3.2.3. Vascular Pathology Part 1 of 3 Flashcards
What is the tunica intima comprised of? What separates it from the tunica media?
tunica intima: single layer of endothelial cells sitting on a basement membrane (underlain by thin layer of ECM -extracellular matrix)
separated from media by internal elastic lamina
Compare the tissue of arteries and veins with respect to their organization on the tissue level
arteries: well-organized, concentric layers of smooth muscle
veins: larger diameters & lumens, with thinner & less organized walls than arteries at the same level of branching
What are large arteries also called and why?
(large) elastic arteries (e.g. aorta): high elastin content
What are our medium arteries and what affects their size?
(medium) muscular arteries: predominantly composed of circumferentially oriented SM cells
autonomic input varies the degree of vasodilation/-constriction
What type of arteries are affected most by blood flow resistance and what affects this resistance the most?
(small) arterioles: principal points of physiologic resistance to blood flow (autonomic changes to lumen diameter profoundly affect amount of resistance)
What are capillaries?What layer of tissue is missing from capillaries that is present in arteries?
capillaries: endothelial lining without media
Where is the tunica adventitia and what comprises it? What separates it from the preceding layer?
tunica adventitia: external to media; usual separated by the external elastic lamina
consists of loose connective tissue containing nerve fibers and vasa vasorum
What do all vessels have in common as far as layers? As review, what comprises these layers?
all vessels except capillaries share a three-layered architecture consisting of an endothelium-lined intima, a surrounding smooth muscle media, & supportive adventitia, admixed with extracellular matrix
What are our congenital vascular anomalies?
developmental or berry aneurysms
arteriovenous fistulas
fibromuscular dysplasia
Describe developmental or berry aneurysms. Where do they occur and what do they do?
occur in cerebral vessels
when ruptured can cause fatal intracerebral hemorrhage
Where do we see arteriovenous fistulas and what can rupture lead to?
direct connections between arteries and veins that bypass the intervening capillary bed
can rupture leading to intracerebral hemorrhage
Describe fibromuscular dysplasia
focal, irregular thickening in med. & lg. muscular arteries
- combined medial & intimal hyperplasia as well as fibrosis which results in luminal stenosis
- immediately adjacent vessels can have markedly attenuated media → vascular outpouchings (aneurysms) that can rupture. Has a “string of beads” appearance on angiography
What are the synthetic and metabolic properties of endothelial cells?
nonthrombogenic surface, modulate medial SM cell tone, metabolize hormones, regulate inflammation, affect growth of other cell types (particularly SM cells)
Effect of cytokines and bacterial products on endothelial cells
elicit inflamm.; extreme: septic shock
Effect of hemodynamic stresses & lipid products on endothelial cells
pathogenesis of atherosclerosis
Effect of advanced glycation end-products on endothelial cells
pathogenesis of diabetes
What 5 items activate endothelial activation?
Normotension Laminar Flow Growth Factors Cytokines Hypoxia/Acidosis
When you activate an endothelial cell what happens?
Stimulates: Growth factors Vasoactive mediators Adhesion molecules Anti-coagulants
Endothelial dysfunction can cause what?
Release of: Growth factors (like with normal activation) Chemokines Cytokines Pro-coagulant proteins Adhesion molecules Vasoactive mediators
What do vascular smooth muscle cells synthesize?
synthesize collagen, elastin, and proteoglycans, elaborate growth factors, & cytokines
responsible for vasodilation/-constriction
Effect of vascular injury on a vessel?
Vascular injury- associated with endothelial cell dysfunction or loss- stimulates smooth muscle cell recruitment and proliferation and associated matrix synthesis; the result is intimal thickening
Excessive thickening of the intima results in what?
excessive thickening of the intima may result in luminal stenosis and vascular obstruction
What can hypotension do to the body?
Hypotension can result in inadequate organ perfusion and can lead to tissue dysfunction and death.
What can hypertension do to the body? What percent of Americans are affected by it?
