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Dr. Pandji Moeljono, Sp.

PD,KEMD
Seksi Diabetes & Endokrinologi - Subdep FK. Universitas wijaya kusuma Surabaya

LIPID
Molekul

organik yang tidak larut dalam air Sebagian besar terdiri dari hidro karbon Dibagi menjadi :
Lipid sederhana : asam lemak Lipid kompleks : Ester asam lemak (gabungan antara asam lemak dengan alkohol; monoacylglycerol triacylglycerol

SUMBER LIPID
Diet

/ makanan ( eksogen ) Sintesis oleh tubuh ( endogen )

FUNGSI LIPID
Sebagai

energi Membentuk tekstur tubuh Fungsi pelindung mekanik Bahan untuk sintesis hormon Bahan untuk sintesis dinding sel Bahan untuk sintesis prostaglandin dll

sumber dan cadangan

TRANSPORTASI LIPID
Jalur

eksogen ( mengangkut lipid yang berasal dari diet ) Jalur endogen ( mengangkut lipid yang berasal dari sintesis oleh hati ) Lipid diangkut oleh Lipoprotein

LIPOPROTEIN

Untuk transportasi Lipid dan kholesterol )

( Trigliserida

Bentuk

bentuk Lipoprotein :

Chylomicrons Very Low Density Lipoprotein ( VLDL ) Intermediate Density Lipoprotein ( IDL ) Low Density Lipoprotein ( LDL ) High Density Lipoprotein ( HDL )

Ada 5 macam komponen terkait dengan lipoprotein transport :


1. Enzim :

LPL (Lipoprotein Lipase) H LPL ( Hepatic Lipoprotein Lipase)

LCAT ( Lechitin Cholesterol Acyl Tranferon) ACAT (Acyl CoA Cholesterol Acyl
Transferon)

2.

Lipoprotein :
Apo (a) , Apo A, Apo B, Apo C, Apo E , bekerja sebagai enzim Aktifator, receptor legands

3. 4.

Cholesterol Ester Transfer Protein Reseptor


Ada 3 reseptor utama di hati : SRBI, LOLR , LRP (Lipoprotein Like Receptor Protein) dan ada 2 reseptor di macrophage : SRA dan CD 36

5. Transporters: Melalui ATP Binding Casette (ABC) yang disebut ABCA 1 Mutasi ABCA I Tangier Disease

LIPOPROTEIN
Kompleks

lipid dengan protein Terdiri dari :


Fosfolipid Apolipoprotein Kholesterol bebas Kholesterol ester Trigliserida

Classification of lipids and lipoproteins

Characteristics of lipoproteins

LIPOPROTEIN
Jenis Lipoprotein Kilomikron VLDL IDL LDL HDL Jenis apoprotein apo B48 apo B100 apo B100 apo B100 apo AI & apo AII Lipid, % Trigliserida Kolesterol Fosfolipi d 80-95 2-7 3-9 55-80 20-50 5-15 5-10 5-15 20-40 40-50 15-25 10-20 15-25 20-25 20-30

Harrisons Principles of Internal Medicine 14th

Triglyceride-rich lipoproteins: size, structure and composition

Klasifikasi Kadar Lipid Plasma (mg/dL)


Sumber : National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) Circulation. 2002;106:3143

Kolesterol Total < 200 200 239 240 Kolesterol LDL < 100 100 129 130 159 160 189 190 Kolesterol HDL < 40 60 Trigliserida < 150 150 199 200 499 500

Yang diinginkan Batas tinggi (borderline high) Tinggi Optimal Mendekati optimal Batas tinggi (borderline high) Tinggi Sangat tinggi Rendah Tinggi Normal Batas tinggi (borderline high) Tinggi Sangat tinggi

LIPOPROTEIN METABOLISM

Digestion and metabolism of dietary fat

HDL metabolism and reverse cholesterol transport

Cholesterol efflux and reverse cholesterol transport is modulated by two receptors

DISLIPIDEMIA
Kelebihan

abnormal / atau kekurangan abnormal dari salah satu bentuk lipid Kelebihan :
hiperkholesterolemia total Hiperkholesterolemia LDL Hipertrigliseridemia

Kekurangan :
Hipo HDL

AKIBAT DISLIPIDEMIA
Pankreatitis

Penyakit

Jantung Koroner

Arterial wall: structure and function

Different stages of atherosclerotic plaque development

Size and apolipoprotein composition are the main factors determining atherogenicity of triglyceride-rich particles

Size and apolipoprotein composition are the main factors determining atherogenicity of triglyceriderich particles

Macrophages and Foam Cells Express Growth Factors and Proteinases


Monocyte

Vessel Lumen

LDL
Adhesion Molecules
Endothelium

MCP-1

LDL
Intima
Growth Factors Metalloproteinases Cell Proliferation Matrix Degradation

Cytokines

Modified LDL

Macrophage

Foam Cell

Ross R. N Engl J Med 1999;340:115-126.

