Pathology of Atherosclerosis and Hypertension

Arteries Classification

• Arteries are categorized by size and structure
• Large arteries (elastic arteries): Examples include the aorta and its branches.
• Medium-sized arteries (muscular arteries): Examples are coronary and renal arteries.
• Small arteries (less than 2mm in diameter) and Arterioles (20 to 100 microns).

Structure of a Normal Artery

• Endothelium: The inner lining.
• Internal elastic lamina: A layer of elastic tissue beneath the endothelium.
• Media: The middle layer, composed primarily of smooth muscle cells and elastic fibers.
• External elastic lamina: An elastic tissue layer found below the media.
• Adventia: The outermost layer, composed mainly of connective tissue.

Arteries vs. Veins vs. Capillaries

• Artery: Thick walls, carry blood away from the heart.
• Vein: Thin walls, carry blood towards the heart.
• Capillary: Single layer of endothelial cells, site of exchange between blood and tissues.

Vascular Anomalies

• Berry aneurysm: A congenital defect in the media of vessels of the Circle of Willis.
• Arteriovenous fistula: An abnormal connection between an artery and a vein, often causing a visible mass.

Arteriosclerosis

• Thickening and loss of elasticity of arterial walls.
• Includes three forms:
  • Atherosclerosis: The most frequent and important type.
  • Monckeberg medial calcific sclerosis: Calcific deposits in muscular arteries of people over 50.
  • Arteriolosclerosis: A disease of small arteries and arterioles, seen commonly in elderly people with hypertension and diabetes mellitus.

Atherosclerosis (ATH)

• Characterized by intimal lesions (atheromas or atheromatous plaques).
• These lesions protrude into the lumen, possibly obstructing blood flow.
• A high contributor (over 50%) to deaths resulting from ischemic heart disease or cerebrovascular accidents.
• Response to injury hypothesis is the most widely accepted theory regarding the development of ATH.
• Chronic endothelial injury is often the trigger for ATH.

Risk Factors of Atherosclerosis

• Unmodifiable risk factors:
  • Age.
  • Male gender. (Women are generally protected by estrogen).
  • Familial Predisposition (likely polygenic).
  • Genetic factors, including lipoprotein abnormalities (like familial hypercholesterolemia).
• Modifiable risk factors:
  • Hyperlipidemia.
  • Hypertension.
  • Smoking.
  • Diabetes mellitus.
• Lesser risk factors: (non-quantifiable but still important)
  • Obesity.
  • Physical inactivity.
  • Stressful lifestyle.
  • High carbohydrate intake.
  • Post-menopausal estrogen deficiency.
  • Unsaturated fat intake.
  • Chlamydia pneumoniae infection.

Clinical Significance of Atherosclerosis

• Small arteries: Atheroma occlusion can lead to ischemia due to thrombosis.
• Large and medium-sized arteries: Atheromatous plaques can weaken vessel walls and contribute to aneurysm formation.

Morphology of Atherosclerosis

• Fatty streaks: Intimal thickening and lipid accumulation from foam cells, but do not significantly obstruct blood flow.
• Atheromatous Plaques: Raised lesions composed of a fibrous cap and lipid core, significantly impacting blood flow.
• Advanced atheromatous lesions: Progress to become diffusely involved in arterial wall.
• Different degrees of atherosclerosis can exist in the aorta.

Complications of Atherosclerosis

• Focal rupture, ulceration, erosion, and superadded thrombosis.
• Hemorrhage into the plaques, sometimes forming a hematoma, often observed in coronary arteries
• Atheroembolism: Plaque rupture releases debris into the bloodstream, resulting in microemboli composed of plaque contents.
• Aneurysmal dilatation: Atherosclerosis-induced aortic aneurysm.

Aneurysms

• A localized abnormal dilatation of a blood vessel (or heart).
• Types:
  • True aneurysm (involves all three layers).
  • False aneurysm (wall consists of hematoma or fibrous tissues).
• Causes:
  • Atherosclerosis.
  • Cystic medial degeneration of arterial media.
  • Trauma.
  • Congenital defects.
  • Infections (mycotic aneurysm).
  • Syphilis.

