dislipidemia u k sur
TRANSCRIPT
![Page 1: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/1.jpg)
LABORATORY TESTFORDYSLIPIDEMIA
Suzanna Immanuel
Department of Clinical PathologyFaculty of Medicine University of Indonesia
![Page 2: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/2.jpg)
THE PLASMA LIPOPROTEINS* LIPID – Insoluble in water,
transported with Apolipoprotein (APO)
– Triglyceride, Cholesterol & Phospholipid
* Remander Lipid transported in Lp Complexs : Chylomicrons, VLDL, IDL, LDL, HDL, Lp(a)
![Page 3: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/3.jpg)
CORE : * HYDROPHOBIC LIPIDS * CHOL ESTERS & TRIGLYCERIDES
IN THE CORES
* CHYLOM : TRANSPORT LIPID FROM INTESTINE
* VLDL : LIVERIN THE CORES : LDL & HDL
SURROUNDING CORE : MONOLAYER
* AMPHOPHILIC (DETERGENT LIKE) LIPIDS* PHOSPHOLIPIDS, UNESTTERIFIED (FREE)
CHOL, APO LP
LIPOPROTEIN ARE SPHERICAL
![Page 4: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/4.jpg)
![Page 5: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/5.jpg)
LIPOPROTEIN ELECTROPHORETIC
PATTERNSCHYLOM
LDLVLDLHDL
Plasma d < 1.006 d > 1.006
LDLLp(a)
HDL
NORMAL PATTERNPlasma d < 1.006
TYPE III PATTERN
ORIGINLDL
VLDL
HDLIDL
BROAD β BAND
ORIGINβ PRE β
α
![Page 6: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/6.jpg)
LIPOPROTEINS OF THE HUMAN SERUM
Lipoprotein
Electrophoretic
Mobility In Agarose Gel
Density Intervalg/cm3
Predominant Core Lipids
Diameter
Nm
Apolipoproteins
Order ofQuantitativeImportance
High Density(HDL)
Alpha 1.21 – 1.063
Cholesteryl esters
7.5 – 10.5
A-I, A-II, C, E, D
Low Density(LDL)
Beta 1.063 – 1.019
Cholesteryl esters 21.5 B-100
Intermediate Density
(IDL)Beta 1.019 –
1.006
Cholesteryl esters,
triglyceride
25 – 30 B-100, some C and E
Very Low Density (VLDL)
Prebeta ; some“slow
prebeta”
< 1.006 triglyceride
30 – 100 B-100, C, E
Chylomicrons
Remain at origin < 1.006 triglycerid
e 60 – 500
B-48, C,E, A-I, A-II, A-IV
Lp(a) Prebeta 1.04 – 1.08 Cholesteryl esters 21 – 30 B-100, Lp(a)
![Page 7: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/7.jpg)
APO B :* MOLECULAR WEIGHT VERY * LIKE INTRINSIC PROTEIN OF CELL ∾
MEMBRANS* DON’T MIGRATE* INTESTINAL & HEPATIC ARE DIFFERENT* LIGAND DOMAIN BINDING LPL* 2 APO B : – APO B – 100 (VLDL LDL)
– APO B – 48
B – 100 ( LIVER) VLDL, IDL, LDL LIGAND DOMAIN BINDING LDL
RECEPTOR
B – 48 ( INTESTIN ) : – IN CHYLOM & REMNANT
– ㊀ LDL
APO LIPOPROTEINS ( APO )
![Page 8: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/8.jpg)
APO C : MOLECULAR WEIGHT < SYNTHESIZED, MAINLY IN LIVER 4 SPECIES : C – I, C – II , C – III & C –
IV APO C - II COFACTOR LPL CHYLOM, VLDL, IDL, HDLAPO E : MAINLY SYNTHESIZED IN HEPATOCYTES CHYLOMICRON, VLDL, IDL & HDL UPTAKE LP IN THE LIVER BY :
LDL RECEPTOR LRP ( LDL REC – RELATED PROT )
3 APO E ALLELES : E2, E3 & E4
BIND LDL REC AFFINITY
![Page 9: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/9.jpg)
APO A :APO A I : * Synthesized in small intestine & liver
* 70 – 80 % Protein of HDL * Chylomicron & HDL * Cofactor LCAT APO A II : * Synthesized in small intestine & liver
* HDLAPO A IV : * Synthesized in small intestine & liver
* Chylomicron & HDL* Cofactor LCAT
APO D : * HDL* LCAT (Transport Chol. from Tissues
Liver) APO (a ) : * Mol weight Glycoprotein * Homolog ~ Plasminogen
* Made by hepatocytes * Forms a covalent linkage + Apo B 100 (LDL) Lp(a)
![Page 10: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/10.jpg)
ENZYMES in Lp METABOLISM
LPL : Synthesized in fat & muscle Hydrolysis trigl. Of chylom & VLDL
FFA & Glycerol Insulin stimulates LPL DM impaired triglyceride CL Homozygotes mutations LPL
Sever Hypertriglyceridemia (Type I Hyperlipidemia)
HTGL : Synthesized in the liver
VLDL remnants LDL
Clearance Chylom remnantsHDL2 HDL3
HTGL
HTGL
( IDL )
![Page 11: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/11.jpg)
LCAT : SYNTHESIZED IN THE LIVER
HDL3 HDL2
(FREE CHOL) (CHOL ESTERS)
CETP : SYNTHESIZED IN THE LIVER
HDL CHYLOM / VLDL (CHOL ESTERS) (TRIGLY)
PLTP : SYNTHESIZED IN THE LIVER & LUNG PLTP MATURE HDL
CETP
LCAT
Apo A1
![Page 12: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/12.jpg)
Chol – Rich Chylomicron
Remnant
LipoproteinLipase
Apoproteins (HDL)
Small Intestine
Chylomicrons
B48
C III
FFA E E
E
.
