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Lipid dan

lipoprotein
Lipid dalam Tubuh

Asam lemak
Trigliserida
Kolesterol
Fosfolipid
Glikolipid
Prostaglandin
Lipid ditransportasikan melalui aliran darah dalam bentuk
lipoprotein
Struktur Lipid
Peranan Biologis Lipid

sumber energi
komponen membran sel dan berbagai struktur sel
menstabilkan membran sel dan memungkinkan terjadinya transport
transmembran
prekursor untuk sintesa hormon.
Absorpsi Lipid
Trigliserida dan kolesterol dari makanan dalam usus dikemas sebagai kilomikron diangkut sal. limfe
darahlipoprotein lipase dalam jaringan lemak menghidrolisis trigliserida asam lemak dan kilomikron
remnantrigliserida/energy dlm jar. Lemak/otot
Kilomikron remnant dibersihkan oleh hati dalam sirkulasikolesterol bebas sintesis berbagai struktur, disimpan
dalam hati/dieksresikan ke empedu (sebagai kolesterol/asam empedu)/lipoprotein endogen (
Kolesterol dapat juga dari asetat dipengaruhi oleh HMG co A reduktase jika kolesterol endogen kurang

Dengan bantuan enzim, trigliserida monogliserida, digliserida dan asam lemak bebas, kolesterol
ester kolesterol bebas, fosfolipid turunan liso-nya
Monogliserida, digliserida, asam lemak bebas, kolesterol diemulsi garam empedu diserap dalam
mikrovili usus
Asam lemak 10 C diserap masuk ke sirkulasi darah berikatan dengan plasma menuju ke hati
Dalam sel mukosa usus, asam lemak rantai panjang diubah menjadi bentuk esternya yaitu
trigliserida dan ester kolesterol dimasukan ke dalam inti kilomikron untuk ditransportasikan dalam
darah
90-95% trigliserida dari makanan terserap
50% kolesterol yang terserap
Reseptor lipoprotein

Reseptor LDL
reseptor ini mengenali apo E dan B-100, memediasi pengikatan
lipoprotein di sel, uptake dan degradasi LDL, VLDL, IDL, berperan
menjaga kesimbangan kesetimbangan kolesterol sistemik dan
selular
Reseptor Remnant
reseptor ini mengenali apo E dan merupakan reseptor utama untuk
pembersihan sisa kilomikron dan beta-VLDL dari sirkulasi darah
Reseptor Scavenger
terdapat di permukaan makrofag dan sel otot,memediasi
pengambilan modifikasi LDL
Hormon yang Berpengaruh

Insulin : inaktivasi lipase, merangsang esterifikasi asam lemak


bebas trigliserida, mengatur sintesis VLDL, berpengaruh pada
aktivitas LPL
Hormon pertumbuhan : meningkatkan produksi apo E dan B-48
dan menstimulasi lipolisis dalam jaringan adiposa dan sintesis
trigliserida dalam hati, menstimulasi sintesis reseptor LDl dan
meningkatkan klirens lipoprotein oleh hati.
Hormon reproduksi : esterogen mempercepat pembentukan
VLDL dan meningkatkan reseptor LDL, Progesteron
menurunkan kecepatan katabolisme menurunkan kadar VLDL
dantrigliserida
Hormon tiroid: meningkatkan sintesa LPL serta meningkatkan
produksi reseptor LDL.
Absorbsi Kolesterol
Lipoprotein
Struktur Dasar Lipoprotein
Struktur LDL
Struktur HDL
Triglycerides are the major constituent of chylomicrons and VLDL
cholesterol is the major lipid associated with LDL and HDL
The cholesterol form most associated with cardiovascular problems
when in excess is LDL cholesterol (LDL-C)
LDL-C is considered harmful when in excess
the elevation of HDL-C is viewed as a positive cardiovascular
biomarker for a patient
HDL removes excess cholesterol from tissues and routes it to the liver for
reprocessing and/or removal.
premenopausal women, persons who exercise regularly,and those who maintain a low but
healthy weight HDL-C
The level is also elevated in menstruating women HDL-C, while the LDL-C
Insulin, estrogen, and thyroxine (T4) have an inverse relationship with total cholesterol levels.
When estrogen levels are higher, as in women who menstruate, the total cholesterol level is
lower, preferably 200 mg/dL.
Diabetes and Cardiac Disease

