AssessmentsAtherosclerosis and arteriosclerosis: Pathology review
USMLE® Step 1 style questions USMLE
A 75-year-old man is brought to the emergency department due to sudden-onset confusion and headaches accompanied by nausea and vomiting. The patient has a history of poorly controlled hypertension and hyperlipidemia due to noncompliance with medications. The patient has smoked a pack of cigarettes daily for 40 years. The patient’s temperature is 37.0°C (98.6°F), pulse is 100/min, and blood pressure is 205/140 mmHg. On physical examination, the patient is dyspneic. Fundoscopic examination reveals bilateral papilledema. Laboratory results are obtained and shown below:
|Blood urea nitrogen||50 mg/dL|
Content Reviewers:Yifan Xiao, MD
Mikhail is a 60 year old man with a history of hypertension, diabetes and dyslipidemia who presents to your clinic complaining of sudden-onset retrosternal chest pain associated with shortness of breath. He has a 35-pack-a-year smoking history, and he mentions that he also develops lower limb pain when walking for more than 15 minutes. His father underwent a below the knee amputation of his right lower extremity and died from a stroke. On physical examination, his BMI is 32. On further workup, his ECG and high troponin levels suggest a myocardial infarction. Mikhail goes to the cath lab to undergo per-cutaneous coronary intervention, which showed a clot occluding the left anterior descending coronary artery. After the procedure, his chest pain resolved. However, he started developing a web-like skin rash.
Mikhail suffers from arteriosclerosis, which is a hardening and thickening of the arterial wall, causing it to lose its elasticity. A specific type of arteriosclerosis is atherosclerosis, which is a chronic inflammatory disorder that affects the endothelium of medium and large arteries, and is characterized by the buildup of cholesterol plaques within the arterial lumen. In a descending order, the most common arteries affected by atherosclerosis are the abdominal aorta, coronary artery, popliteal artery and then the carotid artery.
Risk factors for atherosclerosis can be divided into modifiable and nonmodifiable risk factors. Modifiable risk factors include hypertension, diabetes mellitus, smoking and dyslipidemia, particularly an increase in LDL levels or a decrease in HDL levels. Non-modifiable risk factors include age, family history, and being of African-American descent.
The pathogenesis of atherosclerosis is essentially an inflammatory response to endothelial cell injury. The endothelium is injured by stress against the arterial wall, like in hypertension. This is especially more prominent at arterial bifurcations, such as the carotid artery bifurcation. Other causes of endothelial injury include tobacco smoking and homocysteinemia, which is elevated levels of the amino acid, homocysteine.
Regardless of the cause, when the endothelium is injured, LDL particles are allowed to leak into the intimal layer, where it gets oxidized. When LDL is oxidized, it becomes a pro-inflammatory antigen that induces an immune response in which inflammatory cells like macrophages come to fight this antigen. These macrophages will enter the arterial walls and eat up the oxidized LDL particles, creating what’s known as foam cells. Accumulation of foam cells underneath the endothelium creates the first marker of atherosclerosis, a fatty streak. Fatty streaks might as well be called “flatty” streaks, because they are not raised, meaning they don’t obstruct the lumen so they don’t produce clinical symptoms like angina. Damage to the endothelium calls upon platelets to join the party. Platelet and endothelial cells release factors like platelet derived growth factor, or PDGF and fibroblast growth factor, or FGF, and transforming growth factor beta, or TGF-beta. These factors stimulate smooth muscle cell proliferation and migration from the tunica media to the tunica intima. Smooth muscle cells then proliferate and stimulate the production of extracellular matrix. This results in the formation of a fibrous cap overlying a lipid core in the center, and this structure is called a plaque. The lipid core is made of cholesterol crystals that under the microscope look like white slit-like spaces. The fibrous cap is what separates the lipid core from the blood vessel lumen. Unlike the fatty streak, an ath-erosclerotic plaque could obstruct the lumen and produce symptoms. Keep in mind that although fatty streaks can form as early as adolescence, they don’t always develop into plaques. Now over time, foam cells within the lipid core undergo necrosis, and release matrix metallo-proteinases, or MMPs. These enzymes begin chewing away at the fibrous cap, making it thinner and thinner, until one day, it ruptures. When this happens, the atheroma is now exposed to the blood vessel lumen. Platelets react as they should, by forming a fibrin clot at the site of rupture. Unfortunately, these clots can occlude the lumen of the artery even more, or they may detach and move to obstruct other blood vessels like the arteries in the brain.
Okay, complications of atherosclerosis include ischemia to the supplied organs. Typically, at least 70% of the lumen must be occluded prior to the onset of the symptoms. Ischemia may manifest as angina if the coronary arteries are involved, claudication in peripheral vascular disease, or chronic mesenteric ischemia if the mesenteric arteries are involved. When the plaque ruptures, clot formation may potentially result in acute infarction of the supplied organ, such as myocardial infarction, ischemic stroke, acute limb ischemia or acute mesenteric ischemia.
Additionally, an atheroma may weaken the vessel wall, causing an aneurysm, especially at areas where the arterial wall is weaker. For example, these can occur in the abdominal aorta below the level of L2 since it lacks the vasa vasorum, which are small blood vessels in the tunica adventitia supplying the aortic wall. Without this vasa vasorum, the tunica media doesn’t get enough nutrients, causing it to weaken, which increases the risk of developing an abdominal aortic aneurysm that could rupture and cause hemorrhaging.
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