An | =


R ■ T ■ ACprot

Na+ balance positive t

Lymphatic drainage r -v ^ /

t Edema , A Compression of lymphatic vessels

Na+ retention


Renin-Angiotensin Blood volume


(radiotherapy) Lymph

Obstruction (bilharziasis)



Atherosclerosis (Ath.; arteriosclerosis) is the cause of more than half of all deaths in the western industrialized nations. It is a slowly progressing arterial disease in which the intima (^ A1) are thickened by fibrous deposits thatgradually narrow the lumen and gradually become the site of bleeding and thrombus formation (^ B).

Fatty streaks are the earliest visible sign of Ath. (as early as childhood). They are subendo-thelial accumulations of large, lipid-contain-c ing cells (foam cells; ^A2). Later, fibrous ■ji plaques or atheroma form (^ A3), which are ula the cause of the clinical manifestation of Ath. ^ These plaques consist of an accumulation of U monocytes, macrophages, foam cells, T lym-"c phocytes, connective tissue, tissue debris, and ™ cholesterol crystals. Plaques are often infected ¡5 with the bacterium Chlamydia pneumoniae. X The most common site of plaques are the abdominal aorta, coronary arteries, popliteal arteries, and the cerebral circulus arteriosus (in order of frequency).

Of the important risk factors of Ath. (^ C1), five can be influenced, namely hyperlipidemia, hypertension, smoking, diabetes mellitus, and hyperhomocysteinemia. It is not clear whether chlamydia infection plays an important part in the pathogenesis of Ath., or whether it perhaps even triggers its development. Risk factors that cannot be influenced are age, male sex, and a genetic predisposition (^ p. 246 ff.). Subordinate factors are overweight and a sedentary or stressful lifestyle.

♦ Hyperlipidemia. Serum cholesterol levels higher than 265 mg/dL (6.85 mmol/L) in those aged 35-40 years increase the risk of coronary heart disease fivefold compared to values of < 220 mg/dL (5.7 mmol/L). 70% of this cholesterol is transported in low-density lipoproteins (LDLs) and the development of Ath. correlates closely with increased LDL levels. A defect in LDL receptors leads to very early Ath. (^ p. 246 ff.). A special risk factor seems to be lipo-protein(a) (= LDL that contains apolipoprotein Apo(a)). Apo(a) resembles plasminogen and binds to fibrin so that Apo(a) may have an an-tifibrinolytic and thus thrombogenic effect.

236 (On the role of triglyceride and high-density lipoproteins [HDL], ^p. 246ff.).

♦ Smoking increases the risk of dying from the effects of coronary heart disease 1.4 to 2.4fold (even light smoking), and in heavy smokers up to 3.5fold. Smoking low tar and low nicotine cigarettes does not lower this risk, but it is significantly lowered if smoking is stopped altogether. It is not clear how smoking promotes Ath. Possible causes are sympathetic nervous system stimulation by nicotine, displacement of O2 in the Hb molecule by carbon monoxide, increased platelet adhesiveness, and raised endothelial permeability, induced by constituents in smoke.

♦ Hyperhomocysteinemia (>14 |g/L plasma, e.g., due to a lack ofmethylenetetrahydrofolate reductase [MTFR]), increases the risk of Ath., a rise of 5 | mol/L corresponding to the risk of a 20 mg/dL increase in cholesterol concentration. Homocystein (HoCys) favors plaque formation, probably in several ways (see below). In the commonly occurring thermolabile gene polymorphism of MTFR, folate deficiency develops (^p. 34). If the latter is removed, the HoCys level becomes normal.

The pathogenesis of Ath. remains unexplained, but endothelial damage (and chlamydia infection?, see above) could be the primary event and the reaction to it may eventually lead to plaque formation (response to injury hypothesis; ^ C). Plaques usually develop at sites of high mechanical stress (vessel bifurcation); in this way also hypertension becomes a risk factor. Among the reactions are an increased lipid uptake in the vessel wall as well as adhesion of monocytes and thrombocytes (^C2,3), helped by HoCys. The monocytes penetrate into the intima and are transformed into macrophages (^ C4). These liberate reactive O2 radicals, especially the superoxide anion -O2- (also helped by HoCys), which have a general damaging effect on endothelial cells and inactivate endothelium-formed NO on its way to the endothelium and the vascular musculature: -NO + -O2- ^ •ONOO- (^C5). This results in the loss of NO action, namely inhibition of platelet and monocyte adhesion to the endothelium as well as antiproliferative and vasodilating effects on the vascular musculature. The latter favor spasms (^ B and C7). Even in the early stages of Ath., O2 radicals

|— A. Vascular Wall Changes on Atherosclerosis


Necrotic nucleus

Intima Media



Endothelial damage and dysfunction

Fibrous cover plate cholesterol crystals) (connective tissue, immigrant muscle cells)

0 0

Post a comment