Module 6 CVS: Arteriole and Atherosclerotic plaque Flashcards
What are characteristics of a dysfunctional endothelial cells?
- Prothrombotic surface
- Increased leukocyte adhesivity (VCAM-1/ICAM)
- Does not produce nitric oxide – constriction
What is Kaposi’s sarcoma as well as angiosarcoma?
Kaposi’s Sacrcoma: AIDS patient with purple lesion on skin
Angiosarcoma: exposure to vinyl chloride
What is cardiomegaly vs cardiac hypertrophy?
Cardiomegaly: increase in cardiac weight or seize
Cardiac Hypertrophy: increase weight and ventricular thickness
The heart wall is composed of what layers?
Epicardium
Myocardium
Endocardium
What are the 4 cardiac valves and some features?
Mitral Tricuspid Aortic Pulmonary maintains a unidirectional blood flow scant blood supply -- thin enough to be nourished by diffusion from the heart's blood
What are the atrioventricular values vs semilunar valves?
AV: mitral and tricupsid
leaflets of valve held in place by chordae tendineae – contiguous with the underlying ventricular wall
SV: aortic and pulonary
3 leaflets or cusps
What is the general blood supply of the heart?
R and Left coronary arteries are end arteries
only supply of oxygen blood to that region of tissue
most blood flow to myocardium = during diastole (contraction)
Collateral circulations
numerous interconnections
contains little blood in normal hearts
open up when 1 artery is severely narrowed
What are the three layers of arteries?
Intima: endothelial cells; blood supply from direct diffusion (internal elastic lamina)
Media: smooth muscle cells, ECM and nerves
(external elastic lamina)
Advantitia: CT
What are the three types of arteries?
- Large elastic: aorta, iliac and pulmonary
- Medium Muscular: Coronary, renal and radial
* regulate pressure: vasoconstriction and vasodilation
* medial calcific Sclerosis (Mockenberg s) - Small Artery, arterioles: inside organs
* Arteriolosclerosis (hyaline or hyperplastic)
What is the function of the tunica intima?
-Maintenance of perm barrier
-Elaboration of antithrombotic and prothrombotic molecules
-Modulation of blood flow and vascular reactivity
(endothelin = vasoconstriction ; NO = Vasodilaation)
In regards to tunica intima and IL1,IL6,and TGFbeta what are the roles of each?
IL6 and IL1 are regulators of inflammation and immunity
–IL1: released by macrophages, endothelial; pro inflammatory= activates endothelial cells
–IL6: macrophages, Ts; induce acute phase proteins= pro inflammatory
PDGF/TGF-B are regulatory of cell growth (pro growth)
Endothelial activation = altered gene expression and protein synthesis. What are the activators and associated induced genes?
Cytokines — Adhesion Molecules (ICAM/VCAM)
Bacterial Product —- Cytokines and Chemokines
Hemodynamic Forces —- growth factors
Viruses —- MHC I molecules
What are the three characteristics of endothelial activation (aka dysfunctional endothelial cell characteristics?
Alteration in gene expression and protein synthesis
1. Pro-Thrombotic Surface: hyper-cogulative
2. Increased leukocyte adhesivity
3. Does not produce NO = then no vasodilation
and impaired endogenous anti inflammation and vasodilation
What is atherosclerosis and atheromatous plaque?
Atherosclerosis = buildup of fat/cholesterol in the arteries = hardening of the arteries
Atheromatous Plaques: lipid core (LDL and inflammatory cells) covered by a fibrous plaque
What are the order of arteries affected by atherosclerotic plaques?
Infra-renal abdominal aorta
Proximal coronary arteries
Branches of abdominal aorta (femoral, popliteal a d iliac) and Thoracic Artery
Carotid Arteries
Circle of Willis (vertebral, basilar and middle cerebral)
What are the 4 modifiable and 3 non modifiable pre-disposing factors for atherosclerotic plaques?
Modifiable: Hypercholesterimia, HTN, Smoking and diabetes
Non-Modifiable: Age, Gender (men more likely), genetics
Less then what percent occlusion of the lumen will the patient stay asymptomatic?
70%
What are the three main components of a fibro-fatty plaque?
Cells (macrophages, SM cells and T cells)
ECM (Collagen, elastic fibers, proteoglycans)
Lipids
At about 10 years of age, individuals start developing what?
Fatty dots (macrophage foam cells – macrophages have ingested fats) and then these fatty dots come together to form fatty streaks these fatty streaks will then become atherosclerotic plaques
Atherosclerosis is considered the disease of what?
Intima
What are the 6 complications of atherosclerotic plaque?
Dystrophic Calcification
Embolism (cholesterol emboli most common and most affected arteries are peripheral arteries of the lower extremities)
Aneurysms
Ulcers when ulcers become deep its a fissure
Hemorrhage (ulcers bleed)
Rupture
What is the pathogenesis of Atherosclerosis?
Fatty dots with macrophage foam cells —– fatty streaks with lipid laden macrophages —- cholesterol plaques (Asymptomatic) —–leads to the 6 complications
What are the 2 components of the atherosclerotic plaque?
Fibrous Cap (made of collagen) Lipid Core (inflammatory cells and LDLs)
What makes a plaque stable?
Thick Fibrous Cap (Collagen) because lipid core is highly thrombogenic (Can attract fibrin, platelets and RBCs) so therefore you never want to expose the lipid core
Smooth muscle cells lay down the collagen from the media to intima.
