Peripheral Circulation and Microcirculation

Question 1

what factors influence blood flow through circulatory system?

Answer 1

local metabolites, different hormones, endothelium-derived mediators and nerves affect blood flow.

Question 2

What determines how much blood flow goes to each organ?

Answer 2

How much constricted or dilated the arterioles are ,
since constriction/dilation of arterioles changes R^4 term, which regulates flow
according pouiselle’s law radius is what we can control to regulate flow.

Question 3

What is the relationship between pressure, flow and resistance? What is an intrinsic property of vascular smooth muscle?

Answer 3

Flow= (PA- Pv)/R
Flow= pressure difference of arterial and venous divided by resistance.
Autoregulation -intrinsic ability of organ to maintain blood flow constant despite, changes in perfusion pressure.

Question 4

What human body parts undergo autoregulation? What must happen to keep flow constant despite increase in pressure? How does this occur?

Answer 4

brain, kidney, and heart experience autoregulation
autoregulation- range of pressure changes between 60 and 140 mm Hg, where even though pressure is increasing, flow is maintained constant
To keep flow constant (despite increase in pressure), RESISTANCE must INCREASE.
As vascular smooth muscle is stretched by higher pressures, it responds by contracting, which causes resistance of blood and keeps flow constant.

Question 5

Is Autoregulation influenced by endothelial cells? What happens if you remove endothelial cells?

Answer 5

Autoregulation- INTRINSIC property that is NOT affected by endothelial cells.
if you remove endothelial cells, vascular smooth muscle still autoregulates.

Question 6

What are local metabolites that regulates vascular smooth muscle dilation?

Answer 6

Lactic acid, increased H+, increased adenosine. Increased K+, increased CO2, decreased PO2, increased osmolarity- are all VASODILATOR influences .When a muscle is working hard, they will have vasodilator effect on arterioles and allows increase blood flow.

Question 7

What is hyperemia? What are the two types of hyperemia?

Answer 7

Hyperemia- increase in blood flow
1. Active hyperemia- during period of increased metabolic rate, blood flow will increase to muscle being used (during exercise). Then blood flow decrease after stopping that activity.
Vasodilators will be released as consequence of metabolic activity.
2. Reactive hyperemia- INCREASE in blood flow that occurs after a period of REDUCED or arrested blood flow.
if you block blood flow for period of time, then restore blood flow, you get an increase blood flow, which is reactive.
this occurs due to metabolites building up in tissue during reduced blood flow.
amount of hyperemia proportional to how long blood flow was limited/reduced.(longer time of reduced blood flow, greater hyperemia) .

Question 8

what is flow-induced vasodilation?

Answer 8

Flow-induced Vasodilation- have pressure gradient causing blood to flow through blood vessel, it results in increase in diameter- Vasodilation
when blood flows through blood vessel, there is something that causes vasodilation to occur. This thing is ENODTHELIAL CELLS.

Question 9

What is the role of endothelial cells in CV.

Answer 9

endothelial cells control the constriction/dilation of vascular smooth muscle.
EDRF (endothelial release factor) - released from endothelial cells which causes vascular smooth muscle to be relaxed.
EDRF found as Nitric Oxide
NO made by endothelial cells and NO can cause relaxation of smooth muscle.
receptors on endothelial cells can bind to histamine, Ach, and cause endothelial cells to release NO, and relaxation of smooth muscle.
Endothelial cells produced vasodilators like NO prostacyclin and also VASOCONSTRICTORS like endothelin and angiotensin II.
Endothelial cells can produce both Vasoconstrictors/Vasodilators that can be modify vascular smooth muscle (cause relaxation or contraction)

Question 10

What is endothelin? How do endothelial cells sense blood flow?

Answer 10

Endothelin- vasoconstrictor produced by endothelial cells.
Endothelial cells control resistance.
When blood flow through tube, it causes dilation of blood vessel, because of production of NO.
endothelial cells are able to sense SHEAR Stress (force caused by blood flowing past stationary cell on vessel wall). They sense if you have shear stress (turbulent flow vs laminar flow)

Question 11

What is the effect of endothelial cells on shear stress?

Answer 11

as blood flows past endothelial cell, endothelial cell sense flow and can modify NO and reactive oxygen species production. Shear stress can be sensed through cytoskeletal interaction.
endothelial cells sense shear stress in normal flow and changes in shear stress environment.
notice low Shear stress, where cells get less NO,.

