A.9 Disorders of Lipid Metabolism Flashcards
A.9 Disorders of Lipid Metabolism
Dyslipidemia: Abnormal levels of lipoproteins (LDL and HDL) that increase the risk of cardiovascular disease.
Hyperlipidemia: Elevated lipoprotein levels (total cholesterol, LDL, triglycerides).
Hypercholesterolemia: High cholesterol levels (total cholesterol > 200 mg/dL).
Hypertriglyceridemia: Elevated triglyceride levels.
Hypolipoproteinemia: Reduced levels of certain lipoproteins.
A.9 Disorders of Lipid Metabolism
Etiology
Congenital (less common)
Type I: Hyperchylomicronemia
Type II: Familial hypercholesterolemia
Type III: Dysbetalipoproteinemia
Type IV: Familial hypertriglyceridemia
Acquired (more common)
Obesity
Hypothyroidism
Metabolic syndrome
Physical inactivity
Cholestatic liver disease
Drugs
A.9 Disorders of Lipid Metabolism
Diagnosis
Fasting Lipid Profile (mg/dL):
Total Cholesterol: < 200
HDL: > 60
Triglycerides: < 150
LDL: < 100
Diagnosis of Dyslipidemia: Dyslipidemia is diagnosed when LDL levels are above 130 mg/dL or if HDL levels are below 40 mg/dL.
A.9 Disorders of Lipid Metabolism
Identify Underlying Causes
- Fasting Blood Glucose Level or HbA1c
- Liver Function Tests
- Thyroid Function Tests
A.9 Disorders of Lipid Metabolism
Treatment
Goal: Enhance serum lipid levels to minimize the risk of cardiovascular disease.
Lifestyle Modifications
Medical Therapy
Statins
Second-line Lipid-Lowering Agents
Management of Congenital Disorders
High-Dose Statin Therapy
Ezetimibe for hypercholesterolemia.
Fibrates for hypertriglyceridemia (Type IV).
Note: LDL apheresis may be necessary in severe cases.
A.9 Disorders of Lipid Metabolism
Hyperchylomicronemia (Type I)
Autosomal Recessive (AR)
Pathogenesis: Caused by defective lipoprotein lipase or apolipoprotein C-II.
Blood Level: Characterized by elevated levels of chylomicrons, triglycerides (TG), and cholesterol.
Clinical Features: Patients may experience pancreatitis, hepatosplenomegaly, and eruptive xanthomas. There is no significant risk for atherosclerosis.
A.9 Disorders of Lipid Metabolism
Familial Hypercholesterolemia (Type II)
Inheritance: Autosomal Recessive (AR)
Pathogenesis: Results from absent or defective LDL receptors or mutations in apolipoprotein B-100.
Blood Level: High levels of LDL cholesterol are observed.
Clinical Features: This disorder is associated with early atherosclerosis, increasing the risk of myocardial infarction (MI) if it occurs after age 20, as well as tendon xanthomas.
A.9 Disorders of Lipid Metabolism
Dysbetalipoproteinemia (Type III)
Inheritance: Autosomal Recessive (AR)
Pathogenesis: Due to defective apolipoprotein E (apoE).
Blood Level: Elevated levels of chylomicrons and triglycerides.
Clinical Features: The condition leads to premature atherosclerosis and the presence of xanthomas.
A.9 Disorders of Lipid Metabolism
Hypertriglyceridemia (Type IV)
Inheritance: Usually acquired.
Pathogenesis: Caused by hepatic overproduction of very low-density lipoproteins (VLDL).
Blood Level: Marked by high levels of VLDL and triglycerides.
Clinical Features: This disorder can result in hypertriglyceridemia, which may lead to acute pancreatitis and is often associated with insulin resistance.
A.9 Disorders of Lipid Metabolism
Abetalipoproteinemia
Autosomal Recessive: Caused by a mutation in the microsomal triglyceride transfer protein (MTTP) gene.
Lipid Profile: Chylomicrons, VLDL, and LDL are absent; characterized by a deficiency in ApoB-48 and ApoB-100.
Clinical Features: Patients typically exhibit failure to thrive, along with gastrointestinal symptoms like fat malabsorption and steatorrhea.
Later Manifestations: Retinitis pigmentosa, spinocerebellar degeneration due to vitamin E deficiency, progressive ataxia, and acanthosis.
Histology: Intestinal biopsy shows lipid-laden enterocytes.
Treatment: Restriction of long-chain fatty acids and high doses of oral vitamin E.
