Disorders of Lipid & Lipoprotein

7 Metabolism Clinical Chemistry 1 (LAB)

DISORDERS OF LIPID & LIPOPROTEIN METABOLISM

REFERENCE RANGE FOR LIPID PROFILE

ANALYTE REFERENCE RANGE
Total Cholesterol (TC) 140-200 mg/dL
HDL-C 40-75 mg/dL
LDL-C 50-130 mg/dL
Triglycerides (TAG) 60-150 mg/dL
Notes: • We have two pictures, the Figure A and B.
• The analytes mentioned above are the Figure A, is the normal artery, so there’s normal
components of LIPID PROFILE blood flow (no problem). When it comes to
• HDL-C – High Density Lipoprotein Figure B, because of the buildup of plaque,
• LDL-C – Low Density Lipoprotein what happens is that the diameter of artery
lessens (lumiliit yung diameter). In
CONVERSION OF REFERENCE RANGE TO SI UNIT atherosclerosis, it affects any artery in the body.
(mmol/L) Atherosclerosis can affect any parts of the
ANALYTE BY DIVISION body including the arteries from the heart,
brain, arms, legs, pelvis, kidneys, etc. as long as
Total Cholesterol (TC)
it is an artery it can be affected and if it does, if
HDL-C 38.67
there’s a buildup of plaque this is what we call
LDL-C
as atherosclerosis.
Triglycerides (TAG) 88.57
ANALYTE BY MULTIPLICATION
Total Cholesterol (TC)
HDL-C 0.02586
LDL-C
Triglycerides (TAG) 0.01129

ATHEROSCLEROSIS & CORONARY HEART DISEASE

ATHEROSCLEROSIS
• Buildup of plaque inside the arteries
o Plaque – According to Calbreath, it is a
semi solid material composed of lipids
and other biochemical components.
So, it is made up of the different lipids
and different components as well.
o Plaque – According to Tietz, it is
composed of lipids, cell debris, and
smooth muscle cells including collagen
and sometimes calcium. (More specific
definition given by Tietz).
ARTERIOSCLEROSIS VS ATHEROSCLEROSIS
• But, what is important is that it is a buildup of
● Arteriosclerosis - Is a general term given
lipids such as cholesterol, triglycerides, etc. and
when arteries are hardened or are
mostly cholesterol (pinagsama-sama na lipids)
thickened which leads to poor blood
• The significance of plaque is that as it builds up
circulation.
over time, it can harden and narrow the artery
○ May be due to any kind of source
which will then limit the flow of oxygen to the
(kahit na anong condition or
different parts of the body. Aside from this,
disease) if the artery hardens and it
plaques can also burst or rupture and when this
narrows, it’s arteriosclerosis.
happens, it allows blood clot inside of the
● Atherosclerosis - Is a specific type of
artery. In the brain, if this happens, it is known
arteriosclerosis which is resulting from a
as stroke. If this happens in the heart, it is known
plaque buildup.
as heart attack.
○ Hardening and narrowing of the
artery due to the buildup of plaque
○ Plaque - it is the buildup of lipids or
cholesterol in the arteries.

