kuliah dylslipedimia 2007

7/31/2019 kuliah dylslipedimia 2007

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Dr. Pandji Moeljono,

Sp.PD,KEMD

Seksi Diabetes & Endokrinologi - SubdepFK. Universitas wijaya kusuma

S u r a b a y a


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LIPID

Molekul organik yang tidak larutdalam air

Sebagian besar terdiri dari hidrokarbon

Dibagi menjadi :

Lipid sederhana : asam lemak

Lipid kompleks : Ester asam lemak(gabungan antara asam lemakdengan alkohol; monoacylglycerol

triacylglycerol


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SUMBER LIPID

Diet / makanan ( eksogen )Sintesis oleh tubuh ( endogen )


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FUNGSI LIPID

Sebagai sumber dan cadanganenergi

Membentuk tekstur tubuh

Fungsi pelindung mekanik

Bahan untuk sintesis hormon

Bahan untuk sintesis dindingsel

Bahan untuk sintesisprostaglandin dll


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TRANSPORTASI LIPID

Jalur eksogen ( mengangkut lipidyang berasal dari diet )

Jalur endogen ( mengangkutlipid yang berasal dari sintesisoleh hati )

Lipid diangkut olehLipoprotein


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LIPOPROTEIN

Untuk transportasi Lipid ( Trigliseridadan kholesterol )

Bentuk bentuk Lipoprotein :Chylomicrons

Very Low Density Lipoprotein ( VLDL )

Intermediate Density Lipoprotein ( IDL )Low Density Lipoprotein ( LDL )

High Density Lipoprotein ( HDL )


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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 AcylTransferon)


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2. Lipoprotein :

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

3. Cholesterol Ester Transfer Protein

4. Reseptor

Ada 3 reseptor utama di hati : SRBI, LOL-R , LRP (Lipoprotein Like Receptor

Protein) dan ada 2 reseptor dimacrophage : SRA dan CD 36


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5. Transporters:

Melalui ATP Binding Casette(ABC) yang disebut ABCA 1

Mutasi ABCA I Tangier Disease


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LIPOPROTEIN

Kompleks lipid dengan protein

Terdiri dari :

FosfolipidApolipoprotein

Kholesterol bebas

Kholesterol ester

Trigliserida


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Classification of lipids and lipoproteins


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Characteristics of lipoproteins


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LIPOPROTEIN

Jenis

Lipoprotein

Jenis

apoprotein

Lipid, %

Trigliserida Kolesterol Fosfolipid

Kilomikron apo B48 80-95 2-7 3-9

VLDL apo B100 55-80 5-15 10-20

IDL apo B100 20-50 20-40 15-25

LDL apo B100 5-15 40-50 20-25

HDL apo AI & apo AII 5-10 15-25 20-30

Harrisons Principles of Internal Medicine 14th


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Triglyceride-rich lipoproteins:size, structure and composition


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LIPOPROTEIN METABOLISM


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Digestion and metabolism of dietary fat


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HDL metabolism and reverse cholesteroltransport


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Cholesterol efflux and reverse cholesteroltransport is modulated by two receptors


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DISLIPIDEMIA

Kelebihan abnormal / ataukekurangan abnormal dari salahsatu bentuk lipid

Kelebihan : hiperkholesterolemia total

Hiperkholesterolemia LDL

Hipertrigliseridemia

Kekurangan : Hipo HDL


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Arterial wall:structure and function


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Different stages of atherosclerotic plaquedevelopment


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Size and apolipoprotein composition are themain factors determining atherogenicity of

triglyceride-rich particles


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Size and apolipoprotein composition are the mainfactors determining atherogenicity of triglyceride-

rich particles


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LDL

LDLEndothelium

Vessel LumenMonocyte

Macrophage

AdhesionMolecules

Macrophages and Foam Cells Express GrowthFactors and Proteinases

Foam Cell

IntimaModified

LDLCytokines

Cell ProliferationMatrix Degradation

Growth Factors

Metalloproteinases

Ross R. N Engl J Med1999;340:115-126.

