Physiology

Lipid levels and metabolism are crucial for health. Imbalances can lead to a range of disorders, particularly cardiovascular disease

Normal States

Normal Lipid Profile: Optimal levels of cholesterol, triglycerides, LDL, and HDL
Balanced Lipid Metabolism: Efficient breakdown and synthesis of lipids, with appropriate energy storage and utilization

Total Cholesterol: < 200 mg/dL (5.18 mmol/L)
LDL Cholesterol: < 100 mg/dL (2.59 mmol/L)
HDL Cholesterol: > 60 mg/dL (1.55 mmol/L)
Triglycerides: < 150 mg/dL (1.7 mmol/L)
Importance
- These levels are associated with a lower risk of cardiovascular disease
- Optimal lipid levels contribute to overall health and well-being

Hyperlipidemia (High Lipids): Elevated total cholesterol, LDL cholesterol, and/or triglycerides
Dyslipidemia (Abnormal Lipids): Imbalances in lipid levels, including high LDL, low HDL, and high triglycerides
Atherosclerosis: Plaque buildup in arteries due to lipid deposition
Fatty Liver Disease (NAFLD/NASH): Excess fat accumulation in the liver
Lipoprotein Disorders: Genetic defects affecting lipoprotein synthesis or metabolism
Lipodystrophy: Selective loss of adipose tissue

Definition: Abnormally high levels of lipids (fats) in the blood
Types
- Hypercholesterolemia: Elevated total cholesterol and LDL cholesterol
- Hypertriglyceridemia: Elevated triglycerides
- Mixed Hyperlipidemia: Elevated cholesterol and triglycerides
Causes
- Primary (Genetic): Familial hypercholesterolemia, familial hypertriglyceridemia, etc
- Secondary (Acquired)
  - Diet: High intake of saturated and trans fats, cholesterol, and simple carbohydrates
  - Lifestyle: Sedentary behavior, smoking
  - Medical Conditions: Diabetes, hypothyroidism, kidney disease, liver disease
  - Medications: Diuretics, beta-blockers, corticosteroids
Symptoms
- Often asymptomatic
- Severe hypertriglyceridemia can cause eruptive xanthomas (small, yellow papules on the skin) and lipemia retinalis (milky appearance of retinal blood vessels)
Complications
- Atherosclerosis: Plaque buildup in arteries, leading to heart disease, stroke, and peripheral artery disease
- Pancreatitis: Very high triglycerides can cause inflammation of the pancreas
- Fatty Liver Disease: Excess fat accumulation in the liver
Clinical Significance
- Hyperlipidemia is a major risk factor for cardiovascular disease
- Early detection and management are essential to prevent or delay the onset of complications
- Management involves lifestyle modifications (diet, exercise), medications (statins, fibrates, etc.), and addressing underlying causes

Definition: An abnormal lipid profile characterized by imbalances in lipid levels
Common Patterns
- High LDL cholesterol, low HDL cholesterol, and high triglycerides
- High LDL cholesterol and high triglycerides
- Low HDL cholesterol and high triglycerides
Causes
- Similar to hyperlipidemia
Symptoms
- Often asymptomatic
Complications
- Similar to hyperlipidemia
Clinical Significance
- Dyslipidemia is a significant risk factor for cardiovascular disease
- Management involves lifestyle modifications (diet, exercise), medications, and addressing underlying causes

Definition: A chronic inflammatory disease characterized by the buildup of plaque (atheroma) in the arteries
Process
1. Endothelial Injury: Damage to the inner lining of the artery
2. Lipid Deposition: LDL cholesterol accumulates in the artery wall
3. Inflammation: Immune cells are recruited, leading to chronic inflammation
4. Plaque Formation: Plaque consists of lipids, cholesterol, calcium, and cellular debris
5. Plaque Rupture: Plaque can rupture, leading to thrombus (blood clot) formation
Risk Factors
- Hyperlipidemia
- Hypertension
- Smoking
- Diabetes
- Obesity
- Family history
Symptoms
- Often asymptomatic until significant narrowing of the arteries occurs
- Angina (chest pain)
- Shortness of breath
- Leg pain with exercise (claudication)
Complications
- Coronary Artery Disease (CAD): Heart attack, heart failure
- Stroke
- Peripheral Artery Disease (PAD)
- Aneurysm
Clinical Significance
- Atherosclerosis is a leading cause of cardiovascular disease and death
- Management involves lifestyle modifications, medications (statins, antiplatelet agents), and procedures (angioplasty, bypass surgery)

Definition: The accumulation of excess fat in the liver
Types
- Non-Alcoholic Fatty Liver Disease (NAFLD): Fatty liver not caused by excessive alcohol consumption
- Non-Alcoholic Steatohepatitis (NASH): A more severe form of NAFLD characterized by inflammation and liver damage
Causes
- Obesity
- Insulin resistance
- Metabolic syndrome
- High-fat diet
- Diabetes
Symptoms
- Often asymptomatic
- Fatigue
- Right upper quadrant abdominal pain
- Hepatomegaly (enlarged liver)
Complications
- Cirrhosis: Scarring of the liver
- Liver failure
- Hepatocellular carcinoma (liver cancer)
Clinical Significance
- NAFLD is a common condition, especially in developed countries
- NASH can progress to cirrhosis and liver failure
- Management involves lifestyle modifications (weight loss, diet, exercise), medications, and addressing underlying causes

Definition: Genetic disorders affecting lipoprotein synthesis, structure, or metabolism
Examples
- Familial Hypercholesterolemia: Mutations in the LDL receptor gene, leading to high LDL cholesterol levels
- Familial Hypertriglyceridemia: Increased VLDL production or decreased triglyceride clearance, leading to high triglyceride levels
- Familial Combined Hyperlipidemia: Elevated cholesterol and triglycerides
- Tangier Disease: Deficiency of ABCA1 transporter, leading to very low HDL cholesterol levels
Symptoms
- Vary depending on the specific disorder
Complications
- Premature cardiovascular disease
- Other lipid-related complications
Clinical Significance
- Early diagnosis and management are essential to prevent or delay the onset of complications
- Treatment involves lifestyle modifications, medications, and sometimes specialized therapies

Definition: A syndrome characterized by selective loss of adipose tissue
Types
- Genetic (Congenital): Rare, often associated with mutations in genes involved in lipid metabolism
- Acquired: Can be caused by HIV medications (lipodystrophy syndrome), autoimmune diseases, or other factors
Symptoms
- Loss of subcutaneous fat in certain areas of the body (e.g., face, limbs)
- Accumulation of fat in other areas (e.g., abdomen)
- Insulin resistance
- Hypertriglyceridemia
- Fatty liver disease
Complications
- Diabetes
- Cardiovascular disease
- Liver disease
Clinical Significance
- Management involves addressing the underlying cause, managing metabolic complications, and sometimes cosmetic procedures