Endothelium, plaque rupture and vascular injury Flashcards
(28 cards)
What is endothelium?
- Tissue consisiting of a single layer of cells that lines the blood and lymph vessels, heart, and some other cavities
- Arteries vs capillaries vs veins vs lymphatics
What are the tissues present in the Tunica Intima?
Tunica intima = endothelium + thin layer of connective tissue (CT)
What are the layers of tissue present in the Tunica Media?
- Tunica Media = vascular smooth muscle and connective tissue
What layers of tissue are present in Tunica Adventitia?
Adventitia = loose CT
In a very BROAD sense what is the difference between large arteries, smaller arteries, and arterioles?
- Large Arteries - more elastin
- Small Arteries - more collagen
- Arterioles - more smooth muscle
What is the effect of inflammatory activation on endothelial and smooth muscle cells?
- Inflammatory activation of these vascular cells corrupts their normal functions and favors proartherogenic mechanisms that drive plaque development
What was the first gas to be discovered as a signaling molecule in the body?
Nitric Oxide (NO)
What is Nitric Oxide’s role in the body?
-
cGMP-mediated vasodilation
- Expressed on luminal side of endothelium
- Made by NO Synthase (enzyme catalyst)
- Come from L-Arginine
What are the 3 main inflamatory molecules that promote an “inflammatory state” in the endothelium?
- Selectins
- Cell Adhesion Molecules (CAM)
- Cytokines
Describe the formation of an atheroscleoritc plaque begining from a monocyte
Hint - Monocyte is the first step
*see attached image for more detailed depiction
Monocytes -> Macrophages -> Foam Cells -> SM cell activation / migration ->
- Apoptosis
- Fibrosis
- Ongoing inflammation
What are the 3 steps of atheroscleoritc plaque progression?
- Fatty Streak formation
- Endothelial dysfunction
- Lipoprotein entry/modification
- Leukocyte recruitment
- Foam cell formation
- Plaque Progression
- SM cell migration & inflammatory state
- Plaque disruption/rupture (unstable plaque)
- Thrombus formation
What are the features of a stable plaque?
Stable Plaques
- Rich in fibrous tissue
- Calcified
- Less lipid content
- Less inflammation
- Less apoptosis
What are the features of vulenrable plaques?
Vulnerable Plaques
- Less fibrous tissue
- Less calcified
- More lipid content
- More inflammation
- More apoptosis
Why do we care about vulnerable vs stable plaques?
Vulenrable plaques rupture, thrombose and lead to clinical events
- e.g. - leads to MI
What molecules regulate thrombosis?
- Heparin sulfate/thrombin - surface of endothelium
- NO / platelet activation - secreted by endothelium
- Prostacyclin - secreted by endothelium
What are the 5 main risk factors for atherosclerosis?
- HTN
- HLD (hyperlipidemia)
- Smoking
- Diabetes
- Age
What are the 5 different mechanisms of ischemia?
See attached
- Narrowing of vessel by fibrous plaque
- Plaque ulceration or rupture
- Intraplaque hemorrhage
- Peripheral emboli
- Weakening of vessel wall
What are the 2 common mechanism of stroke?
Atheroembolization from carotid bifurcation lesion
- Source lesion does not need to be obstructive (<70% diameter reduction)
- Ophthalmic artery
Thromboembolization from left atrial appendage in setting of atrial fibrillation
- MI and stable angina are both manifestations of what?
- What are the pathologies of MI and stable angina?
- Coronary Artery Disease (CAD)
- MI has a different vascular pathology vs angina
- MI – ruptured plaque, in-situ thrombosis, not necessarily obstructive prior to rupture
- Angina - stable, obstructive (>70% diameter reduction) lesion
Describe the progression of a Myocardial Infarction?
Not all the same severity
- Plaque rupture-> non-occlusive thrombosis -> some flow but intermittent occlusion or embolization -> stabilize with anticoagulation / vasodilators
- Plaque rupture -> occlusive thrombus -> no flow -> clinical emergency -> recanalize
What are two manifestations of Peripheral Arterial Disease (PAD)?
- Claudication
- obstructive, stable plaque)
- Acute Limb Ischemia
- Acute event obstructs blood flow without prior development of collaterals (anastomosis)
What is the difference between a stable plaque and an unstable/vulnerable plaque?
**Likely a test question, make sure you know this**
-
Stable plaques
- Less biologically active
- Cause angina and claudication (exertional ischemia) if obstructive (>70% diameter reduction)
- Less likely to cause thrombotic and embolic events
-
Unstable / Vulnerable plaques
- More biologically active
- Cause MI and stroke
- More likely via thrombotic and embolic mechanisms
What is Venous Thomboembolic Disease (VTD)?
Includes: Deep Vein Thrombosis (DVT) & Pulmonary Embolism (PE)
Venous thrombosis is different than arterial thrombosis
What are the characterisitcs of a venous thrombosis?
**Likely more background than memorization**
Venous Thrombosis
- Fibrin rich
- Have lots of RBC
- Occur in areas of stasis
- Often involve genetic/environemental predisposition
- Treated with anticoagulation