C II B48
EC II
C II
C III
Liver
TRANSPORT OF EXOGENOUS LIPIDS
![Page 13: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/13.jpg)
FFALipoprotein
Lipase E
C III
E
C II
B100
C II
VLDL
HTGL
(IDL)
E
C III
B100
E
E VLDLRemnants
B100LDL Peripheral
Tissues
B100 TG
PLCHOL
TRANSPORT OF ENDOGENOUS LIPIDS
( THE APO B-100 LP SYSTEM)
![Page 14: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/14.jpg)
FreeCholesterol
Biliary Cholesterol+
Bile Acids
HDL3
LCAT
Blood Vessel
HDL2
Liver
CholVLDL IDL LDL
CETPCholesteryl
Ester
TG
TRANSPORT OF ENDOGENOUS LIPIDS
( THE APO AI LP SYSTEM)
![Page 15: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/15.jpg)
THE FREDRICKSON (WHO) CLASSIFICATION
Fredrickson type Electrophoretic picture Lipoprotein increased
I. Increased chyclomicrons ChylomicronsIIa. Increased β-lipoprotein LDLIIb. Increased pre-β and β-lipoprotein VLDL and LDL
III. “Broad-β” band IDL IV. Pre βLipoprotein VLDL
V. Increased chylomicrons and pre-β lipoprotein Chylomicrons & VLDL
![Page 16: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/16.jpg)
FAMILIAL DYSLIPIDEMIAS
Genetic DisorderFredricso
n Type
Biochemical Defect
Plasma Cholester
ol
Plasma Triglycerid
es
Familial LPLdeficiency I
Absence of LPLactivicty
↑ ↑↑↑
Familial apo C-IIdeficiency I or IV
Absence or abnormal
structure of apo C-II
↑ ↑↑↑
Familial hypercholesterolemi
aIIa or IIb
Deficiency of LDL
receptors ↑↑↑ N(a) or
↑(b)
Familial dysbetalipoproteine
mia III
Abnormal apo E and defect in
triglyceride rich metabolism
↑↑ ↑↑
Familial combinedhyperlipidemia
IIa, IIb or IV Unknown ↑ or N ↑ or N
Familial hypertriglyceridemi
as
IVV
UnknownUnknown
N↑
↑↑↑↑
![Page 17: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/17.jpg)
DYSLIPIDEMIA :
Numerous classifications, none is satisfactory
FREDRICKSON : Classification hyperlipidemia based on ectrophoretic patterns
Same individual with primary hyperlipidemia
Have different patterns at different timesSimpler classification is sufficient for th/ dyslipidemia
DYSLIPIDEMIAS : Classified as follows * Hypercholesterolemia * HDL Chol * Hypertriglyceridemia * Combined Hyperlipidemia
CAN BE : * Primary* Secondary
![Page 18: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/18.jpg)
HYPERCHOLESTEROLEMIAATP III CLASSIFICATION OF LDL, TOTAL, and HDL CHOLESTEROL
LDL CHOLESTEROL<100 OPTIMAL100-129 NEAR OR ABOVE OPTIMAL130-159 BORDERLINE HIGH160-189 HIGH≽190 VERY HIGH
TOTAL CHOLESTEROL<200 DESIRABLE200-239 BORDERLINE HIGH>240 HIGH
![Page 19: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/19.jpg)
ATP III CLASSIFICATION (CONTINUED)
HDL CHOLESTEROL<40 LOW≥ 60 HIGH
♠ HYPOTHYROIDISM♠ NEPHROTIC SYNDROME♠ CHOLESTASIS♠ DIURETICS♠ CYCLOSPORINE♠ HEPATOMA
IMPORTANT TO RULE OUT SECONDARY CAUSES
![Page 20: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/20.jpg)
FAMILIAL HYPERCHOLESTEROLEMIA
* Classical single gene disorder* Autosomal dominant disorder* LDL : Genetic defect activity LDL receptors <
HOMOZYGOTE : CHOL 600 - 1000 MG / DL
HETEROZYGOTE : CHOL 300 - 450 MG/ DL
HOMOZYGOTE : Children FEW / – LDL Receptors : LDL CHOL Premature atherosclerosis
![Page 21: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/21.jpg)
HETEROZYGOTE :* Adult (Frekw 1 : 500)
* 50 % LDL Receptors 2 X LDL CHOL
* Premature atherosclerosis in early / middle adulthood
* Mutation of the LDL receptor gene
RECEPTOR – (MOST COMMON)
RECEPTOR DEFECTIVE
INTERNALIZATION DEFECTIVE
![Page 22: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/22.jpg)
FAMILIAL HYPERCHOLESTEROLEMIA :
2 types, Depending on the triglyceride : II a : TRYGL N II b : TRYGL
PRIMARY MODERATE HYPERCHOLESTEROLEMIA :
LDL (common cause)E/ ?, Because complex interaction of genetic &
