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CARDIOVASCULAR PATHOLOGY 1 - Coggle Diagram
CARDIOVASCULAR PATHOLOGY 1
ATHEROSCLEROTIC DISEASES
atherosclerosis
systemic disease affecting large and medium caliber arteries
M>F
women in fertile age are protected by estradiol
the hormone acts on the arterial muscle cells as an anti-inflammatory and anti-proliferative agent
the endothelial cells are made to vasodilate through modulation of eNOS
risk factors
modifiable
hyperlipidemia
diet
hypertension
smoke
insulin resistance and DM
low physical activity
non-modifiable
age
sex
familiarity for early-onset (<20y) angina pectoris, MI, peripheral vascular diseases
site
branching points of vessels
here the flow is more turbolent, generating alterations of the endothelium (cuboidal shape)
pathogenesis
endothelial damage due to LDL
sub-endothelial matrix involvement
(sometimes extenfing also to the tunica media)
LDL may enter into the intima and become oxidized
different stages
LESION INITIATION: LDL retention with other apoB-containing lipoproteins in the subendothelial matrix, which undergo a process of oxidation due to the release of ROS and other oxidizing factors
INFLAMMATION PHASE:LDL induces modifications in permeability and activates the adhesion of leukocytes and monocytes, activated in the intima
oxidation can be inhibited by HDL
FOAM CELL FORMATION (FATTY STREAK):
LDL molecules aggregation in the vessels and formation of highly-oxidized aggregated LDL
enzymes involved: SMases, sPLA2s, lipases, MPOs
oxidized LDL aggregates are recognized by macrophages, which intake molecules and transform into FOAM CELLS
fatty streak formation
FIBROUS PLAQUE FORMATION:
fibrous plaques formation is a consequence of muscle cells activation at the sub-endothelial matrix
elevated levels of homocysteine and angiotensin II stimulate the proliferation of smooth muscle cells and their migration to the endothelium
COMPLEX LESION and THROMBOSIS:
a complex lesion may cause thrombosis, due to the fact that the fibrous cap is not always so thick (thus, it is prone to rupture)
the fibrous cap can be degraded by the activation of different proteinases (collagenases, gelatinases, stromolysin and cathepsins) and by inhibition of matrix
elementary lesions
fatty streak: yellow patch due to lipids accumulation in macrophages under the endothelial layer
atheroma or fibroatheroma: smooth muscle cell with lipid pools and fibrous cap
fibrotic plaques: fibroatheroma with deposition of connective tissue and calcifications
AHA classification
type I (initial) lesion --> isolated macrophage foam cells
type II (fatty streak) lesion --> IC lipid accumulation
type III (intermediate) lesion --> IC lipid accumulation + small EC lipid pools
type IV (atheroma) lesion --> IC lipid accumulation + core of EC lipids
type V (fibroatheroma) lesion --> lipid core and fibrotic layer, multiple lipid cores and fibrotic layers, mainly calcific / fibrotic
type VI (complicated) lesion --> surface defect, hematoma-hemorrhage, thrombus
complications
epithelial ulcerations (cracks)
thrombosis (unstable plaques)
embolization
calcification (--> hypertension?)
