Page 257 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

An increase in blood lipids can affect choles- (→ A1). This increases the fresh synthesis of
terol, triglycerides or both (hypercholesterol- bile salts from cholesterol in the liver and
emia, hypertriglyceridemia or combined hy- thus reduces the intracellular cholesterol con-
perlipidemia). Hyperlipoproteinemia is cur- centration. In heterozygotes this increases the
rently the all-inclusive term. LDL receptor density (→ A5). However, it also
With most patients who have hypercholes- stimulates cholesterol synthesis, but this in
terolemia (> 200–220 mg/dL serum) there is turn can be prevented by administering inhibi-
an increased familial prevalence of the condi- tors of 3-HMG-CoA reductase (e.g., lovastatin)
tion, but the cause remains unknown (poly- (→ A5). The treatment of homozygotes in-
genic hypercholesterolemia). However, over- cludes the removal of LDL from plasma by
weight and diet play an important role. LDL- plasmapheresis.
cholesterol can be lowered most importantly In another single-gene defect, combined hy-
by a preference in the diet for vegetable (un- perlipidemia (hyperlipoproteinemia type IIb), Metabolism
saturated) fats. Animal (saturated) fats, on the the TGs as well as cholesterol are slightly
other hand, raise cholesterol synthesis in the raised. The cause is possibly an overproduction
liver and in consequence lower its LDL recep- of ApoB, so that an increased synthesis of VLDL
tor density (→ A7) so that the concentration occurs (→ A4) and therefore more LDL is also Lipoprotein
of cholesterol-rich LDL in serum is raised formed. Familial dys-β-lipoproteinemia predis-
(LDL-cholesterol > 135 mg/dL). As a result, poses to hyperlipoproteinemia type III. In this
there is an increased binding of LDL to the condition, instead of the normal ApoE 3 , an
scavenger receptor that mediates the incor- ApoE 2 variant is expressed that is not recog-
poration of cholesterol in macrophages, skin, nized by the E receptor. As a result, the hepatic
and vessel walls (→ A8). Hypercholesterol- uptake of chylomicron remnants and of IDL is
emia is thus a risk factor for atherosclerosis disturbed (→ A9,13), so that their plasma con-
(→ p. 236ff.) and coronary heart disease (→ centration rises (high risk of atherosclerosis;
p. 218). → p. 236ff.).
In familial hypercholesterolemia (hyperli- Primary hypertriglyceridemia is due to in-
poproteinemia type IIa; incidence of homozy- creased TG synthesis in the liver (→ A11) or
gotes is 1:10 ; of heterozygotes 1:500) the (rarely) to abnormalities in the breakdown of
6
plasma cholesterol is markedly raised from chylomicrons and VLDL (hyperlipoproteinemia
birth (twice as high in heterozygotes; six times type I), the result of a deficiency of LPL or
as high in homozygotes) so that myocardial in- ApoCII (→ A2,3). They predispose a person to,
farction may occur even in children. The pri- for example, pancreatitis (→ p.158ff.); in addi-
mary causes are defects in the gene for the tion HDLs are reduced and thus the athero-
high-affinity LDL receptor which prevents the sclerosis risk is increased (reduced removal of
cellular uptake of LDL (→ A7,14). The defect cholesterol from the vessel wall?).
can cause: 1) diminished transcription of the Gene defects can also result in subnormal
receptor; 2) receptor proteins remaining in LP concentrations (hypolipoproteinemia). Fa-
the endoplasmic reticulum; 3) a reduced in- milial hypo-α-lipoproteinemia (Tangier dis-
corporation of the receptor into the cell mem- ease) is due to a defect of ApoA and there is a
brane; 4) reduced LDL binding; or 5) abnormal HDL deficiency (→ A10), increasing the ath-
endocytosis. Serum cholesterol rises as a re- erosclerosis risk. In A-β-lipoproteinemia there
sult, firstly, of a reduction in the cellular up- are no LDLs in plasma (hypocholesterolemia).
take of cholesterol-rich LDL and, secondly, of This is caused by an abnormal synthesis of
extrahepatic tissues synthesizing more choles- ApoB, so that chylomicrons cannot be exported
terol, because the reduced LDL uptake in these from the gut mucosa, nor can VLDL from the
tissues fails to inhibit the action of 3-HMG- liver. This produces accumulation of TG in
CoA reductase (→ A5). Treatment consists, in both organs.
addition to an appropriate diet (see above), of
administering ionic exchange resins (choles-
tyramine) that bind bile salts in the gut and 247
thus prevent their enterohepatic recirculation
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Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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