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CORONARY HEART DISEASE (CHD)
● A type of Ischemic Heart Disease
○ CHD is also known as coronary
artery disease which is a type of
ischemic heart disease
○ Ischemic means that the heart (an
organ) is not getting enough blood
and oxygen which is caused by the
plaque buildup in the artery. So,
when can you experience ischemic
heart disease? It’s during periods of
stress or physical effort. This is when
you need a lot of oxygen because
your heart pumps faster (e.g.
exercising- your heart starts to pump
faster than the usual so that it can
support enough blood to the
different parts of the body) but if
you have atherosclerosis, your heart
will not receive enough oxygen and
the patient will encounter Heart
attack.
○ Other term for heart attack:
Myocardial Infarction
● Caused by the buildup of plaque in the
Coronary arteries that supply oxygen-rich
blood to the heart
○ Atherosclerosis (buildup of plaque)
and coronary arteries is known as
the Coronary Heart Disease (CHD)
● National Institutes of Health & National
Heart, Lung, and Blood Institute (NIH-NHLBI)
● For Coronary heart disease
● These are standardizing institutes for
medicine. If for medical technologist, we
have CLSI and ISO, for medicine they have
their own organizations that make sure that
their diagnosis and processes are also
standardized
INCIDENCE OF CHD
• The incidence of a person having a coronary or
developing coronary heart disease (CHD) is
strongly associated with a very high cholesterol
serum concentration or serum cholesterol
concentration (ppt)
• When it says that they have a correlation, it just
means that the higher cholesterol level you
have in the blood, the more chances of having
CHD
• If cholesterol is too high, it builds up in the walls
of your arteries then overtime, this build up will
be known as atherosclerosis
• As we have mentioned earlier, atherosclerosis
can cause CHD
• In 1988, the first NCEP ATP developed a list of
heart disease risk factors
• In 2002, the NCEP ATP III updated the guidelines
• Adults must have a fasting lipoprotein profile
TRANSFORMERS
Clinical Chemistry 1 (LAB)
once every 5 years
o NCEP ATP – National Cholesterol
Education Program-Adult Treatment
Panel
o Organization in-charged of giving the
standard
*There’s also ATP I and ATP II
CHD RISK FACTORS
Age (Male: ≥ 45 y; Female: ≥ 55 y)
POSITIVE
Family History of CHD
RISK
Cigarette smoking
FACTORS
Hypertension (≥ 140/90 mmHg)
(AT RISK
Diabetes mellitus or Metabolic
FOR CHD)
syndrome
Notes:
• When we say positive, these are the conditions
that would most likely increase your chances of
developing CHD
• For ease of memorization: positive risk factors
are also known as AT RISK FOR CHD
o A = age
o F = family history
o C = cigarette smoking
o H = hypertension
o D = diabetes mellitus
• When you have diabetes = higher risk to
develop CHD but also goes the other way. If
you have CHD = high chances of developing
DM
o Why? Because these two different
conditions affect the blood vessels
themselves, so kapag meron ka ng isa
puwede ka rin magkaroon ng isa, buy 1
take 1
o Kaya dapat bawal magkasakit
• If you have DM = it is associated with
approximately 2-4 fold increase in mortality risk
for heart disease
• LDL and HDL can be a basis of saying If you
have a positive risk for CHD
Normal value of LDL- 50-130 mg/dL
o A value of 160 is acceptable to be a
positive risk.
o 130 is a normal value, however, If you
have a value of 130 and other 2 risk
factors, 130 is not healthy anymore.
o A value of 100 is very normal, but if you
already have CHD, 100 is not safe.
o In the lab, there were patients that will
ask you, if their results are normal. So, if
we base the result according to the
reference value, we can answer them
that it is normal. But we have to
remember that the patient’s diagnosis
will depend on other factors as well.
That is why Medical Technologists are
not allowed to interpret results, because
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 Disorders of Lipid & Lipoprotein
7 Metabolism
maybe there are some underlying
factors that we don’t know. Always say
that “Sir, punta nalang po kayo sa
doctor. Balik nalang po kayo sa Doctor.
Or sir kailangan niyo po makitq ito”
Normal Value of HDL- 40-75 g/dL
o It’s good to have good cholesterol
If you have low HDL, that would be bad.
METABOLIC SYNDROME
• This is a group of risk factors that is given, that
would raise your risk higher for Coronary Heart
Disease. And to be diagnosed with Metabolic
syndrome, you have to have at least three (3)
of the different metabolic factors. And what
are these different metabolic factors:
METABOLIC RISK FACTORS
Large waistline
• More on abdominal obesity (so, yung mga
1 malalaki ‘yung tyan). This is truncal obesity,
that’s means you have higher risk, you are in
higher risk of developing CHD.
High Triglyceride
• Tapos meron ka pang, High triglyceride
2 level (tumataas lalo iyan) more chances of
winning ‘yung nangyayari, when you have
more of these risk factors.
Low HDL-C
• Another one, when you have low HDL.
Remember with low…; HDL is your good
3 cholesterol. So, it’s good to have a lot of
good cholesterol. Also, if you have low
amounts of HDL, then it increases your risk
for CHD.
High BP
4 • High Blood Pressure (mga Hypertension,
kapag matataas ang BP.
High FBS
5 • Since DM is always related with the heart. If
you have high fasting blood sugar.
LDL-C ≥ 160 mg/dL, with ≤ 1 risk
factor
OTHER
LDL-C ≥ 130 mg/dL, with ≥ 2 risk
POSITIVE
factors
RISK
LDL-C ≥ 100 mg/dL, with CHD or risk
FACTORS
equivalent
HDL-C < 40 mg/dL (< 1.0 mmol/L)
Notes:
• These are the other positive risk factors that
shows the relationship of two laboratory tests to
CHD.
o LDL-C ≥ 160 mg/dL, with ≤ 1 risk factor
▪ If a patient has at least 1 risk
factor, a value of 160 mg/dL of
LDL will already increase the risk
for CHD.
o LDL-C ≥ 130 mg/dL, with ≥ 2 risk factors
▪ But, if a patient has at least 2 risk
TRANSFORMERS