environmental factors Polygenic Hypercholesterolemia
Chol (240 – 350 mg/dL) Triglyceride & HDL Chol. N Diet, age, physical activity
![Page 23: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/23.jpg)
FDB (Familial Defective APO B – 100) :
Dominantly inherited disorder E/ Substitution of glutamine for arginine
in position 3500 in APO B –100 Affinity LDL receptor catabolism LDL
FCH (Familial Combined Hyperlipidemia) :
LDL Chol
Hyperalpha Lipo Proteinemia Moderate Chol HDL Chol ( < 35 mg/dl, < 40 mg/dl)
![Page 24: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/24.jpg)
Independent Risk Factor for CAD (Framingham Heart Study)
CAUSE : - Smoking- DM- Renal Desease - Obesity - Drugs : – Blockers
![Page 25: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/25.jpg)
Hypertriglyceridemia :
Classification to the ATP : TRIGL Levels
Normal < 150 MG/DL Boderline High 150-199 MG/DL High 200-499 MG/DL Very High > 500 MG/DL
TRIGL + Correlated with risk for CAD in univariate
– To predict CAD in multivariate analysis when other factors (Chol. Total & HDL) are added
![Page 26: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/26.jpg)
TRIGL CAD COMPLEX
EXPLAINED BY THE ASSOCIATION WITH HDL & PREDOMINANCE SMALL DENSE LDL
VLDL (TYPE IV) / COMBINATION VLDL & CHYLOM (TYPE V)
TRIGL > 1000 mg/dL CHYLOMICRONEMIA SYNDR (TYPE I) RISK OF PANCREATITIS
CAUSE SECONDARY HYPERLIPIDEMIA (HYPERTRIGLICERIDEMIA) :
OBESITY PREGNANCY DM ALCOHOLISM RENAL FAILURE ESTROGEN
THERAPY STEROID THERAPY – BLOCKER TH/
![Page 27: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/27.jpg)
HYPERTRIGLYCERIDEMIA FAMILIAL :
E.G. : DYSLIPIDEMIA TYPE IV (PRIMARY ENDOGENOUS HYPERTRIGLYCERIDEMIA)
AUTOSOMAL DOMINANT HYPERTRIGLYCERIDEMIA
TRIGL
ASSOCIATED WITH HEPATIC OVERPRODUCTION OF TRIGL & VLDL
– RISK FOR CAD
OBESE
AB N GLUCOSE INTOLERANCE
HYPERTENSION
HYPER URICAEMIA
![Page 28: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/28.jpg)
MECHANISM PANCREATITIS WITH HYPERTRIGL :
HYDROLYSIS OF TRIGL & PHOSPOLIPIDS
LYSOLECITHIN & FFA IN PANCREAS
FUNCTION AS & NOXIOUS AGENT ON THE PANCREATIC ACINAR CELLS RESULTING IN ACUTE
PANCREATITIS
LPL DEFICIENCY :
RARE AUTOSOMAL RECESSIVE DISORDER OR DUE TO
DEF COFACTOR LPL CATABOLISM TRIGL CHYLOM CHILDHOOD WITH PANCREATITIS,
HEPATOSPLEMONEGALY, ETC
![Page 29: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/29.jpg)
D/ – INCUBATED PLASMA 4 °C
CREAMY LAYER (CHYLOM)
FAMILIAL APO C II DEF :
AUTOSOMAL RECESSIVE (RARE) CLINICAL LPL DEF∾ CHILDREN & ADULT WITH PANCREATITIS ELECTROPHORESIS : APO C II ⊝
![Page 30: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/30.jpg)
COMBINED HYPERLIPIDEMIA * CHOL & TRIGL * Causes : FCH (Familial Combined
Hyperlipidemia) Type III
( DYBETALIPOPROTEINEMIA )HYPERTRIGL COMBINED
* AUTOSOMAL DOMINANT TRAIT* – CHILDHOOD* MOLECULAR DEFECT –
![Page 31: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/31.jpg)
FCH* Familial multiple Lp – Type Hyperlipidemia* Hypercholesterolemia* Hypertriglyceridemia* Combination* Lp patterns ~ Disorder gene * E.g : Defect LPL Hypertriglyceridemia
Inefficient Catabolism VLDL
VLDL CHOL LDL CHOL
* Variations : VLDL Catabolism Genetic Heterogeneity Environmental
* Atherosclerotic : IDL / LDL* Clear plasma
Patient & I degree relatives
Form variable phenotype
![Page 32: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/32.jpg)
TYPE III
FAM DYSBETA LP, REMNANT REMOVAL DISEASE, BROAD DISEASE
AB N APO E HOMOZYGOUS APO E 2 / DEF APO E
DEFECT APO E : – VLDL TRIGLY / CHOL CHYLOM REMNANTS
– ATHEROSCLEROSIS – ONSET FOURTH & FIFTH DECADES
– PERIPHERAL VASC DISEASE
