Vascular Path Robbins Part 1 Flashcards
blood vessels- 3 concentric layers
-intima (internal elastic lamina) -media (external elastic lamina) -adventitia
intima- consists of
- endo cells (single layer) on basement membrane
- demarcated from the media by internal elastic lamina
media- consists of
smooth m cells
media- in elastic a’s (aorta)
-have high elastin content
media- in muscular a’s
- composed predominantly of circumferentially oriented smooth m cells
- smooth m contraction and relaxation- reg by inputs from autonomic NS and local metabolic factors
principal points of physiologic resistance to blood flow
arterioles
adventitia- consists of
- separated from the media by external elastic lamina
- loose CT containing n fibers, vasa vasorum (small arterioles that supply the outer portion of the media)
a’s divided into 3 types
- large/elastic arteries (aorta, major branches of aorta)
- medium-sized/muscular a’s- smaller branches of aorta)
- small a’s (<2 mm diameter) and arterioles (20-100 um diameter)
capillaries- size? consists of
- 7-8 um diameter (size of red cell)
- have endo cell lining, but no media
- pericytes (resemble smooth m cells) lie deep to endo
veins- diff from a’s
- larger diameters, larger lumens, thinner/less organized walls
- contains 2/3 of total blood volume
- less rigid walls-subject to dilation and compression, as well as infiltration by tumors and infl process
lymphatics
- thin-walled channels- lined by specialized endo
- provide conduits to return interstitial tissue fluid and infl cells to bloodstream
- can also transport microbes and tumor cells- important potential pathway for disease dissemination
vascular anomalies
- berry aneurysms
- arteriovenous fistula
- fibromuscular dysplasia
berry aneurysms- found where? asssoc with? can cause?
- circle of willis
- autosomal dominant polycystic kidney disease
- fatal subarachnoid hemorrhage
arteriovenous fistulas- arise from? can cause?
- direction connections b/w a’s and v’s that bypass the capillary bed
- most often developmental defects
- may arise secondary to infl, trauma, rupture
- can rupture- leads to hemorrhage
- can cause high-output cardiac failure- by shunting blood from arterial to venous circulation, forcing heart to pump additional volume
fibromuscular dysplasia
- focal thickening of intima and media of medium/large muscular a’s- results in stenois
- “string of beads”
- young women- most often
endo cells- normal state
-nonthrombogenic surface
endo cells- activated state- what stimuli?
- turbulent blood flow
- HTN
- complement, bacterial products, lipid products, glycation end products
- viruses
- hypoxia, acidosis
- tobacco smoke components
activated endo cells- characterized by expression of?
- adhesion molecules
- procoagulants, anticoagulants
- vasoactive factors, GFs
endothelial dysfxn- characterized by?
- procoagulation
- proinfl
- smooth m stimulation
- partly responsible for initiation of thrombus formation, atherosclerosis, and vascular lesions of HTN
predominant cellular element of vascular media- fxns
vascular smooth m cells
- roles in vascular repair and pathologic processes
- can proliferate when stimulated
- can syn collagen, elastic, proteoglycans, GFs, cytokines
- responsible for vasoconstriction.dilation
vascular injury- assoc with?
endo cell dysfxn or loss
- stim smooth m recruitment/proliferation (from media to intima)
- assoc matrix syn
vascular injury- stereotypical response?
-intimal thickening!!
HTN- risk factor for?
- atherosclerosis, aortic dissection
- Hypertensive heart disease (cardiac hypertrophy and HF)
- stroke
- hypertensive renal disease
hypertensive vascular disease- increased prevalence in?
- advancing age
- african americans
90-95% of HTN- cause?
-idiopathic (essential HTN)
5% of HTN- cause?
secondary HTN
- renal or adrenal disease
- renal a stenosis
- endocrine
- CV
- neurologic
risk factors for essential HTN
- high Na intake
- obesity
- stress
- smoking
- physical inactivity
malignant HTN- characterized by?
- small % of HTN pts show a rapidly rising BP that if untreated leads to death within 1-2 yrs
- severe HTN (>200/120), renal failure, retinal hemorrhages/exudates
BP =
CO x PVR
CO= SV x HR
most important determinant of SV?
filling pressure- reg thru sodium homeostasis
PVR- constrictors
- ang II
- catecholamines
- thromboxane
- leukotrienes
- endothelin
PVR- dilators
- prostaglandins
- Kinins
- NO
blood volume and vascular tone- maintained by?
renin-angiotensin-aldosterone system!
-low volume- renin released by JG cells- cleaves angiotensinogen to form angI–ACE–> angII
angII- fxns
- vascular constriction
- aldosterone secretion by adrenal gland
- increase tubular Na reabs
volume expansion- induces?