Question 12

where does atherosclerosis occur in blood vessels?

Answer 12

Atherosclerosis usually occurs in branch points in the vessel, which can lead to blockage of coronary arteries and heart attack. beginning of this condition likely due to changes in shear stress (produce less NO) and hence normal endothelial cell function.
endothelial cell- important for normal CV function and path logical CV function.

Question 13

what happens to our endothelial cells as we age?

Answer 13

As we age, we change endothelial cell function, make less NO (nitric oxide).

Question 14

under normal condition, what does endothelial cells produce more? What happens if endothelial cells are damaged?

Answer 14

Normal conditions: endothelial cells produce more NO than endothelin
If endothelial cells are damaged- less NO are produces MORE ENDOTHELIN made.
Endothelial damage occurs with NICOTINE, AGING, HYPERTENSION, or ISCHEMIA leading to oxidative stress (produce reacive oxygen species), various illnesses.

Question 15

Differentiate between role of vasodilators vs vasocosntrictors?

Answer 15

Vasodilators (eiocosanoids, kinins, histamine, adenosine, NO, atrail peptide) - cause vascular smooth muscle to relax
Vasoconstrictors (angiotensin Ii, vasopressin, endothelin, eicosanoids, NE, epinephrine) CONTRACT smooth muscle.

Question 16

What is arachidonic acid? How is this substance released from membrane lipids?

Answer 16

arachidonic acid- polyunsaturated fatty acid (20 Cs, 4 double bonds).
It is present in membrane phospholipids (in all organs of body).
PHOSPHOLIPASE-2 releases arachidonic acid (enzyme cleaves the acid from membrane phospholipid).

Question 17

What is cyclooxygenase enzyme?

Answer 17

The cyclooxygenase enzyme- metabolizes arachidonic acid and causes PROSTOGLANDINS to be formed.
This enzyme produces Vasodilators and Vasoconstrictors.
prostaglandins (aka Eicosanoids) which are vasodilators
and TxA2 and PGF2 are vasoconstrictors.

Question 18

What happens when you take aspirin? what enzyme are you trying to inhibit? What enzyme is inhibited when you take Steroids?

Answer 18

Taking Aspirin INHIBITS Cyclooxygenase, which produces prostaglandins.
taking this medicine will block production of prostaglandins (inflammatory mediator)
Taking STEROIDS to reduce inflammation, inhibits phospholipase (which releases arachidonic acids)
Eicanosoids (prostoglandins) are vasodilators/constrictors and mediate inflammation, can be produced by any organ in the body by releasing arachidonic acid with phospholipase.

Question 19

What is Lipoxygenase?

Answer 19

Lipoxygenase- enzyme that forms Leukotrienes, which are VASOCONSTRICTORS (LTB4, LTC4, LTE4) and constrict vascular smooth muscle and airways (mediate asthmatic symptoms).
this enzyme can metabolize arachadonic acid too.

Question 20

What are the two isoforms of cycloxygenase?

Answer 20

1. Cylcoxygenase-1 - responsible for producing Physiological amounts of PROSTAGLANDINS (eicosanoids)
2. Cycloxygenase-2- activated in pathophysiological conditions that produce LARGE amounts of prostaglandins (like rheumatoid arthritis, and other inflammatory disease.

Question 21

How do omega-3 Fatty acids relate to arachidonic acid?

Answer 21

omega-3 fatty acids (look like arachidonic acid; 20 Cs, 5 double bonds). consuming a lot of omega-3 FA’s release eicosapentanoic acids which are less inflammatory substances, less constrictor effect, retain vasodilator effects.
consuming diet high in these acids- move balance of arachidonic acid towards VASODILATOR side (and prevent platelet aggregation)

Question 22

How does NE and Epinephrine bind to different receptors?

Answer 22

vascular smooth muscle:
Alpha 1 receptors (mediates constriction, strongly activated by NE
-Epinephrine can bind to alpha receptors at HIGH [ ], but typically epinephrine binds to Beta-2 receptors.
Beta-2 receptor- Epinephrine binds to this receptor mediates DILATION (vasodilator)
both NE/E binds to beta-1 receptor also which can increase HR, contractility.
Both NE/E can affect peripheral resistance through alpha1 or B2 receptor; while affect heart by beta 1 receptor.

