Introduction
Defective metabolism of lipids results in several important health disorders, including atherosclerosis, fatty liver, and hypercholesterolemia. These conditions arise due to disturbances in lipid synthesis, transport, or degradation, often leading to severe metabolic and cardiovascular complications.
Atherosclerosis
Atherosclerosis is a chronic disorder associated with abnormal cholesterol metabolism, characterized by the accumulation of lipids in the arterial walls.
Key Features:
- Blood cholesterol levels are persistently high in this condition.
- Genetic factors also play a role in the development of atherosclerosis.
- Initially, cholesterol esters—especially cholesterol oleates—deposit in the arterial smooth muscle cells forming fatty streaks, which are reversible.
- Continuous deposition of cholesterol esters and apolipoprotein B-100 of lipoproteins leads to plaque formation in the arterial wall.
- The plaque narrows the arterial lumen, reducing blood flow—a condition called atherosclerosis.
- Clot formation (thrombosis) may occur on the plaque surface.
- If a clot develops in the coronary artery, it reduces oxygen supply to the heart, leading to myocardial infarction (heart attack) or stroke.
- Atherosclerosis is therefore a major cause of coronary artery disease (CAD).
- It can also occur secondary to diseases like diabetes mellitus, hypothyroidism, nephrotic syndrome, and other lipid metabolism disorders.
- Some atherosclerotic lesions develop even with normal cholesterol levels due to inflammatory factors and low HDL concentrations, leading to foam cell and plaque formation.
Fatty Liver (Hepatic Steatosis)
The normal liver contains about 5% lipid, of which one-fourth is triglyceride. When the lipid content increases to 25–30% or more, the condition is known as fatty liver.
In this condition, triglycerides and fatty acids fill the hepatocyte cytoplasm, impairing liver function.
Causes of Fatty Liver:
1) Raised Plasma Free Fatty Acid Levels:
- Occurs due to excessive fat mobilization from adipose tissue during starvation, diabetes, carnitine deficiency, or high-fat diet.
- Liver uptakes the fatty acids and converts them into triglycerides faster than they can be released as VLDL, leading to fat accumulation.
2) Metabolic Block in Lipoprotein Formation:
- When VLDL (Very Low-Density Lipoprotein) synthesis is impaired, triglycerides accumulate in the liver even if triglyceride synthesis is normal.
- This may occur due to deficiency of substances required for VLDL synthesis such as choline, methionine, and betaine, known as lipotropic factors.
- Choline deficiency affects phospholipid biosynthesis and membrane formation, blocking VLDL production and leading to fatty liver.
- Other lipotropic factors include PUFAs (polyunsaturated fatty acids), Vitamin E, pyridoxine, and pantothenic acid.
3) Toxic Substances:
- Hepatotoxic agents such as carbon tetrachloride, chloroform, phosphorus, arsenic, alcohol, lead, and orotic acid can cause fatty liver.
- Inhibitors of protein synthesis like puromycin and ethionine also induce fatty liver.
Medical Importance:
Chronic fat accumulation in the liver causes fibrosis of hepatocytes, progressing to cirrhosis and liver failure.
Hypercholesterolemia
Hypercholesterolemia is a condition where blood cholesterol levels exceed normal limits (greater than 200 mg/dL). Cholesterol, a waxy substance found in all body cells, is essential for cell membranes and hormone synthesis. However, excessive cholesterol contributes to cardiovascular diseases.
Causes of Hypercholesterolemia:
- Diabetes Mellitus: Increased cholesterol synthesis due to excessive acetyl-CoA availability.
- Hypothyroidism (Myxedema): Decreased HDL receptor levels on hepatocytes, slowing cholesterol clearance.
- Obstructive Jaundice: Cholesterol excretion through bile is blocked.
- Nephrotic Syndrome: Elevated plasma globulins and lipoproteins increase blood cholesterol.
High LDL cholesterol is directly associated with atherosclerosis and coronary heart disease (CHD), while HDL cholesterol protects against them.
Good and Bad Cholesterol
Cholesterol plays an essential role in maintaining membrane structure and acting as a precursor for steroid hormones and bile acids. However, its impact on health depends on its carrier lipoprotein:
| Lipoprotein Type | Nicknamed As | Function | Health Impact |
|---|---|---|---|
| LDL (Low-Density Lipoprotein) | Bad Cholesterol | Transports cholesterol from liver to tissues | High levels promote plaque formation and atherosclerosis |
| HDL (High-Density Lipoprotein) | Good Cholesterol | Removes excess cholesterol from tissues and returns it to the liver | High levels protect against heart disease |
The most dangerous form of LDL is small dense LDL (sdLDL), strongly linked with coronary heart disease, while high HDL levels are considered protective.
Effect of Lifestyle on Serum Cholesterol
Lifestyle and personal habits significantly influence serum cholesterol levels and play a major role in the development of coronary heart disease (CHD).
Factors that Increase Serum Cholesterol:
- High blood pressure
- Emotional stress
- Smoking
- Excess alcohol consumption
- Obesity, especially abdominal obesity
- Physical inactivity
- High intake of saturated fats and trans fats
- Excessive coffee consumption
- Use of soft water instead of hard water
In contrast, regular exercise, a balanced diet low in saturated fats, stress control, and quitting smoking can help reduce serum cholesterol and improve cardiovascular health.
Detailed Notes:
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