Hypertension (HTN) can cause end-organ damage and is one of the major risk factors for atherosclerosis, CHF and renal failure. Hypertension is a common disorder affecting roughly 30% of adults in the U.S.
Increased risk of atherscelerotic disease is associated with sustained diastolic pressures above ___ mm Hg or sustained systolic pressure above ___ mm Hg.
Increased risk of atherscelerotic disease is associated with sustained diastolic pressures above 89 mm Hg or sustained systolic pressure above 139 mm Hg.
95% of hypertension is of unknown etiology and is referred to as _______ _______. aka _______ _______.
95% of hypertension is of unknown etiology and is referred to as primary hypertension. aka essential hypertension
Risk factors of HTN
Risk factors include age, race (increased risk in African American, decreased risk in Asians), obesity, stress, lack of physical activity, and high-salt diet.
5% of hypertension is of known etiology and is called _____ _____.
5% of hypertension is of known etiology and is called secondary hypertension.
Common cause of secondary HTN
Renal artery stenosis is a common cause (renovascular hypertension)
What does stenosis do to the kidney?
Stenosis decreases blood flow to the glomerulus.
Once bloodflow is reduced to the glomerulus, what happens?
Juxtaglomerular apparatus (JGA) responds by secreting renin, which converts angiotensinogen to angiotensin I.
What does ACE do?
Angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE).
What does Angiotensin II do?
Angiotensin II raises blood pressure by:
Contracting arteriolar smooth muscle, which increases total peripheral resistance
Promoting adrenal release of aldosterone, which increases resorption of sodium in the distal convoluted tubule.
What does increased blood pressure do to the kidneys?
Leads to hypertension with increased plasma renin and unilateral atrophy (due to low blood flow) of the affected kidney. Neither of these features is seen in primary hypertension.
Gene defects affecting enzymes involved in aldosterone metabolism ⇒ leads to what?
Gene defects affecting enzymes involved in aldosterone metabolism ⇒ lead to increased aldosterone secretion, increasing salt and water resorption
What is Liddle Syndrome and what kind of mutation is it?
Mutations affecting proteins that influence sodium reabsorption; moderately severe form of salt-sensitive hypertension is called Liddle syndrome (gain-of-function mutation).
2 most important causes of stenosis:
Atherosclerosis (elderly males)
Fibromuscular dysplasia (young females)
What is fibromuscular dysplasia and what does it cause?
Developmental defect of the blood vessel wall that results in irregular thickening; commonly affects the renal artery
The most important determinant of stroke volume is the ____ ____, which is regulated through ________________________.
The most important determinant of stroke volume is the filling pressure, which is regulated through sodium homeostasis and its effect on blood volume.
Cardiac output is a function of ____ _____ and _____ _____.
Cardiac output is a function of stroke volume and heart rate
Hypertension can also be classified as _____ or _____.
Hypertension can also be classified as benign or malignant.
What is benign HTN?
Benign HTN is a mild or moderate elevation in blood pressure; most cases of HTN are benign.
Clinically silent, vessels and organs are damaged over time.
What is malignant HTN? How does it present?
Malignant HTN is severe elevation in blood pressure; comprises <5% of cases.
May rise from preexisting benign HTN or de novo (present suddenly)
Presents with acute end-organ damage (e.g. acute renal failure, headache, and papilledema) and is a medical emergency
What two forms of small blood vessel disease are associated with hypertension?
Hyaline arteriolosclerosis
Hyperplastic arteriolosclerosis
What is arteriosclerosis?
Literally means “hardening of the arteries” - due to thickening of the blood vessel wall
What are the three pathological patterns of arteriosclerosis?
Atherosclerosis - most frequent
Arteriolosclerosis - affects small arteries and arterioles
Monckeberg medial calcific sclerosis - characterized by calcification of the walls of muscular arteries, typically involving the internal elastic membrane.
In descending order, the most extensively involved vessels are: (5 of them).
