Atherosclerosis and Venous Disorders Quiz

Pathology of Cardiovascular System

• This is a presentation on the pathology of the cardiovascular system, by Prof. Dr. Rafal Al-Saigh.

Diseases of Blood Vessels

• Function of endothelial cells lined blood vessels:

  • Maintenance of Permeability Barrier
  • Elaboration of Anticoagulant, Antithrombotic, Fibrinolytic factors
  • Regulators: Prostacyclin, Thrombomodulin, Heparin-like molecules, Plasminogen activator
  • Elaboration of Prothrombotic Molecules: Von Willebrand factor, Tissue factor, Plasminogen activator inhibitor
  • Extracellular Matrix Production (collagen, proteoglycans)

• Modulation of Blood Flow and Vascular Reactivity:

  • Vasconstrictors: endothelin, ACE
  • Vasodilators: NO, prostacyclin

• Regulation of Inflammation and Immunity:

  • IL-1, IL-6, chemokines
  • Adhesion molecules: VCAM-1, ICAM, E-selectin, P-selectin
  • Histocompatibility antigens

• Regulation of Cell Growth:

  • Growth stimulators: PDGF, FGF
  • Growth inhibitors: heparin, TGF-β

• Oxidation of LDL:

• Endothelial cells: Activated by cytokines and bacterial products; also affected by inflammation and septic shock, hemodynamic stress, lipid products, critical to atherosclerosis pathogenesis, advanced glycosylation end products (important in diabetes), viruses, complement components, and hypoxia.

• Vascular smooth muscle cells: Response to stimuli resulting in vasoconstriction and dilation. Synthesize collagen, elastin, and proteoglycans; elaborate growth factors and cytokines; migrate to intima; and proliferate after injury.

Vascular Structure and Function

• All vessels are lined by endothelium, sharing homeostatic properties.
• Endothelial cells in specific vascular beds (e.g., renal glomeruli) have special features for tissue-specific functions.
• The relative smooth muscle cell and matrix content of vessel walls varies according to hemodynamic demands (e.g. pressure, pulsatility).
• Endothelial cell function is tightly regulated in both basal and activated states.
• Pathophysiological stimuli induce endothelial activation and dysfunction altering the phenotype (e.g. pro- versus anticoagulative, pro- versus anti-inflammatory, and non-adhesive versus adhesive).

Atherosclerosis

• Intimal lesions (atheromas) protrude & obstruct vascular lumens, causing ischemic heart disease.

• The American Heart Association classifies into six types based on nomenclature and histology, progression sequences, main growth mechanism, earliest onset, and clinical correlation.

• Atherosclerosis is an intima-based lesion: Composed of a fibrous cap and an atheromatous core (smooth muscle cells, ECMs, inflammatory cells, lipids, and necrotic debris).

• Driven by vessel wall injury and inflammation.

• Multiple risk factors cause dysfunction, influencing smooth muscle cell recruitment/stimulation.

• Plaques slowly develop over decades; stable plaques cause chronic ischemia, unstable plaques cause potentially fatal ischemic complications related to rupture, thrombosis, or embolization.

• Stable plaques have dense fibrous caps, minimal lipid accumulation, and little inflammation.

• Unstable plaques have thin caps, large lipid cores, and relatively dense inflammatory infiltrates.

• Type I lesion: increase in macrophages & formation of macrophage foam cells.

• Type II lesion (fatty streaks): lipid-laden smooth muscle cells.

• Type III lesion: intermediate stage between Type II & IV (atheroma).

• Type IV lesion: larger, confluent, and more disruptive lipid core.

• Type V lesion: Extracellular lipid with thick layers of fibrous connective tissue.

• Type VI lesion: extracellular lipid containing fibrous tissue, fissure, hematoma, or largely calcified.

• Fatty streaks are the earliest lesion of atherosclerosis.

• Subendothelial lipid-filled foamy cells with few T lymphocytes.

• Progresses to atheromatous plaques, damaging arteries.

• Plaques can disrupt & precipitate thrombi, obstructing blood flow.

• Components include cells (SMCs, macrophages, leukocytes), ECM (collagen, elastic fibers, proteoglycans), & intracellular/extracellular lipid (cholesterol & cholesterol esters).

