Pathology of blood and lymphatic vessels

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Pathology of blood and lymphatic vessels
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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)
• 
  
• 
  

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Pathology of blood and lymphatic vessels

• Endothelial cells
• a) serve as a semipermeable membrane,
  
• b) regulate thrombosis, thrombolysis and platelet
  adherence,
• c) influate 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.

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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 !!
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Pathology of blood and lymphatic vessels

• Endothelial dysfunction
• Endothelial activation

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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.
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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), as well as viruses,
complement components and hypoxia. 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.
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Pathology of blood and lymphatic vessels
2) Smooth muscle cells are capable a)to mediate
vasoconstriction, b) to mediate vasodilatation,
c) to synthesize the collagen, elastin, and
proteoglycans, d) to elaborate the growth
factors and cytokines, e) to proliferate, and
f) to migrate to the intima.  3) Pericytes have
role as supportive and connective elements.
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Pathology of blood and lymphatic vessels
The final result of vascular injury is intimal
thickening !!
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Vascular Diseases

• Diseases of arteries
• Diseases of veins and lymphatics
• Tumors

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Diseases of arterias

• A) Congenital anomalies
• B) Atherosclerosis
• C) Hypertensive vascular disease
• D) Inflammatory disease Arteritides
  (Vasculitides)
• E) Raynaud disease
• F) Aneurysms a dissections

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Diseases of arterias
A. Congenital Anomalies Aberrations of the usual
anatomic pattern of branching, shape and
anastomosing. Importance have only berry
aneurysms (developmental aneurysms involving
cerebral vessels) and arteriovenous fistulas or
aneurysms (abnormal communications between
arteries and veins usually arised as
developmental deffect, 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.
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Diseases of arterias
B. Atherosclerosis It is a generic term for three
patters 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)
Arteriosclerosis the hyaline and hyperplastic
thickening of small arteries and arterioles which
causes luminal narrowing and down stream ischemic
injury.
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Diseases of arterias

• 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.
• Myocardial infarction (heart attack), cerebral
  infarction (stroke), and aortic aneurysms are the
  major consequences of this disease.
• There are also other important consequences such
  as gangrene of the legs, mesenteric occlusions,
  sudden cardiac death, chronic ischemic heart
  disease, and ischemic encephalopathy.

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Diseases of arterias
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).
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Diseases of arterias
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.
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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.
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Diseases of arterias
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.
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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.
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Diseases of arterias
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.
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Diseases of arterias

• B. Atherosclerosis
• Risk Factors
• Age (advanced age), sex (male, postmenopausal
  women, the protective effect of estrogens),
  genetics (polygenic familiar predisposition,
  genetic abberrations in lipoprotein metabolism
  resulting in excessively high blood lipid
  levels), diet, life style, personal habit. There
  are 6 major well-accepted conditions such as
• hyperlipidemia,
• hypertension,
• smoking,
• diabetes mellitus,
• elevated plasma homocysteine,
• factors affecting hemostasis and thrombosis.