In descending order, the most extensively involved vessels are: abdominal aorta, coronary arteries, popliteal arteries, internal carotid arteries, and the vessels of the circle of Willis
What is and what is caused by an intimal plaque?
Intimal (tunica intima layer) plaque obstructs blood flow (caused by intimal thickening and lipid accumulation)
Consists of a necrotic lipid core (mostly cholesterol) with a fibromuscular cap; often undergoes calcification
What are the types of risk factors of artherosclerosis?
Modifiable and Nonmodifiable
Modifiable risk factors of artherosclerosis
Modifiable: HTN, Hypercholesterolemia (LDL increases risk, HDL decreases risk), Smoking, Diabetes
Nonmodifiable risk factors of artherosclerosis
Nonmodifiable: Age, Gender (estrogen is protective), Genetics (family history is highly predictive of disease)
Risk factors have a roughly _____ effect
Risk factors have a roughly MULTIPLICATIVE effect
Risk factors that are not in the category of modifiable or nonmodifiable risk factors
Inflammation (C-reactive protein), Hyperhomocysteinemia, Metabolic syndrome, Lipoprotein a
Damage to endothelium allows _____ to leak into the intima
Damage to endothelium allows lipids to leak into the intima
The two most important causes of endothelial dysfunction are _____ _____ and _____.
The two most important causes of endothelial dysfunction are hemodynamic disturbances and hypercholesterolemia.
What happens to lipids that breach the intima?
Lipids are oxidized and then consumed by macrophages via scavenger receptors, resulting in foam cells.
Inflammation and healing of the intima leads to what?
Inflammation and healing leads to deposition of extracellular matrix and proliferation of smooth muscle.
Stages of artherosclerotic plaque buildup
Begins as fatty streaks (flat yellow lesions of the intima consisting of lipid-laden macrophages)
Progresses to atherosclerotic plaque
Stenosis of medium-sized vessels results in impaired blood flow and ischemia leading to:
Stenosis of medium-sized vessels results in impaired blood flow and ischemia leading to:
Peripheral vascular disease (lower extremity arteries)
Angina (coronary arteries)
Ischemic bowel disease (mesenteric arteries)
In regards to plaque, what causes a myocardial infarction? How about a stroke?
Plaque rupture with thrombosis results in myocardial infarction (coronary arteries) and stroke (e.g. middle cerebral artery)
Plaque rupture with embolization results in what?
Plaque rupture with embolization results in atherosclerotic emboli, characterized by cholesterol crystals within the embolus.
What causes an aneurysm in regards to plaque?
Weakening of vessel walls results in aneurysm (e.g. abdominal aorta)
What is Arteriolosclerosis?
Narrowing of small arterioles
What causes Hyaline arteriosclerosis? Why is it called this?
Caused by proteins leaking into the vessel wall, producing a vascular thickening
Proteins are seen as pink hyaline on microscopy
What are the effects of Hyaline arteriosclerosis?
Results in reduced vessel caliber with end-organ ischemia; classically produces glomerular scarring (arteriolonephrosclerosis) that slowly progresses to chronic renal failure
What causes hyperplastic arteriosclerosis?
Thickening of the vessel wall by hyperplasia of smooth muscle (“onion skin” appearance)
Hyperplastic arteriosclerosis is a consequence of what?
What does it result in?
Consequence of malignant hypertension
Results in reduced vessel caliber with end-organ ischemia
What causes “flea-bitten” appearence?
Hyperplastic arteriosclerosis may lead to fibrinoid necrosis of the vessel wall with hemorrhage; classically causes acute renal failure with a characteristic ‘flea-bitten’ appearance
What is Monckeberg Medial Calcific Sclerosis? How dangerous is this?
Calcification of the media of muscular (medium-sized) arteries.
It is nonobstructive.
_____ can be confused for cancer.
Presence of calcifications on a mammography usually indicate cancer - this can be confused for cancer (but Monckeberg is benign)
There are true and false anuerysms. What is the difference?
