Pathology of lipid

metabolism
LIPOPROTEIN METABOLISM
• Fredrickson (WHO)
classification is based on the
appearance of a fasting
plasma sample after
standing for 12 hours at 4’C
and analysis of it’s
cholesterol and triglyceride
content.
FREDRICKSON (WHO) CLASSIFICATION OF DYSLIPIDAEMIA
GENETIC REASONS OF DYSLIPIDAEMIA

IIa IIb

IIa IIb

I
I
XANTHELASMAS in younger individuals (age <40
years) usually indicate hypercholesterolaemia
TENDON XANTHOMAS are associated with
familial hypercholesterolaemia
ARCUS SENILIS
ERUPTIVE XANTHOMAS
(hypertriglyceridaemia)
COMMON REASONS OF SECONDARY HYPERLIPIDAEMIA
LIPID- LOWERING DIETARY GUIDELINES
LIPID-LOWERING DRUGS
PALMAR XANTHOMAS BEFORE TREATMENT
AFTER TREATMENT
• Atherosclerosis is a wide-
spread pathology, manifested
chiefly by the deposition of
cholesterol in arterial walls,
which results in the formation of
lipid plaques (atheromas).
ATHEROMA IN CORONARY ARTERIES
• Lipid plaques are specific
foreign bodies around which
the connective tissue develops
abnormally (this process is
called sclerosis). This leads to
the calcification of the impaired
site of a blood vessel .
• The blood vessels become
inelastic and compact, the
blood supply through the
vessels is impeded, and the
plaques may develop into
thrombi.
• The main reason of atherosclerosis is
hyperlipoproteinemia.
• All of the lipoproteins, excepting
chylomicrons (large size), are capable
of penetrating the vessel wall.
• However, α -lipoproteins (HDL) which
are rich in proteins and phospholipids,
are liable to an easy breakdown within
the vessel wall or can be easy removed
because of their small size.
∀ β -lipoproteins (LDL) and, partly, pre-β -
lipoproteins (VLDL) containing much
cholesterol exhibit atherogenic
properties.
Composition
of the
plasma
lipoproteins.
• It is considered to be that modified
(oxidized) LDL are very dangerous.
Because they are captured by the cells
(macrophages with non-specific receptors in
non-regulating process). That’s why
antioxidants as V. E., β -carotene and
ascorbic acid can decrease development of
atherosclerosis.
Role of oxidazed lipoproteins in plaque
formation in arterial wall.
 The vascular wall can exert a
substantial effect on both:

• 1) the rate of penetration of

lipoproteins inside the vessel and

• 2) their subsequent history (for

example, hypertension)
 The main internal factors of
atherosclerosis development are:

• 1) hypercholesterolemia;