Question 23

What is the role of angiotensin II in CV system? what is the enzyme that produces angiotensin II? Where is it stored. When can Renin be released?

Answer 23

Angiotensin II- important mediator in CV system
RENIN- controlling enzyme for production of angiotensin II.
Renin is stored in kidneys (in juxtaglomerular cells)
in afferent arteriole, cells contain renin which can be released from the cells when there is DECREASED BLOOD FLOW, or INCREASED SYMPATHETIC STIMULATION can release renin.

Question 24

What happens when Renin is released? What is ACE (angiotensin converting enzyme)? What are ACE inhibitors?

Answer 24

when Renin is released, it acts upon Angiotensinogen (made in liver), which cleaves Angiotensin I (10 aa) from itself.
Kininase-2 is aka ACE (Angiotensin Converting Enzyme)
ACE converts Angiotensin I into Angiotensin II.
ACE inhibitors- Anti-hypertensive drugs
(give drug that blocks ACE, it is a good anti-hypertensive drug since it prevents formation of angiotensin II)

Question 25

What is the purpose of Angiotensin II?

Answer 25

Angiotensin II is strong VASOCONSTRICTOR, that causes constriction of peripheral vasculature, INCREASING peripheral RESISTANCE and INCREASING BLOOD PRESSURE, increase SYMPATHETIC Activity, increase CATECHOALMINE release

Question 26

what is Bradykinin?

Answer 26

Bradykinin- VASODILATOR; produced in SWEAT glands

it vasodilates peripheral vasculature in SKIN, also part of INFLAMMATORY reactions.

Question 27

What is Atrial Natriuretic Peptides (aka ANP)?

Answer 27

Atrial Natriuretic Factor/ANP (peptides)- VASODILATORS
substance released when atria or ventricles are STRETCHED significantly.
ANP- promotes SODIUM EXCRETION (gets ride of sodium and fluid). ANP also VASODILATOR.

Question 28

What is ADENOSINE? What is it’s purpose in the heart?

Answer 28

Adenosine- Vasodilator, important in the heart (cardiac muscle)
Adenosine links tissue Oxygen levels with INCREASING BLOOD FLOW to the heart (deliver more O2 to muscles, which make ATP)
it Matches oxygen supply and oxygen demand
can also be produced in skeletal muscle and have dilator effect
Adenosine- Anti-inflammatory effects

Question 29

What determines how constricted or dilated your vascular smooth muscle is?

Answer 29

The SYMPATHETIC INNERVATION, determines how constricted or dilated vasculature is (as well as the amount of vasoconstrictor or dilator present)
95% patients have central hypertension- (high blood pressure, but we do not know why)
can have high blood pressure, because you have Higher amount of Vasoconstrictors or Fewer amount of Vasodilators.
Cause of increase vascular smooth muscle tone- could be multifactorial.

Question 30

Distinguish between vasodilators and vasoconstrictors

Answer 30

Vasodilators- dilate blood vessels, widen them to improve blood flow and lower pressure.
Vasoconstrictors- constrict and tighten blood vessels, increasing blood pressure

Question 31

What is baroreceptor reflex?

Answer 31

Baroreceptor reflex- stretch receptors in aortic arch and carotid sinus which are constantly sensing degree of stretch in arterial system and sending information back to brain stem.
each time your heart beats, stretch receptors stretch, send AP, As pressure increases (75-120), more APs sent back to carotid sinus.
Sense stretch proportional to pressure, and send info to brain stem in medulla.
neurons in medulla cause dilation or constriction to occur in vasculature (causing bp increase or decrease)

Question 32

What happens if you inhibit sympathetic tone in vasculator?

Answer 32

sympathetic Nervous system also releasing Norepinephrine
If inhibit sympathetic tone to vasculature by anesthesia, block sympathetic fibers that innervate smooth muscle, blood pressure would DECREASE (from 100 mm Hg to 50).
Each individual has their own sympathetic basal tone, whicn

Question 33

What happens if you inhibit sympathetic tone in vasculator?

