Blood Vessels Flashcards
Regional specializations of the vasculature
aorta: elastic tissue to accommodate high pulsatile forces, with the capacity to recoil and transmit energy into forward blood flow.
muscular arteries and arterioles: concentric rings of medial smooth muscle cells whose contractile state regulates vessel caliber and, thereby, blood flow and blood pressure.
venous system: relatively poorly developed medial layers that permit greater capacitance.
capillary wall: permits ready diffusion of oxygen and nutrients because it is comprised only of an endothelial cell and sparse encircling pericytes.
Thus, loss of aortic elastic tissue in a large artery may result in aneurysm, while stasis in a dilated venous bed may produce a thrombus.
Arteries
Large or elastic:
aorta, its large branches and pulmonary arteries
Medium-sized or muscular
other branches of the aorta
Small: less than 2 mm in diameter vasa vasorum feed medium and large arteries outer 1/2 to 2/3 of the media
Arterioles
20 - 100 μm diameter
Within the substance of tissues and organs
Arterioles (and small muscular arteries) are primary regulators of arterial blood pressure (autonomic system and other local and systemic controls)
Medial smooth muscle contraction changes lumen diameter
Resistance to fluid flow is inversely proportional to the fourth power of the diameter/radius
(i.e., halving the diameter/radius increases resistance 16-fold)
Veins
Venous valves in the extremities
Large lumen
Approximately 2/3 of all the blood is in veins
Thin less well organized walls
***Postcapillary venules
Site of leukocyte exudation and vascular leakage
Walls vs lumen in arteries and veins
Because it must sustain higher pressures, the artery has a thicker wall with more-organized elastin architecture than in the corresponding vein. Conversely, the vein has a larger lumen with diffusely distributed elastin, permitting greater capacitance.
Capillaries
Approximately the diameter of a red blood cell (7-8 μm) or larger
Endothelial cell lining (no media)
Surrounding pericytes
Rapid exchange of diffusible substances
Lymphatics
Endothelial cell lining (no media)
Valves in larger lymphatic vessels
System for returning interstitial tissue fluid and inflammatory cells to blood
Important pathway for disease dissemination
Endothelial cells contain what important structure?
what types exist?
Contain Weibel-Palade bodies [membrane-bound storage organelles that contain von Willebrand factor (vWF)]
Junctions normally impermeable to large molecules (proteins) with exceptions:
- Fenestrated endothelial cells
- Discontinuous (sinusoidal)
endothelium
Vascular Smooth Muscle- regulated by?
Responsible for vasoconstriction and dilation
Regulated by:
* promoters (PDGF, endothelin-1, thrombin, FGF, IFN-γ, and IL-1)
* inhibitors (heparan sulfates, NO and TGF-β)
* renin-angiotensin system, catecholamines, estrogen, and osteopontin (part of extracellular matrix)
Migrate to the intima and proliferate following injury
Synthesize collagen, elastin, and proteoglycans
Elaborate growth factors and cytokines
Developmental (congenital, berry) aneurysms
saccular type aneurysm arising in an artery
with a developmental wall abnormality
seen in 2% of autopsies
mostly found in circle of Willis
Arteriovenous fistulas
rare abnormal communications between arteries and veins
most congenital; some produced (rupture of an arterial aneurysm into adjacent vein, injuries that pierce walls of artery and vein, or inflammatory necrosis of adjacent vessels)
short-circuit blood and cause heart to pump additional volume (high-output cardiac failure can ensue)
vascular anomalies that can rupture
developmental aneurysms (congenital, berry) and arteriovenous fistulas
Fibromuscular dysplasia
focal irregular medial and intimal hyperplasia with thickening of walls of medium and large muscular arteries
occurs more commonly in young women
can cause HTN (affecting renal artery, –> compensatory renin)
Hypertension (HTN)
