Академический Документы
Профессиональный Документы
Культура Документы
3 patterns of arteriosclerosis
Atherosclerosis
Arteriolosclerosis
Monckeberg medial calcific sclerosis
DrTTW 2
Arteriolosclerosis
2 types:
Hyaline ATS: essential hypertension, DM
Hyperplastic ATS: Malignant hypertension
DrTTW 4
Atherosclerosis
DrTTW 5
Risk Factors of atherosclerosis
Age
clinically evident in middle age or later
(between ages 40 & 60 - MI by 5 times)
Sex
Males more prone than females
uncommon in pre-menopausal females (Estrogen improves endothelial
function & play a protective role)
After menopause incidence
Genetics
Familial predisposition of hypertension, DM, hyper-cholesterolemia
DrTTW 7
Hyperlipidaemia/hypercholesterolemia
DrTTW 8
Hypertension Cigarette smoking
Major risk factor at all ages Well established risk factor
BP >169/95 mm of Hg has 5 fold 1 or more pack / day increases
greater risk of IHD than normotensive risk by 200%
Antihypertensives reduce the risk of Cessation of smoking reduces
IHD risk substantially
Diabetes mellitus
Induces hypercholesterolemia increased
predisposition to AS
Risk of MI twice compared to non diabetics
AGEs (Advanced glycosylation end products)
trap LDL in the intima and retard efflux of
LDL
DrTTW 9
Other risk factors
Inflammation C-reactive protein (CRP)
Homocystinurea with premature vascular disease
metabolic syndrome: a number of abnormalities that are associated
with insulin resistance
increased Lipoprotein Lp(a): altered form of LDL increased risk of
ischemic heart & cerebrovascular ds
Type A personality (lack of exercise; competitive, stressful lifestyle)
increased risk
Multiple risk factors have a multiplicative effect
DrTTW 10
Pathogenesis of atheroma
DrTTW 11
Normal histology of blood vessel wall
DrTTW 12
Chronic endothelial injury
1
Hyperlipidemia
Hypertension
Smoking Endothelium
Homocysteine
Viruses
Toxins
Immune reactions
Hemodynamic factors Intima
Media Adventitia
DrTTW 13
Endothelial Dysfunction:
Increased permeability & Leukocyte adhesion 2
Monocyte adhesion & emigration
Platelet adhesion Response to injury
platelet
DrTTW 14
monocyte
Smooth muscle emigration from media to intima
(d/t released factors from activated platelet,
macrophage & endothelial cells) 3
Macrophage activation
DrTTW 15
4
Macrophages & smooth muscle cells engulf lipid
resulting foam cells
DrTTW 16
Smooth muscle proliferation
5
Collagen & other ECM deposition
Accumulation of lipid intracellularly &
extracellularly
DrTTW 17
Role of endothelial injury
Chronic/repetitive injury
Mechanical denudation, hemodynamic force, immune complex
deposition, irradiation, chemicals, hyperlipidemia
non-denuding endothelial dysfunction:
- increased permeability
- enhanced leukocyte adhesion
- alteration of gene products
DrTTW 18
Role of inflammation
DrTTW 19
Role of lipids
DrTTW 20
Role of smooth muscle cells
Smooth muscle cells migrate from media to intima, where they
proliferate and deposit ECM components, converting fatty streak into
a mature atherosclerotic lesions stabilize the AS plaques
Smooth m/s proliferation by growth factors (PDGF, FGF, TGF-)
Infection
Herpes virus, cytomegalovirus, Chlamydia pneumoniae: detected in
AS plaques but not in normal arteries -
contribute to the local prothrombotic state.
