Basics of hyperlipoproreinemia in an easy and understandable way.gives a brief picture of the disease , it's cauusitive agents and clinical sequelae following it.

1. Rida Nisar
Pharm.D

2. Plasma lipids are transported in the form of
complexes called lipoproteins. Metabolic
disorders that involve elevations in any
lipoprotein species are termed
as hyperlipoproteinemias
or hyperlipidemias.

3. Lipid metabolism can be divided into two
basic pathways: the exogenous pathway,
which is associated with the metabolism of
exogenous (dietary) lipids , and the
endogenous pathway, which is associated
with the metabolism of endogenously
produced lipids

4.  After digestion enterocytes absorb the fatty acids and
cholesterol from the lumen of the gut, re-esterify
them to glycerol and secrete them in chilomicron.
 the CM enter the venous circulation at the subclavian
vein. In the systemic circulation the CM acquire many
apoproteins from HDL. Muscle and adipose tissue
synthesise LPL that attaches to proteoglycans on the
endothelial cells. ApoCII on the CM activates LPL in
these vascular beds and it digests triglyceride to fatty
acids. The core of the CM diminishes in volume, and
excessive surface area forming HDL.
 The CM remnants bind to hepatic receptors (LDLR as
well as LDLR like lipoprotein) by virtue of apoE.

5.  The liver assembles fatty acids into triglycerides for
export in VLDL. Triglyceride, CE, phospholipids and
un-esterified cholesterol are blended into a VLDL
particle before secretion into the venous circulation.
 Circulating VLDL undergoes similar metabolism to CM
forming VLDL remnants under the action of LPL.
These remnants are cleared from the circulation by
virtue of apoE-binding hepatic receptors. However,
almost half of the VLDL remnants are further
metabolised by HL to LDL. The LDL particles contain
only apoB100 and this is now in the appropriate
conformation for binding to the LDLR.

6.  Hyperlipoproteinemia can be a primary or secondary
condition. Primary hyperlipoproteinemia is often
genetic. It’s a result of a defect or mutation in
lipoproteins. These changes result in problems with
accumulation of lipids in your body. Secondary
hyperlipoproteinemia is the result of other health
conditions that lead to high levels of lipids in your
body. These include:
 diabetes
 hypothyroidism
 pancreatitis
 use of certain drugs, such as contraceptives and
steroids
 certain lifestyle choices

7. Mechanism dylipidemia Pathphysiology Cause
plasma lipoprotein
pattern
Increased production
Increased VLDL production
Familial
hypertriglyceridemia
Decreased LPL
activity,high VLDL
production Genetic Type IV and V
Polygenic
hypercholsetrolemia Multifactorial Type II A, II B and IV
Familial combined
hyperlipidemia VLDL overproduction Multifactorial
Defective removal
Decreased LDL removal
Familial
hypercholestrolemia
Defective or absent LDL
receptors Genetic Type II A and II B
Familial defective apoB-
100
LDL receptor binding
decreased due to
defective Apo B Genetic
Abnormal LPL function Familial LPL deffeciency
mutation in gene:No
expression Genetic Type I, IV and V
Familial Apo C-II
defeciency
mutation in gene:No
expression Genetic
Decreased remnant removal Dysbetalipoproteinemia
Mutation in ApoE that
serves as ligand for
binding to hepatic
reeceptors Multifactorial Type III

8.  Type I: In these individuals elevated chylomicrons are found due
to lipoprotein lipase or Apo CII deficiency, causing elevated
levels of triglycerides.
 Type IIa: In these individuals elevated LDL cholesterol and total
cholesterol are observed mostly due to genetic defects.
 Type IIb: In these individuals elevated LDL and VLDL are seen as
observed in individuals with familial combined hyperlipidemia.
Both cholesterol and triglyceride levels may be elevated.
 Type III: is a recessively inherited disorder These individuals
have elevated IDL, Both cholesterol and triglyceride levels may be
elevated.
 Type IV: These individuals have elevated VLDL , As a result,
triglyceride levels are elevated. Type IV disorder also may be due
to secondary causes such as diabetes and nephrotic syndrome.
 Type V: These individuals have elevated VLDL and chylomicrons
causing elevated triglycerides.

9.  Lipid deposits are the main symptom of
hyperlipoproteinemia. the location of lipid deposits can
help to determine the type. Some lipid deposits, called
xanthomas, are yellow and crusty. They occur on your
skin.
 Other signs and symptoms of hyperlipoproteinemia
include:
 Pancreatitis
 abdominal pain
 enlarged liver or spleen
 lipid deposits or xanthomas
 family history of heart disease
 family history of diabetes
 heart attack
 stroke

10.  The major clinical sequelae of
hyperlipidemias are acute pancreatitis and
atherosclerosis which eventually leads to
coronary heart disease.

11.  Hyperlipidemia is the most important risk factor for
atherosclerosis ,which is the leading cause of death for both
genders. characterized by the accumulation of lipids,
cholesterol and calcium and the development of fibrous
plaques within the walls of large and medium arteries
 Low Density Lipoprotein (LDL) is pro-atherogenic. Hence high
levels of LDL increase “Coronary Heart Disease” (CHD) risk.
High density lipoprotein (HDL) is anti-atherogenic. Hence low
levels of HDL also increases CHD risk.

12.  Coronary heart disease (CHD) is the cause of
about half of all deaths in the United States. The
incidence of CHD is correlated with elevated
levels of low-density lipoprotein (LDL) cholesterol
and triacylglycerols and with low levels of high-
density lipoprotein (HDL) cholesterol.
 characterized by the accumulation of lipid and
the formation of fibrous plaqueswithin the wall of
the arteries resulting in narrowing of the the
arteries that supply blood to the myocardium,
and results in limiting blood flow and insufficient
amounts of oxygen to meet the needs of the
heart.

14.  The mechanism by which
hypertriglyceridemia induces pancreatitis is
not clear, but it has been suggested that
serum triglycerides are hydrolyzed by the
action of pancreatic lipase, leading to
excessive production of free fatty acids,
which are toxic to the pancreas

15.  MI is a condition which occurs when blood
and oxygen supplies are partially or
completely blocked from flowing in one or
more cardiac arteries, resulting in damage or
death of heart cells. The occlusion may be
due to ruptured atherosclerotic plaque.

16.  Stroke is the fourth leading cause of death.
Usually strokes occur due to blockage of an
artery by a blood clot or a piece of
atherosclerotic plaque that breaks loose in a
small vessel within the brain.

17. Normal and abnormal lipid and lipoprotein metabolism,A D MARAIS, MB ChB,
FCP (SA) Head, Lipidology Division of Internal Medicine, Groote Schuur
Hospital and University of Cape Town Health Science Faculty and MRC Cape
Heart Group
 https://www.healthline.com/health/hyperlipoproteinemia
 Lipids and disorders of lipoprotein metabolism
 Graham R. Bayly, inClinical Biochemistry: Metabolic and Clinical Aspects
(Third Edition), 2014
 A Review Article on Hyperlipidemia: Types, Treatments and New Drug
 Targets
 Ghassan F. Shattat
 College of Science and Health Professions, King Saud Bin Abdulaziz
University for Health Sciences, Riyadh, Saudi Arabia.
 Hyperlipidemia Background and Progress Isam Karam¹*, Ya Jun Yang² and
Jian Yong Li²
 An Update on Hyperlipiclemia and its Management
 Riaz A. Memon ( Department of Physiology and Pharmacology, Faculty of
Health Sciences, The Aga Khan University, Karachi. )