• Complications include rupture, ulceration, erosion, hemorrhage, thrombosis, and aneurysmal dilation.

Hypertension

• Common disorder affecting 25% of the population.
• Major risk factor for atherosclerosis, congestive heart failure, and renal failure.
• Essential hypertension: 95% of cases; complex, multifactorial disorder involving environmental and genetic influences.
• Genetic polymorphisms influence sodium resorption, aldosterone pathways, and the renin-angiotensin system.
• Sometimes caused by single-gene disorders or secondary to kidney, adrenal, or other endocrine organ diseases.

Vasculitis

• Inflammation of vessel walls, frequently associated with systemic manifestations (fever, malaise, arthralgias) and organ dysfunction.

• Vasculitis can result from infections, but more commonly from immunologic basis (immune complex deposition, anti-neutrophil antibodies, and anti-endothelial cell antibodies).

• Different forms of vasculitis selectively affect vessels of specific caliber and location.

• Non-infectious vasculitis: Including the giant cell arteritis, Takayasu's arteritis, polyarteritis nodosa, Kawasaki disease, microscopic polyangiitis, and Henoch-Schönlein purpura.

• Giant cell arteritis: Affecting temporal arteries, associated with destructive giant cell granuloma.

• Takayasu's arteritis: Involving carotids, subclavian, and arch aorta, often resulting in fibrosis leading to pulse less syndrome.

• Polyarteritis nodosa: Involves medium-sized arteries, commonly extending to renal arteries, characterized by necrotizing fibrinous inflammation.

• Kawasaki disease: In children; affects coronary arteries.

• Microscopic polyangiitis: Leukocytoclastic vasculitis affecting smaller arterioles, capillaries, and venules (occurs in conditions like Henoch-Schonlein purpura and Churg-Strauss syndrome).

• Wegener's granulomatosis: Affects lungs and kidneys, characterized by acute necrotizing granulomas, necrotizing vasculitis of small & medium-sized vessels, and renal disease.

• Thromboangiitis obliterans (Buerger's disease): Segmental, thrombosing, and inflammatory condition affecting medium-sized arteries, mainly in hands and feet, almost exclusively affecting heavy smokers.

Vascular Tumors

• Vascular ectasias not neoplasms, but dilations of existing vessels.
• Vascular neoplasms derive from blood vessels or lymphatic vessels.
• Composed of endothelial cells, or other vascular wall cells.
• Most vascular tumors are benign (e.g. hemangiomas), some are intermediate/locally aggressive (e.g. Kaposi sarcoma), and others are highly malignant (e.g. angiosarcoma).
• Benign tumors form obvious vascular channels lined by normal-appearing endothelial cells.
• Malignant tumors are solid, cellular, exhibit cytologic atypia, and lack well-defined vessels.

Congenital Cardiac Diseases

• Various congenital cardiac malformations are described, with percentages (%) mentioned for each.

Ischemic Heart Disease (IHD)

• Diminished coronary perfusion relative to myocardial demand, with several factors including complex interactions of fixed atherosclerotic narrowing/intraluminal thrombosis overlying a disrupted atherosclerotic plaque, platelet aggregation, and vasospasm.
• Obstruction of 75% or more of the coronary artery lumen causes symptoms on exertion, and while 90% + obstruction causes symptoms even at rest (angina pectoris).
• Acute plaque change leads to thrombosis and total occlusion with myocardial infarction. Acute plaque changes include rupture/fissuring, erosion/ulceration, & hemorrhage.

Morphologic Changes in Acute MI

• Describes the gross and light microscopic changes in acute myocardial infarction (MI) over time (0-12 hours and later).

Consequences of MI

• Contractile dysfunction.
• Arrhythmias.
• Myocardial rupture.
• Pericarditis.
• Infarct extension.
• Infarct expansion.
• Mural thrombus.
• Ventricular aneurysm.
• Papillary muscle dysfunction.
• Progressive late heart failure.

Infective Endocarditis (IE)

• Colonization or invasion of heart valves/mural endocardium by microbes, with formation of bulky, friable vegetations; often associated with destruction of underlying cardiac tissues.
• Classified into: Acute & Subacute endocarditis. Acute IE is caused by highly virulent microorganisms; subacute IE is caused by low virulent microorganisms infecting an abnormal heart.
• Predisposing factors such as rheumatic heart disease, myxomatous mitral valve, degenerative calcific valvular stenosis, neutropenia, immunodeficiency, malignancy, diabetes mellitus, alcoholism, and intravenous drug abuse.