APO E 3 MAJOR ALLELE CAUSE : * HOMOCYGOUS APO E2 (1 : 100) ( TYPE III : 1 : 5000 - 1 : 10.000 ) * SECONDARY FACTOR : – OBESITY – DM –
HYPOTHYROIDISM
![Page 33: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/33.jpg)
* ELECTROPHORESIS : BROAD ß BAND* BASIC LP PROFILE < , FURTHER TEST : ULTRACENTRIFUGATION ( VLDL ) & RATIO VLDL
LABORATORY ANALYSIS OF LIPID
PRAANALITIC : > A FAST OF 12 – 14 HOURS (CHYLOM + IN PLASMA 1 HOUR AFTER MEAL ⇉
TRIGL 600 MG/DL ) PROLONGED :
ALCOHOL
POSTPONED 2 – 3 WEEKS AFTER MINOR ILLNESS 3 MONTHS AFTER MAJOR ILLNESS,
SURGERY, TRAUMA
POSTURE STANDARDIZED CHOL 10% UPRIGHT THAN
RECUMBENT POSITION
TRIGL 0,30
![Page 34: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/34.jpg)
RESTING 5‘ DRUGS AFFECT LIPID METABOLISM - > 3 WEEKS STANDARDISED COLLECTION : PLASMA / SERUM
SEPARATED FROM CELLS AS SOON AS POSSIBLE
INSPECTION SERUM : BEFORE & AFTER OVERNIGHT (4oC, 18 HOURS ) TRIGL OPALESCENCE TRIGL ( TRIGL > 200 MG/DL CLINICAL SIGNIFICANCE BEGINS )
CREAMY LAYER : CHYLOMICRONCREAMY LAYER + TURBID INFRANATE : CHYLOM + VLDL
BINDING IG - LP : CURD - LIKE LP AGGREAGATE / SNOWY PRECIPITATE AS SERUM COOLS
BLOOD 370C (FORMATION CLOT & SEPARATION OF SERUM)
![Page 35: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/35.jpg)
ANALYTIC :
CHOL & TRIGL : ENZYMATIC METHODSHDL : SERUM + HEPARIN + Mn CENTRIFUGE HDL
CHOL IN SOLUTIONTRIGL EXCHANGE INTO CORE HDLHDL CHOL CAN’T INTERPRETED WITHOUT TRIGL
E.G : Normal TRIGL : HDL 45 mg/dL TRIGL 200 MG/DL : HDL 37 mg/dL 500 MG/DL : 30 mg/dL
FRIEDEWALD :
LDL CHOL = TOTAL CHOL - ( HDL CHOL + TRIGL/5 )
NOT RELIABLE IF TRIGL > 400 MG/DL
![Page 36: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/36.jpg)
NOW : FRIDEWALD NOT RECOMMEND BECAUSE VARIABILITY OF 3
INDEPENDENT MEASUREMENTS (TOTAL CHOL, HDL CHOL & TRIGLY)
NCEP – LSP : DIRECT HOMOGENOUS ENZYMATIC
METHODS FOR HDL & LDL CHOL : ⊚ WITHOUT CENTRIFUGATION
⊚ 2 STEPS : ⊳ INACTIVATE NON HDL /
LDL ⊳ HDL / LDL CHOL was
measured
![Page 37: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/37.jpg)
ELECTROPHORESIS IS NOT RECOMMENDED
HAS 2 USEFUL :
* TYPE III : BROAD BAND DIFFERENTIATE FROM* TYPE II B : + PRE BANDS
TYPE I :PRESENCE OF CHYLOMICRONS
LP ( a ) :* RELATED TO PREMATURE ATHEROSCLEROSIS* LP SIMILAR TO LDL & PROTEIN CONTAINS HIGHLY GLYCO SYLATED PROTEIN ( APOLIPOPROTEIN a ) LINKED a DISULFIDE BRIDGE TO APO - B 100
![Page 38: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/38.jpg)
* STRONG GENETIC INFLUENCE* IMPORTANT RISK FACTOR FOR CEREBROVASCULAR & CVD* LP ( a ) > 25 MG / DL CARDIOVASCULAR RISK* RELATIONSHIP TO CVD STRONG IN SUBJECTS < 60 YEARS
CONSULUSION :
LIPID DISORDERS CAN BE MANAGED BY :MEASUREMENT OF CHOL TRIGL HDL CHOL LDL CHOL
![Page 39: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/39.jpg)
![Page 40: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/40.jpg)
METABOLISME LEMAKEndah WulandariModul Metabolik dan Endokrin
![Page 41: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/41.jpg)
Lipid Jaringan
Menyimpan kalori non-aktif aktif bila kurang sumber energi
Schoenheimer & Rittenberg jumlah lemak tubuh konstan
![Page 42: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/42.jpg)
Pendahuluan
Bentuk energi simpanan Vertebrata: Triasilgliserol & glikogen
Glikogen : sumber ATP kontraksi otot utk 1 jam pertama
Triasilgliserol: - lemak utama makanan manusia - sumber ATP untuk kerja intensif. misal: migrasi burung, lari maraton.
![Page 43: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/43.jpg)
ASAM LEMAK
tubuh: Asam lemak & triasilgliserol Gliserofosfolipid & sfingolipid (membran sel &
LP) Eikosanoid (prekursor: Prostaglandin,