Answer 33

sympathetic Nervous system also releasing Norepinephrine
If inhibit sympathetic tone to vasculature by anesthesia, block sympathetic fibers that innervate smooth muscle, blood pressure would DECREASE (from 100 mm Hg to 50).
Each individual has their own sympathetic basal tone, which influence basal level of release of NE in circulatory system and determine how constricted or dilated vascular smooth muscle is.

Question 34

What controls the sympathetic Nervous system in vasculature?

Answer 34

sympathetic basal tone, influencing release of NE,

and Baroreceptor reflex

Question 35

What is the afferent and efferent limb for baroreceptor reflex? How does reflex work?

Answer 35

afferent limb- carrying information from stretch receptors in carotid sinus in aortic arch back to brainstem
efferent- sending information from brainstem to heart in vasculature.
Increase stretch for carotid sinus (Increase BP) hence increase FIRING rate for Afferent nerves , it STIMULATES PARASYMPATHETIC, and INHBITS sympathetic nerve
Decrease sympathetic firing to heart, release less NE, slope of prepotential and DECREASE HR, LESS CALCIUM RELEASE, SV DECREASES, and CO decreases, bring blood pressure back down.
Decrease sympathetic tone, less NE, Vascular smooth muscle DILATE (decreased constriction), reduce resistance, reduce Blood pressure, Decrease CO AND VASCULATURE.
Reflex bring us back to beginning set point.

Question 36

What happens in baroreceptor reflex if parasympathetic is stimulated?

Answer 36

Increase firing of nerves, stimulates parasympathetic.
-increase firing of vagus nerve to SA Node, increase Ach bind to muscarinic, opening up K+ channels moving toward RMP, flatten slope of prepotential, decrease HR,
Ach on cardiac muscle- decreases adenylate cyclase, decrease in stroke volume, and HR)

Question 37

What would happen in baroreceptor reflex if you lost 2L of blood?

Answer 37

Lose 2L of blood: reduce venous return to heart, LESS PRELOAD, LESS Stretch, SV Decreases, CO Decreases, and carotid baroreceptors drop and DECREASE in FIRING.
Decreased firing causes decrease inhibition of SYMPATHETIC (now STIMULATE SYMPATHETIC.
Increase Sympathetic firing- Increase Na/Ca permeability, increase slope of potential, Increase HR,
INCREASE SYMPATHETIC to cardiac muscle: more NE binds to B1 receptor, MORE Calcium channel released, increase SV, Increase CO.
Vascular smooth muscle: increase Sympathetic tone, release more NE, bind to alpha 1 receptors and Get CONSTRICTION
Constriction INCREASES RESISTANCE, bring BLOOD PRESSURE.
increase Sympathetic nerves goes to Kidney: Increase RENIN which causes increase in ANGIOTENSIN II, raise peripheral resistance and bring blood pressure back to control
Increase sympathetic innervation to veins: reduce compliance, increase blood pressure and force more blood back to right atrium and increase preload and increase venous return and CO
Venoconstriction, DECREASES Compliance, which increases venous return, increase preload (Stretch ventricle, better SV)
These are effects that offset blood loss.

Question 38

Why does this baroreceptor reflex not prevent hypertension?

Answer 38

reflex regulates pressure at a certain set point.
baroreceptor is NOT good at setting bp at absolute pressure, it is just good at preventing abrupt changes in blood pressure.
baroreceptor works well when you wake up in the morning ( you jump up quick, and feel light headed), When you stand up from supine(laying down) to upright position, gravity helps blood pool in lower extremity (venous side) and your venous return drops, CO drops, SV drops.
baroreceptor senses change and reduces firing, bring bp back in balance.

Question 39

What is the relationship between blood pressure and CO and peripheral resistance

Answer 39

Blood pressure is related to CO and resistance
CO and peripheral resistance determine blood pressure
patient given drug cause blood pressure to increase, but reduced peripheral resistance, Had to STIMULATE CO to overcome drop

Question 40

What is microcirculation composed of?

Answer 40

Microcirculation- arterioles and capillaries; part where all of exchange of oxygen and nutrients occur in tissue.(blood vessels under 100 microns)
Largest cross-sectional area in CV are in microcirculation, lot of opportunity for diffusion, exchange of fluids
-area of circulation where if things do not work properly, excess fluid in tissue space (EDEMA)
edema- swelling of extremeties?

