Blood vessels
Chapter 10
Blood vessels
• Components of circulatory system that transport blood cells, nutrients, and oxygen to tissues
of the body. They also take waste and carbon dioxide away from the tissues.
• There are five types of blood vessels:
1. Arteries: which carry the blood away from the heart
2. Arterioles (most responsible for BP(Large surface area & sphincters help control BP)—sphincters can divert blood to diff
parts of body
3. Capillaries: exchange of water and chemicals (gas exchange) between blood and
tissues
4. Venules
5. Veins: which carry blood from capillaries back to heart
• Avascular structures: cartilage, epithelium, lens and cornea
•
Slower healing time d/t less blood & cannot repair (blood always for inflammation—blood carries healing warriors to get in /repair)
• Away from heart: arteries, arterioles, capillaries (gas exchange), venules, veinsback to heart (circles back)
Structure and function
Vascular specialization based on thickeness/composition
d/t hemodynamic forces/tissue requirement.
• Smooth muscle cells (SMC)
• Extracellular matrix (ECM)
• Endothelial cells (EC)
• Arteries: higher pressure generated from heart so
reinforced w/ layers of SMCs ((lose pressure as we
come back up towards heart). Most oxygen
• Arterioles: the ratio of wall thickness to lumen
diameter increases to allow for precise regulation of
intravascular pressure.
• Capillaries: single-cell lining of EC. On basement
membranes ((gas exchange))
• Veins: thin-walled walled
• Veins: valvesrely on muscles to squeeze the
valves to increase the pressure and push
blood upward.
• Venules: are not deoxygenated, a little left.
• Vessel walls in 3 concentric layers: intima,
media, adventitia. (present in all vessels,
more apparent in larger vessels=arteries.
• Intima: EC monolayer on basement
membrane w/ minimal underly ECM
• Media: ((muscle layer of vessel)),
mostly SMC and ECM, surrounded by
loose connective tissue, nerve fibers
• Vessel walls in 3 concentric layers: intima, media, adventitia. (present in all
vessels, more apparent in larger vessels=arteries)
• Intima: EC monolayer on basement membrane w/ minimal underly ECM;
separated from media by dense elastic membrane called internal elastic
lamina
• Media:mostly SMC and ECM, surrounded by loose connective tissue, nerve
fibers, and smaller vessels of adventitia. External elastic lamina present in
arteries to define transition btw media and adventitia
• Adventitia ( tunica externa)
Endothelium
• Endothelium is a continuous sheet of cells lining entire
vascular tree that regulates aspects of blood and blood
vessel function
•
Single cell layer. Endo=inner part that touches blood in the veins/arteries.
•
Endothelium cells (EC)-line vascular, regulates blood flow/function
•
EC maintains non-thrombogenic, modulate inflammation, influence growth/behavior of cell
(particularly SMCs)
•
Impermeable, except during hemodynamic stresss (HTN) OR vasoactive
(histamine,chemokines-inflammation/immune).
•
EC’s—active role in recruit of WBC during inflammation
•
Atherosclerosis- d/t EC damage
• Basal state normal BP, laminar flow, stable growth factors & this
maintains antithrombosis, surface and SM tone.
•
Want Laminar flow—want blood straight, NO turbulence OR stagnation
• Injury/exposure to mediators endothelial activation(EC develop
adhesives, procoagulant surface, factors to contract SM and/or
proliferation .
Endothelia damage leads to inflammation and can cause hypercoagulable state (triad- vessel damage, hypercoag state, turbulent flow= recipe for clot)).
Vascular smooth muscle cells
•
Smooth muscle cells (SMC) participate in BOTH normal & pathologic process (atherosclerosis)
• When stimulated by various factors
• Proliferate
• Upregulate (proliferate)- ECMincrease collagen, elastin, and
proteoglycan production (building blocks, form new cells)
• Elaborate growth factors and cytokines
•
SMC’s mediate vasoconstriction/vasodilation (response in physiology or pharmacologic)
•
Platelet derived growth factor & recruit more. SMCs maintenance factors—heparan, NO, growth factors
•
Smooth muscle—SM cells regulate repair and scar. Production of collagen for scar formation —(scar meansglue genitor)
Vascular smooth muscle cells
• When Endothelium damage---SM cells will leave spot, may go through endothelium, & producing the extracellular matrix
• Elaborate extracellular matrix is NOT good in excessive amts—can cause vessel damage, seeding of atheroscleroma.
