Atherosclerosis Flashcards
Pathogenesis of Atherosclerosis
Response to injury hypothesis
Pathogenesis of atheroma forming
Chronic injury 1 => NO
Chronic injury 2 => Adhession molecule
Chronic injury 3 => Endothelium sticky
After 1+2+3=4 => CROSS TALK
After 4 comes 5 =>
After 5 comes WAR
WAR => Role of Vitamin E
[1] Atherosclerosis: Diet and Drugs: Diet and Drugs
By Arnold von Eckardstein - Page 24
[2] Atherosclerosis: Treatment and Prevention
edited by Christian Weber, Oliver Soehnlein - Page 303
[3]Current Developments in Atherosclerosis Research - Page 10
[4] Atherosclerosis Risk Factors
By James J. Maciejko - Page 51
[5] Porth Pathophysiology: Concepts of Altered Health States - Page 521
[6] Olive Oil and Health
By Joules L. Quiles - Page 201
Fibrofatty plaques formed in intima of the vessels
Response to injury hypothesis
Pathogenesis of atheroma forming
Cells involved
- Endothelium
- Platlet
- Monocyte
- T cells
- Smooth muscle
Atheromas are formed in the intima in response to repeated injury or chronic injury
1.
Chronic injury
=>NO production decreased (NO blocks platlet adeshion)
2.
Chronic Injury
=> Adhesive molecule increase(healthy does not do that) Ex: VCAM-1 (Vascular Cellular Adhesion Molecule - 1)
=> Endothelium Sticky: Monocytes, Lymphocytes, Platlets
3.
Chronic injury
=> endothelial cells more permeable
=> influx of LDL in intima
After 1+2+3 = 4 :
The cells are moving to intima: the cells CROSS TALK: (GF / Cytokine production)
Monocyte -> Macrophage(Secrete: IL-1, TNF, MCP1 (monocyte chemotactic protein1) they are secreted from below and iritate endothelial cell more )
=> and activate Lymphocytes T ( CD8 & CD4+ (stimulate macrophages)) Gama IFN, Lymphotoxin). Platlets (PDGF - Platlet Derived Growth factor)
After 4 comes 5 :
some Media Smooth muscle cells will migrate in intima they no longer contract (change in behaviour, Myosin and actin disolved and the muscle cells gain propriety to ploriferate (physio not) =>
After 5 Comes war
Macrophages Phagocitise LDL through Scavanger Receptors
Smooth muscles
- Engulf LDL
- Secrete extracellular matrix & collagen fibers 4
=> Macrophages and Smooth Muscle become FOAM CELLS
=> Foam cells bursts (apoptosis) 1and necrosis2 (necrotic core) (and will release fat in the intima)
=> Lipid core 3 will be formed from the derbis of the apoptotic cell
=>Macrophages Produce free radical and oxidised LDL
Oxidised LDL !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
- Chemotactic agent for Monocytes & smooth msc
- Superstimulate Mono(produce more cytokines& free R) & smooth
- Increase uptake by Macrophages and Smooth msc
=>Oxidised LDL will create a positive feedback on the whole process
ANTIOXIDANTS PREVENT OXIDATION OF LDL
High LDL produces necrosis and apoptosis of Endothelial cells
=> Platlets secrete growth factors that will induce proliferation in smooth msc under the endothelium (in vecinity) and stimulate the production of colagen and cellular matrix 4 . this will result in the Fibrous Cap6 The Fibrous cap will be impregnated with Macrophages that will stimulate it’s ploriferation
“The major determinants of increased plaque vulnerability to rupture include a large lipid-rich core, a thin and unstable fibrous cap, 5”
More synthesis of growth factors will be present that wil produce ploriferation of vasa vasorum on margins, and will grow towards lesion (they will cause hemorage in the plaque)
Types of Atherosclerosis
Type 1 Atherosclerotic lesion
Also called Initial lesion or Fatty Dots
- Scattered macrophages with few lipids
- Yelow plaques apear in aorta at 1 y of life
- At 10 years all children have, they can progress to type 2
PROGRESSION DEPENDS ON ACUMULATION OF LIPIDS
Clinicaly silent
Type 2 Atherosclerotic lesion
Called Fatty streaks
Precursor of mature plaques
Elongated lesion (made from serial fusion of Type1)
- Lot of macrophages loaded with fat aranged in a liniar fashion
- Few T cells
Apear in most adolescence
Hypertension / DM / Obesity / Smoking
Increase chances to develop in atherosclerotic plaque