Hypertension = Sustained chronically elevated pressure
Systolic > 140 mm Hg
2014 Evidence Based Guidelines suggest > 150/90 mm Hg for those > 60 years.
Diastolic > 90 mm Hg
Prehypertension
Systolic 120-139 mm Hg
Diastolic 80-89 mm Hg
29% of persons in the general population are HYPERTENSIVE
Risk for coronary artery disease, cerebral vascular accidents, hypertensive heart disease, aortic dissection, renal failure, etc
Systolic blood pressure is more important than diastolic blood pressure as a determinant of cardiovascular risk
Blood Pressure Regulation
Blood pressure is proportional to cardiac output and peripheral vascular resistance
Major factors that determine blood pressure
Age, gender, body mass index, and diet (principally sodium intake)
Genetic variation in genes of renin-angiotensin-aldosterone system
Essential hypertension probably initiated by increased sodium retention with later coexisting increased vascular resistance
Essential hypertension means
secondary
Benign (essential) hypertension
controlled hypertension with no short term problems
Hypertensive urgency
systolic >220 mm Hg or diastolic >120 mm Hg with no evidence of target organ damage
Hypertensive emergencies
Accelerated hypertension- significant increase in B. P. associated with target organ damage (flame-shaped hemorrhages or exudates of fundus, renal failure, headache, angina, etc.)
Malignant hypertension- papilledema +/- accelerated HTN symptoms
licorice ingestion
can cause hypertension
3 patterns of arteriosclerosis
Arteriolosclerosis in small arteries and arterioles
Atherosclerosis (atheromas=atheromatous plaques=fibrofatty plaques) develops primarily in elastic arteries and muscular arteries
Monckeberg medial calcific sclerosis in muscular arteries of >50 y. o. with no vessel lumen narrowing (can ossify)
Arteriolosclerosis (2 types)
1. Hyaline arteriolosclerosis Protein deposition (hyalinized) Seen in aging diabetes mellitus benign nephrosclerosis (hypertension)
- Hyperplastic arteriolosclerosis
Cell death (onion-skinning)
+/-necrotizing arteriolitis
Seen in malignant hypertension
Atherosclerosis- levels of prevention
50% of deaths and serious morbidity in the Western World
ischemic heart disease mortality in US 5X Japan
1ry prevention – prevent the onset of disease (susceptible)
cigarette smoking, dietary habits, statins, and HTN control
2ry prevention – early diagnosis/risk factor assessment (asymptomatic)
3ry prevention – prevent recurrences with disease (symptomatic)
aspirin, statins, beta blockers, surgery
Improved treatments keeping patients alive
Atherosclerotic Plaques
Can disrupt and precipitate thrombi or grow to cause decreased flow (obstruction)
→myocardial infarction, cerebral infarction, aortic aneurysms, peripheral vascular disease (gangrene), mesenteric occlusion, sudden cardiac death, chronic ischemic heart disease, and ischemic encephalopathy
Vasoconstriction can compromise lumen and disrupt plaque
Thrombus in/on plaque can eventually be incorporated into plaque
Can shed emboli
→focal and regional ischemia (TIAs, microinfarcts, ischemic digits)
Can encroach on media and weaken the vessel wall
→aneurysms and ruptures
** Turbulent flow and low shear stress →areas prone to atherosclerosis
Turbulent flow causes endothelial trauma and dysfunction
Laminar flow induces endothelial genes for products that protect against atherosclerosis (superoxide dismutase)
Where is atherosclerosis associated?
the intima
three outcomes of atherosclerotic plaques
aneurysm and rupture
occlusion by thrombus
critical stenosis
Obesity
Definition: “an accumulation of adipose tissue that is of sufficient magnitude to impair health”
Body mass index (BMI)
(weight in kilograms)/(height in meters)2
risks of obesity
diabetes, hypertension, hypertriglyceridemia, and low HDL cholesterol
Also increased risk of
nonalcoholic steatohepatitis, cholelithiasis, hypoventilation (Pickwickian) syndrome, hypersomnolence, secondary polycythemia, osteoarthritis, and cancers [endometrial and breast (hyperestrogenemia), thyroid, colon, kidney, gallbladder and esophageal (adenocarcinoma)]
Metabolic syndrome:
Obesity, dyslipidemia, hypertension, and insulin resistance (can also have hypercoagulability and inflammatory state)
Predisposes to cardiovascular disease and type 2 diabetes
Cholesterol Metabolism (breakdown)
2/3 LDL receptor pathway
1/3 Scavenger receptor pathway (oxidized LDL)!!!!