• Protective and healing but Want to keep this under control.
• SM cells also contract
Blood pressure
Blood pressure-
various factors, important to know factors in order to know how to treat BP
• Function of cardiac output and vascular resistance
• CO = HR x SV (amt of blood pushing out & how quickly)
• (BP=CO x VR)
• Vascular resistance is primarily a function of arterioles (large surface area & sphincters-help
squeeze/shunt blood to areas that need it). Ex: when exercising your muscles need more blood, arterioles help this w/ shunting. When digesting
more blood towards digestive organs & arterioles responsible for this)
•
CO influenced by blood volume. Blood volume influenced by renal sodium excretion /resorption
•
SV (heart squeeze): filling pressure (regulated Na and its effect on blood volume ) ---Na rolesatrial natriuretic peptides, renin, angio, aldosterone
• Second SV factor: HR & myocardial contractility (both regulated by alpha/beta-adrenergic systems)
•
Peripheral resistance: mainly d/t arterioles by neural & humoral inputs
• Balance btw vasoconstriction (Ang II, catecholamines, endothelin, thromboxane, leukotrienes) & vasodilators (kinin, prostaglandins, NO)
•
Humoral—SNS & PNS work together to regulate peripheral resistance (antagonistic)
•
Increased blood flow causes vasoconstriction to protect against hyperperfusion
•
Local BP factors: autoregulation by tissue pH & hypoxia/metabolic demands
•
Other: inflammation, diseases (also work on vascular as well)
Blood pressure
Hypertension
Hypertensive vascular disease
• Genetic and environmental factors that conspire to increase blood
volume and/or peripheral resistance
• Essential HTN: results from interplay of several genetic factors, that individually may not cause increase. Environmental factors—which increase
blood volume and/or peripheral resistance
• Age, atherosclerosis, build up of cholesterol, increase blood volume, sluggish blood
• HTN: increase risk for atherosclerosis d/t damaging endothelial layer---breaks off—plaque forms
Clinically
• > 140 mm Hg Systolic (ventricle contraction)
• > 90 mm Hg Diastolic (ventricle relaxation)
• Increased risk for atherosclerosis (narrows b.v)
• High pressure (BP) causes damage to vessel walls d/t turbulence (bc when pressure high & hits something, will not be laminar anymore.
•
Vessel damage & turbulence = build up extracellular matrix, scarring (which makes blood flow even less)  eventually can lead to atherosclerosis(is
build up of proteins, fats @ area of vessel damage)
• 95% of cases are idiopathic(primary/essential)
• Increased CO= increased BP
• Increased blood volume & resistance
Mechanisms of essential (primary/idiopathic) hypertension
Primary (essential/idopathic) vs secondary will have different treatments (so, we need to know this)
• Reduced sodium excretion (too much H20=too much blood). **Hydrostatic pressuremajor role in getting blood where it needs go.
More Na in b.v & water follows salt
• Increased vascular resistance (going to resist flow from capillaries to venules bc there’s backup—bc hard to push through or backup
at arterials. Either way hard to squeeze fluid into OR from capillaries= HTN
• Genetic/environmental
• Primary (essential/idiopathic): unknown cause (probably d/t aging & less flexible vessels)
• Ex: reduced Na excretion in presence of normal arterial pressure**
•
•
(incr Na=incr fluid=incr blood vol=incr CO=incr BP)
Other ex: increase VR from vasoconstriction /structural changes in vessel walls, genetic factors, environmental –stress, wt, smoking, fitness, diet
• Secondary: identifiable underlying condition (renal dx, renal artery stenosis, adrenal disorders, cancer
or tx of cancer). HTN is secondary to known cause.
