young women)
Secondary Raynaud phenomenon; vascular
insufficiency of the extremities due to arterial
disease from other entities (SLE, scleroderma,
Buerger disease or atherosclerosis).

10.VEINS AND LYMPHATICS

Varicose Veins
Superficial veins (usually of the legs) become
distended, more cosmetic than anything else
Obesity,
jobs with legs dependent
(barber, surgeon), and pregnancy are
disposing factors
Stasis of blood, rupture of valves, or thinning
of walls allows distention
May cause ulceration, but are generally
asymptomatic (do not cause emboli)
Can also be in the esophagus (esopheal
varices) and in the anus (hemorrhoids).

 Thrombophlebitis and Phlebothrombosis

Aka Deep Vein Thrombosis, DVT.
The distinction between thrombosis of the vein
(phlebothrombosis) and inflammation of the
Vein with thrombosis (thrombophlebitis) is not
relevant, they are all DVTs
Presents with pain in the calf with red,
tender lesions, with a positive Homans
Sign(dorsiflexion induces pain)
Risk increases with Estrogen, Birth Control,
Smoking, Age, Hypercoagulability
Can result in pulmonary embolism or edema

 Superior and Inferior Vena Caval

Syndromes
Something blocks these large veins
(invasive neoplasm, mural thrombosis) that
causes a back up distally, without a failure
of the heart
Massive edema inferiorly for IVC (ankle,
ascites, pelvis) or superiorly for SVC (face,
neck, arms)

 Lymphangitis and Lymphedema

Infection gets into the lymph nodes.
Red streaks from site of penetration, follows
along lymph tract, finished at lymph node.
Lymphadenopathy is present with PMNs and
Lymphocytes infiltrating site of infection.
Caused by Cancer or Virulent Bacteria
(Staph).

11.TUMORS
Classification of Vascular Tumors and Tumor-like
Conditions
Benign Neoplasms, Developmental and Acquired Conditions
Hemangioma
Capillary hemangioma
Cavernous hemangioma
Pyogenic granuloma Lymphangioma
Simple (capillary) lymphangioma
Cavernous lymphangioma (cystic hygroma)
Glomus tumor
Vascular ectasias
Nevus flammeus
Spider telangiectasia (arterial spider)
Hereditary hemorrhagic telangiectasis (Osler-Weber-Rendu disease)
Reactive vascular proliferations
Bacillary angiomatosis
Intermediate-Grade Neoplasms
Kaposi sarcoma
Hemangioendotheliom
Malignant Neoplasms
Angiosarcoma
Hemangiopericytoma

 Benign Tumors and Tumor-like Conditions

Hemangioma
Capillary Hemangioma
Cavernous Hemangioma
Pyogenic Granuloma

Lymphangioma
Simple (Capillary) Lymphangioma
Cavernous Lymphangioma (Cystic Hygroma)

Glomus Tumor (Glomangioma)

Vascular Ectasias
Nevus Flammeus
Spider Telangiectasia
Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu
Disease)

Bacillary Angiomatosis

 Intermediate-Grade (Borderline
Low-Grade Malignant) Tumors
Kaposi Sarcoma
Chronic KS
Lymphadenopathic KS (also called African or
endemic KS)
Transplant-associated KS
AIDS-associated (epidemic) KS

Hemangioendothelioma
Epithelioid hemangioendothelioma

 Malignant Tumors
Angiosarcoma
Hepatic angiosarcomas
Lymphangiosarcoma

Hemangiopericytoma

12.PATHOLOGY OF VASCULAR
INTERVENTION
Endovascular Stenting
Vascular Replacement