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Hyperlipoproteinemia


Overview :

It is commonly known that oil and water do not mix unless another substance like a detergent is added. Yet the body needs to transport both lipids (fats) and water-based blood within a single circulatory system. There must be a way to mix the two, so that essential fatty nutrients can be transported in the blood and so that fatty waste products can be carried away from tissues. The solution is to combine the lipids with protein to form water-soluble packages that can be transported in the blood.

These packages of fats are called lipoproteins. They are a complex mixture of triglycerides, cholesterol, phospholipids and special proteins. Some of these chemicals are fatty nutrients absorbed from the intestines on their way to being made part of the body. Cholesterol is a waste product on its way out of the body through the liver, the bile, and ultimately the bowel for excretion. The proteins and phospholipids make the packages water-soluble.

There are five different sizes of these chemical packages. Each package needs all four chemicals in it to hold everything in solution. They differ in how much of each they contain. If blood serum is spun very rapidly in an ultracentrifuge, these five packages will layer out according to their density. They have, therefore, been named according to their densities—high-density lipoproteins (HDL), low-density lipoproteins (LDL), intermediate-density lipoproteins (IDL), very low density lipoproteins (VLDL), and chylomicrons. Only the HDLs and the LDLs will be discussed in the rest of this article.

If there is not enough detergent in the laundry, the oily stains will remain in the clothes. In the same way, if the balance of chemicals in these packages is not right, cholesterol will stay in tissues rather than being excreted from the body. What is even worse, if the chemical composition of these packages changes, the cholesterol can fall out of the blood and stay where it lands. On the other hand, a different change in the balance can remove cholesterol from tissues where there is too much. This appears to be exactly what is going on in atherosclerosis. The lesions contain lots of cholesterol.

The LDLs are overloaded with cholesterol. A minor change in the other chemicals in this package will leave cholesterol behind. The HDLs have a third to a half as much cholesterol. They seem to be able to pick up cholesterol left behind by the LDLs. It seems that atherosclerosis begins with tiny tears at stressed places in the walls of the arteries. Low density lipoproteins from the blood enter these tears, where their chemistry changes enough to leave cholesterol behind. The cholesterol causes irritation; the body responds with inflammation; damage and scarring follow. Eventually the artery gets so diseased blood cannot flow through it. Strokes and heart attacks are the result.

But if there are lots of HDLs in the blood, the cholesterol is rapidly picked up and not allowed to cause problems. Women before menopause have estrogen (the female hormone), which encourages the formation of HDLs. This is the reason they have so little vascular disease, and why they rapidly catch up to men after menopause, when estrogen levels fall. Replacement of estrogen after menopause has been prescribed to for protection through the later years. However, in 2003, the Women's Health Initiative, a large clinical trial involving postmenopausal women, was halted in July 2002 because of the many detrimental effects of combined estrogen and progesterone therapy (called hormone replacement therapy). Among the effects was increased risk of heart disease, sometimes within the first year of use.

Cholesterol is the root of the problem, but like any other root it cannot just be eliminated. Ninety percent of the cholesterol in the body is created there as a waste product of necessary processes. The solution lies in getting it out to the body without clogging the arteries.

Of course the story is much more complex. The body has dozens of chemical processes that make up, break down, and reconfigure all these chemicals. It is these processes that are the targets of intervention in the effort to cure vascular disease.

Diseases

Near the dawn of concern over cholesterol and vascular disease a family of hereditary diseases was identified, all of which produced abnormal quantities of blood fats. These diseases were called dyslipoproteinemias and came in both too many and too little varieties. The hyperlipoproteinemias found their way into five categories, depending on which chemical was in excess.

  • Type 1 has a pure elevation of triglycerides in the chylomicron fraction. These people sometimes get pancreatitis and abdominal pains, but they do not seem to have an increase in vascular disease.
  • Type 2 appears in two distinct genetic patterns and a third category, which is by far the most important kind, because everyone is at risk for it. All Type 2s have elevated cholesterol. Some have elevated triglycerides also. The familial (genetic) versions of Type 2 often develop xanthomas, which are yellow fatty deposits under the skin of the knuckles, elbows, buttocks or heels. They also may have xanthelasmas, smaller yellow patches on the eyelids.
  • Type 3 appears in one in 10,000 people and elevates both triglycerides and cholesterol with consequent vascular disease. In 2003, researchers discovered the molecular mechanism that contributes to high triglycerides in those with this type of hyperlipopoproteinemia.
  • Type 4 elevates only triglycerides and does not increase the risk of vascular disease.
  • Type 5 is similar to Type 1.
  • Dyslipidemia refers to a normal amount of cholesterol that is mostly in LDLs, where it causes problems.

All but Type 2 are rare and of interest primarily because they give insight into the chemistry of blood fats.

In addition to the above genetic causes of blood fat disorders, a number of acquired conditions can raise lipoprotein levels.

  • Diabetes mellitus, because it alters the way the body handles its energy needs, and also affects the way it handles fats. The result is elevated triglycerides and reduced HDL cholesterol. This effect is amplified by obesity.
  • Hypothyroidism is a common cause of lipid abnormalities. The thyroid hormone affects the rate of many chemical processes in the body, including the clearing of fats from the blood. The consequence usually is an elevation of cholesterol.
  • Kidney disease affects the blood's proteins and consequently the composition of the fat packages. It usually raises the LDLs.
  • Liver disease, depending on its stage and severity, can raise or lower any of the blood fats.
  • Alcohol raises triglycerides. In moderate amounts (if they are very moderate) it raises HDLs and can be beneficial.
  • Cigarette smoking lowers HDL cholesterol, as does malnutrition and obesity.

Certain medications elevate blood fat levels. Because some of these medications are used to treat heart disease, it has been necessary to reevaluate their usefulness:

  • Thiazides, water pills used to treat high blood pressure, can raise both cholesterol and triglycerides.
  • Beta-blockers, another class of medication used to treat high blood pressure, cortisone-like drugs, and estrogen can raise triglycerides.
  • Progesterone, the pregnancy hormone, raises cholesterol.

Not all of these effects are necessarily bad, nor are they necessarily even significant. For instance, estrogen is clearly beneficial. Each effect must be considered in the overall goal of treatment.




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