Diabetics often have low HDL-C levels with elevated LDL-C and
triglyceride levels.
The National Cholesterol Education Program (NCEP) committee states
that diabetics with elevated cholesterol develop plaque formation in
their blood vessels leading to narrowing of the vessel lumen.
In type 2 diabetics who exhibit elevated triglyceride levels the
cholesterol level needs to be less than 200 mg/dL and the LDL-C level
needs to be maintained at 100 mg/dL or less low risk for plaque
formation in the blood vessels.
Because type 2 diabetics cannot move glucose from the bloodstream
into the tissues for metabolism as efficiently as the nondiabetic person,
they convert the excess glucose into fatty acid chains (in the liver) and
make more triglycerides.
HDL (good) cholesterol levels and triglyceride levels
cardiovascular problems
National Cholesterol Education
Program
The NCEP provides guidelines for evaluation of lipid panel results in
regard to risk factors for cardiovascular problems.
HDL (good) cholesterol protects against heart disease, so for HDL,
higher numbers are better.
HDL-C level less than 40 mg/dL is considered abnormally low and a
major risk factor (HDL levels of 60 mg/dL or more help to lower risk for
heart disease)
High amounts of triglycerides can also raise risk of heart disease.
Individuals with triglyceride levels that are borderline high (150 to 199
mg/dL) or high (200 mg/dL or more) may need treatment.
Type 2 diabetics often exhibit elevated cholesterol, triglycerides, and
LDL-C with low HDL-C.
Decreasing the LDL-C level is necessary to decrease the risk of
cardiovascular disease in the type 2 diabetic.
Glucose, total cholesterol, triglycerides, and hs-CRP These results
indicate medication changes may be needed to better control her
glucose levels.
hypertriglyceridemia, as may be common with type 2 diabetes.
inadequate or poorly functioning insulin leads to more triglyceride
formation in the liver VLDL cholesterol (VLDL-C), total cholesterol , HDL-
C, which means less removal of LDL-C. LDL-C deposits as plaque in the
blood vessels, narrowing and decreasing blood flow to all tissues and
especially to coronary arteries may lead to atherosclerosis, or hardening
and obstruction of her coronary blood vessels, and possibly lead to heart
attacks.
more utilization of triglycerides by the tissues for energy. Increased
demand leads to more triglyceride mobility from the liver to the tissues.
Pembentukan Fatty Streak
Lesi Arterosklerosis Lanjut
Plak Tidak Stabil
Primary and Secondary
Hyperlipoproteinemia
Elevations of LDLs and HDLs can rarely result from inborn errors of metabolism such as
enzyme or apoprotein deficiencies or, more commonly, from secondary causes or
underlying diseases (diabetes mellitus, blood pressure medication, and certain
estrogen hormone replacement therapies)
nephrotic syndrome, chronic renal failure, hepatic disorders including biliary
obstruction, other acute and transient stressrelated conditions, and medications such
as corticosteroids total cholesterol, LDL, and triglyceride
Hypertriglyceridemia can result from enzyme deficiency or from abnormal forms of
VLDL.
One fairly common condition of triglyceride excess is familial hypertriglyceridemia
(FHTG). In FHTG, the particle size but not the amount of VLDL is usually large
One notable cause of primary hypertriglyceridemia is deficiency in lipoprotein lipase
activity (enzyme is found in peripheral cells and the liver) dietary fats are not
properly metabolized, and circulating levels of chylomicrons cause lipemic serum
even in a fasting state and serum triglyceride levels that are well in excess of 500
mg/dL. These patients are also prone to acute pancreatitis and skin and eye
disorders.
Apoproteins

Apoproteins are the proteins associated with the four main


lipoproteins functioning as transport proteins for the lipids.
Apoproteins are made by the liver, are packaged with the VLDL
and HDL as they are released from the liver.
In the circulation, cells containing lipoprotein lipase metabolize
VLDL, leading to LDL formation.
The loose apoproteins can be taken up by circulating HDL particles
or they can be degraded into their amino acid constituents.
The main types of apoproteins (A-I, A-II, B-48, B-100, C-I, C-II, C-III,
and E) are listed in Table 84 along with the main lipoproteins
associated with each apoprotein.
Klasifikasi dan Fungsi
Apolipoprotein
Enzim Metabolisme Lipoprotein
Plasma
Hypoalphalipoproteinemia

The absence or a nondetectable level of apoprotein A-I is exhibited


by a severely decreased or absent level of HDL-C (Tangiers disease
or hypoalphalipoproteinemia) leads to elevated LDL in the
circulation
Apoprotein AI is the major apoprotein associated with HDL and is
necessary for the enzyme LCAT to function LCAT joins a fatty acid
to cholesterol, an alcohol, to make a cholesterol ester which can be
packaged into the HDL particles
Hyperbetalipoproteinemia

