basics of blood flow regulation

what does darcy’s law of flow explain

explains how fluids move through materials with resistance

how can you apply darcy’s law to blood flow around the body in an equation

MAP= CO x TPR

mean aortic pressure = cardiac output x total peripheral resistance

• what is the pressure change from the aorta to venules

• how is arterial pressure regulated (which reflex)

• a change in what leads to a change in pressure

• decreases (systolic, diastolic and mean arterial pressure)

• baroreflex

• alter the resistance by changing radius of lumen

what is poiseuille’s law

• how is the law proven in the equation

• SMALL CHANGES IN THE RADIUS OF THE LUMEN OF BVs HAVE A SIGNIFICANT EFFECT ON THE RESISTANCE OF THE VESSELS  

  • (evident as in the equation the radius is to the power of 4 showing how significant the change is) 

  • the vessels alter RADIUS because blood viscosity and the vessel length arent easily modified

poiseuilles law

• how can you calculate total resistance when vessels are joined in series

• how can you calculate total resistance when vessels are joined in parallel

• Poiseuilles law describes flow in a single vessel 

• When vessels are joined together in SERIES, the total resistance is the SUM of the resistance (R) of each vessel

R total = R1 + R2..

• When vessels are joined together in PARALLEL, (capillary bed), the conductance  is the sum of conductance = 1/R

R total = 1/R1 + 1/R2….

• The summation of a large number of conductance in parallel contributes to the low resistance of the capillary bed  

• Low velocity of blood flow in capillaries enhances nutrients exchange  

structure of BVs

• which BV type has the highest resistance (resistance vessels)

• what are VSMCs

  • which layer are they most abundant in

  • which BV type are they not found in

  • how do they alter resistance

  • what other pressure does it regulate (H)

• Arterioles are responsible for the most resistance to BF, so they are called resistance vessels  

• VSMCs= vascular smooth muscle cells

  • are abundant in the tunica media of resistance vessels

  • (none in capillaries) 

  • Contraction or relaxation of VSMCs cause constriction/vasodilation altering blood flow  

  • Vasoconstriction/dilation of pre capillary arterioles can alter hydrostatic pressure in capillaries  

VSMCs – vascular smooth muscle cells

• striation and cell shape

• under which type of control

• what is the unit type

• how do they respond to stimuli 3

• what feature allows for tension to be maintained for a long time at little energy cost

• They are non-striated and spindle shaped  

• Non voluntary control  

• Multi unit smooth muscle cells  

  • Wide range of cell surface receptors to respod to a variety of vasoactive compounds  

  • They have different ion channels on the membrane -> necessary in some vessels for electromechanical contraction (via increase of intracellular Ca2+) 

  • In other vessels, contraction is a pharmocomechanical process  

• Long cross bridge duration ensures tension is maintained for a long time at little energy cost 

 

vascular smooth muscle contraction

(there are no T tubules)

• where does Ca2+ come from

• what does it bind to

• what is activated and activates myosin heads

• how does contraction happen

what does VSMC contraction depend on 2

1. Increase in sarcoplasmic [Ca2+] 

2. Ca2+ binds and activates calmodulin  

3. Activated calmodulin activates myosin light chain kinase MLCK  

4. Activated MLCK phosphorylates myosin heads  

5. Phosphorylated myosin chain binds to actin chain -> cross bridge cycling -> VSMC contraction  

(Amt of Ca2+ in the cytosol + Sensitivity to Ca2+ (balance between MLCK and myosin light chain phosphatase (MLCP) activity) )

how does Ca2+ conc rise in the sarcoplasm in large arteries

• what is well developed, and what do they not mave much of (L type)

• where does most of the Ca2+ come from

• what hormone is Gq linked

• what does it not rely on for contraction

• In large arteries, VSMCs have well developed SRs and few L type, voltage gated Ca2+ channels  

• Most of the sarcoplasmic Ca2+ comes from the SR  

• Pharmaco-mechanical process (NTs/hormones)

• Eg of noradrenaline signalling via a1-adrenoreceptor (Gq linked) 

• VSMCs depolarisation and Ca2+ entry via VG Ca2+ channels is not needed  

how does Ca2+ conc rise in the sarcoplasm in arterioles

• what is the SR like, L type VG Ca2+ channels

• does it NEED depolarisation for contraction

• VSMCs in arterioles have small SR and high number of L type, VG Ca2+ channels -> entry of Ca2+ via VG Ca2+ channels is required for contraction  

• Membrane depolarisation may lead to Ca2+ based AP firing but not required for contraction  

vascular tone

• what is basal tone

• for vasodilation and constriction what are the intrinsic and extrinsic factors affecting it

• the baseline, continuous partial constriction of blood vessels (specifically arteries and arterioles) maintained by VSMCs

VASODILATION 

• Basal level local signs (intrinsic) 

• Circulating hormones (extrinsic) 

VASOCONSTRICTION 

• Basal level local signs (intrinsic) 

• Circulating hormones (extrinsic) 

• Tonic sympathetic activity  

• Ca2+ entry via VG Ca2+ channels  

define

• extrinsic and intrinsic factors

examples of both

extrinsic factors

• regulation of BF to an organ by factors originating outside the organ

  • (endocrine - angiotensin, ADH)

