2018A09 Discuss the determinants of renal blood flow.

 

List:

·         Normal renal blood flow

·         Vascular anatomy

·         Flow dynamics

·         Myogenic autoregulation

·         Chemical autoregulation (TGF)

·         Hormonal autoregulation (RAAS)

·         Other systems

 

Normal renal blood flow:

Average

·  1100mL/min

·  420mL/min/100g

Cortex

·  500mL/min/100g

·  Low EO2 0.2

·  For fluid/electrolyte/acid-base homeostasis

Medulla

·  20mL/min/100g

·  High EO2 0.8

·  To preserve hyperosmotic interstitium

·  Vulnerable to ischaemia

 

Vascular anatomy:

Arteries

·  Renal artery / interlobar artery / arcuate artery / interlobular artery / afferent artery / efferent artery

Veins

·  Mirror image configuration

Significance

·  Many parallel pathways -> low resistance -> high flow rate

·  Relatively high resistance at afferent and efferent arterioles facilitates flow modulation

 

Flow dynamics:

From Ohm’s law

·  RBF = (mAP – CVP) / RVR

o mAP ~100mmHg

o CVP ~2mmHg

Resistance

·  R = (8 x length x viscosity) / (π x radius4)

·  Factors increasing resistance:

o ↓Radius (major factor since power 4)

o ↑Viscosity (e.g. ↑haematocrit)

o ↑Length (not under control)

 

Myogenic autoregulation:

Description

·  Almost constant flow if renal perfusion pressure 70-170mmHg

Mechanism

·  ↓Pressure -> ↓stretch activation of renal baroreceptors -> reflex relaxation -> ↑flow rate

Impairment

·  Shock -> renal hypoperfusion -> anuria

·  Severe hypertension -> pressure diuresis

 

Chemical autoregulation:

Description

·  i.e. tubuloglomerular feedback

·  ↓Filtration results in reflex afferent arteriolar relaxation

Mechanism

·  ↓n(NaCl) to macula densa > ↓adenosine release

 

 

Hormonal autoregulation:

Description

·  i.e. renin-angiotensin-aldosterone system

·  ↓Perfusion or ↓filtration results in afferent arteriolar relaxation, generalized vasoconstriction and increased blood volume

Pathway

·  Note negative feedback

o Direct: AT2 binds AGTR1 on granular cell -> ↑Ca2+ -> ↓renin release

o Physiological: AT2 and aldosterone inhibit release of renin

Stimuli for renin release

·  ↓Afferent arteriolar pressure -> ↓renal baroreceptor stretch

·  ↓GFR -> ↓NaCl to macula densa -> ↑PGE2 and ↓adenosine

·  ↓mAP -> baroreceptor reflex -> ↑SNS output onto β1 adrenoceptor

Effects of angiotensin

·  ↑Na+/H2O reabsorption from proximal tubule -> ↑blood volume -> mAP -> ↑RBF

·  Efferent > afferent arteriolar vasoconstriction -> ↑filtration fraction -> ↑GFR with ±↓ RBF

·  Generalised vasoconstriction -> ↑mAP -> ↑RBF

Stimuli for aldosterone release

·  CRH -> ACTH (necessary for synthesis, minor release stimulus)

·  Angiotensin 2 (major)

·  Hyperkalaemia (minor)

Effects of aldosterone

·  ↑Na+K+ATPase synthesis and activity and ↑ENaC activity in connecting tubule and collecting duct

·  Direct effect: ↑ECF [Na+]

·  Indirect effect: ↑ECF tonicity -> ↑ADH release -> ↑blood volume -> ↑mAP -> ↑RBF

 

Other systems:

Baroreceptor response

·  Stimulus: ↓mAP -> ↓stretch activation of high pressure baroreceptors

·  Response: ↑SNS output, ↓PSNS output

·  Effect: ↑mAP, ↑renal perfusion pressure and flow

Atrial natriuretic peptide

·  Source: right atrium

·  Release stimulus: distension

·  Effects:

o Afferent arteriolar vasodilatation -> ↑GFR, washout of medullary interstitium

o Decreased Na+/H2O reabsorption in distal nephron -> ↓blood volume -> ↓mAP -> ↓RBF

 

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