• 2) hypertension.
 3 groups of patients
1) Concentration of cholesterol in the blood is
less than 2 g/L
2) Concentration of cholesterol in the blood
is within 2-3,5 g/L (carry out prophylaxis,
dietetics)
3) Concentration of cholesterol in the blood is
more than 3,5 g/L (drug therapy and radical
methods (plasmophoresis, hemosorbtion)
 Risk factors of atherosclerosis development
• Genetic predisposition (high
concentration of LDL)
• Action of stress (increase in FFA
and Acetyl-CoA ⇒ more substrate for
cholesterol synthesis). Epinephrine cause
hypertension, which helps deposition of
cholesterol.
• Overeating of food especially reach in
cholesterol, fats and carbohydrates
(Acetyl-CoA and NADPH2 are necessary
for cholesterol synthesis). Usually in
humans with obesity.
• Smoking.
It has been observed that ischemia of
heart occurs by 2-2,5 times more
frequent , if the patient is smoking
(smoking decreases HDL concentration
in the blood).
• Hypodynamia.
Physical exercises promote to the
increase of HDL concentration (that is
why hypodynamia is risk factor of
atherosclerosis development).
 Dietetics.
• We should limit
concentration of cholesterol
and saturated fatty acids.
• Fats of animal origin we
must try to exchange on
vegetable fats, because they
contain unsaturated fatty acids mainly
which are necessary for the synthesis of
phospholipids.
 Dietetics.
• We should include in the diet the
products of vegetable origin,
because heteropolysaccharides
absorb cholesterol and remove it
out of the intestine.
• We must increase the concentration of
vitamins (especially E, C and A) in the
diet.
 Treatment
• Drug therapy:
• Cholesteramine,
• Cholestipole,
• Clofibrate (activate lipoproteinlipase),
• Nicotinic acid (decrease the secretion of
VLDL)
• Radical methods: plasmopheresis,
hemosorbtion.
We decrese concentration of cholesterol in
plasma. That is why it’s concentration in the
cells also decreases.
 Fatty liver (FL)
Normal liver contains about 4% as total lipids
(three-fourths of which is phospholipids (PL)
and one-fourth as neutral fats (TG).
For a variety of reasons, lipid – mainly as
triacylglycerol – can accumulate in the liver.
When accumulation of lipid in liver becomes
chronic, fibroid changes occur in the cells that
progress to cirrhosis and impaired liver
function.
NORMAL LIVER HISTOLOGY
NORMAL LIVER HISTOLOGY
FATTY LIVER
ACUTE FATTY LIVER
ACUTE FATTY LIVER
CHRONIC FATTY LIVER
CIRRHOTIC LIVER
 Accumulation of lipids depends upon activation
factors that lead to increase of liver fat and inhibition
of factors that lead to decrease of liver fat. When
there is an imbalance between
4) Mobilization
1) Influx of Dietary of fats into
Lipids (fat fuding) blood to depots
from liver
(hepatotoxic
substances,
2) Synthesis of FA
Total lipids in normal DH, starvation)
(fat fuding) liver = 4%
¾ as PL and ¼ as TG
5) Degradation of FA in
3) Mobilization of FA the liver (PM, starvation
from Depots to liver )
(DM, starvation)

Factors that lead to Factors that lead to

increase liver fat decrease liver fat
2 main categories of Fatty liver

–FL which is associated with raised

levels of plasma free fatty acids.
–The second type of FL is usually due
to a metabolic block in the production
of plasma lipoproteins (VLDL).
 – FL which is associated with raised levels of
plasma free fatty acids.
– Increasing amounts of FA are taken up by the
liver and esterified. The production of VLDL
doesn’t keep pace with the influx of FFA. TGs are
accumulated, causing FL.
Increased influx of FFA and development of FL
can be in cases of
1) feeding of high fat diets,
2) starvation,
3) uncontrolled diabetes mellitus.
In starvation and DM it can be also due to decreased
ability to secrete VLDL, because of low levels of
insulin and impaired protein synthesis.
 – The second type of FL is usually due to a
metabolic block in the production of plasma
lipoproteins (VLDL).
– The lesion may be due to
a)a block in apolipoprotein synthesis,
b)a block in the synthesis of the lipoprotein
from lipid and apoliprotein combination,
c)a failure in the secretory mechanism itself.
• Several antibiotics (puromycin)
inhibit protein synthesis and can
cause FL.
• Other hepatotoxic substances act
similarly. They include, for example,
carbon tetrachloride(CCL4),
chloroform, phosphorus, lead and
arsenic.
• Chronic consumption of alcohol can
induce FL.
 Lipotropic factors
All substances that increase the synthesis of PLs decrease the tissue
deposition of TGs. Such substances are called lipotropic factors.
They include
choline,
serine,
structural components of phospholipids,
pyridoxal phosphate (as an agent facilitating the
decarboxylation of serine phosphatides,
methionine (as a donor of methyl group)
folic acid (B9)
cobalamin (B12).
They may be used as drugs preventing excessive deposition of
triglycerides in the liver.
• 1 gr.: There is no need to carry out prophylaxis
of atherosclerosis in the first group.
• 2 gr.: In group number 2, it is necessary to
(carry out prophylaxis) of atherosclerosis by
means of diet and optimal physical exertion,
refusal from smoking, limitation of stress.
• 3 gr.: >3,5 g/L. It is necessary the measures of
drug therapy and radical methods of treatment
(plasmophoresis, hemosorbtion)
• Carbon tetrachloride induces the formation of
free radicals (CCL3) that disrupt lipid
membranes in the endoplasmic reticulum by
the formation of lipid peroxides.
• As the result, this affects the secretory
mechanism itself or the conjugation of the lipid
with apolipoprotein.
• That’s why some protection against carbon
tetrachloride can be provided by the
antioxidant action of vitamin E – supplemented
diets.