DrTTW 21
Cellular interaction in atherosclerosis
DrTTW 22
Morphology of Atherosclerotic plaque
DrTTW 23
Morphology of Atherosclerotic plaque
Fatty streaks
Earliest lesions of AS
Composed of lipid-filled foam cells
Begin as multiple yellow, flat spots <1mm in diameter that coalesce
into elongated streaks, 1cm long or longer
Contain smaller amounts of T lymphocytes and extra cellular lipids
Commonly found in children, as early as < 1 year of age
DrTTW 24
Fatty Streaks
DrTTW 25
Atherosclerotic plaque
Key processes in AS - Intimal thickening
- Lipid accumulation
Atheromatous plaque: a raised focal lesion in intima having soft yellow
grumous core of lipid covered by a firm white fibrous capsule
DrTTW 26
Microscopic appearance of an athroma
Cholesterol cleft
Foam cell
L
F
L: lumen
F: fibrous cap
C: lipid core
DrTTW 28
Coronary narrowing in atherosclerosis
proximal
DrTTW 29
Atherosclerotic Stenosis
1. Calcification
2. Rupture/fissuring, Ulceration/erosion - exposure of highly thrombogenic
substance - thrombus formation
3. Thrombosis superimposed thrombus formation, partially or
completely occluded the lumen
4. Atheroembolism rupture plaque discharge atherosclerotic debris
into the blood stream, producing microemboli
5. Haemorrhage into a plaque due to rupture of plaque or thin wall
capillaries that vascularize plaque
6. Aneurysmal dilatation atrophy of underlying media with loss of
elastic tissue causing weakness and potential rupture
DrTW 31
Calcification
Narrow lumen
calcification
DrTTW 32
Calcification
Ulceration &
haemorrhage
DrTTW Cholesterol cleft 34
Gross views of atherosclerosis in the aorta.
A, Mild atherosclerosis composed of fibrous plaques, one of which is denoted by the arrow.
B, Severe disease with diffuse and complicated lesions. Plaque rupture (blue arrow) and
superimposed thrombosis(green arrow), some of which have coalesced.
DrTTW 35
Ulceration
DrTTW 36
Hemorrhage into the plaque
Coronary thrombosis
A. a pink to red recent thrombosis in this B
narrowed coronary artery. The open,
needle-like spaces in the atheromatous B. Anterior surface of the heart with the left
plaque are cholesterol clefts. anterior descending coronary artery opened
longitudinally to show coronary thrombosis, one
of the complications of atherosclerosis. The
occlusive dark red thrombus is seen within the
lumen of the coronary artery. This produces an
DrTTW acute myocardial infarction. 39
Thrombosis
At high magnification, the dark red thrombus is apparent in the lumen of the
coronary. The yellow tan plaques of atheroma narrow this coronary
significantly, and the thrombus occludes it completely.
DrTTW 40
Narrowing of coronary artery with Organization & recanalization of previous
atherosclerosis by 60 -70% thrombosis with additional recent thrombus
in small lumen
DrTTW 41
The natural history, morphologic features, main pathogenic events,
and clinical complications of atherosclerosis.
DrTTW 42
Aneurysm
Congenital or acquired
DrTTW 43
Aneurysm
DrTTW 44
Different shapes of aneurysm
DrTTW 45
Pathogenesis of Aneurysm
DrTTW 47
Cystic medial degeneration
DrTTW 50
Clinical consequences of aneurysm
(Thoracic aortic aneurysms)
DrTTW 51
Aortic dissection
Dissecting
haematoma
Aortic lumen
DrTTW 53
Dissection aneurysm which is filled with red-brown thrombus on both
sides of the section, resulting double lumen. Many atherosclerotic
plugs are seen on the intima surface of aorta.
DrTTW 54
Aortic dissection (Dissecting aneurysm)
Classification of dissections
DrTTW 55
Aortic dissection (Dissecting aneurysm)
Most serious complication: dissections that involve the aorta from the
aortic valve to the arch
Common cause of death: rupture of the dissection outward into the
pericardial, pleural, or peritoneal cavities
sudden onset of excruciating pain, usually beginning in the anterior
chest, radiating to the back between the scapulae, and moving
downward as the dissection progresses; the pain can be confused
with that of myocardial infarction.
DrTTW 56
70
60
40 COMPLICATIONS:
Thrombosis
Plaque rupture
30 Hemorrhage
Wall weakening
Calcification
20
FIBROUS PLAQUE
10 ? ?
FATTY STREAK
DrTTW 0 57
To practice (multiple true false questions)