Question 41

What are the factors govern the movement of fluid in microcirculation?

Answer 41

Lymphatic channels- pick up excess protein and fluid from interstitial space and bring it back to vascculature to venous side of circulation
another part of microcirculation

Question 42

What are meta-arterioles? What branches off them?

Answer 42

lot of smooth muscle in arteriole,
metaarterioles- connect arterioles to venules
branching off metaarterioles are capillary channels.
precapillary sphincters- structures at beginning of capillary channels that can constrict or dilate to allow blood to flow from meta-arteriole through capillaries.
only small % of capillaries are open (tissue does not need a lot of blood flow)
many capillaries are closed.

Question 43

What is the role of capillary sphincters? What are they controlled by? How do they function during exercise?

Answer 43

pre-capillary sphincters- constricted, and do not conduct flow to capillaries.
When you exercise and produce metabolites like lactic acid, K+, H+, the precapillary sphincters dilate, open and allow blood flow through capillaries.
pre-capillary sphincters are CONTROLLED by local METABOLITES
arterioles and metaarterioles- get sympathetic innervation and have more SMOOTH muscle , under control of sympathetic NS.

Question 44

What are the two types of blood flow in microcirculation.

Answer 44

blood flow:
1. Nutrient blood flow- any blood flow that can travel through capillary channel (arteriole to meta-arteriole) and oxygen and nutrients can diffuse to tissue and provide nutrition.
2. Non-nutrient blood flow- indicated by AV shunt channel; blood flow directly from arteriole to venule without passing through capillary.
from arteriole to AV shunt to venule. Blood is non-nutrient blood flow.

Question 45

What is the advantage of non-nutrient blood flow?

Answer 45

non-nutrient blood flow is primarily present in SKIN in CUTANEOUS circulation (which regulates body temperature) way the body REGULATES HEAT
when dissipate heat to environment, blood flows from arteriole to venule , which is near skin.

Question 46

How is microcirculation regulated?

Answer 46

microcirculatory channels can be all the way open or completely constricted and convert blood flow to any organs that need it.
microcirculation can be ALL OR NONE depending on amount of constriction or dilation.

Question 47

What are the factors that control arterioles? Can these factors affect capillaries?

Answer 47

prostaglandins, NO, endothelin, angiotensin II which all affect microvessels (arterioles, meta-arterioles and venules).
But they CANNOT affect CAPILLARIES since capillaries do not have smooth muscle.

Question 48

What regulates flow in capillaries?

Answer 48

PRE-CAPILLARY Sphincters!!!
capillary itself is just composed of endothelial cells and it cannot constrict on its own
regulation by sympathetic ns, only occur in arterioles and venules
endothelial cells are 1 cell thick that line vessels in circulatory system.

Question 49

Which blood vessels experience laminar blood flow? What kind of flow does capillary have?

Answer 49

vessels that are 20 microns in diamater or larger, experience laminar blood flow.
vessels < 20 microns (LIKE SMALL CAPILLARIES) - experience TURBULENCE FLOW (RBC’s flow single file of flow or formed elements, turbulent flow of plasma)

Question 50

What are the factors of microcirculation that affect vasculature smooth muscle?

Answer 50

endothelium derived mediator (release NO)- vasodilator
-prostaglandin- vasodilator (mediates relaxation)
-adenosine, H, CO2, K- local metabolites that are VASODILATORS.
all these vasodilators have an effect in microcirculation.
Relax smooth muscle, decrease in resistance and increase in blood flow.
if you constrict vascular smooth muscle, increase resistance, decrease in blood flow.

Question 51

What constricts or dilates vessel diameter?

Answer 51

Circulationg EPI and NE, blood pressure, O2, and SNS all constrict vessel
Tissue metabolites  (H+, Lactic acid) dilate the vessel
Endothelial cells is a relaxer with NO, 
and it also has ENDOTHELIN- that CONSTRICTS
Endothelial cells produce vasodilator (NO, prostacyclin)  and produces constrictor (like endothelin, Angiotensin II).

Question 52

Why does blood pressure cause constriction?

Answer 52

When you increase pressure in blood vessel, vessel responds by constricting.
Increase Blood pressure, causes local constriction of vascular SMOOTH MUSCLE (autoregulation).
Adenosine- vasodilator
Vasopressin- vasoconstrictor
Histamine- vasodilator

Question 53

What are the different kind of endothelia cells?