Clinical Chemistry 1 (LAB)
factors that was mentioned
earlier, a borderline value of 130
will increase the risk.
o LDL-C ≥ 100 mg/dL, with CHD or risk
equivalent
▪ But if a patient already has
CHD, a normal value LDL of 100
mg/dL will already impose a
threat.
o HDL-C < 40 mg/dL (< 1.0 mmol/L)
▪ But for HDL, a decrease value of
less than 40 mg/dL, will increase
the chance for CHD.
NEGATIVE HDL-C greater or equal to 60 mg/dL
RISK LDL-C less than 100 mg/dL
FACTORS
Notes:
• HDL is inversely proportional to CHD
development, while LDL is directly proportional.
• HDL (Good Cholesterol)- Meaning the higher,
the better. Inversely proportional which is since
the higher the good cholesterol, the lesser you
are in developing CHD.
• LDL (Bad Cholesterol)- The higher it is, the higher
chance of the patient developing CHD, which
is a direct relationship.
OTHER DISEASES RELATED TO ATHEROSCLEROSIS
1 CAROTID ARTERY DISEASE (Seen in Carotid)
• What is significant about this is that the
carotid arteries are found at the side of the
neck. If it is located at the side of the neck,
it means that it makes its way towards the
brain, so if there is lack of supply in this
area, there would also be lack of oxygen
rich blood supply going to the brain.
What happens if the blood flow in the brain is
reduced?
• The patient would suffer from stroke. In
addition, it is not limited to the arteries in
the brain, whereas it may also be caused
by the carotid artery.
2 PERIPHERAL ARTERY DISEASE (Seen in periphery)
• It has something to do with the arteries that
are present in the limbs. So, if there is
decreased blood supply in the arms, legs,
pelvis.
• Peripheral Artery Disease could also lead to
infection.
What would you feel after you sit on your legs?
- Same as the patients with Peripheral
Artery Disease, you would feel
NUMBNESS (PAGMAMANHID)
3 CHRONIC KIDNEY DISEASE (Seen in the artery in
the kidney)
• The artery affected in CKD is the Renal
Artery, which supplies oxygen-rich blood to
the kidneys, so they could function
properly.
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 Disorders of Lipid & Lipoprotein
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Clinical Microscopy Review:
What is the Function of the Kidney?
• It removes wastes and extra water in the
body.
DYSLIPIDEMIA
Diseases associated with ABNORMAL LIPID
CONCENTRATIONS
✓ Abnormal levels/Unhealthy concentrations of
different lipids or fats in the blood
o Fats/Lipids in dyslipidemia is referring to
different lipids such as Cholesterol,
Triglyceride, and LDL
▪ Increase of the three could
cause dyslipidemia.
What about HDL?
• Decreased in HDL can caused dyslipidemia
If good cholesterol decreases, we would have
dyslipidemia
CAUSES OF DYSLIPIDEMIA
Primary/Direct dyslipidemia are
mainly caused by:
• Genetic Abnormalities
✓ Genetic mutations
• Environmental/Lifestyle
DIRECT
Abnormalities/ Imbalances
✓ This is how a person lives
and lifestyle such as
exercising, what they are
eating.
Can have dyslipidemia if a person
eats excess fatty foods.
Secondary dyslipidemia may be
caused by:
• Can also be cause by lifestyle
factors.
• Cause by underlying disease
SECONDARY
or other diseases such as
abdominal obesity.
• OTHER DISEASES like:
o Diabetes Mellitus
o Obesity
Having too much fat in abdominal
area may cause health problems.
FORWARD AND REVERSE TRANSPORT OF LIPIDS
• Dyslipidemias are involved or can happen in
both the forward transport and the reverse
transport of lipids.
• Forward transport – Transport of lipids to the
blood vessels or to the peripheral tissue. (Mostly
triglyceride).
o Remember that triglyceride is a dietary
lipid. From the intestines, it will be
absorbed and would bind to a
lipoprotein kaya we have chylomicrons
from the intestines. And then it delivers it
to the different parts of the body where
TRANSFORMERS
Clinical Chemistry 1 (LAB)
triglyceride or where the lipid is needed.
It can also bring the triglyceride to the
adipose tissues.
• Reverse transport – The removal of cholesterol
from the peripheral tissue into the liver.
o Kapag napasobra ang cholesterol build
up on the different parts of the body, we
have a negative feedback which is the
reverse transport.
• It takes the cholesterol from the tissues and
brings it to the liver so that they can be disposed
of.
DISORDERS ASSOCIATED WITH FORWARD TRANSPORT
OF LIPIDS
CHYLOMICRON RETENTION DISEASE
• AKA – Anderson’s Disease
• ApoB-48 DEFECT
o Mainly affects the ApoB-48, which
is the main lipoprotein for
chylomicrons. Hence the name
Chylomicron Retention Disease.
• This also mainly presents in Childhood.
• Together with this would be fat
malabsorption and a decrease in plasma
lipid values.
o ↓ Total Cholesterol (TC) and Low
Triglyceride Level (TAG)
• In Chylomicron Retention Disease, we are
talking about the deficiency or the defect
of the ApoB-48 lipoprotein. This lipoprotein
is mainly found in chylomicrons. The lipid
found in the chylomicron is the triglyceride.
Therefore, this has something to do with
triglyceride. There is ApoB-48 deficiency,
meaning the triglyceride from the food
that we take will supposedly bind with the
1
lipoprotein and then it forms the
chylomicrons and would be delivered to
the different parts of the body. But since
there is a defect in the ApoB-48, the
triglyceride is not absorbed properly
because there is a defect in the lipoprotein
that would carry the triglyceride. What
happens then is that it ends up in fat
malabsorption. The triglyceride is not
absorbed properly. Since it is not absorbed
and is not in the blood, when blood is
tested, the result would be a decreased
level of triglyceride and cholesterol.
SIGNS AND SYMPTOMS
• Hypocholesterolemia
o Kase nga mababa yung total
cholesterol.
• Chronic Diarrhea
o Failure to thrive, ibig sabihin
nahihirapan kang to survive/live.
▪ Remember, lipids including
triglyceride, the have many
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functions, kase kailangan early age. the normal