Other genetic variants of apoproteins common to people of


European descent include hyperbetalipoprotein or familial
defective apoB-100 lacking of LDL uptake by the steroid-
generating tissues because of poor receptor specificity deposition
of cholesterol esters in tissues, hepatomegaly, and even loss of
eyesight due to clouding of the cornea. A pattern for a patient with
hyperbetalipoproteinemia would be as follows:
Abnormalities With Apoprotein E

Variants of apoprotein E may have significance for atherosclerosis,


Alzheimers disease, and cerebrovascular accidents such as strokes.
Variants of apoE may have importance in characterizing a type of
hyperlipoproteinemia :IDL
Pemeriksaan Kolesterol Total

using cholesterol oxidase reactions along with cholesterol esterase and


usually a peroxidase reaction for the color or final determination

Interference :
Remove sample from red cells after blood clots or plasma has been spun
down.
The peroxidase assay can be susceptible to increases in uric acid, ascorbic
acid, bilirubin, hemoglobin, or other reducing substances. Samples should
have only the normal amount of these substances present.
The Specimen :
Nonhemolyzed serum or plasma, free from clots.
The patient need not be fasting if this is the only lipid test requested. However, if total cholesterol is
requested as part of a lipid panel, the patient must be fasting for 10 to 12 hours.
LDL CHOLESTEROL

LDL cholesterol (LDL-C) may be calculated or measured directly.


Testing for LDL-C involves a calculation that includes total
cholesterol, HDL cholesterol (HDL-C), and trigylceride (TG) values
using the formula:

TG/5 approximates the VLDL cholesterol concentration in the


sample
Interference : Cannot be used for TG over 400 mg/dL
Specimen : None required for this portion, but 10- to 12-hour fasting
serum specimen for lipid panel
Direct Measurement of LDL-C

With the advent of homogeneous reagents, LDL-C is now measured


using the cholesterol reaction along with reagents that block the
contribution of HDL and VLDL which products from forming colored
chromogens Only the LDL-C forms a colored chromogen that can
be measured spectrophotometrically by automated systems or
designated analyzers.
The Specimen : Serum, plasma.
The patient need not be fasting if this is the only lipid test requested.
TRIGLYCERIDE

Triglycerides are composed of three fatty acids and a glycerol


moiety.
Analyzing a serum or plasma sample for triglycerides typically
involves four reactions.
The Specimen : Serum, fasting 10 to 12 hours.
HDL CHOLESTEROL (precipitation
methods)
Interference : Chylomicrons from nonfasting specimens will interfere
in these precipitation methods
The Specimen : Serum, plasma (depending on the precipitating
reagent used); 10 to 12 hours fasting
HDL CHOLESTEROL (The
Homogeneous Reaction)
Homogeneous HDL-C assays do not use precipitation, nor do they require a centrifugation
separation step. This improves the yield of HDL recovered from the specimen
One method uses an antibody to apolipoprotein B-100 to bind LDL and VLDL in the sample.
This leaves the HDL-C to react with the second reagent, which contains enzymes and substrate
for cholesterol analysis.
In a second method, a synthetic polyanion reagent binds the sites on VLDL and LDL particles,
blocking their products from forming cholesterol colored products. The second reagent added
has detergent, enzymes, and substrate that react with the HDL-C in the sample. Only the HDL
particle cholesterol is allowed to form a colored product and be measured.
The Specimen : Serum, plasma (depends on the method used).
C-Reactive Protein

C-reactive protein (CRP) is a sensitive acute-phase protein, an


important but nonspecific aspect of the immune response.
appears in the blood following infection or tissue damage.
CRP binds to tissue break down products released following myocardial
infarction, stress, surgery, trauma, and infection and aids in resolution of
inflammatory responses.
Older methods of analysis for CRP were based on immunoassays that
were sensitive to measuring concentrations in the 0.5- to 2.0-mg/L (0.05-
to 0.2-mg/dL) range.
Newer methods are more sensitive and are capable of detecting
amounts as low as 0.1 to 0.3 mg/L (0.01 to 0.03 mg/dL).
CRP levels greater than 8.6 mg/L (0.86 mg/dL) are generally released 6
to 12 hours following AMI.
HIGH-SENSITIVITY
C-REACTIVE PROTEIN
hs-CRP (sample) + anti-CRP antibody complex
At present, it is recommended to take two measurements spaced 2
weeks apart, average them to monitor risk for atherosclerosis
inflammation (> 10 mg/L, the sample is invalid).
High values are due to the presence of active infection or another
inflammatory stimulus
The Specimen : Serum, plasma (nonfasting is acceptable).
Reference Ranges
Male 0.38.6 mg/L
Female 0.29.1 mg/L 12.20 13.20

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