Blood Vessels

• Arteries based on their size and structural features

  • Large or elastic arteries (aorta, major branches of aorta, pulmonary arteries)
  • Medium-sized or muscular arteries (smaller branches of aorta, e.g. coronary and renal arteries)
  • Small arteries (≤2 mm in diameter) and arterioles (20 to 100 μm in diameter) (within tissues and organs)

  
• Capillaries


  Approximately the diameter of a red cell (7 to 8 μm); they have an endothelial cell lining but no media
• Congenital vascular anomalies


  • Developmental or berry aneurysms
  • Arteriovenous fistulas
  • Fibromuscular dysplasia
  • Anomalous coronary artery

  
• Hypertension


  Individuals with diastolic pressures above 80 mm Hg or systolic pressures above 120 mm Hg are considered to have clinically significant hypertension
• Approximately 90% to 95% of hypertension is idiopathic—so-called essential hypertension
• Secondary hypertension may result from an underlying renal or adrenal disease (e.g., primary aldosteronism, Cushing syndrome, or pheochromocytoma), or renal artery stenosis
• Malignant hypertension


  Characterized by severe pressure elevations (i.e., systolic pressure more than 200 mm Hg, diastolic pressure more than 120 mm Hg), renal failure, and retinal hemorrhages and exudates, with or without papilledema
• Liddle syndrome


  A form of salt-sensitive hypertension caused by mutations in an epithelial Na+ channel protein that increase distal tubular reabsorption of sodium in response to aldosterone
• Renin-angiotensin system


  1. Renin is released in response to low blood pressure or low sodium levels

  2. Renin cleaves plasma angiotensinogen to angiotensin I

  3. Angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE)

  4. Angiotensin II raises blood pressure by inducing vascular contraction, stimulating aldosterone secretion, and increasing tubular sodium resorption

  5. Adrenal aldosterone increases blood pressure by increasing sodium resorption (and thus water) in the distal convoluted tubule, which increases blood volume
• Small blood vessel disease associated with Hypertension

  • Hyaline arteriolosclerosis
  • Hyperplastic Arteriolosclerosis
• Hyaline arteriolosclerosis


  Arterioles show pink hyaline thickening with associated luminal narrowing. More generalized and severe in patients with hypertension and diabetes
• Hyperplastic Arteriolosclerosis


  Exhibits concentric, laminated ("onion-skin") thickening of the walls with luminal narrowing. Seen in malignant hypertension, which is characterized by severe hypertension, renal failure, and retinal hemorrhages
• The rapidly rising blood pressure, if untreated, leads to death within 1 to 2 years in malignant hypertension
• Pulmonary hypertension


  Can be caused by several entities including left heart failure, congenital heart disease, valve disorders, obstructive or interstitial lung disease, and recurrent thromboemboli
• Arteriosclerosis


  Arterial wall thickening and loss of elasticity
• Patterns of arteriosclerosis


  • Arteriolosclerosis
  • Mönckeberg medial sclerosis
  • Fibromuscular intimal hyperplasia
  • Atherosclerosis

  
• Arteriolosclerosis


  Affects small arteries and arterioles (hyaline and hyperplastic)
• Mönckeberg medial sclerosis


  Characterized by calcification of the walls of muscular arteries, typically involving the internal elastic membrane. Calcifications do not encroach on the vessel lumen. Usually not clinically significant
• Fibromuscular intimal hyperplasia


  Occurs in muscular arteries larger than arterioles. Driven by inflammation or by mechanical injury and can be considered as a healing response
• Atherosclerosis


  The likelihood of atherosclerosis is determined by the combination of acquired (e.g., cholesterol levels, smoking, hypertension) and inherited (e.g., LDL receptor gene mutations) risk factors
• Atheromas (atheromatous or atherosclerotic plaques)


  Intimal lesions that protrude into vessel lumens. Consists of a raised lesion with a soft grumous core of lipid (mainly cholesterol and cholesterol esters) covered by a fibrous cap
• Atherosclerotic plaques can rupture leading to catastrophic obstructive vascular thrombosis
• Atherosclerotic plaques can also increase the diffusion distance from the lumen to the media, leading to ischemic injury and weakening of the vessel wall, changes that can result in aneurysm formation
• Constitutional risk factors for atherosclerosis

  • Genetics (family history)
  • Age (40-60 y/o)
  • Gender (premenopausal women are relatively protected)
• Modifiable major risk factors for atherosclerosis

  • Hyperlipidemia
  • Hypertension
  • Cigarette smoking
  • Diabetes mellitus
• Hyperlipidemia


  Major risk factor for atherosclerosis. LDL ("bad cholesterol") delivers cholesterol to peripheral tissues, while HDL ("good cholesterol") mobilizes cholesterol from the periphery and transports it to the liver for catabolism and biliary excretion
• Statins

  A class of drugs that lower circulating cholesterol levels by inhibiting hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase, rate-limiting enzyme in hepatic cholesterol biosynthesis
• Exercise and moderate consumption of ethanol raise HDL levels whereas obesity and smoking lower it
• Inflammation


  A number of circulating markers of inflammation correlate with ischemic heart disease, including C-reactive protein (CRP)
• Hyperhomocystinemia

  Serum homocysteine levels correlate with coronary atherosclerosis, peripheral vascular disease, stroke and venous thrombosis
• Metabolic Syndrome


  Associated with central obesity. Characterized by insulin resistance, hypertension, dyslipidemia (elevated LDL and depressed HDL), hypercoagulability, and a proinflammatory state
• Lipoprotein a [Lp(a)]


  Altered form of LDL that contains the apolipoprotein B-100 portion of LDL linked to apolipoprotein A (apo A). Lp(a) levels are associated with coronary and cerebrovascular disease risk
• Factors associated with a less pronounced and/or difficult to quantitate risk include lack of exercise; competitive, stressful lifestyle (type A personality); and obesity
• Endothelial Injury


  The cornerstone of the response-to-injury hypothesis. Early lesions begin at sites of morphologically intact endothelium that exhibit features of endothelial dysfunction. The three most important causes are hemodynamic disturbances, hypercholesterolemia, and inflammation
• Fatty streaks


  Early lesions containing lipid-Milled macrophages. Begin as small flat yellow macules, they eventually coalesce into elongated streaks 1 cm long or longer
• Atheromatous plaques


  Yellow-tan and are raised above the surrounding vessel wall; superimposed thrombus over ulcerated plaques will be red-brown. Patchy, and are rarely circumferential, therefore appear "eccentric"
• Vessels most extensively involved by atherosclerosis


  • Lower abdominal aorta
  • Coronary arteries
  • Popliteal arteries
  • Internal carotid arteries
  • Vessels of the circle of Willis

  
• Principal components of atherosclerotic plaques

  • Smooth muscle cells, macrophages, and T cells
  • Extracellular matrix, including collagen, elastic fibers & proteoglycans
  • Intracellular and extracellular lipids
  • Calcifications in later stage plaques
• Adrenergic stimulation


  Can increase systemic blood pressure or induce local vasoconstriction, thereby increasing the physical stresses on a given plaque
• Plaque erosion or rupture


  Typically promptly followed by partial or complete vascular thrombosis, resulting in acute tissue infarction (e.g., myocardial infarction)