L39 Vascular Disease Flashcards
What makes up the intima of blood vessels?
- Endothelium (simple squamous epithelial cells)
2. Small subendothelial component
What makes up the media of blood vessels?
Smooth muscle; surrounded by internal elastic lamina and external elastic lamina on either side
What makes up the adventitia of blood vessels?
Connective tissue, collagen, vasovasorum
How can we distinguish the aorta from other high caliber blood vessels with a lot of smooth muscle in the media?
The aorta has a lot of elastic tissue, which stains black
Describe the intimal response to vascular injury.
When a vessel is injured:
- Recruitment of smooth muscles cells (and their precursors) to the intima from the media
- Smooth muscle cell mitosis (proliferation)
- Elaboration of ECM (intima thickens and expands)
What is arteriosclerosis, broadly?
Hardening of the arteries (arterial wall thickening and loss of elasticity)
What are the four major types of arteriosclerosis?
- Atherosclerosis
- Monckeberg’s medial calcific sclerosis
- Fibromuscular intimal hyperplasia
- Arteriolosclerosis
What kind of blood vessels are affected by atherosclerosis?
- Large elastic arteries (aorta, carotid, iliac)
2. Muscular arteries (coronary, popliteal, renal, mesenteric)
Describe the “response to injury” hypothesis of atherosclerosis.
Atherosclerosis is a chronic inflammatory response of the arterial wall to endothelial injury. The lesion progression involves interaction of lipoproteins, monocyte-derived macrophages, T-cells, and the cellular constituents of the arterial wall.
What is an atheroma?
The basic pathological entity that drives atherosclerosis; it is composed of a necrotic center filled with cell debris, cholesterol crystals, foam cells and calcium, as well as a fibrous cap filled with smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, and neovascularization.
True or false - atherosclerosis tends to affect the thoracic aorta more than the abdominal aorta.
False - it affects the abdominal aorta more than the thoracic aorta.
What are some possible outcomes of complicated plaques?
- Rupture/ulceration/erosion
- Emboli
- Hemorrhage
- Weakening of the media and aneurysm formation
- Calcification, growth, and lumen occlusion
- Thrombosis
Why is rupture a bad thing?
Rupture leads to exposure of the sub-endothelium to platelets and ultimately to thrombus formation
What are the spindle-like structures seen in histological slides of plaques?
Cholesterol clefts
Why can hemorrhage occur in plaques?
Because the atheroma gets neovascularized with new blood vessels
What is an aneurysm?
An outpouching of the blood vessel
What leads to an aneurysm?
Invasion of the atheroma into the media, loss of smooth muscle cells/strength
What are the important complications that stem from atherosclerosis?
- Myocardial ischemia (angina, infarction, sudden death)
- Cerebral ischemia (stroke, transient ischemic attack)
- Peripheral vascular disease (claudication, gangrene)
- Aneurysms (rupture)
What is Monckeberg’s medial calcific sclerosis?
Non-obstructive calcific deposits found in medium sized muscular arteries; centered on internal elastic lamina and media; appear chunky and purple on H&E stain
What is fibromuscular intimal hyperplasia?
Form of arteriosclerosis that affects muscular arteries larger than arterioles; involves a marked intimal thickening caused by smooth muscle cell proliferation and increased ECM
What are the etiologies of fibromuscular intimal hyperplasia?
- Vascular injury (particularly from stents and angioplasties)
- Inflammation (healed arteritis, transplant-associated arteriopathy)
What are the two types of hypertension induced arteriolosclerosis?
- Hyaline
2. Hyperplastic
What is hyaline arteriolosclerosis?
Arteriosclerosis seen in the arterioles and caused by hemodynamic stress (long standing high blood pressure); the endothelium is injured, plasma proteins leak out, ECM and smooth muscle cells increase; this all leads to a homogenous pink hyaline thickening of the media of the arterioles and a narrowing of the lumen
What is hyperplastic arteriolosclerosis?
Arteriosclerosis seen in patients with chronic severe hypertension or an abrupt increase in BP (malignant hypertension); processes of stress and repair lead to concentric thickening of smooth muscle cells and a progressive lumenal narrowing
How does hyperplastic arteriolosclerosis appear on H&E stain?
Onion skin
What is an aneurysm?
Localized abnormal dilatation of a blood vessel
What is the difference between a true aneurysm and a false aneurysm?
True: the entire vessel wall itself forms an out-pouching
False: a hematoma forms under the vessel
They look the same
What is the difference between a saccular and fusiform true aneurysm?
Saccular: portion of the wall outpouches
Fusiform: whole wall is dilated
What are the three broad causes of aneurysms?
- Abnormal connective tissue synthesis
- Excessive tissue degradation
- Loss of smooth muscle cells
What are two causes of abnormal connective tissue synthesis?
- Marfan syndrome (defective fibrillin synthesis and loss of elastic tissue)
- Ehlers Danlos (defective type III collagen)
What is one cause of excessive tissue degradation?
Increased matrix metalloprotease (released from macrophages)
What is one cause of loss of smooth muscle cells?
Ischemia (as a result of atherosclerotic thickening of the intima or narrowing of the vasovasorum)
What is cystic medial degeneration?
Elastin fragmentation and loss of smooth muscle cells lead to areas resembling cystic spaces filled with proteoglycans; sometimes seen in patients with aneurysms
What are 5 major causes of aneurysms?
- Atherosclerosis
- Hypertension
- Congenital defects (berry aneurysm)
- Inflammation (infections and vasculitis)
- Trauma
What is the etiology and pathogenesis of an aneurysm of the abdominal aorta?
ECM degradation mediated by MMPs released from inflammatory infiltrates leads to compression of the media and compromised nutrient and waste diffusion from the vascular lumen into the arterial wall; the media undergoes degeneration and necrosis and the arterial wall weakens and thins
What is the characteristic location of an abdominal aortic aneurysm?
Infrarenal (below the renal bifurcation) and above the aortic bifurcation
Abdominal aortic aneurysms are commonly seen in which populations?
Men, smokers, people over 50
What can be felt on a physical exam vis a vis an abdominal aortic aneurysm?
Pulsatile abdominal mass
What are the possible complications of AAA?
Compression, obstruction, and embolism
What is an aortic dissection?
Tear in the intima; occurs when blood splays apart laminar planes of the media to form a blood filled channel within the aortic wall (usually happens in the thoracic aorta)
What are the etiologies of aortic dissections?
- Hypertension (pressure related mechanical or ischemic injury - medial hypertrophy of vasovasorum and degenerative changes of media/loss of SMC)
- People with connective tissue disorder (abnormal vascular ECM)
- Bicuspid aortic valves
What is the difference between Type A and B dissections?
Type A: involve proximal aorta
Type B: do not involve proximal aorta
What is a major symptom of aortic dissection?
Sudden onset ripping chest pain radiating to the back
What are the complications of aortic dissection?
Rupture or extension
How is aortic dissection treated?
Blood pressure control and surgery
What is an angiosarcoma?
Cancer of endothelial cell origin; can involve any body site (common in skin, soft tissue, breast), highly malignant
What type of stain is used for angiosarcoma?
Immunohistochemical for endothelial maker CD31 and VW factor
Hepatic angiosarcoma is often caused by exposure to carcinogens, such as…
…arsenic (pesticides), thorotrast (formerly used radioactive contrast agent), polyvinyl chloride (plastic)
What is the connection between lymphedema of the arm and angiosarcoma?
Radical mastectomy and lymph node dissection is sometimes correlated with development of angiosarcoma
What are hemangiomas?
Common benign neoplasms of blood vessels, often seen in children