hemorrhage
organs affected
heart (MI)
CNS (cerebral infarction)
body periphery (gangrene)
vessels (aneurysm)
media calcification with arterial stenosis or Monckeberg's sclerosis
vessels become more stiff
frequently incedentally found
M=F
involvement of medium and small arteries (lower limb>>>)
infiltration of smooth muscle layers by lipids, with deposits of connective tissue and calcium
CALCIFICATION LESIONS ARE ONLY IN THE MEDIA
important DD with an in situ carcinoma
(atherosclerosis and excessive PTH secretion)
arteriolosclerosis
very symptomatic, associated with hypertension and diabetes
small arteries involvement, with hyaline material deposition
proteinaceous material, intensely pink (= eosinophilic), likely to completely occlude the vessel's lumen
forms
hyaline form: activation of cells that produce hyaline material as a consequence of hemodynamic stress (diabetes or benign arterial hypertension)
hyperplastic form: onion/concentric growth of smooth muscle cells, due to malignant hypertension
arteriolar damage may cause fibrinoid necrosis
histology: concentric smooth muscle cell layer, thickened basement membrane
consequences on the kidneys, which may happen to be affected by ischemia and acute kidney failure
ANEURYSMS
permanent and localized increase of the lumen diameter of the arteries by >50%
true: involvement of all layers (intima, media and adventitia)
false: dissociation of muscle layer
morphology
symmetrical: fusiform, cylindrical, sac-like
asymmetrical: sac-like, berry form
histology
enlargement is due to the rupture of the elastic fibers
both internal and external elastic laminae may be affected due to deposits
sites
cerebral vessels (in particular, in the branching point of the Willi's polygon and cerebral arteries)
BERRY ANEURYSM
either congenital or due to hypertension
its rupture may cause subarachnoid hemorrhages
patients have around 45-50 ys
aorta and its main branches
abdominal aorta
risk factors
smoking
old age (>60y)
M>F
oxidative stress
inflammation of aortic wall
hyertension
dyslipidemia
fusiform or sac-like, located between the iliac artery and the renal artery
blockage of renal and iliac arteries, eventually leading to ectasia of the entire aorta
on the aneurysm, plaques of atherosclerosis may be observed and also thrombi (--> emboli, hemorrhages)
INFLAMMATORY ANEURYSM
(5-10%)
particular type of abdominal aneurysm typical of old patients / patients treated with RT
chronic inflammtion, retroperitoneal fibrosis and periaortic fibrosis, adherences to adjacent structures
clinical triad
abdominal or back pain
weight loss
high serological inflammatory markers
thoracic aorta
ascending aortic aneurysms
generally fusiform, rare
association with luetic aortitis
symptoms are a consequence of heart valves compression
aortic arch aneurysms
risk factors
Marfan syndrome
bicuspid aortic valve
family history of aortic dissection
Ehles-Danlos syndrome
descending thoracic /
thoracoabdominal aneurysms
genetic anomalies resulting in loss of elastic and muscular fibers in the medial layer of the aorta
+++
accumulation of mucopolysaccharides in cyst-like spaces
(ERDHEIM'S) CYSTIC MEDIAL NECROSIS
AORTIC DISSECTION
false aneurysm / "dissecting aneurysm"
blood separates the laminar planes of the media to form a blood filled channel within the aortic wall
sometimes associated with radiologically detectable aortic dilation
patients may be very young or old (>70ys)
risk factors
predisposing and triggering causes of hypertension
cocaine use
trauma
arterial catheterization, surgery, chest injuries
genetic disorders
Marfan syndrome (FBN1 mutation)
media cystic degeneration, appearing pink (Periodic acid-Schiff stain)
ectasia of the sinus of Valsalva, aortic valve insufficiency, aneurysmal dilation
Gsell-Erdheim syndrime
anesthetic death
myxoid degeneration od the valces with widespread fragmentation of elastic fibers
Ehler-Danlos syndrome
defect in pro-collagen formation
Loeys-Dietz syndrome
TGFbeta receptor mutation, elastin and collagen (I and III) anomalies
osteogenesis imperfecta
impaired collagen synthesis
pseudoxanthoma elasticum
fragmentation of the media elastic fibers
dissection mechanism
between the internal 2/3 and the external 1/3 of the media (intramural hematoma)
