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A. LIPID TRANSPORT
Klasifikasi lipids and lipoproteins (Pengangkutnya lipid):
Lipoprotein ada 2 :
-HDL = menangkut 80%
kolesterol
Characteristics of lipoproteins:
- Semakin kecil TG nya, kolesterol & pospolipid akan
semakin besar (kok gak sesuai ya sama tabel)
Triglyceride-rich lipoproteins::
Chylomicrons : berasal dari usus + very high
TG content.
VLDL : berasal dari liver + cleaved by LPL jadi
IDL
Jika lipoproteins decrease in density, makaTG
content decreases, & cholesterol and
phospholipid content increases.
Overview of Cholesterol Metabolism: Absorption and Synthesis
PPT
Key Point:
Plasma cholesterol levels depend on the balance of
cholesterol production and intestinal absorption.
After absorption from the intestine: Cholesterol is esterified and packaged dibawa chylomicrons ke sirlukasi
darah sampai nyampe liver.
Changes in intestinal cholesterol absorption affect blood cholesterol levels. Decreasing cholesterol
absorption provides a key target for lipid-lowering therapy, especially when combined with statin therapy, which
decreases hepatic cholesterol synthesis Lemak dimakan (TAG>>) diemulsi garam
empedu + phospholipids bentuk micelles di
Digestion and metabolism of dietary fat:
small intestine didiuresis o/ enzim
pankreas (amilase, lipase) bentuk
cholesterol, free fatty acids, and
monoglycerides masuk ke cairan
mukosa gabung dgn apoprotein, free
cholesterol, phospholipids bentuk
kilomikron ngangkut lipid ikut sirkulasi
o/ lipoprotein lipase dihidrolisis jd
kilomikron remnant ke jalur berikutnya
bentuk free beta HDL. Kilomikron remnant
(lipid yg aterogenic) disimpan di hati, jika
kilomikron remnant numpuk jd fatty liver
hepatoseluler karsinoma.
PPT:
2. Cholesterol-rich lipoproteins
o Low-density lipoprotein (LDL)
o High-density lipoprotein (HDL)
LDL cholesterol:
o Increased risk atherosclerosis & CVD events
o Peningkatan 10% meningkatkan risiko CHD 20%
o Most of the cholesterol in plasma ditemukan dlm bentuk LDL particles
o Semakin kecil dense LDL artinya semakin atherogenic jadi smakin mudah masuk ke tunica intima
o Faktor risiko peningkatan LDL-C:
-low HDL-C [Tidak terjadi transfer lipoprotein yg kaya TAG]
- smoking
- hypertension
- diabetes
HDL cholesterol:
o HDL-C punya protective effect u/ mengurangi atherosclerosis & CHD
o Lower the HDL-C level, smakin tinggu risiko atherosclerosis & CHD
o low level (<40 mg/dL, 1 mmol/L) increases risk. [Laki normal: >40 ; Wanita: >50]
o HDL-C akan tetap low ketika triglycerides high
o HDL-C menurun akibat smoking, obesity and physical inactivity
o ApoA-I is the major apolipoprotein in HDL &peningkatan apoA-I menurunkan risiko CVD
Triglycerides
o increased risk of CHD events
o Peningkatan risiko CHD jika:
Direct effect bikin smaller TAG-rich lipoproteins atau
Berhubungan dengan:
low HDL levels Jika diperiksa:
highly atherogenic forms of LDL-C -LDL normal maka periksa Apo B (krn blm
hyperinsulinaemia/insulin resistance tentu non HDL yg lain sudah bagus)
procoagulation state
hypertension
abdominal obesity
Apolipoproteins
o Protein content dari lipoproteins (Protein yg mengikat lipoprotein)
o ApoB levels u/ estimasi jumlah LDL particle & meningkatkan risiko CVD
o ApoA-I - major apolipoprotein in HDL & menurunkan CVD risk
o Fungsi apolipoproteins:
facilitation of lipid transport
activation of three enzymes in lipid metabolism
lecithin cholesterol acyltransferase (LCAT)
lipoprotein lipase (LPL)
hepatic triglyceride lipase (HTGL)
binding to cell surface receptors
NCEP Guidelines
-Jika punya penyakit jantung, diabetes dll penurunan harus high intencity (dosis obat tingi +
golongan statin paling kuat) krn targetnya nurunin LDL 50% dari base line
- Jika very high risk target LDL <70 ----------------------- (+) diabetes& gangguan jantung
-Jika high risk target LDL < 100 ------------------------(+) diabetes / gangguan jantung
-Jika borderline risk target LDL < 120 ------------------ (+) 2 atau lebih risk
- Jika low risk target LDL < 160
B. LIPID DISORDERS
1. HYPERTRIGLYCERIDEMIA
Penyebabnya:
Primary
Deficiency LPL (Lipoprotein Lipase) /cofactornya shg pembentukan kilomikron &free beta HDL
tidak terjadi
Endogenous & mixed lipemias
Familial combined hyperlipidemia
Familial dysbetalipoproteinemia (Type III hyperlipoproteinemia)
2. HYPERCHOLESTEROLEMIA 3. HYPOLIPIDEMIA
Penyebabnya: Penyebabnya:
Primary Primary
Familial hypercholesterolemia Due to deficiency of HDL
Familial combined hyperlipidemia Tangier disease
LP (A) hyperlipoproteinemia Familial hypoalphalipoproteinemia
Familial ligand-defective apo B Deficiency of lecithin-cholesterol
Cholesterol 7a-hydroxylase deficiency acyltransferase
Due to deficiency of Apo B-containing
Secondary lipoproteins
Hypothyroidism Recessive abetalipoproteinemia
Nephrosis Familial hypobetalipoproteinemia
Immunoglobulin disorders Chylomicron retention disease
Anorexia nervosa Secondary
Cholestasis Diseases characterized by chronic
cachexia (eg. Advanced cancer)
COMPLICATION OF DYSLIPIDEMIA
Kalau Hypertriglyceridemia:
Atherosclerosis
Pankreatitis: krn kan enzim pankreas ni
berperan penting dipaksa kerja bisa
inflamasi
Hypercholesterolemia
Atherosclerosis
Low HDL
Atherosclerosis
C. LIPID LOWERING DRUGS (STATIN BUAT NGATASIN LDL yaitu ngambat sintesis di hati, kl fibrate
nurunin TAG, ezetimibe ngambat kolestrol diet)