Vascular Pathology 1 Flashcards
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
Complications of atherosclerotic plaques
Rupture and ulceration
◦ May lead to thrombosis
Hemorrhage
◦ May follow plaque rupture
Embolism
◦ May follow plaque rupture
Aneurysm formation
Stenosis of the arterial lumen in atherosclerosis
◦ Plaques tend to continually grow because of repeated cycling through the injury-healing process
◦ The lumen of the affected vessel gradually shrinks, eventually leading to ischemia downstream (a point known as critical stenosis – approximately 70% occluded)
◦ This may lead to chronic ischemia of myocardium, bowel, brain, the extremities, etc.
Acute plaque change
An acute thrombus may form over the plaque, occluding the artery. This may occur secondary to
◦ Rupture of the plaque
◦ Erosion or ulceration of the plaque surface
Hemorrhage into the plaque may acutely expand its volume
Factors making some plaques more prone to rupture than others
◦ The fibrous cap is continually being degraded and resynthesized (remodeled)
◦ Increased inflammation in the plaque can accelerate fibrous cap degradation and inhibit its resynthesis, thus reducing the amount of collagen in the cap and weakening it
◦ Physical stresses can cause plaque rupture
- Changes in blood pressure
- Vasoconstriction
Aneurysm
Localized abnormal dilation of a blood vessel or the heart that may be congenital or acquired
True vs false aneurysm
True: characterized by an intact, but thinned, muscular wall at the site of the dilation
False: defect through the wall of the vessel or heart, communicating with an extravascular hematoma
Aneurysm pathogenesis
Occur whenever connective tissue of vascular wall is weakened
◦ Defective vascular wall connective tissue
-Marfan syndrome (defective fibrillin synthesis)
◦ Net degradation of vascular wall connective tissue
-Inflammatory conditions (such as atherosclerosis) → increased matrix metalloprotease
◦ Weakening of the vascular wall by ischemia
- Atherosclerosis → ischemia of inner media
- Hypertension → ischemia of outer media
- Tertiary syphilis → ischemia of outer media (thoracic aorta)
Cystic medial degeneration
loss of vascular wall elastic tissue or ineffective elastin synthesis
disrupted and disorganized elastin filaments and increased ground substance (proteoglycans)
final common result of different conditions (ischemic medial damage, Marfan syndrome)
Most common causes of aortic aneurysms
atherosclerosis
HTN
Abdominal aortic aneurysm
usually below renal arteries, often involve common iliac arteries
More frequent in men, smokers, 60s
Characterized by severe atherosclerosis of the aorta, covered with mural thombus
Pulsating mass in abdomen
Complications of AAA
rupture (risk related to size) and hemorrhage
Occlusion of branching arteries and downstream ischemia
Embolism
Impingement on another structure
Thoracic aortic aneurysm
Often due to HTN or Marfan
Clinical presentation:
Impingement: lower respiratory tree, esophagus, recurrent laryngeal nerves
Aortic valvular insufficiency
Rupture
Aortic dissection
Occurs when blood enters a defect in the intima and travels through a tissue plane within layers of the aortic media.
Aortic dissection occurs in
◦ Hypertensive males, 40-60
◦ Patients with disorders of vessel connective tissue (Marfan)
The primary risk factor is hypertension.
Classic presentation: severe chest pain, radiating to the back between the scapulae
Aortic dissection pathogenesis
Blood enters aortic wall via an intimal tear (cause generally unknown), forming an intramural hematoma
Hypertensive patients, there is some degree of cystic medial degeneration (many there is little or none)
Most dissections arise in the ascending aorta
Type A vs Type B aortic dissections
Type A: involve ascending aorta, more common, higher morbidity and mortality; treated with antihypertensive therapy and surgical repair of intimal tear
Type B: does not involve ascending aorta
Most common cause of death is rupture
Dissection may extend along arterial branches causing occlusion of those vessels