DeBakey classification
I: ascending aorta is involved and it affects all the aorta
II: affects only the ascending part of the aorta
IIIa: the descending part is affected
IIIb: all the length of the descending aorta until the iliac vessels is affected
evolution / complications
proximal or distal rupture with adventitia laceration
aortic valve prolapse
rupture in pericardium with cardiac tamponade
second distal laceration and decompression of dissection
THROMBOSIS /
THROMBOEMBOLISM
Virchow's triad
endothelial alteration
blood flow alteration
blood coagulability alteration
platelets can adhere to the endothelium, forming the pale thrpmbus and the coagulation cascade starts
RBCs are then able to accumulate, with the formation of the so-called red thrombus
microscopy
nuclear debris
dibrin
RBCs
different from a blood clot, which is elastic and well-demarcated (the thrombus is friable and not well-demarcated)
risk factors
arterial thrombosis
atherosclerosis
diabetes
pregnancy
age
chemotherapeutics
infectious burden
HIV
common
SLE
hormone therapy
venous thrombosis
anemia
advanced cancer, CT
hematological malignancies
genetic mutations (factor V of Leiden)
mutations in pro-thrombin and fibrinogen
elevated MPV
evolution
lysis if treated correctly
reorganization with vessels formation in the vessel itself
embolism (arteries and veins)
special types
thrombophlebitis migrans
(Trousseau's syndrome)
paraneoplastic syndrome in pts affected by pancreatic carcinomas
it moves from one side of the vein to another
infected thrombi
due to pyremia and distant abscesses
EMBOLI
detachment of a piece of thrombus
not only formed by blood cells
adipose emboli
mainly due to bone marrow release due to bone fracture
gas emboli
generally iatrogenic or as a result of overexpansion of the lung by decompression barotrauma or paradoxical embolism
VASCULITIS
inflammation and necrosis of blood vessels (arteries, veins and capillaries)
etiology
immune mechanisms (deposition of immune complexes, direct attack of vessels by circulating antibodies, cell-mediated immunity)
infectious pathogens
trauma
radiation
toxins
idiopathic
classification
etiological criteria
affected tunica
vessels' caliber
vasculites of large vessels
GIANT CELL ARTERITIS
(Horton temporal arteritis)
the most frequent
old pts (>70ys)
F>M
focal inflammation, chronic, granulomatous
symptoms: headache, pain at the pressure of the artery, visual decrease, polymyalgia rheumatica
most common site: temporal arteries
diagnosis: based on biopsy
macro: nodular thickness
micro: granulomas, giant cells (single cells with multiple nuclei), macrophages infiltration, internal elastic membrane fragmentation, thickened intima and fibrotic media
evolution: benign and self-limiting, excellent response to CS
TAKAYASU ARTERITIS
more frequent in young females (<30ys)
likely autoimmune
sites: confined to the aortic arch and branches; confined to thoracic, descending, abdominal aorta and branches; mixed involvement of thoracic and abdominal aorta
"absent pulse disease"
symptoms: dizziness, dyspnea, syncope, intermittent claudication of arms and legs
macro: segmental or multifocal alterations, wall thickening and tenacious adhesions, obstruction of collateral branches
micro: monocytes, lymphocytes, plasma cells and rare giant cells --> irrgular fibrosis and lumen thrombosis
vasculites of medium vessels
POLYARTERITIS NODOSA
multicentric, medium- and small- sized arteries
aneurysmal dilation, able to form nodules
necrotizing vasculitis affecting muscular arteries
organs involved: kidneys, heart, GI, liver, skin, CNS (NO LUNGS)
M>F
symptoms: fever, weight loss, IRA, hypertension, arthralgias
fatal course if not treated
90% remission after CS
unknown pathogenesis
diagnosis: biopsy of the kidney or skin nodules (multiple, 2-4 mm, different colours)
stages: acute (granulocytes), healing (fibroblasts), cicatricial (marked fibrosis with collagen plaque)
allergic angiotis variant (leukocytoclastic)
BUERGER DISEASE
(thromboangiitis obliterans)
M>F
25-40 ys
rare in the West, more common in Israel and East
main risk factor: smoking
sites: extremities (popliteal and ulnar arteries)
macro: segmentary inflammatory process
