Vascular Pathology 1 Flashcards
(39 cards)
Berry aneurysms
Typically found in the Circle of Willis
Associated with AD polycystic kidney disease
Rupture can cause fatal subarachnoid hemorrhage
Arteriovenous fistulas
artery –> vein
most commonly a developmental defect, may arise secondary to inflammation, trauma, rupture
may lead to rupture and hemorrhage, or to high-output cardiac failure
Fibromuscular dysplasia
Focal thickening of intima and media of middle to large muscular arteries, resulting in stenosis
Vascular response to injury - endothelial cell activated state
Stimuli: Turbulent blood flow HTN Complement, bacterial products, lipid products, glycation end products Viruses Hypoxia, acidosis Components of tobacco smoke
Characterized by expression of:
Adhesion molecules
procoagulants and anticoagulants
vasoactive factors, growth factors
Endothelial dysfunction
prolonged activated state
characterized by:
pro coagulation
pro inflammation
smooth muscle stimulation
Vascular injury
loss of endothelial cells secondary to tissue damage or prolonged endothelial dysfunction
Response: intimal thickening
- smooth muscles cells from the media migrate to the intima, where they proliferate and elaborate ECM
- Intima thickened, potentially affecting blood flow in that vessel
Vascular intimal thickening seen in response to any injury to the vessel, regardless of cause
HTN is a risk factor for:
Atherosclerosis, aortic dissection
Hypertensive heart disease
Stroke
Hypertensive renal disease
Factors that alter cardiac output
Blood volume - sodium, mineralocorticoids, ANP
Cardiac factors - HR, contractility
Factors impacting peripheral resistance
Humoral factors:
Constrictors: AngII, catecholamines, thromboxane, leukotrienes, endothelin
Dilators: prostaglandins, kinins, NO
Neural factors
Constrictors: alpha-adrenergic
Dilators: beta-adrenergic
Local factors: auto regulation, pH, hypoxia
Renin
released by juxtaglomerular cells in afferent arterioles in the kidney in states of low volume or low peripheral resistance, or decreased GFR
Cleaves angiotensinogen to angiotensin I
Angiotensin II
ACE converts angiotensin I to angiotensin II
short lived vasoconstrictor
stimulates adrenal cortex release of aldosterone - renal reabsorption of Na+ and water
Resistance and volume increased, raising BP
Atrial natriuretic peptide
released by myocardial cells in response to volume expansion.
Leads to Na+ excretion and diuresis as well as vasodilation –> lower BP
Hyaline arteriolosclerosis
Increased smooth muscle matrix synthesis
Plasma protein leakage across damaged endothelium
Homogenous pink (hyaline) thickening of the vessel wall, with associated luminal narrowing
Hyperplastic arteriolosclerosis
Occurs in severe hypertension
Smooth muscle cells form concentric lamellations (“onion skinning”) with resultant luminal narrowing
Constitutional risk factors for Atherosclerosis
family hx
age
gender
Modifiable risk factors (major) for Atherosclerosis
Hyperlipidemia (especially LDL)
HTN
Smoking
DM
Minor modifiable risk factors for Atherosclerosis
inflammation
hyperhomocystinemia
Metabolic syndrome
Response to injury model for atherosclerosis pathogenesis
chronic injury and/or dysfunction of endothelium, leading to chronic inflammation and attempting to repair the tissue
1) chronic endothelial injury due to: hyperlipidemia, HTN, smoking, homocysteine, hemodynamic factors, toxins, viruses, immune reactions
2) Endothelial dysfunction (increased permeability leukocyte adhesion), monocyte adhesion and emigration
3) macrophage activation, sm.m. recruitment
4) macrophages and sm.m. cells engulf lipid
5) Sm.m. proliferation, collagen and other ECM deposition, extracellular lipid
Fibrofatty atheroma characteristics
Fibrous cap - smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularization
Necrotic center - cell debris, cholesterol crystals, foam cells, calcium
Media
Hemodynamic turbulence associated with endothelial injury and dysfunction in the pathogenesis of atherosclerosis
◦ Atherosclerosis does not occur randomly in vessels, nor does it occur everywhere uniformly
◦ Most lesions tend to occur at openings of exiting vessels, branch points, posterior abdominal aorta—due to flow disturbances normally seen in these locations
Circulating lipids associated with endothelial injury and dysfunction in the pathogenesis of atherosclerosis
◦ Lipids in atheromatous plaques are predominantly cholesterol and cholesterol esters
◦ Accumulate in the intima, are taken up by macrophages and partially oxidized
◦ This modified LDL further accumulates within macrophages and smooth muscle cells, forming foam cells and a lesion known as a “fatty streak”
◦ This stimulates an inflammatory response to accumulation of this toxic form of LDL
Inflammation in the pathogenesis of atherosclerosis
◦ Accumulation of cholesterol crystals within macrophages is recognized by the inflammasome, which leads to IL-1 secretion
◦ More macrophages and T-lymphocytes are recruited and activated
◦ Inflammatory cytokines further activate endothelial cells, and growth factors stimulate smooth muscle cells to migrate to the intima and proliferate
Smooth muscle proliferation and matrix deposition in the pathogenesis of atherosclerosis
◦ Proliferating smooth muscle cells synthesize extracellular matrix, including collagen
◦ Due to the intimal expansion from foam cells and extracellular lipid, recruited inflammatory and smooth muscle cells and increased ECM, an atheromatous plaque is formed
◦ Over time, a soft fibrofatty plaque becomes covered with a fibrous cap (dense collagen fibers). The center of the plaque is necrotic, containing lipid, debris, foam cells and thrombus, surrounded by a zone of inflammatory and smooth muscle cells.
Atherosclerosis - Common sites of involvement
In decreasing order of frequency/severity of involvement: ◦ Abdominal aorta ◦ Coronary arteries ◦ Popliteal arteries ◦ Internal carotid arteries ◦ Circle of Willis