More smooth muscle cells then more stable the plaque because more collagen
Less inflammatory cells
Less Lipid Core
What makes a plaque unstable?
Usually the rupture (via turbulent flow)– cap is lifted off and exposes the core to the lumen
Moderately Stenotic
Thin Fibrous Cap
Core rich in lipids
Less smooth muscle proliferation
If core gets in contact with lumen — superimposed thrombosis (made of fibrin, platelets and RBCs) — pale infarct in the heart and patient will get a transmural MI and coagulative necrosis
What is the best investigation for an atherosclerotic plaque?
Angiogram
but remember this can lead to embolism
Complications of atherosclerosis following rupture are what?
MI –> early MI is the yellow part in the picture and white part is late MI in the picture
Stroke — Red infarct in brain and coagulative then liquefactive necrosis
Gangrene — when cap comes off
Monckeberg’s Medial Calcific Sclerosis, is dystrophic calcification of which part of the blood vessel?
Media and affects small to medium arteries usually
never encroach on the vessel lumen
What is the etiology of Monckeberg’s Medial Calcific Sclerosis?
Aging and wear and tear
Monckeberg’s is sometimes compared to aortic stenosis, how are they different?
Aortic Stenosis: Syncope, Angina, and Dyspnea
Monckeberg’s: No symptoms (incidental finding on autopsy)
What arteries are the most affected by Monckeberg’s??
- Radial
2. Renal
Arteriolosclerosis affects what type of arteries?
Small vessels of organs (aka arterioles)
affects full thickness of vessel
Afferent comes in
Efferent goes out
The first type of arteriolosclerosis is hyaline arteriolosclerosis what is the most common cause?
Chronic Benign HTN
slightly high about 140/90
How does hyaline arteriolosclerosis look on histology?
Pink: due to leakage of plasma proteins from the lumen to the tunica media
In regards to chronic benign HTN hyaline arteriolosclerosis, what arterioles are/is affected?
Only affects the incoming arteriole (afferent) because blood pressure only affects the incoming vessels
What is an additional cause of hyaline arteriolosclerosis and what arterioles are/is affected?
Diabetes Mellitus
–affects both afferent and efferent because sugar goes everywhere basically
What is the most common symptom of hyaline arteriolosclerosis?
No symptoms (incidental findings) however you can get bilateral renal atrophy which leads to chronic renal failure (if you get significant lumen narrowing)
The next arteriolosclerosis is hyperplastic and onion skin of arterioles, what is the etiology and what arterioles are affected?
Chronic Malignant HTN (210/120)
Affects the afferent (because this is the only etiology of chronic malignant HTN)
no diabetic involvement
can also have sudden malignant HTN both lead to end organ damage
What is the pathogenesis for sudden malignant HTN?
damage to endothelium of afferent arterioles and therefore you form a thrombus and the media gets its oxygen from the lumen and therefore media undergoes fibrinoid necrosis and you get necrotizing arteriolitis
What the affects of end organ damage for both sudden and chronic malignant?
Kidney: hematuria, oliguria, and edema (both kidneys are affected)
Brain: Hemorrhagic stroke (pops the cerebral arteries – vomiting due to increased intracranial pressure)
Eyes: Retinal detachment (due to retinal hemorrhages — blindness)
Heart: left heart failure
Aorta: Aortic Dissection
What are some general characteristics for HTN?
25% of persons in gen population are hypertensive
leading risk for: MI and stroke
Silent kiler: painless complications
complications finally –> lead to diagnosis but often too late
chronic end organ damage and vascular damage
What factors regulate BP (cardiac output x peripheral resistance)?
- Endocrine factors: renin, angiotensin, ANP, ADH and Aldosterone
- Neural Factors: SNS and PSNS
- Blood Volume: sodium, mineralcorticoids, ANP (vasodilation)
- Cardiac factors : heart rate and contractility
Primary/essential HTN is in 95% of patients and secondary is 5% of patients, what are some reasons for secondary HTN?
- Renal: glomerulonephritis, RAS, renin tumors (Ex. atherosclerosis of renal artery near the ostia of branching vessels)
- Endocrine: Cushings, oral contraceptives, thyrotoxicosis, myxedema and pheochromocytoma , acromegaly
- Vascular: Coarctation of aorta, PAN, aortic insufficiency/regur
- Neurogenic: psychogenic, intracranial pressure
What is the pathogenesis of primary and secondary HTN?
Essential: multifactorial (idiopathic): 95% of cases ; increased peripheral resistance; SNS tone = increased vasoconstriction; stress/hormone/neural ; genetic/familial/ life style/smoking/obesity/salt consumption
Secondary: Renovascular (known as abnormal control): increase blood volume (Sodium retention, ADH, aldosterone) , increased SNS tone (Adrenal tumors), Increased vasoactive hormones (Cushing, phechromocytoma)
Malignant hypertension can cause necrotizing arteriolitis, which is a type of hyperplastic arteriolosclerosis, what is necrotizing arteriolitis?
Vascular damage due to increased HTN = increased vascular permeability to fibrinogen ----- leads to endothelial damage and fibrinoid necrosis of the media of arterioles; characteristic again of malignant HTN leads to end organ damage: --renal failure --LV failure ---HTN encephalopathy
