VIA EXÓGENA DEL TRANSPORTE DE LIPIDOS

VIA ENDOGENA DEL TRANSPORTE DE LIPIDOS

TRANSPORTE REVERSO DE COLESTEROL

PROTEINOGRAMA ELECTROFORETICO

ETIOLOGIA DISLIPIDEMIAS 1° PRIMARIA: 1. DESORDENES GENETICOS 2° SECUNDARIA: 1. EXCESO DIETA CALORÍAS, GRASAS, HC, ALCOHOL 2. ENFERMEDADES 3.MEDICACION

DISLIPIDEMIAS PRIMARIAS

DISLIPIDEMIAS PRIMARIAS II

XANTOMA TÚBERO ERUPTIVO

XANTOMA TUBEROSO

ARCO CORNEAL - XANTELASMA

ESTUDIOS COMPLEMENTARIOS LIPIDOGRAMA ELECTROFORETICO GEL DE AGAROSA. Cualitativo Disbetalipoproteinemia: Banda ancha entre Beta y preBeta Tipo V: Quilomicrones. Dif IV GEL DE POLIACRILAMIDA.Separación por carga y tamaño Disbetalipoproteinemia: Ausencia de LDL OTROS: Disbetalipoproteinemia: VLDL colest/TG: >0.3 Genotipo E2/E2 IDL post precipitación con heparina. IDL >40 mg/dl Hipercolesterolemia familiar Actividad de LPL

DISLIPIDEMIAS SECUNDARIAS PATOLOGÍAS ASOCIADAS A HIPERCOLESTEROLEMIA HIPOTIROIDISMO: Recep. y Catab. LDL Activ. LPL SINDROME NEFRÓTICO: Sint. Catab. HEPATOPATIA SINDROME DE CUSHING DISGLOBULINEMIA: Complejos Inmunes Catab. PORFIRIA INTERMITENTE AGUDA FARMACOS: CORTICOSTEROIDES, ANABOLICOS, PROGESTÁGENOS. PATOLOGÍAS ASOCIADAS A HIPERTRIGLICERIDEMIA DIABETES OBESIDAD HIPOTIROIDISMO: LPL INSUFICIENCIA RENAL CRONICA: TG LPL SINDROME DE CUSHING: Cortisol Lipólisis PANCREATITIS: (-) LPL EMBARAZO ALCOHOLISMO: B oxidación FARMACOS: GLUCOCORTICOIDES, BETA BLOQUEANTES ( LPL), DIURETICOS ( lipólisis), ESTRÓGENOS OTROS: PORFIRIA INTERMITENTE AGUDA, DISGLOBULINEMIA

DISLIPIDEMIAS SECUNDARIAS II DISLIPIDEMIA COMBINADA HIPOTIROIDISMO: Recep. y Catab. LDL Activ. LDL TG SINDROME NEFROTICO: Sint. Hepat. Pérd. Renales Apo C II y HDL LPL FÁRMACOS: CORTICOSTEROIDES OTRAS : PORFIRIA INTERMITENTE AGUDA, DISGLOBULINEMIA DIABETES AUMENTO: TG, VLDL, LDL pequeña y densa, APO B DISMINUCIÓN: HDL, APO A I

SINDROME METABOLICO (ATP III) OBESIDAD CENTRAL: CINTURA > 102 cm H > 88 cm M TRIGLICERIDOS:  150 mg/dl HDL c: < 40 mg/dl H < 50 mg/dl M TA:  130 / 85 mg/dl GLUCEMIA EN AYUNAS:  110 mg/dl DIAGNOSTICO CON LA PRESENCIA DE 3 O MAS ELEMENTOS

ATEROSCLEROSIS E INSULINO RESISTENCIA Hipertensión Obesidad Hiperinsulinemia Diabetes Hipertrigliceridemia LDL Pequeñas y Densas HDL Bajo Hipercoagulabilidad Insulino Resistencia Aterosclerosis Interrelation Between Atherosclerosis and Insulin Resistance Insulin resistance is associated with a panoply of abnormalities, including hypertension, hyperinsulinemia, hypertriglyceridemia with small, dense low-density lipoprotein (LDL) and low high-density lipoprotein (HDL), and hypercoagulability. Of course, insulin resistance is a major risk factor for the development of diabetes. Obesity plays a role both in exacerbating insulin resistance and as an independent risk factor for atherosclerosis. Therefore, any patient with insulin resistance has numerous reasons to be at very high risk for atherosclerosis.

CLASIFICACION SEGÚN RIESGO CARDIOVASCULAR ADULT TREATMENT PANEL III (ATP III) C. TOTAL LDL TG OPTIMO <200 mg/dl <100 mg/dl <150 mg/dl Cercano óptimo 100-129 Bordeline alto 200-239 130-159 150-199 ALTO  240 160-189 200-299 MUY ALTO  240 >500 HDL BAJO <40 mg/dl ALTO  60

DISLIPIDEMIA E INSULINO RESISTENCIA Células Grasas Hígado FFA X IR Mechanisms Relating Insulin Resistance and Dyslipidemia (I) The pathophysiologic basis for diabetic dyslipidemia and its relation to insulin resistance is presented over the next four slides. In the first, we see that insulin-resistant fat cells undergo greater breakdown of their stored triglycerides and greater release of free fatty acids into the circulation. This is a common abnormality seen in both obese and nonobese insulin-resistant subjects and those with type 2 diabetes. Increased fatty acids in the plasma leads to increased fatty acid uptake by the liver; in the fed state and in the presence of adequate glycogen stores, which is the common situation in patients with type 2 diabetes that is reasonably well controlled and certainly the case in the insulin-resistant nondiabetic subject, the liver takes those fatty acids and synthesizes them into triglycerides. Insulina