Morphology
HTN accelerates atherogenesis AND also causes degenerative changes in walls of large/medium-sized arteries that can lead to
aortic dissection, cerebrovascular hemorrhage. Silent Killer……but…..Once histology changes--severe
• Hyaline arteriosclerosis
(benign, long-term longer HTN will eventually lead to hyaline
arteriosclerosis)
• Benign hypertension
(deposits of protein that are normally soluble in blood—get
concentric rings/concentric thickening). The pressure so high that soluble proteins (like albumin) are pushed
out of solubility and deposit overtime along lumen wall ==narrowing (lead to turbulence & damage)
• Arterioles wall thicken w/ deposit of protein over time = narrow lumen
• Ex: hyaline arteriosclerosis in kidney = nephrosclerosis (glomerular scarring)
• Hyperplastic arteriosclerosis
• Severe hypertension (malignant) (above 200’s)
•
•
Can cause Onion skinning unraveling of b.v bc so much pressure (2nd picture)
• BP so high is kind of blows out vessel = onion skinning
• Ex: fibrinoid—vessel wall necrosis= necrotizing arterioles (mostly in kidney)
Autopsy-this is how they know HTN--histology
Vascular disorder
Vascular wall injury (particular to EC)
• Injury to the vessel walls is the fundamental basis for majority of vascular
disorders
• Injury d/t: biochemical, immunological, hemodynamic (HTN)
•
Endothelial cells-& underlying SMC  critical for vasculature response for homeostasis
• Can lead to weakened walls
• Can lead to thickened walls (fibrosis of dead cells) and stenosis (hardening & narrowed of lumen)
•
The smooth muscle cells that are trying to protect you, start adding more matrix, if continued damage then more and more matrix. Builds up and narrows
vessel (stenosis)
• Weakened stimulates recruitment for to repair damage but this in turn creates more damage and if recurrent insults= thickening
(narrowing of vessel)
• EC injury/dysfunction=pathologic process including thrombosis, atherosclerosis, HTN vascular lesion, infection, inflammation,
immune response, trauma, toxic exposure
Vascular wall injury
Smooth muscle cells multiple thr mitosis –produce extracelluar matrix and maybe too much of it (if constantly happening)
Arteriosclerosis
Arteriosclerosis (hardening vessels (arterioles)
this is not
atherosclerosis*
• Literally “hardening of the arteries”; generic term for thickening and loss of
elasticity. (less pliable)
• Affects small arteries and arterioles and may cause downstream ischemic injury.
• Hypoperfusion-hypoxia-ischemia-infarction/necrosis (cell death d/t lack of perfusion=infarction but example of necrosis)
• Arterial wall thickening = loss of elasticity
•
?class notes?--elastic to pump blood out to body, when small arterioles/capillaries harden difficult to repair. Capillaries-where gas exchange= (this leads to loss of O2
and ischemia). Recruitment of repair factors 1st go to arteries ?
• Arteriolosclerosis—affects small arteries/arterioles  causing downstream
ischemic injury
• 2 types: hyaline & hyperplastic arteriolosclerosis
Atherosclerosis
Atherosclerosis
(intimal lesions called atheromas—the fat ball. But if atheroma ruptures & breaks off,
travels thr body to small vessel= Embolus)
• Characterized by intimal lesions called atheromas that impinge on
vascular lumen and can rupture to cause sudden occlusion
•
Endothelia lesion-- Narrow lumen—Rupture. Could then cause embolus—stuck in lungs or even brain
• Ubiquitous (everywhere) among developed nations (put statins in water)
• Cause of pathogenesiscoronary,cerebral,PVD
• Atheromas-plaque w/ raised lesions, lipid core (cholesterol, necrotic debris), covered by fibrous cap.
• Enlarged atherosclerotic plaques—obstruct lumen=stenosis
• If rupture thrombosis/occlusion of vessel (ischemia)
Atherosclerosis risk factors---aging sucks!
•
Modifiable=environmental (all diet and also smoking—destroys small bv like DM—neuropathies=damaged capillaries)
• **DM II & smoking **** ************************
• Smoking: internal damage
• *(Nutrition)*  hyperlipidemia (cholesterol) major risk factor, even if other risk factors were excluded.