siya inside the body. That’s level. So kapag
why we need dietary lipids, nahati na, like
and that’s why you are also yung kanina
synthesizing lipids on your kapag 100, it
own hindi lang kapag can be sign of
kinakain niyo, remember in Familial
lecture there is an Hypobetalipopr
endogenous and oteinemia
exogenous production of which is
lipids. We do that because heterozygous.
we need the lipids. It’s not • There are also
just for energy reserve they different
are also needed to regulate conditions that
the hormones, or to transmit are related to
nerve impulses, they also heterozygous
cushion the vital organs, hypobetalipopr
and they transport fat oteinemia.
soluble nutrients. What can
• Deficiency of fat-soluble vitamins happen in
▪ Ano kaya ang fat-soluble heterozygous?
vitamins that is mainly You can
affected in the chylomicron develop
retention disease? Its progressive
vitamin E, so vitamin E is neurologic
mainly affected in the degenerative
chylomicron retention disease. You
disease. can also have
• Vitamin E main role is an antioxidant. retinitis
Without Vitamin E, this can result to pigmentosa
neurologic deficits. So connected with and
chylomicron disease, aside from acanthocytosis
hypocholesterolemia we also have o Acanthocytes –
neurologic deficits. these are
FAMILIAL HYPOBETALIPOPROTEINEMIA abnormal RBC
• Abbreviated as FHBL morphology. When
• Familial because it is inherited on they have spikes.
AUTOSOMAL DOMINANT DISORDER of the Usually Asymptomatic
Apo B gene, the mutation of this gene, NONFAMILIAL HBL
when we say point mutation, its either a • They can come secondary to other
nonsense or missense, we will learn more conditions.
about this when we get to molecular • Examples of these conditions that can
biology. cause Nonfamilial so ibig sabihin that
• The significance of the mutation of Apo B it’s not because of genetic disorder, its
gene, is that it impairs the ability of the secondary to something else such as
body to absorb and transport fat. cancer, liver disease or severe
2
• Associated with a decreased risk for CHD malnutrition.
• It may either be heterozygous or ABETALIPOPROTEINEMIA
homozygous • AKA Bassen-Korzweig Syndrome
HOMOZYGOUS HETEROZYGOUS • Rare, Autosomal recessive disorder that
It is the total A lot of decreased involves the mutation in the MTTP gene
cholesterol and values for LDL, Total • The mutation in MTTP gene leads to
triglycerides with Cholesterol (TC) and 3 defective ApoB synthesis
decreased levels, Triglycerides (TAG) with • MTTP is in the chromosome 4 with a size of
with total cholesterol HDL is in normal or 894 amino acid
of usually less than slightly increased • MTTP decreases the value of lipid
50mg/dL (<50mg/dL) value. • MTTP stands for Microsomal Triglyceride
It also presents at • LDL is half of Transfer Protein

