Diseases of Blood Vessels

Diseases of Blood Vessels

• Endothelial cells line blood vessels and maintain permeability barrier. They produce anticoagulants, antithrombotics, and fibrinolytics, including prostacyclin, thrombomodulin, heparin-like molecules, and plasminogen activator.
• They also produce prothrombotic molecules like von Willebrand factor and tissue factor, and plasminogen activator inhibitor.
• Endothelial cells produce extracellular matrix (collagen, proteoglycans) and modulate blood flow/reactivity (e.g., vasodilators like NO and prostacyclin, vasoconstrictors like endothelin and ACE).
• Endothelial cells regulate inflammation and immunity, using molecules like IL-1, IL-6, chemokines, VCAM-1, ICAM, E-selectin and P-selectin.
• They also regulate cell growth, with stimulators like PDGF and FGF, and inhibitors like heparin and TGF-β.
• Endothelial cells can be activated by cytokines, bacterial products, hemodynamic stresses, and lipid products, leading to inflammation, and contributing to atherosclerosis.
• Advanced glycosylation end products (important in diabetes), viruses, complement components, and hypoxia can activate endothelial cells.
• Vascular smooth muscle cells respond to stimuli to control vasoconstriction and dilation. They synthesize collagen, elastin, and proteoglycans; elaborate growth factors and cytokines; migrate to the intima, and proliferate after vascular injury.

Vascular Structure and Function

• All blood vessels are lined by endothelium, with specialized features in specific vascular beds (e.g., fenestrated endothelial cells in renal glomeruli).
• Vessel wall composition (smooth muscle, matrix) varies according to hemodynamic demands (pressure, pulsatility) and function.
• Endothelial cell function is tightly regulated in both basal and activated states, with various stimuli inducing activation and dysfunction.

Atherosclerosis

• Atherosclerosis forms intimal lesions called atheromas, obstructing vascular lumens.
• It's the root cause of ischemic heart disease.
• The American Heart Association classifies atherosclerotic lesions into six types.
• Atherosclerosis is an intima-based lesion with a fibrous cap and atheromatous core, containing smooth muscle cells, ECM, inflammatory cells, lipids, and necrotic debris.
• Atherogenesis stems from vessel wall injury and inflammation; various risk factors cause endothelial dysfunction and influence smooth muscle cell recruitment/stimulation.
• Plaques develop slowly, with stable plaques causing chronic ischemia by narrowing vessels, and unstable plaques causing acute ischemic complications from rupture, thrombosis, or embolization.
• Stable plaques have a dense fibrous cap, minimal lipid, and little inflammation, while unstable plaques have thin caps, large lipid cores, and dense inflammatory infiltrates.
  • Initial lesions (Type I) show macrophage increase and foam cell formation
  • Fatty streaks (Type II) are lipid-laden smooth muscle cells, followed by intermediate stages (Type III) with scattered extracellular lipid.
  • Atheromas (Type IV) have larger confluent lipid cores.
  • Type V plaques have thicker fibrous connective tissue, and Type VI lesions show more advanced stages with fibrous tissue, fissure(s), hematoma, and a thrombus.
• Fatty streaks, the earliest lesion, are composed of lipid-filled foamy cells and are seen in the aorta of children over 10 years old. Some streaks can progress to atheromas, mainly in elastic and muscular arteries.
• Atherosclerotic plaques have three components: cells (SMCs, macrophages), ECM (collagen, elastic fibers, proteoglycans), and intracellular/extracellular lipids (cholesterol, cholesterol esters).
• Complications: rupture, ulceration, hemorrhage, thrombosis, and aneurysm formation.

Risk Factors of Ischemic Heart Disease (IHD)

• Major (Non-modifiable): increasing age, male gender, family history, and genetic abnormalities.
• Potentially Controllable: hyperlipidemia, hypertension, cigarette smoking, and diabetes.
• Minor: obesity, physical inactivity, stress, postmenopausal estrogen deficiency, high carbohydrate intake, alcohol intake, lipoprotein Lp(a), and hardened fats.
• Infection: Chlamydia pneumoniæ

Atherosclerosis Pathogenesis

• Chronic endothelial cell injury.
• Accumulation of lipoproteins (mainly LDLs).
• LDL oxidation.
• Monocyte migration to intima, phagocytosis of lipids (foam cells).
• Platelet adhesion.
• Smooth muscle cell migration and proliferation.
• Enhanced lipid accumulation.

Hypertension

• Hypertension affects 25% of the population and is a major risk factor for atherosclerosis, heart failure, and renal failure.
• Essential hypertension (95% of cases) is complex and multifactorial, involving environmental and genetic influences on sodium resorption, aldosterone pathways, and the renin–angiotensin system.
• Other causes: single-gene disorders, kidney, adrenal, or other endocrine diseases.
• Major risk factor for coronary artery disease and cerebrovascular accidents.
• Can lead to heart hypertrophy, heart failure, aortic dissection, and renal failure.