DISLIPIDEMIA E INSULINO RESISTENCIA Células Grasas Hígado FFA  TG  ApoB  VLDL VLDL X IR Mechanisms Relating Insulin Resistance and Dyslipidemia (II) The presence of increased triglycerides stimulates the assembly and secretion of the apolipoprotein (apo) B and very low density lipoprotein. The result is an increased number of VLDL particles and increased level of triglycerides in the plasma, which leads to the rest of the diabetic dyslipidemic picture. Insulina

DISLIPIDEMIA E INSULINO RESISTENCIA Células Grasas Hígado FFA CE (Lipasa Hepática)  TG  Apo B  VLDL VLDL (CETP) HDL X IR TG Apo A-1 Mechanisms Relating Insulin Resistance and Dyslipidemia (III) In the presence of increased VLDL in the plasma and normal levels of activity of the plasma protein cholesteryl ester transfer protein (CETP), VLDL triglycerides can be exchanged for HDL cholesterol. That is, a VLDL particle will give up a molecule of triglyceride, donating it to the HDL, in return for one of the cholesteryl ester molecules from HDL. This leads to two outcomes: a cholesterol-rich VLDL remnant particle that is atherogenic, and a triglyceride-rich cholesterol-depleted HDL particle. The triglyceride-rich HDL particle can undergo further modification including hydrolysis of its tryglyceride, probably by hepatic lipase, which leads to the dissociation of the structurally important protein apo A-I. The free apo A-I in plasma is cleared more rapidly than apo A-I associated with HDL particles. One of the sites of clearance is the kidney. In this situation, HDL cholesterol is reduced, and the amount of circulating apo A-I and therefore the number of HDL particles is also reduced. Riñón Insulina

DISLIPIDEMIA E INSULINO RESISTENCIA Células Grasas Hígado FFA CE (Lipasa Hepática)  TG  Apo B  VLDL VLDL (CETP) HDL X IR TG Apo A-1 (CETP) CE TG Mechanisms Relating Insulin Resistance and Dyslipidemia (IV) On the last slide in this series, we see a similar phenomena leading to small, dense LDL. Increased levels of VLDL triglyceride in the presence of CETP can promote the transfer of triglyceride into LDL in exchange for LDL cholesteryl ester. The triglyceride-rich LDL can undergo hydrolysis by hepatic lipase or lipoprotein lipase, which leads to a small, dense, cholesterol-depleted—and, in general, lipid-depleted—LDL particle. Riñón Insulina SD LDL LDL (LPL ó lipasa hepática)

INTERROGATORIO ANTECEDENTES FAMILIARES: DISLIPIDEMIA ENFERMEDAD CARDIOVASCULAR PREMATURA F. 1er GRADO HOMBRES < 55 años F. 1er GRADO MUJER < 65 años DIABETES (tipo) HTA ANTECEDENTES PERSONALES: EDAD: HOMBRES  45 años MUJERES  55 años TABAQUISMO ACTIVIDAD FISICA ANAMNESIS ALIMENTARIA . INGESTA ALCOHOLICA MEDICACION ENF: HTA . ENFERMEDAD CARDIOVASCULAR DIABETES HIPOTIROIDISMO. HEPATOPATIAS. IRC

EXAMEN FISICO PIEL Y FANERAS: XANTOMAS: PLANOS: Diseminados, aspecto queloide TUBEROSOS : 0.5- 3cm Codos, rodillas, palmas, plantas, vainas tendinosas . ERUPTIVOS: 1cm Superficies de extensión miembros, tronco, palmas XANTELASMAS: Párpados OCULAR: GERONTOXON (Arco corneal) LIPEMIA RETINALIS: Vasos blanquecino amarillento. Suero lechoso PESO, TALLA, BMI, CINTURA EVALUACIÓN CARDIOVASCULAR ABDOMEN PALPACIÓN TIROIDEA

ESTUDIOS COMPLEMENTARIOS LABORATORIO: PERFIL LIPIDICO: C.TOTAL-LDL-HDL-TG (>20/ 5años) FUNCION RENAL TSH HEPATOGRAMA CURVA DE TOLERANCIA CON INSULINEMIA LIPIDOGRAMA ELECTROFORÉTICO CASOS ESPECIALES: Apo A1 y B: XANTELASMAS + ANTECED. FAMILIARES Apo A1/B: >1 (Riesgo) Subfracciones HDL: HDL2 Lp(a): apo B 100-apo A. Pre beta 1 (Riesgo) LDL: Subclases: Pequeña y densas- Oxidadas

CATEGORIAS DE RIESGO PRIMERA CATEGORIA: (ldl <100) PACIENTES CON ENFERMEDAD CORONARIA ENF EQUIVALENTE: ENF ERMEDAD ATEROSCLEROTICA PERIFERICA ANEURISMA DE AORTA ABDOMINAL ENFERMEDAD CAROTIDEA SINTOMATICA DIABETES DOS O MÁS FACTORES DE RIESGO MAYORES (DBT-LDL-HDL -HTA-TAB-ANTEC FAMILIARES-EDAD) Y RIESGO FRAM. +20% 10 AÑOS SEGUNDA CATEGORIA: (ldl <130) DOS O MAS FACTORES DE RIESGO MAYORES RIESGO DE IAM O MUERTE CORONARIA POR FRAM . 10-20% TERCERA CATEGORIA (ldl <160) PACIENTES CON 0 a 1 FACTOR DE RIESGO