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 Disorders of Lipid & Lipoprotein
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• Laboratory results for
Abetalipoproteinemia:
➢ Decreased Total Cholesterol and
TAG
➢ Undetectable VLDL, LDL, and CM
• Patients with Abetaproteinemia usually
presents sign and symptoms during
childhood
• It is a genetic disease therefore pagbata
pa lang lumalabas na siya >.<
• Apo B defect therefore there is fat
malabsorption
MAIN DIFFERENCE BETWEEN HBL AND
ABETALIPOPROTEINEMIA
• From the word hypo- meaning mababa
yung levels while in Abetalipoproteinemia
they can be undetected
▪ Undetected meaning yung machine
hindi na madetect yung level because
even machines have certain values na
kaya lang niya madetect. How much
or how low can it detect? When it goes
under the detection level
▪ Example: The machine can only detect
starting from 5 mg/dL but your HDL is
lower than that therefore the machine
will not produce a result. So
magpapanic ka kasi walang result
then you’ll perform quality control pero
wala pa rin until you reach a diagnosis
na pwede mo pala yun irelease since
yung patient mo meron palang
Abetalipoproteinemia.
DIFFERENCE OF ABETA AND HBL TO
CHYLOMICRON
• HBL and ABETA is in general ApoB
lipoproteins but for chylomicron it is very
specific on which type of lipoprotein
▪ In HBL and ABETA general ApoB
meaning kahit ano dun sa ibang forms
ng ApoB can be deficient while sa
Chylomicron specific siya for ApoB48
• Deficient so may malabsorption of fats and
vitamins are connected as well. In
chylomicron, vitamin E lang mostly yung
affected while in ABETA, the other fat-
soluble vitamins (Vit. A, K, E are the only
ones affected since Vit. D does not require
the chylomicrons for its absorption) are
also affected.
LPL DEFICIENCY
• Rare autosomal recessive disorder
4 (affecting the LPL either a defect in LPL is
seen or an absence in its concentration)
involving the defect or absence of LPL
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• LPL – means Lipoprotein Lipase which is an
enzyme
o The one responsible for the
hydrolysis of triglycerides
o Without LPL, there will be an
increase in triglycerides level
• Since total cholesterol is not involved, it will
have a normal concentration
Function/s of LPL:
• Responsible for separating (like
triglycerides (TAG), it is made up of 3 fatty
acids (FA) and glycerol. When the
chylomicron brings all the TAG to the parts
where they are needed there is an LPL
which separates the FA and glycerol.
When the FA are free, it can now be used
by the peripheral tissues for energy. If FA is
free in the adipose tissues, it can now be
stored as reserve fats.)
Notes:
• If there is no LPL, the TAG will retain as a
TAG so the FA will not be separated.
• If there is a defective or an absent LPL, this
would create an inability to clear the
chylomicrons.
o This means that the chylomicrons
still carry the TAG because it
cannot be separated into its
functional parts. That’s why there is
high TAG level because the
chylomicrons are still present in the
bloodstream because the FA are
not distributed properly from the
TAG.
• LPL is essential for TAG hydrolysis
o Separation of the 3FA and glycerol
Remember:
• Chylomicrons carry around 80-95% TAG
meaning that they are mostly made up of
TAG
• Patients with LPL deficiency usually do not
develop premature coronary heart
disease because even the chylomicrons
are high, they are not atherogenic.
o Atherogenic means that they
promote atherosclerosis which is
the buildup of plaque inside the
walls of the arteries.
• Among all the lipids, cholesterol is
atherogenic. So, when your cholesterol
levels are high, the risk of having
atherosclerosis is high.
• For chylomicrons, even if it elevated so
much, it’s not really atherogenic meaning
it is not able to stay at the sides of blood
vessels.
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 Disorders of Lipid & Lipoprotein
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*Even if you have LPL deficiency, you will not