Answer 53

Some endothelial cells have;
tight junctions- have a very little fluid moves across membrane (blood-brain)
discontinous- gaps in membrane, allows fluid to move (intestine)
fenestrated endothelium
different kinds of endothelial cells pose different limitations to movement of fluid across cell.

Question 54

What will facilitate diffusion? What are the factors that limit diffusion?

Answer 54

diffusion is dependent on having large cross sectional area, and high [ ] gradient.
High [ ] substance and large Surface area- facilitates diffusion
limitations to diffusion in microcirculation:
1. flow limited transport- some substances are not allowed to leave capillary, because their size is larger than pore in membrane
SUBSTANCE DOES NOT LEAK OUT OF CAPILLARY EASILY (plasma)
Flow limited transport- movement of nutrient is limited by capillary flow bringing substance to capillary.
if flow is increased and you bring more substance to area, concentration gradient of red substance higher and more of it diffuse to cell.

2. Diffusion limited transport- since interstitial fluid volume is larger, the distance from capillary to cell is large.
   diffusion is NOT efficient over long distances,
   (short distance, large SA is best for diffusion)
   Increase interstital fluid, lengthen or increase distance, fewer molecules get to cell.
   Interstitial fluid volume would increase during EDEMA (excess fluid in interstitial fluid, distance of diffusion increases limiting how much nutrient gets to tissue)
   individuals with edema- fatigue easily, longer diffusion for oxygen and nutrients to go muscle.

Question 55

What factors help control size of interstitial fluid space?

Answer 55

amount of fluid in interstitial fluid space is controlled by:
Fluid Movement= k [ Pc + PI i)- (Pi + PI p)}
this equation is starling’s hypothesis/equation: represent 4 variables that regulate fluid movement
1st part of equation- filtration
2nd part of equation- reabsorption.
2 main filtration forces:
Pc= capillary hydrostatic pressure (pressure inside capillary) tend force fluid along cap or out of.
pI i= interstital oncotic pressure (proteins out in interstitial space, pulls fluid toward them)
2 primary reabsorptive forces:
Pi- interstitial fluid hydrostatic pressure (pressure in interstial fluid
PI p- plasma protein oncotic pressure (proteins retained in capillary, attract fluid toward them)

Question 56

What is altarfiltration? What is filtration and reabsorption?

Answer 56

atrial filtration- movement of fluid across capillary membrane
filtration- movement of fluid from capillary to interstitial space
reabsorption- fluid moves back from interstitial space into capillary

Question 57

What is the purpose of capillary hydrostatic pressure?

Answer 57

Capillary hydrostatic pressure pc: primary FILTRATIN FORCE.
if you increase resistance, by constricting the arterioles, hydrostatic pressure (pc) will DECREASE
Flow- constrict arteriole, and reduce radius, volume of flow will decrease. less volume flow from arteriole to capillary, pressure deceases.

Question 58

What happens if you constrict veins in microcirculation?

Answer 58

Constrict veins, capillary hydrostatic pressure, leave arteriole normal, pressure go up.
whatever increases venous-constriction or increase in venous pressure, will increase capillary hydrostatic pressure
capillary hydrostaic pressure drops as you move from arterial to venous side.
cap hydrostatic pressure filters on arteriole side and at midpoint reabsorb on venous side to maintain fluid balance.

Question 59

What can cause edema?

Answer 59

Edema can be caused by:
1. increased venous congestion (increased volume, high venous pressure which will back up in veins and raise capillary hydrostatic pressure, favoring filtration and edema
2. if lymphatic channels are constructed, extra fluid in interstitial fluid leading to edema
3. also patient with heart problems have PULOMONARY edema or ALVEOLAR edema- if Left atrial pressure gets high in patient, since left ventricle not pumping enough blood into aorta, Left atrial pressure rises, which back up into venous end of pulmonary capillaries, raise pulmonary hydrostatic pressure, filter more fluid in lungs, and fluid does not have a lot of interstitial space. many alveoli, filled with fluid.
alveolar edema- make person have dysmnea (shortnesss of breath), due to fluid being filtered in pulmonary capillaries and move into alveloi, fills it with fluid, no gas exchange and nutrients.