ATHEROSCLEROSIS

Group 7
Reporters:
SALONGA, TRIXIA
SAMONTE, ERICK
SAMSON, JOYCE

SALAZAR, MICAH
SANCHEZ, LORNA
SANTIAGO, MAHALLA
(moderator)
 OBJECTIVES:
 To define atherosclerosis and describe an
atheroma citing its contents
 To know how atherosclerosis develop and the
theories that explain atherogenesis
 To understand how cholesterol and associated
fat associated with atherosclerosis
 To review how cholesterol is transported in the
blood
 To explain why LDL and HDL directly and
inversely associated with atherosclerosis
respectively
 To determine the risks factors for atherosclerosis
and explain how each factor increases the risk
of having atherosclerosis
 To identify which of the risk factors is
modifiable/non-modifiable and learn the
significance of knowing suh
 To enumerate the complications of
atherosclerosis
 To know the role of increased homocysteine
levels in the development of atherosclerosis
 Atherosclerosis derives from “greek”:

 “sclerosis” = hardening - thickening

 “athere” = lipid accumulation

Atherosclerosis is an extremely common arterial

disease characterized by the deposition of
elevated focal, fatty-fibrous plaques, known as
artheromas, within the intima and inner media of
the walls of arteries.

- lipid deposition & cell proliferation at the intima

layer of larger & medium size arteries
 Contents

Atheroma is an accumulation and

swelling in artery walls that is made up of
(mostly macrophage cells), or debris,
that contain lipids (cholesterol and fatty
acids), calcium and a variable amount of
fibrous connective tissue.
 Young Atheromas are soft and have a
mealy, semisolid consistency and are the
most dangerous because they are prone
to sudden thrombosis and occlusion with
infarction of downstream tissue
Development of Atherosclerosis

Atherogenesis is the developmental

process of atheromatous plaques. It is
characterized by a remodeling of arteries
involving the concomitant accumulation of
fatty substances called plaques.
Pathogenesis of Atherosclerosis
Endothelial Cell Damage
Inflammation
Abnormally high concentration
of blood uric acid or blood
homocysteine
Rheologic Forces such as High Blood
Pressure or High blood glucose
levels
Accumulation of lipid ( mainly
Cholesterol)
Vascular
Inflammation
 Damaged endothelial
cells-“Sticky”
Neutrophils and
Lymphocytes
Macrophages invade the site and
engulf the lipid

Scar tissue matures and

calcification may occur
 Smooth muscle cells
Fibrocytes
Scar Tissue

Macrophage-like cells

Engulf and store cholesterol

 Endothelial Injury
Cholesterol seeps across the
damaged endothelium

Arterial Wall
Macrophages and other cells
Foamy appearance “Foam
Cells”
 Inflammatory cells, smooth
muscle cells and macrophages
Soft, Fatty mass
Early, soft atheromas obstruct
flow

Break open or hemorrhage

Acute Thrombosis and
Infarction
Old Atherosclerosis Lesions

Scarred, Hard and calcified

Impede blood flow

Ischemia
 Theories
 The Aging or senescence theory -
proposes that atherosclerosis is a
consequence of the progressive senile
deterioration of the walls of arteries leading
to fatty degeneration of the structural
elements and the progressive accumulation
of lipids. It is known that there is synthesis
of lipids within the arterial walls
 Acid mucopolysaccharrides
 Intramural Hemorrhage has been proposed as the
source of the fatty-fibrous plaques that comprise the
artheromatous deposits of atherosclerosis (Winteritz
et. Al)

 The thrombogenic theory this concept proposes

that the artheroma represents an organized small
mural thrombus attached to the intimal surface of
arteries.