have coronary heart disease because
chylomicrons themselves are not atherogenic.
• Since this is an autosomal recessive
disorder, that means that LPL deficiency
also presents in childhood and the signs
and symptoms include: • Arcus – the cholesterol deposit is seen in
o Abdominal pain the cornea of the eye
o Pancreatitis
ApoC-II DEFICIENCY
• Mostly the same with LPL deficiency
because APOC-II is the activating cofactor
for LPL
• With the absence or deficiency of APOC-II,
5 there would also be a deficiency in LPL, DEFECTIVE ApoB
that’s why these two are generally the • An autosomal dominant disorder of the
same ApoB gene that interferes with the
• Laboratory results are also the same with recognition of ApoB-100 by the LDL
the normal total cholesterol and an receptor
increase triglyceride level • Laboratory results would be: increase total
FAMILIAL HYPERCHOLESTEROLEMIA (FH) cholesterol (TC) and LDL
• This is an autosomal dominant disorder • Relatively the same with FH, therefore they
affecting the LDL-receptor gene have the same signs and symptoms or
• A defect in the receptor for LDL means physical characteristics (xanthomas and
that these receptors cannot bind or clear premature heart disease or premature
the LDL from the circulation, therefore coronary disease
having an increase total cholesterol and DIFFERENCE BETWEEN FH & DEFECTIVE ApoB
LDL level • In FH, there is a mutation in the receptor
• The mutated gene is seen in chromosome itself that prevents the binding of the LDL
19 7 which leads to the accumulation of LDL in
HOMOZYGOUS FH HETEROZYGOUS FH the circulation
Increase total Increase LDL & total • In the defective ApoB, the receptors are
cholesterol (teenage cholesterol (20s to okay but there is a defect in the ApoB
years) 50s) gene that does not permit the binding of
• Homozygous is • More the LDL to the receptor as well also leading
the rare type frequent to the accumulation of LDL in the
with only 1:1 than circulation
million in the homozygous
6
population with a 1:500
• They have high in the
total cholesterol population
levels of usually • The
800-1000 mg/dL cholesterol
• They can have level is
their first heart usually 300-
attack during 600 mg/dL DYSBETALIPOPROTEINEMIA
their teenage If this is not treated, • Caused by the presence of a rare
years it becomes lipoprotein which is ApoE-2/2
symptomatic to • ApoE-2/2
heart disease in ▪ This lipoprotein has a lower affinity to
their 20s or up to the LDL receptors leading to its
their 50s accumulation in the circulation.
8
SIGNS AND SYMPTOMS Therefore, a high total cholesterol and
a high triglyceride level
• Xanthomas – having cholesterol deposits
• This type of disorder affects adults and
under the skin (it can form anywhere as
men more than women
long as there is cholesterol buildup)
• Other names are Remnant Removal
Disease, Type III Hyperlipoproteinemia,
and Broad Beta Disease.