tromboksan, leukotrien, lipoksin) Kolesterol (stabilisator membran) Garam empedu (prekursor: kolesterol) Hormon steroid (prekursor: kolesterol) Vitamin larut lemak
![Page 44: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/44.jpg)
Triasilgliserol
Struktur: 1CH2 – O – C – R1
R2 – C – O – 2CH2
3CH2 – O – C – R3
O
O
O
![Page 45: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/45.jpg)
LEMAK
Lemak utama makanan : triasilgliserol Sebagai pembawa untuk vitamin: A, D, E,
K Mengalami emulsifikasi di usus halus oleh
garam empedu Dicerna oleh lipase pankreas Hasil pencernaan:
Asam lemak + 2-monoasilgliserol
![Page 46: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/46.jpg)
Triasilgliserol
Sebagai sumber utama energi dibanding karbohidrat dan protein* kalorinya 2 kalilipat* mengandung sedikit air* energi potensial dapat disimpan* dibutuhkan dalam jumlah yang sedikit* melarutkan vitamin-vitamin tertentu* Absorpsi saluran pencernaan
![Page 47: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/47.jpg)
Jalur metabolisme lipid
Gliserol FFA Steroid
LIPOLISIS
STEROIDOGNESIS
aktivasi Triasilgliserol aktivasi
+ LIPOGENESIS Kolesterol
Fosfolipid
ESTERIFIKASI
Gliserol-P Asil-KoA KOLESTEROLOGENESIS
-Oksidasi
Sfingolipid ASETIL-KoA
Triosa –P Piruvat
SAS KETOGENESIS
Glukosa 2CO2 Benda keton
![Page 48: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/48.jpg)
Penyerapan lipid
Masalah: Lemak makanan + yang disintesis hati
harus diangkut ke jaringan & organ Jalur melalui pembuluh darah = aquaeus
Solusi: Mengaitkan lipid nonpolar, amfipatik dan
protein membentuk lipoprotein
Lipid nonpolar: triasilgliserol, esterkolesteril
Lipid amfipatik: fosfolipid, kolesterol
![Page 49: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/49.jpg)
Lipoprotein
Jenis (densitas): Kilomikron VLDL (Very Low Density Lipoprotein) LDL (Low Density Lipoprotein) HDL (High Density Lipoprotein) IDL (Intermediate Density Lipoprotein)
Jenis lipid utama: Triasilgliserol Fosfolipid Kolesterol Esterkolesteril Asam lemak bebas
![Page 50: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/50.jpg)
Struktur Lipoprotein
Inti terdiri dari:
- triasilgliserol
- ester kolesteril
![Page 51: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/51.jpg)
Lipoprotein dalam plasma manusia
Kilomikron VLDL IDL LDL HDL
Berat molekul (10-6) > 400 10-80 5-10 2-3 0,18-0,36
Densitas (g/cm3) < 0,95 0,95-1,006 1,006-1,019 1,019-1,063 1,063-1,210
Komposisi Kimia (%)
Protein 2 10 18 25 33
Triasilgliserol 85 50 31 10 8
Kolesterol 4 22 29 45 30 Fosfolipid 9 18 22 20 29
![Page 52: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/52.jpg)
Apolipoprotein/apoprotein
Adalah protein pada lipoprotein Jumlah: 1 tiap lipoprotein Jenis:
Apoprotein A(I,II,IV) utama: HDL (-lipoprotein) Apoprotein B utama: LDL & VLDL (B-100), Kilomikron (B-48) Apoprotein C(I,II,III) VLDL, HDL, Kilomikron Apoprotein D subfraksi HDL Apoprotein E VLDL, IDL, HDL, Kilomikron
Apo B-48: disintesis di usus
Apo B-100: Disintesis di hati
![Page 53: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/53.jpg)
Kilomikron
Fungsi: mengangkut triasilgliserol makanan ke jaringan
otot & adiposa Mengangkut kolesterol makanan ke hati
Disintesis: usus Jalur sirkulasi: jalur limfatik ke pembuluh
vena Tujuan: endotelium kapiler jaringan otot
dan adiposa Mengalami:
hidrolisis triasilgliserol oleh LPL (lipoprotein lipase) di endotelium kapoler jaringan otot & adiposa
Sisa kilomikron ke hati membawa kolesterol
![Page 54: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/54.jpg)
VLDL Fungsi:
Membawa kolesterol makanan di hati & TAG yang dihasilkan hati ke pembuluh darah di jatingan otot & adiposa
Disintesis : hati Tujuan: endotel kapiler jaringan otot &