 The Lipid theories the hypothesis in its simpliest

form suggests that an unbalanced diet with regard to
fats or some factor closely associated with dietary
fats leads, over course of time, to a discovered fat
metabolism resulting in atherosclerosis.
 The Acidity theory In a recent research study, it
was found out that for unknown reasons,
leukocytes, such as monocytes, or basophils, begin
to attack the endothelium of the artery lumen in
cardiac muscle. The ensuing inflammation leads to
formation of atheromatous plaques in the arterial
tunica intima, a region of the vessel wall located
between the endothelium and the tunica media. The
bulk of these lesions is made of excess fat,
collagen, and elastin. At first, as the plaques grow,
only wall thickening occurs without any narrowing,
stenosis of the arterial lumen; stenosis is a late
event, which may never occur and is often the result
of repeated plaque rupture and healing responses,
not just the atherosclerosis process by itself
 How are cholesterol and
saturated fat associate with
artherosclerosis?
Cholesterol is an essential component of cell
membranes; this is its major use. Other uses
of cholesterol are as raw material for
synthesis of corticosteroid and sex hormones,
and for synthesis of bile acids. These are
quantitatively minor. Hence excess cholesterol
tends to be deposited in the intimal layers of
blood vessels to contribute in the formation of
atherosclerotic plaque.
Cholesterol Levels
– A diet that is high in saturated fats causes LDL
cholesterol levels to increase in susceptible
people. Cholesterol levels also increase as
people age and are normally higher in men than
in women, although levels increase in women
after menopause. Several hereditary disorders
result in high levels of cholesterol or other fats.
People with these hereditary disorders can have
extremely high levels of cholesterol and (if
untreated) die of coronary artery disease at an
early age.
Saturated fat can come from animal or vegetable
products. But only animals make cholesterol.
When food is eaten and then digested by the body,
saturated fat is sent to the liver. The liver packages
any cholesterol into low-density lipoproteins (LDL)
particles. It can also make cholesterol from animal
or vegetable saturated fat and assemble it into
LDL particles. The particles are placed into the
bloodstream where they travel to the cells for use.
Atherosclerosis is an abnormal inflammatory
process inside artery walls as the result of complex
interactions among "bad" cholesterol (LDL),
platelets, calcium, and inflammatory cells. It is the
hardening and narrowing of the arteries caused by
the slow buildup of plaque on the inside walls of
the arteries. Plaque is made up of fat, cholesterol,
calcium, and other substances found in the blood.
CHOLESTEROL TRANSPORT IN
THE BLOOD
CHOLESTEROL
 a sterol
 classified nutritionally as lipid (fat)
 wax-like compound, which is hydrophobic,
meaning that it will naturally separate from
a watery environment
 found in foods such as eggs and dairy
products and is also manufactured in the
body, especially the liver
 LOW DENSITY LIPOPROTEIN
(LDL)
 a.k.a. the “Bad Cholesterol”
 major cholesterol carrier in the blood
 very light in weight, containing 10 percent
fat, 25 percent protein and 45 percent
cholesterol
 delivers cholesterol to tissues for use,
explaining why nearly half of its total
content is cholesterol
Why is LDL DIRECTLY associated
with atherosclerosis?
PLAQUE
FORMATION
 HIGH DENSITY LIPOPROTEIN
(HDL)
 a.k.a. “The Good Cholesterol”
 carries about one-third to one-fourth of blood
cholesterol
 heavier in weight than LDLs because they
contain 5 percent fat, 45 percent protein and 20
percent cholesterol
 performs a function called "reverse cholesterol
transport," which describes escorting cholesterol
from the tissues to the liver for recycling
 Why is HDL INVERSELY
associated with atherosclerosis?
 Generally, the higher your levels of HDL
cholesterol are, the lower risk you have for heart
disease.

HDL “Good” Blood What These Levels

Cholesterol Levels Mean For You

Below 40 mg/dL Bad – High Risk for

Heart Disease
40 – 59 mg/dL Lower Risk for Heart
Disease
60 mg/dL and above Excellent – this
should be your goal
 RISK FACTORS OF
ATHEROSCLEROSIS
A. NON-MODIFIABLE
Heredity, including race (+ family history)
Age (> 40 yrs old)
Gender (M>F)
B. MODIFIABLE
Cigarette smoking
Hypertension
Diabetes Mellitus
Physical inactivity
Obesity
Stress
 ATHEROSCLEROSIS

C. Their Significance In Atherosclerosis

The more risk factors, the greater the risk

for atherosclerosis.
 Role of Homocysteine in the
Development of Atherosclerosis
 What is Homocysteine?
-an amino acid homologous to cysteine
-biosynthesized from methionine by the removal of
its terminal C methyl group.
-can be recycled into methionine or converted into
cysteine with the aid of B-vitamins.