TRANSFORMERS 7
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• There is an inability to remove the between VLDL and LDL, it is a

chylomicron remnants diagnostic for Dysbetalipoproteinemia.
o Ano naman ang chylomicron remnants • Other name for the abnormal band na
na to? makikita sa electrophoresis is
- Remember triglyceride from the Abnormally Migrating Beta Lipoprotein
food is packed with lipoproteins or also known as Floating Beta
mainly Apo B-48 and then they Lipoprotein
become chylomicrons. It na yung SUMMARY
lipoprotein natin. Yung lipid with a DYSLIPIDEMIAS: FORWARD TRANSPORT
protein. Yung lipid mo is the Chylomicron Retention
Apo B-48 Defect
triglyceride while yung protein mo is Disease
the Apo B-48 and other Apo B. This Familial Apo B Gene Low TC
Hypobetalipoproteinemia Mutation
will travel to the different parts of and
the body and when it gives out the Defective Apo B TAG
triglyceride to the adipose tissues Abetalipoproteinemia Synthesis (MTTP
and the peripheral tissues, wala na Gene Mutation)
siyang trigly. This now what we call LLP Deficiency LPL Deficiency Normal
as the chylomicron remnant. TC
Apo C-II
• Ang deficiency naman ni Apo C-II Deficiency High
Deficiency
Dysbetalipoprotein, hindi niya naalis ng TAG
maayos si chylomicron remnant. Familial LDLR Gene
Hypercholesterolemia Mutation High TC
o What happens if there is the presence Dysfunctional Apo and LDL
Familial Defective Apo B
of the ApoE? B-100
- ApoE has a lower affinity for LDL High TC
Apo E-2/2
receptors and with this, the Dysbetalipoproteinemia and
Presence
lipoprotein particles will TAG
accumulate in the blood. So DISORDERS ASSOCIATED WITH REVERSE TRANSPORT
dadami ang mga chylomicron OF LIPIDS
remnants. TANGIER DISEASE
• Signs and Symptoms when there is • Rare, Autosomal Recessive Disorder
accumulation of chylomicron remnants characterized by complete absence
in the bloodstream: of HDL due to a MUTATION in the
➢ Premature Vascular Disease ABCA1 gene
➢ Coronary Heart Disease o The mutation leads to the
➢ Peripheral Artery Disease ineffectivity or inability to
transfer cholesterol, which is
inside the cell going to the
plasma thus HDL cannot be
formed leading to the
decreased value
o ABCA1 gene – It belongs with
other types of genes which is
1 known as the ABCA
o ABCA1 gene – ATP Binding
Cassette
• This shows the electrophoretic pattern o In normal cells, the ABCA1
for the diagnosis of protein enables the cholesterol
Dysbetalipoproteinemia. to exit the cell.
• The one on top is normal while the one o Reverse transport, (from the
on the bottom shows cells going back to the liver)
Dysbetalipoproteinemia. meaning the cholesterol should
• This is diagnosed by the presence of a exit the cell but since there is
broad band in between the LDL/beta an abnormality in the ABCA1
and the VLDL/pre-beta. gene, the cholesterol cannot
▪ Sa taas you can clearly see the band exit the cell.
lines/widths for HDL, VLDL, and LDL. But o Cholesterol needs to exit the
if there is a very broad band, this is cell to bind with a lipoprotein
considered as an abnormal band in

