Vascular Injury, Arteriosclerosis, Hypertension, Aneurysm, Dissection Flashcards
Structures of vascular intima
Endothelium + internal elastic lamina
Structures of vascular media
Smooth muscle + elastic fibers
See autosomal dominant polycystic kidney disease…
Think ____
Berry aneurysms (circle of willis)
3 types of congenital anomalies in vascular walls
- Berry aneurysms
- AV fistulas
- Fibromuscular dysplasia
Berry aneurysms can lead to…
Fatal subarachnoid hemorrhage
Large AV fistulas can lead to…
High-output heart failure via L–>R shunt (increased venous return)
Most common cause of AV fistula
Developmental defect
Focal thickening of intima and media of medium to large muscular arteries, causing stenosis
Fibromuscular dysplasia
Young woman + renal artery stenosis
Fibromuscular dysplasia
Stimuli that can induce endothelial cell damage/activation
- Turbulent flow
- Hypertension
- Complement, cytokines
- Bacterial or lipid products, glycation products (DM)
- Viruses
- Hypoxia, acidosis
- Tobacco smoke
An ACTIVATED endothelial cell does what?
Expresses… (thrombogenic state)
- Adhesion molecules (inflammatory cells)
- Pro- and anti-coagulants
- Vasoactive and growth factors, cytokines
How does DM cause endothelial cell activation?
Glycation end-products activate endothelial cells
Endothelial activation vs. endothelial dysfunction
Activation = short-term stimulus that can be removed
Dysfunction = result of CHRONIC stimulus
- Coagulation, inflammation, smooth muscle stimulation
Chronic vascular injury (via any stimulus) leads to what stereotypical response? What is it?
INTIMAL THICKENING
- Smooth muscle cells migrate to intima, proliferate and elaborate extracellular matrix
- Blood flow is thus potentially affected
People w/ hypertention are at risk for what 5 things?
- Atherosclerosis
- Heart disease
- Stroke
- Renal disease
- Aortic dissection
Risk factors for essential HTN (5)
- High Na+ intake
- Obesity
- Stress
- Smoking
- Physical inactivity
2 components of blood pressure
Cardiac output, peripheral resistance
Components that affect cardiac output (5)
- Sodium
- Aldosterone
- ANP
- Heart rate
- Contractility
Components that affect peripheral resistance (many)
- Adrenergics
- Angiotensin 2
- PGs/LTs/Tx
- Vasodilator substances (NO, kinins)
- Autoregulation
- pH
- Hypoxia
MAIN regulator of blood pressure
RAAS system, ANP
Pathologic things that increase blood volume
- Excess sodium intake
- Renal failure
- Hyperaldosteronism
- Increased sodium reabsorption (Bartter, etc.)
Pathologic things that increase peripheral resistance
- Increased sympathetics (pheochromocytoma)
- Increased RAAS baseline
Main vascular change in chronic HTN or DM
What is it?
Hyaline arteriolosclerosis
- Increased SM matrix –> damaged endothelium –> proteins leak into vessel wall –> vessel narrowing
Main vascular change in malignant HTN or DM
Hyperplastic arteriolosclerosis
- SM concentric hyperplasia (“onion skin”) –> vessel narrowing
Constitutional risk factors for atherosclerosis (3)
- Family history
- Age (> 60)
- Gender (male, post-menopause female)
Modifiable risk factors for atherosclerosis (4)
- Hyperlipidemia (high LDL, low HDL)
- Hypertension
- Smoking
- DM
Describe why high LDL and low HDL are risk factors for atherosclerosis
LDL takes cholesterol to vessel walls (periphery) to be stored, while HDL brings it back to be broken down
- More LDL = more deposition
- Less HDL = less breakdown
How to increase HDL w/o drugs? (2)
- Moderate alcohol, exercise
How are obesity and smoking risk factors for atherosclerosis?
Both cause chronic immune system activation, causing vascular inflammation and endothelial damage
Metabolic syndrome
Central obesity, HTN, Type-2 DM
5 steps of atherosclerotic plaque formation
- Chronic endothelial injury (see risk factors above)
- Endothelial dysfunction (permeability, immune migration)
- Macrophage activation, SM recruitment to intima
- Macrophages and SM cells engulf lipids (FATTY STREAK)
- SM proliferation, collagen/matrix deposition, necrosis
Contents of the necrotic core in atherosclerosis (5)
Foam cells, inflammatory cells, dead cells, lipids, cholesterol ester crystals
Purpose of the fibrous cap on a plaque
Attempt to contain and heal the process
The location of an atherosclerotic plaque tends to be related to what?
Places of TURBULANCE
5 most common locations of atherosclerosis
- Posterior abdominal aorta
- Coronary arteries
- Popliteal arteries
- Internal carotid arteries
- Circle of Willis
Where are fatty streaks often found?
At ostia of vessels branching from aorta
What is a foam cell?
Endothelial cell stuffed w/ cholesterol trying to metabolize it, making it CLEAR and FOAMY
Potential consequences of atherosclerotic plaques (6)
- Rupture/ulceration
- Thrombosis –> occlusion
- Hemorrhage (into plaque or body cavity)
- Embolism
- Aneurysm of vessel wall
- Stenosis of arterial lumen
Describe the gradual lumen stenosis from a plaque
- Plaques grow over time due to injury/healing cycle
- Eventually CRITICAL STENOSIS (70%) causes ischemia downstream
- Get chronic ischemia of end-organs
Organs/structures prone to ischemia from atherosclerosis
Myocardium, bowel, brain, extremities
Causes of plaque rupture (3)
- Increased inflammation in plaque –> weakens fibrous cap
- Changes in blood pressure (want to keep it level)
- Vasoconstriction
Vulnerable vs. stable plaque
Vulnerable = thin cap, likely to rupture Stable = thick cap, unlikely to rupture
True vs. False aneurysm
True = thinned wall, ALL wall layers in tact False = defective wall, hematoma under connective tissue
Aneurysm vs. Dissection
A = Dilation of blood vessel due to weak/broken wall D = Splitting of muscle layer via escape/movement of blood
Marfan syndrome
Defective fibrillin –> defective vascular connective tissue
2 ways atherosclerosis can cause aneurysm
- Degrade vascular wall via inflammation
- Weaken vascular wall (media) via ischemia
See abdominal aortic aneurysm…
Think?
ATHEROSCLEROSIS –> vessel wall weakening
See ascending thoracic aortic aneurysm…
Think?
HYPERTENTION –> outer media ischemia (vaso vasorum)
No matter the cause, ALL aneurysms result in what w/in them?
What is it?
Cystic medial degeneration (disrupted and disorganized elastin and increased proteoglycans)
Severe chest pain that radiates to back between the scapulae
Aortic dissection - CLASSIC PRESENTATION
2 risk categories for aortic dissection
- HYPERTENSIVE males, 40-60 (MOST COMMON)
- Marfan syndrome
Most common location of aortic dissection
Ascending aorta
See intramural hematoma…
Think?
Aortic dissection
Type A (DeBakey 1) aortic dissection
Involves ascending aorta AND descending aorta
Type A (DeBakey 2) aortic dissection
Involves ascending aorta ONLY
Type B (DeBakey 3) aortic dissection
Involves descending aorta ONLY
Most common cause of death w/ aortic dissection
Rupture
Common complication of aortic dissection besides rupture
Occlusion of arterial branches (renal arteries, etc.)
Treatment of aortic dissection
Anti-HTN therapy + surgery to repair the intimal tear
