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Learning Outcomes

• Describe atherosclerosis.

• List the predisposing factors of atherosclerosis.

• Describe the pathogenesis of atherosclerosis.

• Define aneurysm.

• Describe the different types of aneurysm.

• Explain the causes of aneurysm.

• Describe the effects & complications of aneurysm.

Structure of Blood Vessels

Major Types

• Artery

• Vein

• Capillary

Layers of Blood Vessels

• Tunica adventitia

• Tunica media: Densely populated by smooth muscle cells.

• Tunica intima: Contains a thin layer of endothelial cells.

Components

• Endothelial Cell: Lining inside the blood vessel.

• Fibroblasts: Cells that contribute to the supportive framework of the blood vessel.

• Pericyte: Regulates blood flow and is involved in endothelial cell development.

Atheroma

• Definition: Atheroma is the accumulation of intracellular and extracellular lipid in the intima of large and medium-sized arteries.

Atherosclerosis

Definition

• Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries characterized by the formation of intimal plaques (atheromas) composed of lipids, inflammatory cells, smooth muscle cells, and connective tissue.

Initial Event in Atherosclerosis

Causes of Endothelial Injury

• Hypertension

• Hyperlipidemia

• Smoking

• Diabetes

Effects of Injury

• Leads to increased permeability and leukocyte adhesion.

Atherosclerotic Plaque Structure

Composition

• Fibrous Cap: Composed of smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, and neovascularization.

• Necrotic Center: Contains cell debris, cholesterol crystals, foam cells, and calcium.

Basic Structure

• Atherosclerosis is an intimal-based process with a complex interplay of cells and extracellular materials.

• Plaques can have secondary effects on the underlying media, including a reduction in smooth muscle cells.

Progression of Ateroma

Steps

1. Endothelial Injury
      - Starts with damage to the endothelium due to high blood pressure, smoking, diabetes, high LDL, toxins, or turbulent blood flow.

2. Lipoprotein Entry and Modification
      - LDL (low-density lipoprotein) particles enter the damaged endothelium and accumulate in the intima.
      - These LDL particles become oxidized, triggering inflammation.

3. Inflammatory Response
      - Oxidized LDL attracts monocytes (a type of white blood cell) into the intima.
      - Monocytes transform into macrophages and ingest oxidized LDL, turning into foam cells.
      - Foam cells form a fatty streak, the earliest visible lesion of atherosclerosis.

4. Smooth Muscle Cell Migration and Proliferation
      - Signals from foam cells and immune cells stimulate smooth muscle cells (SMCs) from the media to move into the intima.
      - These SMCs proliferate and start producing extracellular matrix (like collagen and proteoglycans), forming a fibrous cap over the fatty core.

5. Plaque Maturation and Complications
      - Over time, the plaque core enlarges due to continued lipid accumulation and foam cell death.
      - The fibrous cap can either remain stable or become thin and weak.
      - If the cap ruptures, it exposes the core to blood, triggering platelet activation and thrombus formation, leading to a blockage of the artery, resulting in a heart attack or stroke.

Stages of Atherosclerosis Progression

Healthy Condition

• Endothelial cells (ECs) that help regulate vascular homeostasis such as vasodilation and vasoconstriction, and proliferation and migration of smooth muscle cells (SMCs).

Initial Lesion / Endothelial Cell Dysfunction

• ECs are activated by various risk factors including disturbed flow (D-flow) and secrete cytokines and adhesion molecules.

Fatty Streak Formation / Monocyte Adhesion

• Monocyte recruitment occurs, and monocytes differentiate into macrophages.

Lesion Progression / Foam Cell Formation

• Macrophages and modified LDL form foam cells, which secrete pro-inflammatory markers.

Plaque Rupture

• Persistent local inflammation leads to the development of a fibrous cap, and a thinner fibrous cap may rupture, triggering coagulation and thrombosis.

Coronary Atherosclerosis Progression

• Stages:
     - Healthy: No symptoms.
     - Fatty streak: Early stage.
     - Preatheroma: Initial atheromatous lesions.
     - Atheroma: Established lesions with outward remodeling.
     - Fibroatheroma: Complicated lesions with a stable fibrous cap.
     - Complicated Lesion: Vulnerable plaque indicating higher risks for events such as cardiac mortality or rupture.

Complications of Atheroma

• Calcification

• Ulceration or Rupture

• Thrombosis

• Hemorrhage into plaque

• Aneurysm formation

Predisposing Factors of Atherosclerosis

Modifiable Factors

• Hyperlipidemia

• Hypertension

• Smoking

• Diabetes

• Obesity

• Physical inactivity

• Stress (‘Type A personality’)

• Postmenopausal estrogen deficiency

• Carbohydrate intake

• Alcohol consumption

Non-modifiable Factors

• Age

• Male gender

• Family history

• Genetic abnormalities

Histological (Microscopic) Features

Affects of Atherosclerosis on Arteries

• Mainly affects large and medium-sized arteries, including the aorta, coronary arteries, and carotids.