micro: occlusive thrombosis, micro-abscesses, necrosis (up to gangrene), amputation
KAWASAKI DISEASE
mucosal-cutaneous and lymph node syndrome
typical of children
70% of cases: coronary arteries
symptoms: high fever, cutaneous rash, conjunctival and oral lesions, lymphadenitis
usually, self-limiting
etiology: unclear (viral, bacterial, superantigens production with activation of a non-specific antigen-immune response
vasculitis of small vessels
GPA (aka Wegner's disease)
M>F
rare, but serious necrotizing autoimmune vasculitis
PR3-ANCA production
sites: nasal cavity, lungs, kidneys
nodules and necrosis ("geographic map-like") are visible on CT scan
signs and symptoms: ulcerations of oral mucosa, cavities and lung infiltrates, nodules and purpura, pseudotumors and conjunctivitis, stuffiness and saddle nose, pericarditis, glomerulonephritis
micro: granulomas, necrosis, giant cells, neutrophilic microabscesses
DD: TBC, infarction
in the lungs
granulomas surrounded by palisading histiocytes and giant cells with central necrosis, not well-formed; giant cells are surrounded by plasma cells, lymphocytes and dendritic cells
liquefaction / coagulative necrosis in the lungs, profuse eosinophils and multinucleated giant cells
in the kidneys
focal necrotizing glomerulonephritis, cellular crescents and glomerular thrombosis; common pyelonephritis and renal papillary necrosis; rare granulomatous glomerulonephritis
EGPA (aka Churg-Strauss disease)
systemic vasculitis
young asthmatic patients
increase in P-ANCA
involvement of small and medium size arteries
micro: eosinophilia around the granuloma; necrosis, fibrosis, dilated vessels, aneurysms
signs and symptoms: tiredness, fevers, sinus problems, nasal blockage, asthma, lung infiltrates, muscle and joint aches, rashes, heart problems, "pins and needles", nerves damage, anemia, blood loss
TUMORAL LESIONS
classifications
clinically
benign (hemangiomas, lymphangiomas)
intermediate
malignant (angiosarcomas)
histologically
tumors originating from endothelial cells
tumors originating from the cells that support and/or line blood vessels
markers
CD31, F8 --> endothelial cells
CD34 --> endothelial cells, stem cells
vimentin --> intermediate filament, not expressed in epithelial cells, positive in sarcomas
SMA --> tumors arising from pericytes
D2-40 --> lymphatic endothelial origin
benign lesions
CAPILLARY HEMANGIOMA
most common vascular tumor
absent at birth, develop during childhood
rapid growth
micro: tangles of capillaries with thin walls, filled with blook, flat endothelium, poor connective tissue, no capsule
seen in vertebrae --> likely to cause fractures pr spinal cord compressions
CAVERNOUS HEMANGIOMA
less common
deep structures (liver, spleen)
likely to cause thrombosis and calcifications
macro: red-blue soft spongy mass
micro: wide and dilated vascular channels, papillary or completelyn filled with blood, no capsule
LYMPHANGIOMA
analogous to hemangioma of the blood vessels
subcutaneous tissue of head-neck and axilla regions
micro: network of lymphatic spaces lined with epithelial cells, absence of RBCs
IHC D2-40+
GLOMIC TUMORS (GLOMANGIOMA
extremely painful
from modified smooth muscle cells of the glomus corpuscles
common in distal phalanges of fingers
surgery is curative (no relapse)
SMA+, CD31-
malignant lesions
ANGIOSARCOMA
either well differentiated or undifferentiated
likely to arise in any part of the body
peak of age: 7th decade
M>F
most common cause: therapeutic radiation, exposure to vinyl chloride
macro: small nodes, defined margins, asymptomatic, red colour; large masses of soft tissue, not sicrumscribed, gray-whitish colour, necrosis and henorrhage
IHC: CD31+ and CD4+
DD with carcinoma (cytokeratin+) and melanoma (S100+ and melan A+)
hallmark of radiation-induced angiosarcoma: chromosome 8 with MYC amplification
HEMANGIOPERICYTOMA
pericyte-derived neoplasia
rare
slow-growing mass, painless, usually present at the level of the lower limbs and retroperitoneal regions
micro: pericytes origin suggestions, branched capillary channels and large open sinusoidal spaces surrounded by masses of cells of variable shape (spindle or rounded)
likely to form metastases at the level of lungs, bones and liver