Hypertension Pathogenesis

• Multifactorial, with unknown causes in most cases.
• Defined as sustained diastolic pressure > 90 mmHg or systolic pressure > 140 mmHg.
• Kidneys play a role: Renin-angiotensin system raises blood pressure, PG/NO lower BP, Na reabsorption maintains blood volume. Natriuretic peptides inhibit Na and renin-angiotensin.
• Impaired renal function increases blood pressure to compensate for reduced volume.
• Etiology: increased vascular resistance (e.g., reactivity, wall thickness), increased cardiac output (plasma/ECF volume → renal sodium and water retention),

Vasculitis

• Vasculitis is inflammation of vessel walls, often associated with systemic symptoms (fever, malaise, arthralgias) and organ dysfunction.
• Can be caused by infections or (more often) immunologic factors (immune complex deposition, ANCA, anti-endothelial cell antibodies).
• Different vasculitis forms affect specific vessel sizes and locations.
• Pathogenesis of non-infectious vasculitis: immune complex deposition, antineutrophil cytoplasmic antibodies (ANCAs), and anti-endothelial cell antibodies.
• Types include Giant cell arteritis (temporal arteries), Takayasu's arteritis (carotids, subclavian), polyarteritis nodosa (medium-sized vessels, often renal involvement), Kawasaki disease (coronary arteries in children), microscopic polyangiitis (small vessels), Wegener's granulomatosis (lungs, kidneys), and thromboangiitis obliterans (Buerger's disease, primarily small arteries, smokers).

Vascular Tumors

• Vascular ectasias are vessel dilations (not neoplasms).
• Vascular neoplasms arise from blood/lymphatic vessels. They can be composed of endothelial cells (e.g., hemangioma, lymphangioma, angiosarcoma) or other vascular wall cells (e.g., glomus tumor).
• Most are benign (hemangiomas), some are locally aggressive (Kaposi sarcoma), and others are highly malignant (angiosarcoma).

Congenital Cardiac Diseases

• List of common congenital heart defects with approximate percentages. (Note: Specific percentages are not provided here; use the list from the original text)

Ischemic Heart Disease (IHD)

• IHD results from diminished coronary perfusion relative to myocardial demand, often from complex interactions among fixed atherosclerosis, intraluminal thrombosis, platelet aggregation, and vasospasm.
• 75% coronary artery obstruction causes exertion-related symptoms, while 90% occlusion causes symptoms at rest (angina pectoris).
• Acute plaque changes leading to thrombosis result in myocardial infarction. Acute plaque changes include rupture/fissuring, erosion/ulceration, and hemorrhage.
• Morphologic changes in acute MI are detailed in a table (Note: a table is unsupported format for this summary)

Infective Endocarditis (IE)

• IE is the colonization/invasion of heart valves/mural endocardium by microbes, forming friable vegetations with thrombotic debris and organisms.
• Types: Acute (destructive, high mortality, needs surgery) and Subacute (low virulence, abnormal heart).
• Etiology & Pathogenesis: Predisposing factors include rheumatic heart disease, myxomatous mitral valve, degenerative calcific valvular stenosis.
• Causative microorganisms: Streptococcus viridans, Staphylococcus aureus, others (enterococci, Hæmophilus, Acinetobacillus, etc.). Gram-negative bacilli and fungi are also sources.
• Seeding of blood with microbes follows events like dental extraction, surgery, injection with contaminated needles or occult sources (gut, oral cavity).
• IE leads to vegetations on heart valves, microabscesses in myocardium, and septic emboli/infarcts.

Rheumatic Heart Disease (RHD)

• RHD is an acute, immunologically mediated, multisystem inflammatory disease following group A streptococcal pharyngitis.
• Acute rheumatic carditis can progress to chronic RHD.
  • Focal lesions (Aschoff bodies) are found in various tissues (most distinctive in the heart), consisting of swollen collagen, lymphocytes, and Anitschkow cells.
  • Pancarditis (inflammation in all heart layers) can occur.
  • Chronic RHD involves inflammation organization and fibrosis, causing lasting valvular changes (mitral valve, aortic valve).
• Pathogenesis: thought to be a hypersensitivity reaction to group A streptococci causing cross-reactivity of antibodies with heart antigens.
• Clinical features: migratory polyarthritis, carditis, subcutaneous nodules, erythema marginatum, and Sydenham chorea. Recurrent attacks are possible, with increasing damage over time.

Varicose Veins

• Dilatation of superficial veins.
• Veins are thin-walled, capacious vessels (70% of blood volume).
• Upright posture, bicuspid valves, muscle pump, and perforant veins between deep and superficial systems are involved.
• Varicose veins have symptoms including cosmetic issues, pain, inflammation, leg ulcers, and rupture.

Aneurysm and Dissections

• An aneurysm is a distended artery due to weakening or destruction of the artery wall, and can be congenital or acquired.
• An aneurysm is a ballooning in an artery.
• Complications include rupture, thrombosis, and embolization.
• Dissection occurs when blood enters the vessel wall and separates its layers, complicating branch vessels.
• Aneurysms and dissections arise from vessel wall structural weakness (loss of smooth muscle or insufficient ECM).
• Types of aneurysms include abdominal aortic, thoracic aortic, cerebral aneurysms, and peripheral aneurysms

Heart Failure

• Heart failure is a clinical syndrome where the heart cannot adequately provide blood flow to meet metabolic needs.
• Etiologies include ischemic heart disease (IHD), hypertension, and diabetes (less common: cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs).
• Compensatory mechanisms often lead to worsening heart failure.
  • Compensation includes the Frank–Starling mechanism, ventricular remodeling, and augmented neurohormonal systems.
• Pathophysiology: inadequate blood flow to tissues, and increased pulmonary/systemic venous pressures causing organ congestion. This can result from systolic/diastolic dysfunction or both.
• Left-sided (LV) failure: decreased cardiac output, increased pulmonary venous pressure, fluid extravasation into interstitial space/alveoli (pulmonary edema), decreased systemic oxygenation, and dyspnea.
• Right-sided (RV) failure: increased systemic venous pressure, fluid extravasation (edema), and organ congestion (liver, abdomen).
• Sequels are detailed regarding issues like hepatic dysfunction, contributing to fluid buildup, and issues in GI absorption and blood loss.