LDL receptor pathway of cholesterol metabolism
75% of LDL receptors are located on hepatocytes
The LDL receptor binds to apolipoproteins B-100 and E on LDL & IDL
→Endocytotic internalization
→↑Cytoplasmic cholesterol
→ Inhibition of cholesterol synthesis
Inhibit 3-hydroxy-3-methylglutaryl (3-HMG) coenzyme A reductase
Rate-limiting enzyme in the synthetic pathway
Statins also inhibit HMG-CoA reductase
Activate acyl-CoA: cholesterol acyltransferase (ACAT)
Favors esterification and storage of excess cholesterol
Down-regulates the synthesis of cell surface LDL receptors
Protects cells from excessive accumulation of cholesterol)
Statins promote synthesis of LDL receptors (↓intracellular cholesterol allows ↑LDL receptor formation )
Statins
block HMG CoA reductase →↓cholesterol levels and ↓cholesterol allows ↑LDL receptor formation
Hyperlipidemia
Mostly hypercholesterolemia
↑ risk with ↑ low density lipoprotein (LDL) LDL–C ≥190 mg/dL
↓ risk with ↑high density lipoprotein (HDL)
Exercise and alcohol ↑ HDL
Obesity and smoking ↓ HDL
↑LDL, ↓ HDL and ↑Lp(a) associated with ↑ atherosclerosis
Lowering cholesterol by diet or drugs slows atherosclerosis
Omega-3 beneficial
Trans-unsaturated fats are bad
Estrogens ↑ HDL &↓ LDL
Replacement therapy does not decrease risk for heart attacks in post menopausal women
↑ risk (2X) of coronary artery disease with oral contraceptive use in women >35 years who also smoke
Familial Hypercholesterolemia
Mutations in the LDL receptor gene
Toxic oxygen species from mФs and endothelium cause oxidation of LDL
Oxidized LDL receptors take over (scavenger receptor pathway)
LDL receptor mutations: > 900 of them
These mutations disrupt the receptor's synthesis in the endoplasmic reticulum ***transport to the Golgi complex* binding of apoprotein ligands clustering in coated pits recycling in endosomes
Class II (most prevalent); receptor protein transport from the endoplasmic reticulum to the Golgi apparatus is impaired due to abnormal protein folding
Familial HypercholesterolemiaGenetics and Phenotype
Autosomal dominant
Heterozygotes 2-3x elevation of plasma cholesterol levels
Homozygotes 5x elevation of plasma cholesterol levels
Develop severe atherosclerosis, mitral valve stenosis, corneal arcus and xanthomas
Die from complications as children or young adults
Other Atherosclerosis Risk Factors
elevated homocysteine
presence of lipoprotein a
elevated plasminogen activator inhibitor 1
Infections may contribute– chlamydia pneumonia, ,herpes, cytomegalovirus
sedentary lifestyle
stress
C-Reactive Protein
Acute-phase reactant synthesized primarily by the liver
Has roles in opsonizing bacteria and activating complement
Involved in endothelial adhesion of WBCs and thrombosis
Strongly and independently predicts the risk of myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death
No evidence that lowering CRP reduces cardiovascular risk,
Smoking cessation, weight loss, statins and exercise all reduce CRP
Pathogenesis of atherosclerosis
Chronic endothelial injury (dysfunction)
Accumulation of lipoproteins (mainly LDL) with subsequent oxidation
Adhesion of monocytes with migration into the intima (now macrophages)
Adhesion and activation of platelets
Migration of smooth muscle cells becoming neointimal smooth muscle cells (proliferate and deposit extracellular matrix/collagen)
Accumulation of lipids in macrophages (foam cells), smooth muscle cells and extracellular spaces
Aneurysms
Localized abnormal dilation of a blood vessel or the wall of the heart
Most important causes of aortic aneurysms are
Atherosclerosis with associated inflammation (abdominal aorta)
macrophage metalloproteinases and inflammation induced smooth muscle apoptosis weaken vessel wall
Hypertension via ischemic medial cystic degeneration (thoracic aorta)
Other causes: Marfan syndrome (fibrillin), Loeys-Dietz syndrome (TGF-β receptors), Ehlers-Danlos syndrome (type III collagen), scurvy (collagen x-linking), trauma (traumatic aneurysms or arteriovenous aneurysms), congenital defects (berry aneurysms), syphilis and vasculitides
Mycotic aneurysms (infections)
from embolization of a septic embolus (infective endocarditis)
from extension of an adjacent suppurative process
from circulating organisms infecting the arterial wall
