Atherosclerosis

Atherosclerosis: An Introduction

Written by Maryum FarooqIllustrated and built by Charlie James

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INTRODUCTION Atherosclerosis is a condition where the arteries become narrowed, reducing blood flow around the body. It's one of the most common condition that can affect anyone, so understanding the process of how it forms, and potential treatment strategies, is vital for clinical practice.But what's actually happening to these arteries? To explore this, lets compare a healthy artery with an atherosclerotic one.An artery has three layers, from inside to outside – the tunica intima, tunica media and tunica adventitia. The lumen should be smooth and wide, ensuring sufficient blood flow through the vessel and to the tissues it supplies. As per Poisueille's law - the wider the radius of the artery, the lower the resistance and the greater the flow.In comparison, atherosclerotic arteries have a build-up of fatty material in the wall of the artery, known as an atherosclerotic plaque. This narrows the radius, increases resistance, and reduces the flow. Downstream tissues receive less blood, fewer nutrients and can become diseased.

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Tunica Media The middle layer can be mixed but is either predominantly elastic tissue [as in the aorta] or smooth muscle [as in the coronary arteries of the heart]. Muscle cells and elastic fibres are embedded within a 'ground substance' which is rich in proteoglycans [sugars bound to proteins]. In arteries, this layer is surrounded by the external elastic lamina.

Tunica Intima The innermost layer consists of a single layer of endothelial cells with a framework of supportive connective tissue. In arteries, this layer is separated from the media by the internal elastic lamina, a thin layer of elastic tissue.

Tunica Adventitia The outermost layer is predominantly fibrous connective tissue [collagen, fibroblasts and a few elastic fibres]. This is also the layer where you can find the blood supply to the vessel itself - the vasa vasorum.

Atherosclerotic Plaque

STAGES OF ATHEROSCLEROSIS So how does these plaques form? Atherosclerosis is a complex process that involves different cells and materials, but there are five main steps.1. Endothelial dysfunction. Due to the endothelial dysfunction, the artery is more permeable to cells and lipids.2. Fatty streak. Lipids accumulate in the vessel wall and are engulfed by macrophages to form foam cells. This creates a 'fatty streak' that can be seen macroscopically.3. Fibrous plaque. Lymphocytes and smooth muscle cells also accumulate as part of the inflammatory process. At this stage, it's become a 'fibrous plaque' - a lipid-rich, necrotic core with a fibrous outer surface.4. Complex plaque. Over time, the plaque becomes more complex with lipid, cells, calcification and even haemorrhage. As it grows, flow through the vessel reduces further and may cause symptoms.5. Atherothrombosis. This plaque can also rupture, exposing the highly thrombogenic core to the blood. Platelets aggregate and the clotting cascade is initiated, resulting in thrombus formation. This significantly reduces the lumen of the artery and impairs blood flow.

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Endothelial dysfunction

Fatty streak

Fibrous plaque

Complex plaque

Atherothrombosis

RISK FACTORS There are certain conditions which increase the risk of developing atherosclerosis.- Dyslipidaemia (imbalance of lipids in the blood)- Family history - Cigarette smoking - Diabetes Mellitus - HypertensionDISEASES Atherosclerosis can develop in arteries throughout the body. Narrowing of an artery will lead to imparied blood supply and reduced blood flow to tissues/organs supplied by the vessel. This means organs are unable to perform their usual function, leading to disease.There are some important terms to know when describing atherosclerotic disease:Ischaemia - inadequate blood supply to a tissueNecrosis - death of cells in body tissue due to injuryInfarction - necrosis of tissue due to inadequate blood supplyHover over the buttons on the left to see the impact of atheroscleroris around the body.

Brain Transient ischaemic attack (TIA)/stroke

Heart Ischaemic heart disease (IHD)

Gut Mesenteric ischaemia

Kidneys Renal failure

Limbs Peripheral vascular disease

ISCHAEMIC HEART DISEASE Atherosclerosis can occur in any (or many!) of the coronary arteries. The resultant impaired blood supply (or “ischaemia”) can cause symptoms. This is known as chronic coronary syndrome.Angina is a term used to describe the typical chest pain that occurs due to myocardial ischaemia. It presents as a heavy/tight, central chest pain that can radiate to the jaw or arms. When the plaque is disrupted (with subsequent thrombus formation and significant obstruction of blood flow), this can result in tissue death (or “infarction”) of the heart muscle (myocardium). This is known as a myocardial infarction, also known as acute coronary syndrome.PHARMACOLOGICAL OPTIONSLipids plays an important role in the atherosclerotic process, particularly low-density lipoproteins (LDL). Raised lipid levels (hyperlipidaemia) are therefore a major risk factor.An important class of drugs in atherosclerosis management are statins. These act as HMG-CoA reductase inhibitors, blocking synthesis of cholesterol in the liver. They alsoincrease clearance of LDL from the bloodstream. Research has shown they reduce the risk of both development and progression of atherosclerotic disease.Statins are used in people with: atherosclerotic risk factors, hyperlipidaemia or established atherosclerotic disease.

Angina commonly presents as tight or heavy chest pain, that can radiate to the jaw and arm.It's triggered by exertion or stress, and normally stops within a few minutes of resting.