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Diseases ofv arterias
B. Atherosclerosis Hyperlipidemia It should be a
major risk factor. Most of the evidences
implicates hypercholesterolemia
(hypertriglyceridemia is a less significant, but
its effect may be greater in women than men).
The major component of the total serum
cholesterol is low-density lipoprotein (LDL)
cholesterol. In contrast, there is an inverse
relationship between symptomatic atherosclerosis
and high-density lipoprotein (HDL) level. HDL is
believed to mobilize cholesterol from existing
atheroma and transport it to the liver for
excretion in the bile (cholesterol bound to HDL
is designated as the good cholesterol. The
various classes of blood lipids are transported
as lipoproteins complexed to specific
apoproteins. They have many functions including
activation and inhibition enzymes, facilitating
transmembrane transport of certain lipoproteins,
serving as ligands to high.affinity cellular
receptors that guide the lipoproteins to specific
sites of catabolism.
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Diseases of arterias
B. Atherosclerosis Hyperlipidemia
Dyslipoproteinemias result either from genetic
mutations involving genes for apolipoproteins or
from some other underlying disorder, such as the
nephrotic syndrome, alcoholism, hypothyreoidism,
or diabetes mellitus.   Four types of
lipoprotein abnormalities are frequently found in
the population 1) increased LDL cholesterol
level, 2) decreased HDL cholesterol level, 3)
increased chylomicron remnants and
intermediate-density lipoproteins IDL, 4)
increased level of an abnormal lipoprotein Lp(a).
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Diseases of arterias
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 a 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.
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Diseases of arterias
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).
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Diseases of arterias
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, e) migration of
monocytes into the intima and their
transforamtion into macrophages and foam cells,
f) adhesion of platelets to focal areas of
denudation or to adherent leukocytes
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Diseases of arterias
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!!   Continuation 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.
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Diseases of arterias
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. 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.
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Diseases of arterias
C. Hypertensive Vascular Disease Morphology Hyper
tension accelerates atherogenesis and causes
changes in the structure of the wall of blood
vessels that potentiate both aortic dissection
and cerebrovascular hemorrhage. In addition,
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) and
hyperplastic arteriolosclerosis (in patients with
more severe elavation of blood pressure, there is
typical onion-skin, concentric thickening of the
walls of arterioles with progressive narrowing of
the lumens).
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Diseases of arterias
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
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Diseases of arterias
D. Inflammatory Disease Arteritides,
Vasculitides   Large Vessel Vasculitis Giant
cell (temporal) arteritis Granulomatous
arteritis of the aorta and its major branches,
with a predilection for extracranial branches of
the carotid artery and the temporal artery.
Usually occurs in patients older than 50 years
and often is associated with polymyalgia
rheumatica. Takayasu arteritis (pulseless
disease) Granulomatous inflammation of the aorta
and its major branches. Usually accurs in
patients younger than 50 years.
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Diseases of arterias
D. Inflammatory Disease Arteritides,
Vasculitides   Medium-Sized Vessel
Vasculitis Polyarteritis nodosa Necrotizing
inflammation without glomerulonephritis or
vasculitis in arterioles, capillaries, or
venules. Kawasaki disease Arteritis associated
with mucocutaneous lymph node syndrome. Coronary
arteries are often involved. Aorta and veins may
be involved. Usually occurs in children. Thromoang
itis obliterans (Buerger disease) Segmental,
thrombosing acute and chronic inflammation of
medium-sized and small arteries, principally the
tibial artery in younger men who were heavy
smokers.
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Diseases of arterias
D. Inflammatory Disease Arteritides,
Vasculitides   Small Vessel Vasculitis Wegener
granulomatosis Granulomatous inflammation
involving the respiratory tract and necrotizing
vasculitis affecting capillaries, venules,
arterioles and arteries. Necrotizing
glomerulonephritis is common. Churg-Strauss
syndrome Eosinophil-rich and granulomatous
inflammation involving the respiratory tract and
necrotizing vasculitis affecting small and
medium-sized vessels associated with asthma and
blood eosinophilia. Microscopic polyangiitis
Necrotizing vasculitis with few or no immune
deposits affecting small and medium-sized
vessels. Necrotizing glomerulonephritis is
common. Pulmonary capillaritis often occurs.
Henoch-Schönlein purpura Vasculitis with
IgA-dominant immune deposits affecting small
vessels. Typically involves skin, gut, and
glomeruli. Associated with arthralgia or
arthritis. Goodpasture syndrome Glomerulitis and
pneumonitis caused by anti-basement membrane of
capillaries antibodies.
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Diseases of arterias
E. Raynaud Disease Paroxysmal pallor or cyanosis
of the digits of the hands or feet and
infrequently the tips of the nose or ears (acral
parts) caused by intense vasospasm of local small
arteries or arterioles. Typically in young,
otherwise healthy women. No organic changes are
present in the arterial walls except late, when
intimal proliferation can appear.
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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).
The 2 most important causes of true aortic (or
any vessel) aneurysms are atherosclerosis and
cystic medial degeneration. Typical is also
syphilitic aneurysm (tertiary stage of syphilis).
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Diseases of arterias
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,
causing massive hemorrhage. In contrast to
atherosclerotic and syphilitic aneurysms, it is
not usually associated with marked dilatation of
the aorta. The more common and dangerous proximal
lesions involving either the ascending postion of
aorta only or both the ascending and the
descending aorta are called types I and II of
DeBakeys classification (often called type A).
Distal lesions not involving the ascending part
of aorta and usually beginning distal to the
subclavian artery are called DeBakey type III
(type B).
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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

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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).
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Diseases of veins and lymphatics
There are two special sites of varix formation
Esophagus (in patients who have cirrhosis of the
liver and portal hypertension, ruptura of an
esophageal varix followed by hemorrhage may be
very serious) and anorectal junction (varicose
dilation of the hemorrhoidal plexus of veins
called hemorrhoids resulting of prolonged pelvic
congestion, source of bleeding and site of
thrombosis).
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Diseases of veins and lymphatics
B) Thrombophlebitis and Phlebothrombosis Venous
thrombosis caused by inflammation or by different
mechanisms (hypercoagulability, immobilization,
postoperative state, pregnancy etc.). The deep
leg veins account for more than 90 of cases of
thrombophlebitis. The venous thromboses have
a tendency to embolization into lung.
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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.
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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.
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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.
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Tumors

• A) Benign tumors and tumor-like lesions
• B) Bordeline tumors
• C) Malignant tumors

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Tumors
A) Benign tumors and tumor-like
lesions Hemangioma (capillary 0 skin, cavernous
liver, arteriovenous skin, pyogenic granuloma
a polypoid form of capillary hemangioma that
occurs as a rapidly growing exophytic red nodule
attached by a stalk to the skin and gingival or
oral mucosa, which bleeds easily and is often
ulcerated) Lymphangioma (simple skin of head
and neck, axilla, cavernous children, neck and
axilla) Glomus tumor ( benign but painful tumor
arising from the modified smooth muscle cells of
the glomus body, a spcialized arteriovenous
anastomosis that is involved in thermoregulation,
located anywhere in the skin, but sometimes also
in soft tissues and in gastrointestinal tract,
most commonly found in the distal portion of the
digits under fingernails). Vascular ectasias
(nevus flammeus, spider telangiectasia,
hereditary hemorrhagic telangiectasia
Osler-Weber-Rendu disease)
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Tumors
B) Borderline tumors Kaposi sarcoma (frequent
occurence in patients with AIDS, classic typ
multiple red-to-purple skin plaques or nodules
primarily in the distal lower extremities, slowly
growing and spreading to more proximal sites, it
is composed of irregular blood vessels which is
difficult to distinguish from granulation tissue,
over time the number of plump spindle cells
accompanied by perivascular aggregates
increases). Hemangioendothelioma (intermediate
between the benign, well-differentiated hemagioma
and the anaplastic angiosarcoma, epitheloid
hemangioendothelioma tumor cells are plump and
often cuboidal, resembling epithelial cells,
well-defined vascular channels are inconspicious).
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Tumors
C) Malignant tumors Angiosarcoma (more often
older adults, anywhere in the body, predilect
sites skin, soft tissues, breast, and
liver). Hemangiopericytoma (rare tumor at any
anatomic site, most common on the lower
extremities and in the retroperitoneum, formed by
sinusoidal spaces surrounded by and enclosed
within nests and masses of spindle-shaped cells,
50 of tumors metastasize to lungs, bone, and
liver).