Causative Microorganisms

• IE caused by various microorganisms such as Streptococcus viridans, Staphylococcus aureus, enterococci, Haemophilus, Acinetobacter, Gram-negative bacilli, and fungi.
• Microorganisms are seeded into blood after dental extraction, surgical procedures, and contaminated needles.

Rheumatic Heart Disease (RHD)

• Acute, immunologically mediated, multisystem inflammatory disease triggered by group A streptococcal pharyngitis.
• Associated with: Focal inflammatory lesions (Aschoff bodies) in tissues, especially those within the heart.
• The inflammatory lesions consist of foci of swollen eosinophilic collagen surrounded by lymphocytes (primarily T cells), and occasionally plasma cells, and plump macrophages, called Anitschkow cells, a feature pathognomonic for rheumatic fever.

Varicose Veins

• Dilatation of superficial veins; Veins are capacious & thin-walled blood vessels (70% of total blood volume); Upright position.
• Bicuspid valves responsible for unidirectional flow; aided by muscle pump; Superficial & deep systems & perforant veins between them.

Deep Vein Incompetency

• Retrograde flow in deep veins, possible complications are crural ulcer & thrombosis; Etiology of incompetency includes thrombosis & congenital factors.

Diagnostics Method

• Venography is recommended in post-thrombotic patients, especially prior to planned intervention; Ascending venography with injection of contrast material into the foot is common.

Aneurysm and Dissections

• Aneurysm: Distention of an artery due to arterial wall weakening/destruction, forming a balloon-like bulge; may be congenital or acquired, involving the entire thickness of heart/blood vessels.
• Dissection: Blood enters the vessel wall, separating the layers.
• Complications result from rupture, thrombosis, & embolization of branching vessels.

Types of Aneurysms

•  Aortic (abdominal and thoracic).
• Cerebral.
• Peripheral (in arteries other than aorta).

Aortic Aneurysms

• Abdominal aortic aneurysm (AAA): Aneurysm in the abdominal portion of the aorta.
• Thoracic aortic aneurysm (TAA): Aneurysm in the thoracic portion of the aorta.

Brain Aneurysms

• Aneurysms in brain arteries, often berry-sized.

Peripheral Aneurysms

• Aneurysms in arteries other than aorta & brain arteries.

Heart Failure

• Clinical syndrome when the heart fails to provide adequate blood flow to meet metabolic needs; Can occur due to:
• Ischemic heart disease.
• Hypertension.
• Diabetes.

Compensatory Mechanisms in Heart Failure

• Increasing cardiac output via Frank–Starling mechanism.
• Increasing ventricular volume and wall thickness via ventricular remodeling.
• Maintaining tissue perfusion with increased mean arterial pressure via neurohormonal systems.

Pathophysiology of Heart Failure

• Heart's inability to provide sufficient blood to meet metabolic needs leads to organ congestion from pulmonary and systemic venous pressure elevation.
• Primary abnormalities include systemic issues from cardiomyocyte dysfunction, collagen turnover of the extracellular matrix, structural cardiac defects, rhythm abnormalities, or high metabolic demands such as thyrotoxicosis.

Left Ventricular Failure (LV Failure)

• Reduced cardiac output.
• Increased pulmonary venous pressure causes fluid extravasation from capillaries to interstitial space and alveoli; reducing pulmonary compliance, increasing breathing work, and altering V/Q relationships.
• Marked fluid accumulation in alveoli (pulmonary edema).
• Decreasing systemic arterial oxygenation, causing dyspnea, increased minute ventilation, decreasing PaCO2, and increasing blood pH.

Right Ventricular Failure (RV Failure)

• Increased systemic venous pressure causing fluid extravasation in dependent tissues (feet, ankles, and abdominal viscera).
• Congestion can affect the liver, stomach, and intestine.
• Fluid accumulation in peritoneal cavity (ascites).
• Sequels include moderate hepatic dysfunction impaired liver breaks down less aldosterone; contributing to fluid accumulation, anorexia, malabsorption, and protein-losing enteropathy.