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PATHOGENESIS OF ATHEROSCLEROSIS
Response
to
injury
hypothesis
(Endothelial cells)
* Recall HEMOSTASIS.
Once you open your endothelium, what will
happen? You expose your SUBENDOTHELIAL
layer. This layer is very active, not inert,
component of the blood vessel and it can
initiate a lot of reactions, aside from
hemostasis. It can also invite your
inflammation and your cholesterol.
* These are some of the things that can be
initiated when you have an endothelial
injury.
Atherosclerosis
as
a
chronic
inflammatory and healing response of
the arterial wall to endothelial injury
Interaction of modified lipoproteins,
monocyte-derived
macrophages,
and T lymphocytes with endothelial
cells and smooth muscle cells of the
arterial wall.
*These are the composition of your
atherosclerosis, it is just an interplay of
these factors.
ENDOTHELIAL INJURY
- The cornerstone of the response to injury
hypothesis
- The intact but dysfunctional endothelial
cells
exhibit
increased
endothelial
permeability, enhanced leukocyte adhesion,
and altered gene expression.
TWO MOST IMPORTANT CAUSES
1. Hemodynamic disturbances
2. Hypercholesterolemia
HEMODYNAMIC DISTURBANCES
- Turbulence plaques occur at the ostia of
the existing vessels, branch points, and
along the posterior wall of the abdominal
aorta.
Mabilis na flow, and this is due to
hypertension
- non-turbulent laminar flow leads to the
induction of endothelial genes whose
products (eg., the antioxidant superoxide
dismutase)
actually
protect
against
atherosclerosis.
Opposite naman is sluggish, or stasis, so
mabagal yung blood flow, nagcocause din
sya ng injury. Bakit? Kasi the cells settle to
the bottom, syempre may platelet yun, mag
aadhere sa endothelium, it can activate your
platelets, leading to coagulation. Stasis is
caused by viscosity brought about by
Lipoprotein A
- Result from mutations that lead to defects
in apoproteins or lipoprotein receptors, or
arise from the underlying disorders that
affect the circulating lipid levels, such as
nephrotic
syndrome,
alcoholism,
hypothyroidism, or Diabetic melitus.
HYPERCHOLESTEROLEMIA
(aka
Dyslipidemia accdg to Doc Eclarin)
Dominant lipids in atheromatous plaques
are cholesterol and cholesterol esters
Genetic defects in lipoprotein uptake and
metabolism
that
cause
hyperlipoproteinemia are associated with
accelerated atherosclerosis
Familial hypercholesterolemia, caused by
defective LDL receptors and inadequate
hepatic LDL uptake, can precipitate
myocardial infarctions before age 20
Accelerated atherosclerosis occurs in
animal
models
with
engineered
deficiencies in apolipoproteins or LDL
receptors.
Other genetic or acquired disorders (eg.
DM,
hypothyroidism)
that
cause
hypercholesterolemia lead to premature
atherosclerosis.
Significant correlation between the
severity of atherosclerosis and the
levels of total plasma cholesterol or
LDL.
Dinedetermine
natin
yung
level
ng
cholesterol or LDL, kasi, the higher level, the
greater or the faster the development of
atherosclerosis. Severity depends of the diet
FATTY STREAKS
Eto yung nakikita niyo sa baby. Sa simula,
pagconsume ng milk, fatty streak na kaagad
yan, kasi lipid - filled foamy cells
macrophages. Kahit yung first few days to
few months ng bata meron na kaagad nito.
Composed
of
lipid-filled
foamy
machrophages
Multiple minute flat yellow spots,
eventually coalesce into elongated
streaks 1cm long or longer
ATHEROSCLEROTIC PLAQUE
Intimal
thickening
and
lipid
accumulation, which together form
plaques
Continuous accumulation of cholesterol,
intimal thickening and lipid accumulation.
White yellow and enroach on the lumen
of the artery, superimposed thrombus
over ulcerated plaqes is red brown
Vary in size but can coalesce to form
larger masses