Lipids

Topics
42. Disturbances of lipid metabolism
43. Atherosclerosis
42. Disturbances of lipid metabolism
• FA p90.
• Causes accelerated atherosclerosis  CAD!
• Primary hyperlipidemias + secondary (Cushing’s syndrome,
hypothyroidism, nephrotic syndrome, or cholestasis. High LDL).
• Mixed hyperlipidemias: due to DM2, alcohol, chronic kidney failure.
- Both high LDL and high triglycerides.
Cont.
• Common hypercholesterolemia.

• Familial dyslipidemias.
1. Hyperchylomicronemia (LPL or ApoC-II deficiency).
2. Familial hypercholesterolemia (defective LDL receptors in liver).
(2a = LDL + cholesterol increased. 2b = VLDL + LDL + cholesterol increased).
3. Dysbetalipoproteinemia (defective ApoE). High IDL.
4. Hypertriglyceridemia (overproduction of VLDL in liver  too much VLDL and TG).

• Abetalipoproteinemia.
- Deficiency of ApoB100, B48. Absent chylomicrons/VLDL/LDL.
- FA p89.
Cont.
• Patients can get xanthelasma (yellow plaques on eyelids), xanthomas
(yellow masses found on achilles tendons), or corneal arcus.
• Acute pancreatitis can occur with hypertriglyceridemia.
• Order lipid panel: total cholesterol, HDL, LDL, TG.
• Also check for secondary causes: TSH (hypothyroidism), LFT
(cirrhosis), BUN/Cr/urinary proteins (nephrotic syndrome), glucose
(DM).
• Treat with statins, cholestyramine, ezetimibe, niacin, gemfibrozil (to
lower TG).
 Normal cholesterol values:

Cont. (Lipoproteins)
a) Infant: 1.2-4.7 mmol/L.
b) Child: 2.8-6.0 mmol/L.
c) Adult: < 5.0 mmol/L.

Normal LDL levels: < 3.0 mmol/L.

Normal fasting TG levels: < 2.1 mmol/L.

Disease Cause Treatment Comments

Common primary
hyperlipidemia
Familial hypercholesterolemia
Polygenic hypercholesterolemia
? Statins. • 70% of hyperlipidemias.
• High LDL only.
Absent LDL-receptors Statins (after 8 years of • AD.
age). • Heterozygotes (1:500) have cholesterol = 7-10 mmol/L.
• Manifested in 30s.
• Accelerated atherosclerosis (may have MI before age 20).
• Tendon (Achilles) xanthomas, xanthelasma, and corneal arcus.
Multifactorial (polygenic) Statins. Higher risk of MI.

LPL deficiency No LPL enzyme Fibrates. • Causes hyperchylomicronemia and elevated TG.
• High TG  Pancreatitis!
• Hepatosplenomegaly.
• Pruritic xanthomas.

Familial combined Dunno Statins (can add fibrates if • AD.

severe). • Most common overall (1:50).
hyperlipidemia • Elevated cholesterol + TG.

Familial dysbetalipoproteinemia Defective ApoE (mediates remnant Fibrates. • Elevated cholesterol + TG.
uptake) • Accelerated atherosclerosis.
43. Atherosclerosis
• Build up of cholesterol plaques in the arteries’ intima.
• Most commonly abdominal aorta (aneurysm), coronary artery (CAD),
popliteal artery (peripheral vascular disease), internal carotid artery (stroke).
• Symptoms: depends on the complication.
• Risk factors:
- Modifiable: smoking, HTN, LDL, DM2.
- Non-modifiable: age, gender (more in men), family history.
• Damage to endothelium of intima  lipids get into intima  lipids get
oxidized and consumed by macrophages  inflammation and healing (ECM
deposition).