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 Disorders of Lipid & Lipoprotein
7 Metabolism
(Apo A1) to form HDL.
• Low/Undetectable HDL
o May be as low as 1-2 mg/dL
• Other name: Familial HDL deficiency
CHARACTERISTICS
• Enlarged, grayish orange tonsils
• Hepatosplenomegaly – enlargement
of spleen and liver
o Remember, the cholesterol
doesn’t leave the cell, so there
is accumulation of it to
different organs and the one’s
visible is in the spleen and liver.
• Peripheral neuropathy
o Where the nerves are found in
the periphery (arms, legs) or
the nerve that is not present on
spinal cord or brain, those can
be affected if there is an
accumulation of cholesterol on
3
the parts that they are near.
• Orange tonsils
o It is pathognomonic for tangier
disease.
o Pathognomonic – definite
characteristics for a condition
• Premature coronary heart disease
o Decrease in HDL
LCAT DEFICIENCY
• Lecithin-cholesterol
acyltransferase(LCAT)
• Function: Enzyme that will help
transport cholesterol going out from
the tissue. “Cholesterol Esterification”.
• It packages the cholesterol into an
HDL.
• VERY RARE, AUTOSOMAL RECESSIVE
DISORDER
• Due to MUTATION of LCAT gene
o without LCAT gene, the
2 4
cholesterol remained
unesterified, and this will
impede in the synthesis of HDL.
Therefore having a low HDL
level.
• ↓ HDL
• LCAT HDL = <10 mg/dL
2 FORMS OF LCAT DEFICIENCY
• Classic or Complete LCAT Deficiency
- Describe as having anemia,
proteinuria and renal failure
TRANSFORMERS
Clinical Chemistry 1 (LAB)
• Partial or Fisheye Disease
- Milder
- Has progressive corneal
opacification.
- Mainly affects the eyes; which is
why it is called “fisheye” but that’s
actually cholesterol build up
- The second organ it affects are the
kidneys, hence the formation of
kidney disease.
FAMILIAL HYPOALPHALIPOPROTEINEMIA
• Common autosomal dominant
disorder
- Has a ratio of 1:400 people in a
population.
• Frequently associated with ApoA-1
- Either a decrease or increase on its
catabolism
• Leads to DECREASE in HDL
- For men, HDL values are usually less
than 30mg/dL, while women will
have approximately less than
40mg/dL
How is it diagnosed? Here are the criteria:
✓ Low HDL level
✓ Normal VLDL and LDL
✓ Absence of diseases that lead to
secondary effects of
Hypoalphalipoproteinemia
✓ Hypoalphalipoproteinemia is a
disorder diagnose by ruling out
other disorders
✓ If there is a relative; a first degree
relative having this condition.
CETP DEFICIENCY
• Autosomal recessive disorder
• Inhibits the transfer of cholesterol esters
from HDL to VLDLs or chylomicrons
o HDL indirectly deliver
cholesterol to the deliver
• Cholesterol cannot transfer to VLDL,
and triglyceride will not be given to
HDL
o Causes HDL to become large
or laden with cholesterol
esters, leading to an increase
in HDL levels in the blood,
typically >100 mg/dL
• Cholesteryl Ester Transfer Protein (CETP)
o Protein needed in the reverse
transport
• HDL
o Lipoprotein mainly responsible
for the reverse transport,
meaning, it removes
cholesterol from the tissues or
cells and return it to the liver so
it can be disposed of and
9
 Disorders of Lipid & Lipoprotein
7 Metabolism Clinical Chemistry 1 (LAB)

does not harm the body ▪ For HDL, it is enriched

▪ DIRECT way of removing with triglycerides.
cholesterol • Characterized by:
o INDIRECT o Xanthoma
▪ HDL asks for the help of o Increased risk of atherosclerosis
VLDL and chylomicron in • Atherosclerosis because of the
delivering cholesterol to increase in the total cholesterol levels
the liver in the blood and the increase in the
▪ VLDL and chylomicrons triglyceride levels.
will not help HDL SUMMARY
▪ CETP to VLDL & DYSLIPIDEMIAS: REVERSE TRANSPORT
Chylomicrons: TANGIER DISEASE ABCA1 gene
“Pagbigyan niyo na, mutation
pupunta ka rin naman ng LCAT DEFICIENCY LCAT gene
liver. Kunin mo na mutation
cholesterol niya, ibigay FAMILIAL Frequently LOW HDL
mo na lang triglyceride HYPOALPHALIPOPRO associated
mo.” TEINEMIA with apoA-1
▪ Exchange of lipids occurs (decreased
▪ HDL will give its production or
cholesterol to the VLDL increased
and chylomicrons, both catabolism)
of which are triglyceride- CETP DEFICIENCY CETP HIGH HDL
rich deficiency
▪ VLDL and chylomicrons HEPATIC LIPASE HL gene HIGH TC &
will give their TAG to HDL DEFICIENCY mutation TAG
via CETP enzyme
• Without CETP, no protein will mediate
the exchange of lipids
HEPATIC LIPASE DEFICIENCY
• Rare familial disorder
• Generally resulting from mutations of
the HL gene. Hence, the name
Hepatic Lipase Deficiency.
• This is described to have a combined
hyperlipidemia with an increase
cholesterol and an increase
triglyceride level.
• ↑ TC & TAG
• Total cholesterol results are usually
between 250 to 1, 500 mg/dL.
• Triglyceride levels are often 400 to 8,
000 mg/dL.
5 • HDL may be normal or increased.
• HDL and LDL are usually described to
have large particles with triglycerides.
• It has similarities and differences with
the CETP.
o Similarity: lumalaki yung HDL. In
both diseases, HDL becomes
big.
o Difference: laman or kung ano
yung nasa loob ng HDL.
▪ For CETP, it is filled with
cholesterol esters.
Madami syang
cholesterol kaya
lumalaki.

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