- myocardial release of ANP (atrial natriuretic peptide)
- leads to Na excretion/diuresis and vasodilation
secondary HTN- renovascular HTN
-renal a stenosis- causes dec glomerular flow- induces renin secretion
single-gene disorders that cause HTN
- gene defects affecting enzymes in aldosterone metabolism (aldosterone synthase, 11-B hydroxylase 17alpha-hydroxylase)- increase secretion in aldosterone- inc Na/water reabs
- mutations affecting proteins that influence Na reabs- Liddle syndrome- gain-of-fxn mutation in epit Na channel protein that increases distal tubular reabs of Na in response to aldosterone
mech’s of essential HTN
- genetic factors
- reduced renal Na excretion
- vasoconstrictive influences
- environmental factors
hyaline arteriosclerosis- morphology
- increased smooth m matrix syn
- plasma protein leakage (across damaged endo)
- homogenous pink (hyaline) thickening of vessel wall- lumen narrows
hyperplastic arteriosclerosis
- seen in severe HTN
- smooth m cells form concentric lamellations (onion skinning)- lumen narrows
arteriolosclerosis- 3 general patterns
- arteriosclerosis- small a’s/arterioles (variants- hyaline and hyperplastic)
- Monckeberg medial sclerosis- calcification of walls of muscular a’s, typically involving internal elastic membrane
- atherosclerosis- most freq and clinically important
atherosclerosis- morphology
- fibrous cap- smooth m cells, macrophages, foam cells
- necrotic center- cell debris, chol crystals, foam cells
- media
atherosclerosis- constitutional risk factors
- family history- most important!!
- age
- gender- premenopausal women protected
atherosclerosis- MAJOR modifiable risk factors
- hyperlipidemia (LDL)- hypercholesterolemia is sufficient to initiate lesion development!!
- HTN
- smoking
- diabetes mellitus- induces hypercholesterolemia
atherosclerosis- MINOR modifiable risk factors
- inflammation- CRP is a marker!
- hyperhomocystinemia
- metabolic syndrome
- lipoprotein a- altered form of LDL that contains apo B-100 portion of LDL linked to Apo A
- factors affecting hemostasis
CRP
acute phase reactant
- expression increased by IL-6
- binds to bacteria, act the classical complement cascade
response to injury model for atherosclerosis
-chronic injury and/or dysfxn of endo- leads to chronic infl and attempts to repair the tissue
atherosclerosis progression- sequence
- endo injury and dysfxn- causes vascular perm, leukocyte adhesion, thrombosis
- accum of lipoproteins and its oxidized forms in vessel wall
- monocyte adhesion to endo- foam cells!
- platelet adhesion
- factor release- induces smooth m cell recruitment
- smooth m cell prolif, extracellular matrix prod, recruitment of T cells
- lipid accumulation
atheroscloersis- arterial wall changes
- chronic endo injury
- endo dysfxn
- macrophage act, smooth m recruitment
- macrophages and smooth m cells engulf lipid (foam cells)
- smooth m proliferation, extracellular matrix deposition
2 most important causes of endo dysfxn are?
- hemodynamic disturbances
- hypercholesterolemia
endo injury- hemodynamic disturbances
-lesions occur at openings of exiting vessels, branch points, posterior abomdinal aorta- due to disturbed flow patterns
enjo injury- circulating lipids/hypercholesterolemia
- lipids in plaques are predominantly chol and chol esters
- accum in intima, taken up by macrophages, partially oxidized
- modified LDL accum in macrophages- foam cells and fatty streak form
- stim infl response!
dyslipoproteinemias- include?
lipoprotein abnormalities
- increased LDL chol levels
- dec HDL chol levels
- inc levels of abnormal lipoprotein
contributes to the initiation and progression of atherosclerotic lesions??
chronic infl!!
- infl triggered by accum of chol crystals and free fa’s in macrophages
- recognized by inflammasome- leads to IL-1 secretion
- macrophages and T-lymphocytes recruited
- infl cytokines- act endo cells and GFs stim smooth m cells to migrate to intima and proliferate
atherosclerosis- smooth m prolif and matrix deposition
- intimal expansion from foam cells and extracellular lipid, infl and smooth m cells and increased ECM- atheromatous plaque formed
- soft fibrofatty plaque becomes covered with a fibrous cap (dense collagen fibers)- center is necrotic (lipid, debris, foam cells, thrombus)
atherosclerosis- morphology
- fatty streaks
- atherosclerotic plaques
atherosclerosis- most common sites of involvement
- abdominal aorta (most common!)
- coronary a’s
- popliteal a’s
- internal carotid a’s
- circle of wilis
atherosclerotic plaques- 3 principal componets
- smooth m cells, macrophages, T-cells
- extracellular matrix- collagen, elastic fibers, proteoglycans
- intracellular and extracellular lipid
atherosclerotic plaques- complications
- rupture and ulceration- may lead to thrombosis
- hemorrhage
- embolism
- aneurysm formation
major consequences of atherosclerosis
- MI
- stroke
- aortic aneurysms
- PVD (gangrene of legs)
atherosclerotic stenosis
- plaques continually grow (cycling thru injury-healing process)
- lumen shrinks- leads to ischemia downstream- critical stenosis- 70% occluded!
- chronic ischemia of myocardium, bowel, brain, extremities (intermittent claudication)
acute plaque change- 3 categories
- rupture/fissuring- exposes thrombogenic plaque constituents- thrombus may form!!!
- erosion/ulceration- also exposes thrombogenic
- hemorrhage into plaque- expands its volume
plaques responsible for MI and other acute coronary symptoms are ?
asymptomatic before the acute change!!
what stabilizes the plaque?
fibrous cap!- undergoes continuous remodeling- can also make it more susceptible to rupture!
-collagen- major structural component!
vulnerable plaque
- thin fibrous cap (not much collagen)
- infl in plaque- can accelerate fibrous cap degradation and inhibit its resn- reduces the amt of collagen! weakens it
extrinsic influences can contribute to acute plaque changes
- BP
- vasoconstriction- increases physical stress
