1. Angiogenicfactors

Shear stress/need for O2 release ofangiogenic factors (VEGF-vascularendothelial growth factors, FGF-fibroblastgrowth factors, angiogenin, etc) bind toendothelial cords (EC) and activate ECproliferate and sprout directionally ECMremodeling, tube and loop formation byfibroblasts growth of new vessels

2. Blood for todifferentorgans/tissuesunder basalconditions

Kidneys - 22% CO - 1100 ml/min - 360ml/min/100g- high flow for mass of organ- kidneys filter blood for metabolites (bloodflows for reasons other than deliveringblood)

Thyroid gland - 1% CO - 50ml/min - 160ml/min/100gAdrenal glands - .5% - 25ml/min - 300ml/min/100g- large flow relative to size of organ

- distribution controlled by autoregulationmethod

3. Contributionof CardiacOutput tovariousorgans

Brain - 14%Heart - 4 (cornoary circulation)Bronchi - 2Kidneys - 22Liver - 27Muscle (inactive) - 15Bone - 5Skin (cool weather) - 6Thyroid gland - 1

4. Effect ofdifferent levelsof arterialpressure onblood flow

- at low pressures inc in P ~linear (likeno autoregulation) inc in blood flow - after arterial P 60mmHg inc in P SMALL inc in blood flow (b/c myogenicresponse vasoconstriction) buffer forpressure changes in normal range- after arterial P ~200mmHg can'tautoregulate anymore ~linear (like noautoregulation) inc in blood flow

5. Effect ofexercise oncirculation

- sympathetic arteriolar constriction inmesenteric circulation

- autoregulator dilation in working skeletalmuscle (constriction in nonworking skeletalmuscle)

6. Entrainmentof small andlarge vessels tooptimizetissue flow

Flow induced dilation

Metabolic vasodilation:- Vasodilator metabolites act onprecapillary sphincters precapillarysphincters relax arterioles dilate- nothing initially telling upstreamvasculature flow increase do to arteriolardilation inc shear stress inc dilation ofupstream vasculature entrainment

7. Functionalhyperemia

- aka active hyperemia - inc in blood flow in response to increasedmetabolic demand (ex: Vit B deficiency)- mech related to buildup of metabolitessuch as adenosine, CO2, lactic acid, K+, etc

8. Long-termautoregulation

angiogenesis - growth of new blood vessels- due to:1) exercise (ischemic tissue and highmetabolic rate)2) retrolental fibroplasia (disorganizedgrowth of retinal blood vessels in prematurebabies)

vs

rarefication - absorption of existing bloodvessels- due to:1) hypertension 2) high salt diet

9. Mech ofentrainment

shear stress activates nitric oxide synthase(NOS) converts L-arginine to NO activate guanylyl cyclase converts GTP tocGMP vasodilation

- nonadrenergic, noncholinergic fiberspresent in the nervi erigentes contain largesamounts of NOS- Sildenafil (Viagra) inhibitsphosphodiesterase that breaks down cGMP enhances arteriolar vasodilation

10. MetabolicAutoregulationTheory 1:Oxygen deficit

Metabolic rate increase or oxygen deliveryto tissue increases pO2 decreases (tissue[O2] dec) capillary sphincters relax decrease in arteriolar resistance (arteriolardilation) inc blood flow

Negative feedback: dec Tissue PO2 incblood flow inc tissue PO2

Only effective acutely

Phys - Block 2 - 06 - Control of Blood Flow by TissuesStudy online at quizlet.com/_8t2z7

11. MetabolicAutoregulationTheory 1: Vasodilatorsubstances

Metabolic rate of cell inc. cellrelease vasodilators sphinctersrelax decrease in arteriolarresistance inc blood flow toorgans

12. Metabolic needs oftissue

- delivery of O2- delivery of glucose, AA's, fattyacids, etc- removal of CO2- maintenance of [iron]- transport of hormones, vitamins

13. Myogenicautoregulation

- contraction response: vascularsmooth muscle stretched contraction until diameter isnormalized or slightly reduced- most important in smallerarterioles

- positive feedback: stretch causescontraction inc P causes morestretch causes contraction - response weak to prevent cycling

- cannot regulate flow precisely b/cresponse depends on wall stretch,not on a sensor of low likemetabolic autoregulation (cannotsense tissue needs)

14. Other nutrientsbeside O2 can affectlocal blood flow

- lack of glucose (dilates)- vitamin deficiency (Beriberi lackVitamin B)- substances such as thiamine,niacin, riboflavin needed foroxidative-phosphorylation and ATP

15. Reactive hyperemia - excess tissue flow followingocclusion - size of overshoot proportional tolength of occlusion

16. Reductions of oxygensaturation increaseblood flow through anisolated perfused dogleg

arterial O2 saturation reduces toabout 25% normal blood flowincreases 3x- after arterial O2 saturationdecreases to 50% normal canonly increase blood flow to meetsame metabolic needs - due to O2 deficiencies altitudehypoxia, pneumonia, COpoisoning, cyanide poisoning

17. Relationship of rateof tissue metabolismto tissue blood flow

- each tissue can control its ownblood flow in proportion to metabolicneeds

- blood flow related to rate of tissuemetabolism - first small increase of flow increase in O2 extraction from Hb small increase in blood flow- after metabolism rate increases to3x normal can't extract more O2from Hb large increase in bloodflow due to vasodilation - an 8 fold increase in metabolismincreases flow rate acutely 4 fold- two phase response

18. Shear stress and therelease ofdilators/constrictors

- shear stress releases vasodilatorsand constrictors- PGI, NO, EET vasodilators- endothelin constrictor

- arachadonic acid generatesprostacyclin (PGI2) andepoxyeicosatrienoic acids (EET's,HETE's)

19. Special examples ofmetabolic control oflocal blood flow

1) functional hyperemia 2) reactive hyperemia

20. Structuralremodeling

- vascular wall hypertrophy due toincreased pressure- Laplace's law T=P*r/M increased wall thickness (M) keepswall tension (T) from getting toogreat to prevent blowouts

- Hypertension inc P vascularwall hypertrophy- greater wall tension in cardiacmuscle thicker walls need moreO2

21. Tissue unit area ofacute local feedbackcontrol of blood flow

Precapillary sphincter controlsamount of blood to tissues

22. Utilization coefficient - utilization coefficient = [art O2 - ven O2]/art O2 utilized/total

VO2 (amount of flow needed for O2 consumption): Rest 750ml/min, Utilization Coefficient 25%Exercise 15k ml/min, Utilization Coefficient 75%- large changes in flow minimally affect utilization coefficient O2 delivery will be limited by flowbefore it's limited by the utilization coefficient O2 delivery is flow limited

23. Utilization coefficients -maximum capabilities

- O2 3x- Glucose 30x- free fatty acids 28x- amino acids 36x- CO2 25x- N2 480x- oxygen most flow limited of nutrients blood flow is determined primarily by O2 needs

24. Vasodilators - Adenosine (most important) - Histamine- K+- CO2- lactic acid- H+ (pH dec)

Phys - Block 2 - 06 - Control of Blood Flow by Tissues