•
ECG heart pattern changes= HIGH risk & harder to treat
•
Genetic disease called: Hypercholesterolemia so much cholesterol builds under skin, cholesterol even build up under eye lids, knees, elbows (called--xanthomas)
Risk factors
• Hyperlipidemia—and, more specifically, hypercholesterolemia
(LDL,HDL, triglycerides)—is a major risk factor for development of
atherosclerosis and is sufficient to induce lesions in the
absence of other risk factors
• Modifiable risk factors
•
•
•
•
•
Diet (less cholesterol/fat)*
Hypertension
Cigarette smoking
Diabetes mellitus
ECG heart pattern changes=high risk/diff to tx
Statins
• Top 3 prescribed drugs U.S.
• Drug that inhibits the rate-limiting
enzyme in hepatic cholesterol
biosynthesis
•
•
Blocks cholesterol building cells in liverinhibits building of chains=less
cholesterol
Cholesterols are good in moderation: need for cell membrane-stability, hormone
synthesis (cause of severe eating disorders—cannot synthesis hormones—loss of
period)
Structure of atheroma
(not functional tissue)
Atheroma---crust w/ gooey center
Endothelium displayed d/t increased harden ECM (via smooth muscle cells)
Fibrous Cap filled w/ collagen (glue) Macrophages that eaten too much fat
Not functional tissue. Center is cholesterol crystals, cell debris, calcium deposits—harder to dissolve (much easier to prevent than treat)
• What happens?
• If this ruptures & from enough damage—fat lead to emboli (if dislodged)
• Narrows lumen
• Underneath atheroma---also damage:
• Another reason atheroma can break off---bc attachment is damaged
Atherosclerosis formation
• The currently held view of pathogenesis is embodied in the response-toinjury hypothesis. This model views atherosclerosis as a chronic
inflammatory response of the arterial wall to endothelial injury.
•
Injury-increase ECM, narrow lumen, more turbulent flow, hypercoag state. More river bends=turbulence & w/ each bend, deposit rocks/branches. Same in
vessel, too much of a bend (narrow lumen) w/ turbulence = deposit proteins & fats
• EC injury-damage blood vessels= atherosclerosis
• Vessel injuryinflammationmore pressure/injury d/t recruit brought to endotheliumbuild up plaque
• Other 2 top causes= hemodynamic disturbance (HTN, turbulent blood flow) & hypercholesterolemia
Correlating inflammation
• CRP=inflammation. Risk of atheroma increases in CRP.
• Marker synthesized by liver in response to inflammatory cytokines.
Atherosclerosis formation
(vessel injury = inflammation = fat deposit @ site = turbulent flow = SMC seals off w/ cap)
1.
EC injury—and resultant endothelial dysfunction—leading to increased permeability, leukocyte adhesion, and
thrombosis (d/t inflammation)
2.
Accumulation of lipoproteins in the vessel wall
3.
Platelet adhesion (PAF)—narrow lumen
4.
Monocyte adhesion to the endothelium, migration into the intima, and differentiation into macrophages and
foam cells
5.
Lipid accumulation within macrophages, which respond by releasing inflammatory cytokines
6.
SMC recruitment due to factors released from activated platelets, macrophages, and vascular wall cells
7.
SMC proliferation and ECM production (more fibrin and collagen)
Atherosclerosis formation
• Endothelia damage—bring inflammatory mediators (army), if consistent damage-build defense force of hardened material
• Initial  Fatty streak is biggest sign of atheroma/atherosclerosis –runway for all things bad ((fatty streak is a sign))
• Eventually Atheroma
Atherosclerosis morphological evolution
• Fatty streak- landing site for atheroma. At this pt
can still reverse things
• Atherosclerotic plaque
Atherosclerosis clinical changes
• Plaque inflammation increases collagen degradation and reduces collagen synthesis, thereby
destabilizing the mechanical integrity of the cap.