Aortic Dissection

• Dissection of blood between (and along) the laminar planes within the aorta media.
• Forms blood-filled channels within the aortic wall.
• Possible causes:
  • Primarily unknown.
  • Hypertension.
  • Marfan syndrome.
  • Complications of arterial cannulation or catheterization (iatrogenic).
  • Sometimes occurring during or after pregnancy.

Hypertensive Vascular Diseases (Hypertension)

• High blood pressure over time (sustained diastolic pressure over 90mmHg or sustained systolic blood pressure over 140mmHg).
• Types:
  • Idiopathic (essential): Making up 95% of cases, often benign but sometimes malignant.
  • Secondary: 5% of cases, caused by various factors.
• Causes of Secondary Hypertension: Renal causes, endocrine causes, cardiovascular causes, and neurologic causes.

Inflammatory Diseases of Blood Vessels (Vasculitides)

• Infectious Vasculitis: Infection-induced inflammation.
• Immune-mediated Vasculitis: Immunological mechanisms trigger inflammation (immune complex deposition, antineutrophil cytoplasmic antibodies (ANCAs), anti-endothelial cell antibodies).
• Vasculitides associated with other disorders: Rheumatoid arthritis, SLE, inflammatory bowel diseases.

Giant Cell (Temporal) Arteritis

• Chronic granulomatous inflammation of large to medium-sized arteries, often the temporal arteries, but can also affect vertebral and ophthalmic arteries.
• Primarily affects older individuals.
• Symptoms include: facial pain/headache (especially along the temporal artery), fever, fatigue, and weight loss.
• High Erythrocyte Sedimentation Rate (ESR).

Polyarteritis Nodosa (PAN)

• Systemic vasculitis of small or medium-sized muscular arteries, often affecting renal and visceral vessels but sparing the pulmonary circulation.

Wegener Granulomatosis

• Necrotizing vasculitis characterized by:
  • Granulomas in the upper respiratory tract (nose, sinuses, throat and lungs).
  • Necrotizing or granulomatous vasculitis in small and medium-sized vessels (especially in the lungs and upper airways).
  • Renal disease with focal necrotizing and often crescentic glomerulonephritis.

Thromboangiitis Obliterans (Buerger Disease)

• Segmental, acute and chronic inflammation of medium and small arteries.
• Primarily affects the tibial and radial arteries.
• Most commonly seen in young male smokers.
• Pathogenesis is suspected to involve:
  • Direct endothelial toxicity from tobacco or Tobacco hypersensitivity.
  • Anti-endothelial cell antibodies.
  • Influence of MHC haplotypes (HLA-A9 and HLA-B5).
  • Genetic factors (seen more commonly in specific ethnic groups)

Raynaud Phenomena

• Exaggerated vasoconstriction of digital arteries and arterioles.
• Characteristic color changes in the fingers resulting from periods of pallor, cyanosis, and redness related to blood flow to the fingers.
• Can be a primary disease entity (Raynaud's disease) or secondary to other conditions (SLE, scleroderma, Buerger disease, atherosclerosis).

Varicose Veins

• Abnormally dilated and tortuous veins due to prolonged intraluminal pressure and loss of vessel wall support.
• Commonly affecting veins in the upper and lower leg.
• Predisposing factors include obesity and pregnancy.
• Genetic and familial tendencies.

Tumors of the Vascular System

• Tumors of blood vessels and lymphatics range from benign hemangiomas through intermediate lesions (Kaposi's sarcoma and haemangioendothelioma) to malignant angiosarcomas.
• Some tumors originate in the endothelial cells (hemangioma, lymphangioma, or angiosarcoma).
• Others originate in cells supporting the blood vessels (glomus tumors or hemangiopericytomas).
• Primary tumors of large vessels (aorta, pulmonary artery and vena cava) are mostly connective tissue sarcomas.