adiposa Mengalami:
Hidrolisis oleh LPL Degradasi menjadi IDL lalu LDL
![Page 55: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/55.jpg)
LDL
Fungsi:mengangkut kolesterol ke hati dan
esterkolesteril ke jar. Ekstrahepatik
Diurai: 30% di jar. Ekstrahepatik 70% di di hati
Korelasi positif dengan aterosklerosis
![Page 56: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/56.jpg)
HDL
Disintesis : Intestinum: hanya apopotein A Hati : Apoprotein C & E
Fungsi: Tempat penyimpanan apoprotein C & E
untuk metabolisme kilomikron & VLDL Pengangkutan-balik kolesterol dari jaringan
ke hati
![Page 57: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/57.jpg)
Lipogenesis (PembentukanTriasilgliserol dari glukosa)
Glukosa
Asetil-KoA
OAA
Piruvat
Piruvat
GLIKOLISIS
Asam lemak sintase
Palmitat
AL-KoA
Gliserol-3PDHAP
Sitrat Asetil-KoA
malonil-KoA
OAASitrat
VLDL
Apoprotein
Lemak lainTG
DARAH
![Page 58: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/58.jpg)
Biosintesis asam lemak
Lintasan utama: sitosol Terjadi di banyak sel, Misal: hati, ginjal,
otak, paru, kelenjar mamae, adiposa. Kofaktor: NADPH, ATP, Mn2+, biotin &
HCO3-
Substrat: Asetil-KoA Produk akhir : palmitat bebas Dipengaruhi: status nutrisi
Meningkat saat kenyang & diet KH tinggi Menurun asupan kalori terbatas & diet lemak
tinggi
![Page 59: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/59.jpg)
Kompleks enzim sintase asam lemak Terdiri dari:
7 aktifitas enzim: Ketoasil sintase Asetil trasasilase Malonil transasilase Hidratase Enoil reduktase Ketoasil reduktase ACP tioesterase
1 ACP (acyl carrier protein) Bentuk: dimer (monomer identik)
![Page 60: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/60.jpg)
Sintesis asam lemak
![Page 61: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/61.jpg)
Peran karnitin
![Page 62: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/62.jpg)
Oksidasi asam lemak(Ketogenesis/-Oksidasi)
Tujuan : menghasilkan ATP Berlangsung di Mitokondria Memerlukan: NAD+ & FAD Terjadi pada keadaan :
Kelaparan DM
Bila berlebihan Ketoasidosis fatal
![Page 63: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/63.jpg)
Proses -Oksidasi
Adalah: pemecahan 2 atom karbon sekaligus dari molekul asil-KoA
Lokasi: diantara karbon (2) dan (3) -Oksidasi
Tahap: Aktifasi Dehidrogenasi Hidratasi Dehidrogenasi tiolasi
![Page 64: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/64.jpg)
ß-OKsidasi
![Page 65: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/65.jpg)
Pembentukan energi pada ß-Oksidasi
Contoh: -oksidasi palmitat
Asetil-KoA (SAS) : 8 x 12 = 96 mol ATP
NADH + H+(7 siklus): 7 x 5 = 35 mol ATP
131 mol ATP
Aktivasi = 2 mol ATP
129 mol ATP
+
-
![Page 66: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/66.jpg)
Oksidasi asam lemak peroxisomal Pada peroksisom peroksida Membantu pemecahan asam lemak
rantai panjang (C20) Dalam mitokondria masuk dengan
karnitin ß- oksidasi berakhir pada oktanoil KoA asetil karnitin
Diinduksi : diit tinggi lemak, konsumsi hipolepimik
![Page 67: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/67.jpg)
α-Oksidasi asam lemak
Pengeluaran 1 karbon dari COOH jaringan otak tidak berikatan dengan KoA dan tidak terbentuk ATP
Pengeluaran Metil 3 C yang menghalangi ß-oksidasi (oksidasi as.fitanat dari fitol)
Refsum : penyakit yang mencegah terjadinya oksidasi asam
fitanat
![Page 68: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/68.jpg)
Oksidasi asam lemak tidak jenuh
![Page 69: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/69.jpg)
KOLESTEROL
Adalah:Lipid amfipatik Asal:
Endogen (biosintesis tubuh): 700 mg/hari Hati, usus & sel berinti lainnya
Eksogen (makanan) Fungsi:
Struktur esensial membran sel Lapisan luar lipoprotein plasma Unsur utama batu mepedu
![Page 70: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/70.jpg)
Biosintesis asam lemak jenuh Sistem ekstramitokondria (Sist. De
novo) Sistem Mikrosom Sistem Mitokondria
![Page 71: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/71.jpg)
Sistem ekstramitokondria
Di dalam sitosol : hati, ginjal, otak, pari, kel. Mammae
Asetil KoA asam palmitat
![Page 72: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/72.jpg)
Produksi malonil-KoA
Tahap awal sintesis as. Lemak Bahan:
HCO3- (sumber CO2)
Asetil-KoA (bahan awal) ATP Asetil-KoA karboksilase
Pers. Reaksi
CH2 – CO~S – KoA -OO*C – CH2 – CO~S – KoA
Enz – biotin – *COO- Enz – biotin
ADP + Pi ATP + H*CO3-
Asetil-KoA Malonil-KoA
![Page 73: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/73.jpg)
2 Jenis Enzim Asam Lemak Jenuh Acyl Carier asam Lemak (ACP) Kompleks multi enzim
1. Asil trasferase2. Malonil trasnasilase3. ß- ketoasil sintetase4. deasilase5. keto asil reduktase6. hidratase7. enoil reduktase
![Page 74: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/74.jpg)
Sistem Mikrosom
Bahan : malonil KoA 2 atom C bertambah
Puasa : perpanjangan rantai menurun Perpanjangan rantai terjadi pada :1. Asam lemak jenuh C10 dan C162. Asam lemak tak jenuh C183. Stearoil KoA (C18) otak4. Asam lemak pembentukan sfingolipid
(C22 dan C24)
![Page 75: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/75.jpg)
![Page 76: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/76.jpg)
Sistem Mitokondria
An-aerob Kebalikan dari ß-oksidasi Rantai lebih panjang 2C
![Page 77: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/77.jpg)
Met Asam Lemak tidak jenuh
Non-esensial Esensial
![Page 78: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/78.jpg)
Sistem desaturasi asam lemak ikatan rangkap tunggal
![Page 79: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/79.jpg)
Sistem asam lemak ik rangkap banyak (polyunsaturated)
Manusia dan hewan mampu mensintesis asam oleat dengan perpanjangan rantai dan desaturasi
![Page 80: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/80.jpg)
Konversi as linoleat menjadi asam arakidonat
Manusia dan hewan tidak mampu mensintesis asam linoleat dan asam linolenat dengan sempurna
Untuk menyempurnakan asam linoleat/asam linolenat di rubah menjadi asam arakhidonat
![Page 81: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/81.jpg)
Asam Lemak Esensial
Th 1928 Evans dan Burr Perc. Tikus : tanpa lipid, hanya vit. A
& D pertumbuhan berkurang defisiensi reproduksi
Tindakan : asam linoleat, asam linolenat dan asam arachidonat
![Page 82: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/82.jpg)
Fungsi asam lemak esensial : Pembentukan prostaglandin Sistem reproduksi fosfolipod Perlemakan hati Metabolisme kolesterol Mengatasi : 1-2% kalori tubuh
![Page 83: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/83.jpg)
Eikosanoid
Asam lemak yang diselang metil, aktif bila hasil sintesis asam lemak esensiaL Siklooksigenase-lipoksigenasi
Prostaglandin, tromboxan, leukotrien
![Page 84: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/84.jpg)
![Page 85: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/85.jpg)
Met Asil Gliserol
Asil gliserol : hasil katabolisme triasilgliserol
![Page 86: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/86.jpg)
![Page 87: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/87.jpg)
Biosintesis Kardiolipin
![Page 88: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/88.jpg)
Skema tempat aktivitas hidrolitik fosfolipid oleh fosfolipase
