1. HYPERLIPIDEMIAS
The Basics

2. I. DISTURBANCIES OF LIPID METABOLISM
Essential types of disturbances
1. Hyperlipoproteinemias
2. Hypolipoproteinemias
3. Dyslipidemias
4. Hyperlipidemias

3. DEFINITIONS Hyperlipoproteinemias : Pathologic process manifested by
 concentration of one or more types of LPs
in the blood
Hyperlipidemia ( plasma cholesterol and/or triglyceride) is present in all hyperlipoproteinemias.
Hypolipoproteinemias : – Decreased concentration of
lipoproteins in the blood (usually VLDL, LDL)
Dyslipidemias – disorder in lipid spectrum
in blood, usually with
increased concentration of
cholesterol (TC, LDL-C, or HDL-C)
and/or TG concentrations

4. ESSENTIAL TERMS
a)Lipoproteins – spheric particles transporting non-polar
lipids (TAGs, cholesterol esters)by blood
Composition and properties
– inside of sphere - non-polar lipids
– surfice of sphere -polar molecules (phospholipids, non-
esterified cholesterol- are important
for transport of particles in plasma
-apo-LPs - are important for LPs
metabolism
Different types of LPs differs by their density, by volume
of transporting lipids, by size, by amount and kind of
apo, by location of their creation, by their metabolism

5. CHARACTERISTICS OF MAIN TYPES OF LPS
• Chylomicrons(CM) – the lowest density, the largest size
• VLDL – smaller and more dense than CM – they
transport endogenous TAGs synthetised in liver,
mainly
• IDL – particles with properties between VLDL and LDL
• LDL – contain cholesterol esters, mainly
• HDL – the smallest size and the highest density – they are able to transport cholesterol from peripheral
tissues to liver (reversal transport of cholesterol)

6. • LDL receptor – it takes up LDL (IDL), it is localised
at cells in different types of tissues,
predominantly at hepatocytes
In predisposed patients
–  intake of cholesterol  down regulation of LDLr
in liver   uptake of LDL from blood
• HDL receptor – it takes up HDL from blood, it is
localised predominantly in cells that
create steroids

7. Scavenger receptors (SR)
– uptake the LDL which were not bound by LDLr
– uptake of oxidized LDL particles
– they are present in macrophages, in smooth muscle
cells in vessel wall  atherogenesis

8. Positive Family History Disease in a first-degree relative
Characteristics That May Identify An Individual with a Genetic Predisposition to Cardiovascular Disease
Positive Family History
Disease in a first-degree relative
Parents, siblings
Disease in female relatives
Disease in the absence of other recognized risk factors
Early age-at-onset
Genetically determined risk often characterized by an earlier age-at onset
Hyperlipidemia resistant to dietary intervention

9. Mortality/Morbidity: If uncontrolled, there is a higher mortality from cardiovascular and cerebrovascular disease.
Age: It may be present in children and young adults but is seen more frequently in later life.
The secondary form is caused by other diseases, such as: diabetes mellitus, pancreatitis, renal disease, or hypothyroidism.

10. Classification of hyperlipoproteinemias (according Necas et al., 2000)
Type
 lipoprotein
 lipid 1 CM
TAG 2a
LDL
cholesterol 2b
LDL,VLDL
cholesterol, TAG 3
IDL,CM- remnants
TAG, cholesterol 4
VLDL 5
VLDL,CM

13. Five classes of LDL-R mutations
1 Null (no protein synthesis)
2 Transport defect (Golgi)
3 LDL binding defect
4 Internalization-defective
5 Recycling-defective
LDL-R bind LDL particles and endocytoses them via clathrin-coated vesicles
LDL-R is recycled

14.  Main types of hyperlipoproteinemias (HLP) Primary
1. Familial combined HLP
– it is the most frequent genetic HLP
– it manifests most likely in phenotypes 2a, 2b, 5
– it is the strong risk factor for development of
atherosclerosis and ischemic heart disease
Mechanisms involved in development HLP
• genetic predisposition
• acquired (due to environmental factors)
secretion
of VLDL
by liver 

15. 2. FAMILIAL HYPERCHOLESTEROLEMIA (FH)
– it manifests predominantly by phenotype 2a
– it leads to significant acceleration of
atherosclerosis development
– myocardial infarction in 4th decade of life
– xantomatosis of tendons and arcus lipoides
corneae
Mechanisms involved in FH development
– mutation of LDL receptor  decreased uptake
of LDL  concentration of LDL in blood

17. Tendon Xanthomas
tendon xanthomas of the achilles and elbow

18. Tendon Xanthomas
tendon xanthomas of the hand

19. Cutaneous Xanthomas

20. Hyperlipidemia signs
Xanthoma- plaques or nodules composed of lipid-layden histiocytes (foamy cells) in the skin, especially the eyelids

21. Familial Hypercholesterolemia Findings in Homozygotes
In patients with homozygous or heterozygous hypercholesterolemia, lipid is depostied along the ascending aorta and aortic valvular and supravalvar stenosis may occur ---- as demonstrated in this aorto-gram
this coronary arteriogram shows ostial stenosis of the left coronary artery that typically occurs in hyperlipidemia.
left coronary artery narrowing
supravalvar lipid deposition

22. Eye Findings in Familial Hypercholesterolemia
Arcus juvenilis----strong indication of hyperlipidemia and premature CAD
Early corneal arcus
Cholesterol deposits in retinal fundus

23. Corneal arcus
Lipid deposit in cornea

26. Secondary Disorders of Lipid Metabolism
Clinical Feature
Obesity
Increased TG, decreased HDL-C
Diabetes mellitus
Increased TG and TC, decreased HDL-C
Chronic renal failure
HIV/AIDS wasting
Increased TG and TC, decreased HDL-C and LDL-C
Hypothyroidism
Increased TG, TC and LDL-C
Nephrotic syndrome
Increased TC and LDL-C
Obstructive liver disease
Increased TC
Medications
Variable
C = Cholesterol; HAART = Highly-active antiretroviral therapy; HDL = High-density lipoprotein; LDL =Low-density lipoprotein; TC = Total cholesterol; TG = Triglyceride.

29. THANKS FOR NOT SMOKING