  • (ANS - NA, adrenaline, NO)

intrinsic factors

• regulation of blood flow to an organ by factors originating from inside the organ

  • (paracrine - adenosine)

  • (endothelial - NO)

• what happens to resistance and bloow flow when you increase and decrease the diameter of arterioles

• ++ diameter in arterioles -> --- resistance -> ++ BF 

• --- diameter in arterioles -> ++ resistance -> --- BF 

myogenic response

• what does it respond to a change in

• where is this response most prominent

• what does it help stabilise

• what becomes activated, what happens that leads to constriction

• This describes the vasoconstriction of resistance vessels in response to a rise or drop in perfusion pressure 

• Prominent in the heart, skeletal muscles, kidneys and brain  

• Stabilises BF to organs and capillary hydrostatic pressure  

• Activation of stretch-activated ion channels -> depolarisation VSMCs -> opening of VG Ca2+ channels -> constriction  

what do vascular endothelial cells do

• what does friction of blood create SS

• what does SS trigger the production of

• how does this production then decrease SS

• what else increases the production of this compound (via what activity)

• vasoconstriction or dilation, what happens to permeability

• Friction of blood on endothelial cells create SHEAR STRESS 

• SS triggers production of NO nitric oxide by endothelial cells -> vasodilation -> decrease in SS  

• NO production is a tonic process  

• Inflammatory mediators (histamine, cytokines) increase endothelial NO production via increase eNOS activity  

• -> vasodilation and ++ permeability  

angina

• what is it

• what type of drug is used

• how does it work (similar to SS response)

• Nitrate drugs used in angina (GNT spray) mimic NO

• -> vasodilation of muscular arteries (coronaries)

• resistance arteries and veins -> decrease of central venous pressure

• -> decrease in cardiac work and ++ myocardial BF  

explaining NO production in response to shear stress

• what transduces information on SS

• what is activated PKB

• what does this phosphorylate → leads to what activity

• what is produced and what cells does it act on

  • (on these cells) what enzyme does it activate

  • what does it produce to activate PKG

  • what kinase is inhibited (the one that activates myosin)

  • what is the result of this

• The glycocalyx transduces information on SS  

• Activation of intracellular protein kinase B (PKB) 

• PKB phosphorylates endothelial NO synthase (eNOS) -> ++ eNOS activity  

• ++ NO production in endothelial cells and diffusion through cell membranes to act locally in VSMCs 

  • NO activates guanylate cyclase in VSMCs

  • -> ++ cGMP production -> protein kinase G (PKG) activation 

  • Inhibition of MLCK -> ---- Ca2+ sensitivity  

  • ^^Ca2+ back in SR via phosphorylation of phospholamban (enzyme that makes SR pump back calcium into storage, decrease free calcium)

example of when BF is increased when metabolic activity increases

• increase in which substances/compounds indicate this

• what is the medical term for an increase in BF

exercise

• k+

• adenosine, from atp degradation

• inorganic phosphate ion

• decrease pO2 or INCREASE pCO2

• increase lactate

hyperaemia

extrinsic factors

• what are the 2 main types of nerve fibres that innervate the vasculature of humans

• how is vasodilation achieved 2

• SYMPATHETIC VASOCONSTRICTOR FIBRES: tonic activity can be increased or decreased. Ubiquitious distribution  

• PARASYMPATHETIC VASODILATOR FIBRES: erectile tissues, salivary glands, pancreas alongside sympathetic vasoconstrictor fibres  

In humans, there are NO SYMPATHETIC VASODILATOR NERVES  

• Vasodilation is achieved via adrenaline-mediated B2 adrenoreceptors signalling or withdrawal of sympathetic activity  

• what are the physiological changes in the fight or flight response

  • what is it triggered by

• what response in BVs does adrenaline cause (which receptors)

• The perception of emotional stress, fear, danger, triggers the alerting response  

Elicits the following changes: 

• Large increase in BF to skeletal muscles  

• Large increase in HR  

• Minimal change in BF to the skin  

• Small increase in ABP  

  • Adrenaline causes vasoDILATION in skeletal muscle arterioles due to the ABUNDANCE of B2 adrenoreceptor (Gs)

how does signalling via B2 adrenoreceptor cause relaxation

• what happens to Ca2+ in the cell

• what type of polarisation happens (due to movement where of what ion)

• which kinase activity is inhibited

1. Increased rate of sequestration of Ca2+ in SR  

2. ^^ open probability of K+ channels -> ^^ efflux of K+ -> HYPERPOLARISATION  

3. Closure of VG Ca2+ channels -> --- Ca2+ influx  

4. Inhibition of myosin light chain kinase activity MLCK  

VASOVAGAL SYNCOPE

• what is it

• what does it trigger in the body

• what is it triggered by

• what are the signs

• A CNS reflex that triggers large changes in BF  

• When the perceived emotional stress becomes too great, a persin may have a vasovagal faint  

(sight of blood, severe pain, fear, intense emotions) 

• Loss of posture and consciousness 

• Highly stereotypical reflex response

(decrease in BF to the brain and BP drop)

what are the 3 ways vascular tone is regulated

(recap)

myogenic response

intrinsic

extrinsic factors (highest control)