• Plaque erosion or rupture triggers thrombosis, leading to partial or complete vascular obstruction and
often tissue infarction
• Rupture/thrombus
• Hemorrhage into plaque
• Atheroembolism
• Aneurysm formation
•
Certain cells/enzymes to degrade some of the plaque but if already fatty center—cannot do this bc destabilizes the cap. Deposit more cap but body has balance system
bc doesn’t want too much scar tissue = Destabilizing mechanical cap (high risk of rupturing)
•
Plaques are unstable-- leak out fat =thrombus, if moves then  embolism (atheroembolism)
•
This can also weaken vessel---increase risk for aneurysm formation. Aneurysm= blown out vessel—too large and ruins laminal flow, risks for dissection (complete rupture
of vessel)
•
Dissection: separating layers of vessel this weakens vessel  risk for compete blow out of vessel.
Atherosclerosis clinical changes
If occlude coronary—no O2 supply to myocardium = infarction
Atherosclerosis clinical changes
Types of plaques
• Certain types of plaques are
believed to be at particularly high
risk of rupturing.
• Stable plaque  ischemia
• Vulnerable plaque  thrombosis
and embolization
•
Stable plaque—underneath plaque can get necrosis bc endothelial cells also need
O2  O2 comes from blood but if endothelium cell covered d/t atheroma or EC get
damaged bc of atheroma ==not receiving much O2
• Everything under has potential to die (necrosis) = death d/t lack of blood =
ischemia
Atherosclerosis clinical consequences
• Myocardial infarction (heart attack)
• Cerebral infarction (stroke)—occlusion in brain (FAST)
• Aortic aneurysm
• Peripheral vascular disease (gangrene of extremities)
• Many plaques are asymptomatic until rupturing
Aneurysms and dissections
Aneurysms and dissections
• Aneurysms are congenital or acquired dilations of blood vessels or
the heart (outpouching of b.v)
• “True” aneurysms involve all three layers of the artery—intima,
media, and adventitia or the attenuated wall of the heart= dissection.
(risk for hemorrhage)***
• Two most important predisposing conditions for aortic aneurysms are
atherosclerosis and hypertension
Aneurysms and dissections
Aneurysms and dissections
• Abdominal aortic aneurysm
(AAA)-
not good, can burst. Under most pressure in body, diseasesMarfan’s syndrome-flexible bc problem w/ connective tissue/fibrin—increased risk.
• Thoracic aortic aneurysm
• Aortic dissection
Vasculitis
Vasculitis
• Vasculitis is a general term for vessel wall inflammation. The two most
common pathogenic mechanisms of vasculitis are immune-mediated
inflammation and direct vascular invasion by pathogens.
Immune complex-mediated hypersensitivity
• Type III
• Immune complexes formed in the
circulation deposit in vessels,
leading to complement activation
and acute inflammation.
• IgG and IgM
• Neutrophils
• Macrophages hard time eating small immune complexes,
deposit vessel walls. Neutrophils destroys area
Vasculitis
Blood vessel hyperactivity
Reynaud phenomenon
• Vasoconstriction of arteries and
arterioles in extremities,
particularly the fingers and toes
• Restricted blood flow induces
paroxysmal pallor or cyanosis
• Cold temperatures or emotional
stress
• Females > Males
•
Extreme loss of blood flow—emotional stress=SNS clamps down
vessels
Varicose veins
• Abnormally dilated tortuous
veins produced by chronically
increased intraluminal
pressures and weakened
vessel walls
• Valves- catch gravity fallen blood, continue to push
blood up (push up,catch, repeat). Valves destroyed—
blown out & not returning blood to heart.
• Small risk for DVT d/t varicose veins.
Varicosities of other Sites
• Esophageal varices
• Liver cirrhosis causes portal venous
hypertension (too much back up of blood=too
much pressure)
• Esophageal varices are prone to
ruptures that can lead to massive
(even fatal) upper GI hemorrhage
• Hemorrhoids
• Varicose dilations of venous plexus
at anorectal junction from prolonged
vascular congestion associated with
pregnancy or straining to defecate
• Source of bleeding and are prone to
thrombosis and painful ulceration