MCP-1

h


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Response-to-Retension Hypothesis

Lumen

Normal intima and media

Nofurther

pathology

A

Lipoprotein retention andearly aggregation

C

Early foam

cell

Nascent fatty streak

MigratingSMC Adhering

monocyte

D

Williams KJ 1994

B

Abundantatherogeniclipoproteins

Predisposingstimuli,e.g.shear stress

Without abundant

atherogeniclipoproteins

Intimal changese.g. altered PGsIncreased LpL &SMase

}

Early responses

Arterial segment predisposedto lipoprotein retention

Adhering


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Nascent fatty streak

Early foam cell

MigratingSMC

Adheringmonocyte

Lipoprotein


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THE VULNERABLE HUMANATHEROSCLEROTIC PLAQUE

Large lipid core

Rich in cholesterol

Thin fibrous cap

Rich inmacrophages

Poor in smoothmuscle cells

Low grade

stenosis

Th di l ti f t


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

The cardiovascular continuum of events

Reduction of future

coronary eventACS

Remodeling

VentricularDilatation

Congestive

Heart Failure

Arrhythmia andLoss of Muscle

End-stageHeart Disease

Reduction of future

coronary event

ATHEROSCLEROSIS

Coronary

Thrombosis

MyocardialIschemia

CAD

Risk Factors

(DYSLIPIDEMIA, BP, DM,Insulin Resistance,

Platelets, Fibrinogen, etc)


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Tendon Xanthomas

What is the abnormality shown in (a) the Achilles tendon

and (b) the dorsum of the hand? What genetic


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Dyslipidemia andatherosclerosis


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Diabetes and atherosclerosis


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Tobacco and atherosclerosis

HTN h d i f d


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HTN, hemodynamic factor andatheroclerosis


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HDL

The protective effect of HDL are1. activates Reverse Cholesterol

2. transport

3. shows antioxidant activity

4. maintain the integrity of endothelial cell

Possible other protective effeect are

1.

anti inflammation2. anti fibrinogenesis

3. anti platelet aggregation


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Protective Mechanisms of high-densitylipoprotein (HDL) against atherosclerosis

HDL INHIBIT ADHESION MOLECULE EXPRESSIONMonocyte

AdhesionMolecule MCP-1

Cytokines

Macrophage

MODIFIED LDL

LDL

LDLVessel lumen

Endothelium

Intima

Foam cell

HDL PROMOTE CHOLESTEROL EFFLUX

HDL INHIBITOXIDATION OF LDL

HDL INHIBIT MCP-1 EXPRESSION


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HDL-C is an anti-atherogenic lipoprotein

Fruchart, 2001


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HDL and Its Vasculoprotective Effects

Its generally accepted that low HDLSyndrome can be categorised as follow

Primary

1.Tangier Disease2.Isolated Low HDL

3.Apo-A1 Gene Mutation

4.LPL or APO

CIIDeficiency

5.LCAT Deficiency


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Secondary

(selected)

1. Hyper TG

2. Diabetes Mellitus

3. Obesity

4. Cigarrete

5. Physical inactivity

6. Renal or hepaticInsufficiency

7. Drugs : Beta Blockers,

Diuretics, Androgen,Probucol


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Drug Class Mechanism of Action

Statin

Inhibit HMG-CoA reductase, a key step in cholesterolbiosynthesis, causing upregulation of the LDL-receptor andreduction of circulating cholesterol levels

Niacin Appears to inhibits free fatty acid mobilisation from peripheral

tissues, reducing hepatic synthesis of triglycerides

Bile acidsequestrants

Bind bile acids in intestine and interrupt bile acid enterohepaticreticulation, increasing conversion of cholesterol into bile acids inliver and reducting circulationg cholesterol levels

Fibrates Activiate PPAR

(peroxisome proliferator-activated receptor

)and act at the level transcription to affect numerouse genesinvolved in the metabolisme of lipoproteins

Cholesterolabsorptioninhibitors

Selectivity inhibit the intestine absorption of cholesterol andrelated phytosterols

Mechanism of Action of Lipid-lowering Drugs


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Referensi

Kursus dasar Lipid , LaboratoriumBiomedik FK Universitas BrawijayaMalang. 2002.

Manual of Endocrinology andMetabolism, Third Edition 2002.

NOS Makassar 2006


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