Response-to-Retension Hypothesis
A
Lumen
Predisposing stimuli,e.g.shear stress

Normal intima and media


Migrating SMC

Adhering monocyte

No further pathology

Without abundant atherogenic lipoproteins Abundant atherogenic lipoproteins

Intimal changes e.g. altered PGs Increased LpL & SMase

Arterial segment predisposed to lipoprotein retention

D
Early responses

Nascent fatty streak Early foam cell

Lipoprotein retention and early aggregation

Williams KJ 1994

Adhering monocyte

Lipoprotein

Migrating SMC

Nascent fatty streak

Early foam cell

THE VULNERABLE HUMAN ATHEROSCLEROTIC PLAQUE Large lipid core Rich in cholesterol Thin fibrous cap Rich in macrophages

Poor in smooth muscle cells


Low grade stenosis

The cardiovascular continuum of events


Reduction of future coronary event ACS
Coronary Thrombosis Arrhythmia and Loss of Muscle

Reduction of future coronary event

Myocardial Ischemia

Remodeling

CAD

Ventricular Dilatation Congestive Heart Failure End-stage Heart Disease


Adapted from Dzau et al. Am Heart J. 1991;121:1244-1263

ATHEROSCLEROSIS
Risk Factors (DYSLIPIDEMIA, BP, DM, Insulin Resistance, Platelets, Fibrinogen, etc)

Tendon Xanthomas

What is the abnormality shown in (a) the Achilles tendon and (b) the dorsum of the hand? What genetic

CV RISK FACTORS
1. Lifestyle Diet Smoking Obesity Physical inactivity 2. Blood Pressure 3. Diabetes/ Insulin Resistance 4. Emerging Risk Factors : - Plasma Homocysteine (tHcy) - Thrombogenic Factors - plasma fibrinogen

3. Plasma lipids
LDL-C TG HDL-C

- Plasminogen Activator Inhibitor


(PAI-1) - Markers of Inflammation - CRP 5. Genetics Family history

Other Lipid Factors :


Apoliproprotein B Lipoprotein (a)

Dyslipidemia and atherosclerosis

Diabetes and atherosclerosis

Tobacco and atherosclerosis

HTN, hemodynamic factor and atheroclerosis

HDL

The protective effect of HDL are


1. 2. 3. 4. activates Reverse Cholesterol transport shows antioxidant activity maintain the integrity of endothelial cell

Possible other protective effeect are 1. anti inflammation 2. anti fibrinogenesis 3. anti platelet aggregation

Protective Mechanisms of high-density lipoprotein (HDL) against atherosclerosis


Monocyte

HDL INHIBIT ADHESION MOLECULE EXPRESSION


LDL

HDL INHIBIT MCP-1 EXPRESSION


Vessel lumen Endothelium

Adhesion Molecule

MCP-1

LDL

HDL INHIBIT OXIDATION OF LDL


Cytokines

MODIFIED LDL

Intima

Macrophage

Foam cell

HDL PROMOTE CHOLESTEROL EFFLUX

HDL-C is an anti-atherogenic lipoprotein

Fruchart, 2001

HDL and Its Vasculoprotective Effects

Its generally accepted that low HDL Syndrome can be categorised as follow
1. Tangier Disease

Primary

2. Isolated Low HDL 3. Apo-A1 Gene Mutation 4. LPL or APO CII Deficiency 5. LCAT Deficiency

1. Hyper TG

Secondary

2. Diabetes Mellitus

(selected)

3. Obesity
4. Cigarrete 5. Physical inactivity 6. Renal or hepatic Insufficiency 7. Drugs : Beta Blockers, Diuretics, Androgen, Probucol

Mechanism of Action of Lipid-lowering Drugs


Drug Class Mechanism of Action
Inhibit HMG-CoA reductase, a key step in cholesterol biosynthesis, causing upregulation of the LDL-receptor and reduction of circulating cholesterol levels

Statin
Niacin

Appears to inhibits free fatty acid mobilisation from peripheral tissues, reducing hepatic synthesis of triglycerides
Bind bile acids in intestine and interrupt bile acid enterohepatic reticulation, increasing conversion of cholesterol into bile acids in liver and reducting circulationg cholesterol levels

Bile acid sequestrants

Fibrates

Activiate PPAR (peroxisome proliferator-activated receptor ) and act at the level transcription to affect numerouse genes involved in the metabolisme of lipoproteins
Selectivity inhibit the intestine absorption of cholesterol and related phytosterols

Cholesterol absorption inhibitors

Referensi
Kursus

dasar Lipid , Laboratorium Biomedik FK Universitas Brawijaya Malang. 2002. Manual of Endocrinology and Metabolism, Third Edition 2002. NOS Makassar 2006