![Page 89: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/89.jpg)
Tugas
Biosintesis Sfingomielin Biosintesis Lipid eter dan
plasmalogen Met Lesitin Met sfingolipid Met Gangliosida
![Page 90: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/90.jpg)
Biosintesis Kolesterol
Bahan asal: Asetil-KoA Terdiri dari 5 tahap:
1. Mavolenat2. Unit isoprenoid aktif (isopentenil difosfat)3. Skualen4. Lanosterol5. kolesterol
![Page 91: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/91.jpg)
![Page 92: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/92.jpg)
Met lipid pada seluruh tubuh
![Page 93: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/93.jpg)
GARAM/ASAM EMPEDU
Asam empedu primer disintesis dari kolesterol
Asam empedu primer: Asam kolat (taurokolat & glikokolat) Asam kenodeoksikolat (taurodeoksikolat &
glikodeoksikolat) Asam empedu sekunder:
Asam deoksikolat Asam litokolat
![Page 94: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/94.jpg)
GARAM/ASAM EMPEDU Asam empedu primer masuk ke getah
empedu dalam bentuk terkonjugasi glisin dan taurin.
Dinamakan garam empedu karena: Getah empedu banyak mengandung K & Na
dan pHnya basa.
Terjadi sirkulasi enterohepatik, yaitu: Asam empedu yang dikeluarkan akan diserap
usus dan kembali ke hati Sebagian kecil disekresikan melalui feses
Daur ulang melalui usus: 6-10 x setiap hari
![Page 95: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/95.jpg)
ATHEROSKLEROSIS
Adalah: mengerasnya pembuluh arteri Penyebab: deposit lipid (umumnya kolesteril
ester) Lokasi: jaringan ikat dinding pembulug arteri Terjadi pada penderita:
DM Nefrosis lipid hipotiroidisme
Lebih parah bila: VLDL, IDL, sisa kilomikron dan LDL meningkat HDL menurun
![Page 96: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/96.jpg)
KAFEIN
Meningkatkan kadar asam lemak bebas dalam plasma manusia
Karena: Kafein menghambat kerja enzim
fosfodiesterase 3’, 5’-nukleotida siklik Enzim tersebut mengurai senyawa cAMP
menjadi 5’-AMP cAMP mengendalikan lipolisis (mengaktifkan
enzim triasilgliserol lipase)
![Page 97: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/97.jpg)
![Page 98: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/98.jpg)
PERLEMAKAN HATI
Penyebab: Tidak seimbang: pembentukan vs pengeluaran
TAG
Ada 2 tipe: Kenaikan FFA Gangguan metabolisme lipoprotein plasma
Penyebab: Kelaparan DM tidak terkontrol alkoholisme
![Page 99: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/99.jpg)
BADAN KETON
Terbentuk jika: terjadi oksidasi as. Lemak dengan kecepatan tinggi di hati
Terdiri dari: Asetoasetat -hidroksibutirat aseton
Fungsi: Bahan bakar jaringan ekstrahepatik. Mis:
otot (asetoasetat & -hidroksibutirat)
![Page 100: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/100.jpg)
KETOGENESIS
![Page 101: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/101.jpg)
Pembentukan, penggunaan dan eksresi BADAN KETON
HATI DARAH JARINGAN EKSTRAHEPATIK
Asil-KoA
glukosa
2CO2
Asetil-KoA
Badan keton
Badan keton
Badan keton
Asetil-KoA
Glukosa Asil-KoA
FFA
2CO2
URINE
PARU
asetonSAS
SAS
![Page 102: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/102.jpg)
HORMON vs METABOLISME LEMAK
Peran: Meningkatkan lipolisis:
mempercepat pelepasan FFA dari jaringan adiposa
Menaikan kadar FFA plasma Contoh: ACTH, epinefrin, norepinefrin, glukagon,
MSH, TSH, GH, vasopresin Meperlambatkan lipolisis
Menghambat sintesis cAMP Menginaktifkan enzim lipase Contoh: insulin, asam nikotinat, prostaglandin E1
![Page 103: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/103.jpg)
![Page 104: Dislipidemia u k Sur](https://reader031.vdocuments.us/reader031/viewer/2022020713/5514430a4a7959c4028b4ee6/html5/thumbnails/104.jpg)