True aneurysm: involves an attenuated but intact arterial wall or thinned ventricular wall of the heart
False aneurysm: defect in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space (“pulsating hematoma”).
What is a Thoracic Aortic Aneurysm and what is it clasically seen with?
Balloon-like dilation of the thoracic aorta
Due to weakness in the aortic wall. Classically seen in tertiary syphilis:
Weakening of the aortic wall is linked to what condition? What appearence does it give to the aorta?
Endarteritis of the vasa vasorum results in luminal narrowing, decreased flow, and atrophy of the vessel wall. Results in ‘tree bark’ appearance of the aorta.
What is the major complication of a thoracic aortic aneurysm?
Major complication is dilation of the aortic valve root, resulting in aortic valve insufficiency.
What are other less urgent complications of a Thoracic Aortic Aneurysm (the worst being dilation of the aortic valve root discussed in a previous card)?
How would a patient with these conditions present?
Other complications include compressions of mediastinal structures (e.g. airway or esophagus) and thrombosis/embolism (due to the disruption of normal laminar flow)
Patient may present with respiratory difficulties, difficulty swallowing, persistent cough, pain caused by erosion of bone (all due to the compressions of mediastinal structures)
What is Thoracic Aortic Aneurysm linked to?
Commonly associated with HTN, but also seen in Marfan’s syndrome and Loeys-Dietz syndrome.
What is an Abdominal Aortic Aneurysm (AAA)?
Balloon-like dilation of the abdominal aorta; usually arises below the renal arteries but above the aortic bifurcation
What causes a AAA?
Primarily due to atherosclerosis; classically seen in male smokers >60 years old with HTN
Atherosclerosis increases the ____ ____ to the media, resulting in ____ and what?
Atherosclerosis increases the diffusion barrier to the media, resulting in atrophy and weakness of the vessel wall
How do AAAs present?
Presents as a pulsatile abdominal mass that grows with time
What is the major complication of AAA and how does it present itself?
Major complication is rupture, especially when >5 cm in diameter; presents with triad of hypotension, pulsatile abdominal mass, and flank pain
AAA can also cause complications that aren’t as immediately life threatening as rupture, but are still very dangerous. What are they?
Other complications include compression of local structures (e.g. ureter) and thrombosis/embolism.
What are the three causes of mycotic aneurysms?
Can originate from embolization of a septic embolus, usually as a complication of endocarditis
Can originate as an extension of an adjacent suppurative process
Can originate by circulating organisms directly infecting the arterial wall
An arterial dissection arises how?
An arterial dissection arises when blood enters a defect in the arterial wall and tunnels between its layers
Aortic dissection occurs when?
Aortic dissection occurs when blood separates the laminar planes of the media to form a blood-filled channel within the aortic wall.
One route is an Intimal tear with dissection of blood through the media of the aortic wall
Most common 2 causes of an arterial dissection?
Most common cause is hypertension (older adults); also associated with inherited defects of connective tissue (younger individuals)
What connective tissue weakening conditions are associated with arterial dissections?
What is the damage they cause specifically called?
Marfan syndrome and Ehlers-Danlos syndrome classically lead to weakness of the connective tissue in the media (cystic medial necrosis)
How do dissections present?
Presents as a sharp, tearing chest pain that radiates to the back
What 3 major concerns do we have with aortic dissections? What is the most common cause of death?
Complications include pericardial tamponade (most common cause of death), rupture with fatal hemorrhage, and obstruction of branching arteries (e.g. coronary or renal) with resultant end-organ ischemia.
What are the types of dissections and what are the DeBakey classifications in relation to them?
The more common (and dangerous) proximal lesions, called Type A dissections, involve either both the ascending and descending aorta or just the ascending aorta only (types I and II of the DeBakey classification)
Distal lesions not involving the ascending part and usually beginning distal to the subclavian artery are called Type B dissections (Debakey type III)
