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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
sustains the protection through the later years.
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 much 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 may also 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.
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, 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 is
usually 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. |