PROGRESSION DEPENDS ON ACUMULATION OF LIPIDS
Type 3 Atherosclerotic lesion
Also called Intermediate Lesions
Diference between type 2 and 3 is
- the lipids are present extracelulary to (not only in macrophages aka Foam Cells)
PROGRESSION DEPENDS ON ACUMULATION OF LIPIDS
Clinicaly silent
Type 4 Atherosclerotic lesion
Also called Fatty Atheroma
Type 3 +
Some extracelular lipid will make a core surounded of Foam Cells
Accelerated acumulation of Smooth muscle and extracelular matrix formation can lead to Type 5
Type 5 Lesion Atherosclerotic lesion
Fatty Atheroma Lesion
The smooth muscle release Extracelular matrix and it is making Fibrous Cap
Lot of Foam cells
Necrotic Core
Some T Lymphocites
Some Neovascularisation
Accelerated acumulation of Smooth muscle and extracelular matrix formation can lead to from Type 4 Type 5
Type 6 Atherosclerotic lesion
Alsso called Complicated Atheroma
- The smooth muscle release Extracelular matrix and it is making Fibrous Cap
- Lot of Foam cells
- Necrotic Core
- Some T Lymphocites
- Some Neovascularisation
TYPE 6 SPECIFIC
- Thrombus
- Endothelium disfunction,
- atract platlets
- => Platlets plugs
- =>platlets secrete chemicals
- =>spasticity
- => Fibrin deposition
- => THROMBUS
- Surface defects
- Intraplaque hemorage
Plaque will enlarge and can obstruct the vessel
- Haemoragee in plaque due to rupture of neovascularisation
- Blood from surface can enter through surface deffects
Most vulnerable vessels for Atherosclerotic Lesions
Large Elastic Arteries
- Abdominal Aorta
- Carotid Artery
- Iliac Artery
Medium size muscular arteries
- Coronary
- Poplipteal
- Cerebral
Most comon sites Ierarchy
- Aorta Abdominal
- Coronary
- Poplipteal
- Carotid
- Willis
Mesenteric ostium
Renal artery ostium
AORTIC CROCODILE POPPING FROM CAR OF WILLIS
Big vessels tehd to form Aneurism
Medium small vessels tend to form platlet plug
Atherosclerosis Complications
GF force smooth muscle to sythetise colagen and subsequential Fibrosis
Necrotic core rupture lead to dystrophic calcification (electronegatively charged proteins from cell cytosol)
Not verry dangerous
Surface defects of Atheroma
1.Erosions
Endothelial cell are shed away
2.Ulcerations
Superficial cells & BM shed away
3.Ruptures
Subendothelial structures are exposed and platlet plug will form (TXA - vasoconstriction + physical obstruction) => fibrin deposit => thrombus formation (thrombogenesis)
4. Atheroembolism
the plaque rupters nd the necrotic core goes away
Intrplaque Hemoragee
Heavy hemoragee from neovascularisation will cause the plaque to baloon in
Through surface deffect will permit blood to enter plaque
Aneurismal dilation
Media sufers because of ateroma from intima and the vessel wall will bulge out
Recent concept
This lesions have more inflamatory activity so persons who have more inflamatory lesions they have high levels of CRP, and they have more chances to develop complications
Clinical consequences of Atherosclerosis
40+ Male
50+ Female
May start earlier (premature IHD, premature Atherosclerosis) in exceptional cases ex: familial hypercholesterolemia
Ab Aorta
Aneurism may form
- Haemorage
- retroperitoneal - posterior aorta
- Peritonem - anterior area
- Lower limb ischemia - due to embolisation
CAD
- IHD
- Angina Pectoris
- MI
- Necrosis cardiac tissue
- Sudden cardia death
- Massive MI
- Arhytmmia
- CR IHD - Heart wall akinetic
- CCF - due to pump ineficiency
Poplipteal artery
- Thrombi
- Aneurism
LL ischemia
Carotid arteries stenosis & Circle of willis
- CNS manifestation
- Aneurisms that may rupture (berry are congenital)
- TIA
- Stroke (infarction, hemoragee)
- Ischemic encephalopathy
Mesenteric artery ostium lesions
Usualy: Male >50 years / smoker
Ischemia of small bowel
Postprandial abdominal pain
Ostium of renal artery
Kidney start release Renin
Leriche syndrome
Advanced aterosclerosis Abdominal Aorta and Iliac arteries
Clinical Presentation
- Impotence (male)
- Claudication (cannot increase blood flow to lower limb with exertion)
- Atrophy of calf muscles