Early Lesion: Fatty Streak

• Characteristics:
     - Intimal thickening
     - Presence of foam cells (lipid-laden macrophages)
     - Minimal inflammation
     - Reversible at this stage

Intermediate Lesion: Fibrofatty Plaque

• Characteristics:
     - More advanced lesion with structural changes
     - Fibrous cap comprised of smooth muscle cells and dense collagen
     - Lipid core composed of cholesterol crystals, foam cells, and necrotic debris
     - Inflammatory cells such as macrophages and T cells are present
     - Disruption of internal elastic lamina

Advanced Lesion: Complicated Plaque

• Characteristics:
     - Can lead to clinical complications (thrombosis, infarction)
     - High risk of rupture
     - Features include a thin fibrous cap, large necrotic lipid core, calcification, ulceration of the plaque, formation of superimposed thrombus, and possible intraplaque hemorrhage.

Gross (Macroscopic) Features

Types of Lesions

Fatty Streaks

• Appearance: Yellow, flat, elongated streaks along the intima, commonly observed in children and adolescents.

• Note: Do not cause obstruction.

Atheromatous Plaques

• Appearance: Raised, yellowish-white plaques with a gritty texture due to calcium.

• Locations include the abdominal aorta, coronary arteries, and carotid arteries.

• May exhibit focal ulceration, hemorrhage, or superficial thrombus.

Complicated Lesions

• Appearance:
     - Ulcerated surface of plaque, superimposed red thrombus, calcification (chalky areas), and aneurysm formation in weakened vessel wall.

Complications of Atherosclerosis

• Thrombosis: Causes myocardial infarction due to clot formation and vessel occlusion leading to heart muscle death.

• Stroke: Results from embolism or ischemia.

• Peripheral Arterial Disease: Can cause limb ischemia, pain, or gangrene.

• Aneurysm: Increases the risk of rupture and fatal bleeding.

• Embolism: Can lead to blockage of distant vessels and progressive organ damage due to chronic ischemia.

Aneurysm

Definition

• An aneurysm is a localized, abnormal dilation or ballooning of a blood vessel wall, usually an artery, due to weakness in that wall.

Types of Aneurysm

True Aneurysm

• Involves all three layers of the arterial wall:
     - Intima
     - Media
     - Adventitia
     - Types:
        - Fusiform: Uniform, circumferential dilation (common in the abdominal aorta).
        - Saccular: Localized, pouch-like bulge on one side.

False Aneurysm

• Also known as Pseudoaneurysm: Occurs when there is a breach in the vessel wall, and blood is contained by the surrounding connective tissue.

• Does not involve all three layers of the wall and is often related to trauma or catheter insertion.

Common Sites for Aneurysm

• Abdominal Aorta (most common - Abdominal Aortic Aneurysm, AAA)

• Thoracic Aorta

• Cerebral Arteries (Berry aneurysm in Circle of Willis)

• Popliteal Artery

Causes and Risk Factors of Aneurysm

• Atherosclerosis: Particularly affects the abdominal aorta.

• Hypertension: Commonly affects thoracic aorta and cerebral arteries.

• Congenital Defects: Examples include Marfan syndrome and Ehlers-Danlos syndrome.

• Trauma

• Infection: Referred to as “mycotic aneurysm.”

• Smoking: Identified as a major risk factor.

Complications of Aneurysm

• Rupture: Can lead to massive hemorrhage and death.

• Thrombosis and Embolism: Clot formation within the aneurysm may dislodge.

• Compression of Adjacent Structures: Can affect nerves, ureters, or veins, leading to ischemia.

• Dissection: Separation of the layers of the arterial wall.

Gross and Histological Appearance

Gross Features

• Bulging or ballooning of the artery wall, especially in the abdominal aorta, which often shows atherosclerotic plaques, mural thrombus, and calcifications.

Histological Features

Microscopy Observations

• Fragmentation of elastic fibers and degeneration of smooth muscle cells.

• Inflammatory infiltrate may be observed in some cases.

• H&E staining reveals cystic medial necrosis with significant loss of elastic lamella and smooth muscle cells, with intralamellar mucoid extracellular matrix accumulation noted.

• In case of abdominal aortic aneurysm after rupture, visible tears along the tunica media and significant fibrin deposition can be appreciated, along with decreased density of smooth muscle cells in the tunica media.

Thank You

• Closing note of appreciation for attention and engagement with the material provided.