Pathology of blood and lymphatic
vessels
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) 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.
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), 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.
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.
Pathology of blood and lymphatic vessels
The final result of vascular injury is intimal
thickening !!
Vascular Diseases
Diseases of arteries
Diseases of veins and lymphatics
Tumors
Diseases of arterias
A) Congenital anomalies
B) Atherosclerosis
C) Hypertensive vascular disease
D) Inflammatory disease – Arteritides (Vasculitides)
E) Raynaud disease
F) Aneurysms a dissections
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.
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.
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.
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).
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.
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 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.
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 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.
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.
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.
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 intermediatedensity lipoproteins – IDL, 4) increased level of an abnormal lipoprotein
Lp(a).
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.
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).
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
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.
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.
Diseases of arterias
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. 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).
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:
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.
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.
Thromoangitis 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.
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 antibasement membrane of capillaries antibodies.
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.
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).
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 DeBakey´s 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).
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
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).
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.
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 (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)
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, welldifferentiated hemagioma and the anaplastic angiosarcoma, epitheloid
hemangioendothelioma – tumor cells are plump and often cuboidal,
resembling epithelial cells, well-defined vascular channels are
inconspicious).
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).