ATHEROSCLEROSIS [ Symptoms / Risk Factors / Pathogenesis / Complication ] 


     Arteriosclerosis is the thickening, hardening, and loss of elasticity of the walls of arteries. This process gradually restricts the blood flow to one's organs and tissues and can lead to severe organ damage. Atherosclerosis, which is a specific form of arteriosclerosis, is caused by the build up of fatty acid-cholesterol plaques in the artery walls.


Definition

     Atherosclerosis develops primarily in large elastic arteries, e.g. aorta and carotid artery, or large or medium-sized muscular arteries such as coronary, cerebral, renal and popliteal arteries. Atherosclerosis can lead to serious complications such as coronary artery disease, cerebral stroke, peripheral arterial disease (gangrene of feet or legs).


Risk factors;

         *Elevated blood cholesterol and triglyceride levels 

         *High blood pressure                                   *obesity

         *Smoking                                                     *Physical inactivity

         *Diabetes mellitus 

Symptoms

     Atherosclerosis develops gradually, Mild atherosclerosis usually does not have any symptoms. Symptoms develop only when narrowing of the artery is so severe that adequate amount of blood does not reach the tissues or organs. At that time symptoms depend on the artery affected.

     *Coronary artery; Symptoms of angina or myocardial infarction.

     *Cerebral artery; Symptoms of cerebral stroke.

     *Renal artery; Development of hypertension or symptoms of renal failure.

     *Popliteal artery; Pain in the legs while walking (claudication)


Pathogenesis of Atherosclerosis 

       Aetiological factors named above induce hypercholesterolemia, which disturbs vascular homeostasis, including a decrease in nitrous oxide bioactivity, an increase in superoxide production, an increase in adhesion molecules and attenuation of endothelium-dependent vasodilatation.

      The earliest pathologic lesion of atherosclerosis is the fatty streak. The fatty streak is the result of focal accumulation of serum lipoproteins within the intima of the vessel wall. Gradually, the fatty streak progress to form a fibrous plaque.


      Circulating monocytes infiltrate the intima of the vessels wall. The combination of diabetes and hypertension appears to have an additive effect on monocyte adhesion. These tissues macrophages act as scavenger calls, taking up LDL cholesterol and forming the characteristic foam cell of early atherosclerosis. These activated macrophages produce numerous factors that are injurious to the endothelium. Atherosclerotic plague is the result of progressive lipid accumulation along with migration and proliferation of smooth muscle. Growth of the fibrous plaque results in progressive luminal narrowing.

      Microscopy reveals lipids-laden macrophages, T-lymphocytes and smooth muscle cells in varying properties. Atheromatous plaques converts the smooth lining of  tunica intima of the blood vessels to roughened surface prone to thrombosis. moreover, developing atherosclerotic plaques are prone to necrosis cap may result in exposure of the thrombogenic contents of the core of the plaque to the circulating blood. This exposure constituents an advanced or complicated lesion. A plaque rupture may result in thrombus formation leading to partial or complete occlusion of the blood vessels.


COMPLICATIONS OF ATHEROSCLEROSIS   

 THROMBOSIS

      Rupture of plaque is followed by thrombus formation (intravascular clotting). The rough endothelial lining of a blood vessel attracts platelet adhesion and activation. The thrombus results in critical narrowing of arterial lumen and ischemia(deficient blood supply) in the tissues supplied by the artery. The clinical response to ischemia caused by obstructive atherosclerosis is dependent on the artery involved:

      Artery involved ,                      Disease produced,

             1.coronary artery                    1.myocardial ischemia

             2.carotid artery                       2.cerebal stroke 

             3.renal artery                          3.renal failure

             4.popliteal artery                    4.gangrene of lower limbs