Atheroma Student Notes PDF

Atherosclerosis Soe [email protected] Case 1 Atherosclerosis Learning Outcomes • Describe the mechanisms involved in the development of atheroma (SBA) • Describe the macroscopic and microscopic appearances (SBA) Normal Artery Cross-Section Collagen smooth muscle cells endothelial...

Atherosclerosis Soe [email protected] Case 1 Atherosclerosis Learning Outcomes • Describe the mechanisms involved in the development of atheroma (SBA) • Describe the macroscopic and microscopic appearances (SBA) Normal Artery Cross-Section Collagen smooth muscle cells endothelial cells Step One: Chronic Endothelial Damage response-to-injury hypothesis : chronic inflammatory response of the arterial wall to endothelial injury. Circulating blood in lumen LDL Endothelial Injury Inflammatory response Endothelium Tunica Intima 1. Endothelium damage- initiates chronic inflammatory response 2. Endothelium becomes leaky (increase permeability) 3. LDL move into Tunica Intima and become oxidized LDL which cause more injury to ECs and smooth muscle cells Step Two: Monocyte migration Monocyte Macrophage 1. Distress signals attract Monocytes (White Blood Cells) 2. Monocytes move through leaky endothelium. 3. Within Tunica Intima Monocytes transform to Macrophages Step Three: Formation of Foam cells and SMC recruitment Foam cell Macrophage Tunica Media SMC in tunica media 1. Macrophage engulfs cholesterol to form foam cells (Monocytes àMacrophage àFoam cells) 2. Macrophage and ECs release factors à recruit smooth muscle cell from the underlying tunica media or from the circulating precursors. Step Four: Formation of Fatty Streaks Lymphocyte Fatty streak Foam cell (macrophage) Foam cell accumulation Foam cell (smooth muscle cell) 1. Macrophages and smooth muscle cells engulf lipid: They are being known as Foam cells. • Foam cells = macrophages or SMC that ingested lipids (intracellular accumulation) In this stage a fatty streak, the earliest lesion of the artheroma, is seen in the lumen of the affected vessels 2. Lymphocytes migrate into the intima as a part of chronic inflammatory response Step Five : Formation of a mature atheroma Foam cell degeneration Fibrous cap (collagen and smooth muscle cell) Lipid core Lipid core collagen • Foam cells die à releasing liquid content into the intima à increases the size of the plaque • Increase in SMCs proliferation à increases synthesis of collagen à hardening of the blood vessel. • a fatty streak transformed into a mature atheroma. Consequences of atheroma Plaque rupture Thrombus Lipid core exposed Increase in plaque size à plaque rupture à àThrombus formed à àobstruction of the blood flow Progression of atherosclerosis LO:Describe the macroscopic and microscopic appearances 1. Fatty streaks Macroscopic (Gross) • Small yellow flat spots, can coalesce into elongated streaks • do not cause any significant flow disturbance. Foam cells Intima Microscopic • lipid-filled foamy macrophages in intimal layer Media LO:Describe the macroscopic and microscopic appearances 2. Atherom Atherosclerosis a Earliest lesions Advanced lesions Fatty streak Stable Plaque Unstable Plaque LO:Describe the macroscopic and microscopic appearances 2. Atheroma (advanced lesions) Macroscopic features • white to yellow raised lesion • Patchy • involve only a portion of arterial wall (eccentric) LO:Describe the macroscopic and microscopic appearances Atheroma (advanced lesions) : Microscopic features Lumen F 1. F L stable plaques • thickened fibrous caps with minimal lipid core • Lesser risk of rupture • Can progress to unstable plaque 2. Vulnerable/unstable plaques • thin fibrous caps and large lipid cores • prone to rupture LO:Describe the macroscopic and microscopic appearances Complications Complications Weakened wall: wall weakenà localized swelling of the wall of an artery (aneurysm) (tutorial by Dr Anjana) Increase in lipid accumulation à Luminal narrowing (stenosis) à reduce blood flow à decrease in blood supply (ischaemia) plaque rupture à formation of a blood clot (thrombosis) Big Thrombusà luminal obstruction à Infarction a piece of thrombus carried by the blood to somewhere and block there (embolism)