* Deficiencies of the vitamins folic acid (B9), pyridoxine

(B6), or cyanocobalamin (B12)) can lead to high
homocysteine levels.
High level of Homocysteine
 is a 'corrosive' of long-living proteins
 degrades and inhibits the formation of the
three main structural components of the
artery:
 Collagen
 Elastin
 Proteoglycans
 permanently degrades cysteine disulfide
bridges and lysine amino acid residues in
proteins, gradually affecting function and
structure
 High level of
Homocysteine

 will
auto-oxidize and react with
reactive oxygen intermediates and
damage endothelial cells and has
a higher risk to form a thrombus.
Atherosclerosis
Complications
 Complications
1. Acute arterial occlusion leading to
ischemic necrosis (infarction /
gangrene)
2. Chronic occlusion leading to tissue /
organ atrophy
3. Aneurysm formation
4. Embolism
 Aneurysm
 vascular dilation caused by weakening of the
tunica media of blood vessels.
 False aneurysms are caused by damage to all
3 layers of the arterial wall and result in
extravascular accumulation of blood. Disruption
of the endothelium associated with a true
aneurysm can cause formation of a thrombus
with subsequent embolization; thus, aneurysms,
thrombi, and emboli may be recognized
simultaneously.
 Embolism
 All
or part of a thrombus may break off
and be carried through the bloodstream
as an embolus that lodges distally at a
point of narrowing..
 Management of
Atherosclerosis
 LIFESTYLE
MODIFICATION
 Regular exercise -
Walking is great!
 Lose weight
 Control your blood
pressure
 Control serum
cholesterol and
triglyceride levels
Management of Atherosclerosis
 Do NOT smoke
 Eat a heart healthy diet of fresh
fruits and veggies, low fat foods,
and lean meats
 Management of
Atherosclerosis
 Cholesterol-lowering medications:
 Statins

-inhibit the enzyme HMG-CoA

reductase, which controls the rate of
cholesterol production in the body. These
drugs lower cholesterol levels from 20%-
60% by slowing the production of
cholesterol.
 Management of
Atherosclerosis
 Cholesterol-lowering medications:
 Bileacid sequestrants
- polymeric compounds which serve as
ion exchange resins. Bile acid
sequestrants exchange anions such as
chloride ions for bile acids.
 Management of
Atherosclerosis
 Cholesterol-lowering medications:
 Nicotinic acid (niacin)
- a B vitamin.
-in treating blood cholesterol and
triglyceride disorders, high doses (1-3
grams a day) of nicotinic acid are
necessary.
 Cholesterol absorption inhibitors
are a class of compounds that prevents
the uptake of cholesterol from the small
intestine into the circulatory system.
 Eg. ezetimibe
 The reduced delivery of cholesterol to the
liver increases hepatic LDL receptor activity
and thereby increases clearance of circulating
LDL. The net result is a reduction in
circulating LDL particles.
Management of Atherosclerosis
  Thrombolytic medications
 Anti-platelet and anti-coagulant medications
 are used to dissolve blood clots in a procedure
termed thrombolysis.
 It limit the damage caused by the blockage in the
blood vessels.
 e.g. Tissue plasminogen activator

Streptokinase
Urokinase
Reteplase (Retavase)
Tenecteplase (TNKase)
Anistreplase (Eminase)
 Management of
Atherosclerosis
  Thrombolytic medications
 advantage of administration is highest
within the first sixty minutes, but may
extend up to six hours after the start
of symptoms.
 The drugs are often given in
combination with intravenous heparin
or low molecular weight heparin,
which are anticoagulant drugs.
Management of Atherosclerosis
 Endarterectomy
 Surgical procedure that removes the
atheromatous plaque material, or
blockage, in the lining of an artery.
 carried out by separating the plaque
from the arterial wall.
Management of Atherosclerosis

•Balloon Angioplasty
•accomplished using a balloon-tipped
catheter inserted through an artery in the
groin or arm to enlarge a narrowing in a
coronary artery.
Management of Atherosclerosis
 Bypass Surgery
 procedure performed to relieve angina
and reduce the risk of death from
coronary, and artery disease. Arteries or
veins from elsewhere in the patient's
body are grafted to the coronary arteries
to bypass and improve the blood supply
to the coronary circulation supplying the
myocardium (heart muscle)
Thank You!