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Flashcards in 3 Renal Hemodynamics Deck (17)
1

Major renal functions

  • Maintain a constant internal environment (homeostasis)
    • Kidney is supplied w/ 20% of CO for this reason
  • Secrete hormones
    • Renin, prostaglandin, & bradykinin
    • Erythropoietin
      • Lower oxygen content --> higher erythropoietin
    • Vitamin D (site of 1 & 24 hydroxylation)
  • Metabolism
    • Protein, glucose, lactate
    • Hormone breakdown (insulin)

2

Definitions

  • Renal blood flow (RBF)
  • Renal plasma flow (RPF)
  • Glomerular filtration rate (GFR)
  • Filtration fraction (FF)
  • To maintain equilibrium

  • Renal blood flow (RBF)
    • Amt of blood that perfuses both kidneys / minute
    • Normal: 1200 ml/min
  • Renal plasma flow (RPF)
    • Rate of plasma flow to the kidneys / minute
    • Normal: 670 ml/min (55-60% of RBF)
  • Glomerular filtration rate (GFR)
    • Volume of plasma filtered by the glomeruli / minute
    • Normal: 125 ml/min (males), 100 ml/min (females)
  • Filtration fraction (FF)
    • Ratio of GFR / RPF
    • Normal: 0.18 - 0.22
  • To maintain equilibrium
    • GFR & RPF must remain nearly constant

3

Blood flow distribution in the kidney

  • Where blood initially goes
  • Pre-glomerular blood flow
  • Post-glomerular blood flow
  • After a high protein or salt meal

  • All blood initially goes to the cortex
  • Pre-glomerular blood flow is related to glomerulus size
    • Larger juxtamedullary glomeruli --> greater blood flow
    • Midcortical or superficial cortical glomeruli --> less blood flow
  • Post-glomerular blood flow
    • 85% --> cortex
    • 15% --> medulla
  • After a high protein or salt meal
    • Increase salt / solute intake
    • --> increase blood flow to superficial glomeruli w/ shorter LOHs
    • --> more efficient excretion of excess solute

4

AffA vs. EffA

  • Role in maintaining blood flow during ischemia
  • Size

  • Role in maintaining blood flow during ischemia
    • EffA is more important in maintaining blood flow in low blood flow states
  • Size
    • Cortical: AffA > EffA
    • Juxtamedullary: EffA > AffA
    • EffA is more robust & has a greater role in blood flow regulation

5

Forces governing GFR

  • Starling principle
  • Equation
  • Terms
    • Kf
    • Pgc
    • Pb
    • πgc
    • πb

  • Starling principle
    • GFR is determined by the balance of hydrostatic & oncotic pressures
    • Hydrostatic pressure
      • Biggest driving force coming into the glomerular capillary (from BP)
      • Pushes fluid out into bowman's space
    • Oncotic pressure
      • Protein concentration increases in capillary
      • Pulls water back into the capillary
    • Equilibiurm point: no net ultrafiltration pressure
  • Equation
    • GFR = Kf * [ (Pgc - Pb) - (πgc - πb) ]
  • Terms
    • Kf = glomerular coefficient or filtering capacity of hte glomerular filtration barrier
      • (Total filtering surface area of the glomerulus) * (hydraulic conductivity of the glomerular membrane)
    • Pgc = glomerular capillayr hydrostatic pressure
      • Related to renal perfusion pressure & AffA & EffA resistances
    • Pb = hydrostatic pressure within bowman's space (negligible)
    • πgc = glomerular capillayr oncotic pressure
    • πb = oncotic pressure in bowman's space (negligible)

6

Forces governing GFR

  • AffA constriction
  • AffA dilation
  • EffA constriction
  • EffA dilation
  • Increased Kf 
  • Decreased Kf
  • Final GFR & RBF depend on...

  • AffA constriction
    • Pre-glomerular
    • Increases AffA resistance
    • Decreases GFR, RBF, & glomerular capillary hydrostatic pressure
  • AffA dilation
    • Increases GFR, RBF, & glomerular capillary hydrostatic pressure
    • Decreases AffA resistance
  • EffA constriction
    • Post-glomerular
    • Increases EffA resistance, GFR, glomerular capillary hydrostatic pressure, peritubular capillary oncotic pressure, & luminal hydrostatic pressure in the proximal nephron
    • Decreases RBF
    • Favors salt & water reabsorption from the proximal tubule
  • EffA dilation
    • Increases RBF
    • Decreases GFR, glomerular capillary hydrostatic pressure, & EffA resistance
  • Increased Kf 
    • Due to mesangial cell relaxation
    • Increases GFR
  • Decreased Kf
    • Due to mesangial cell contraction
    • Decreases GFR
  • Final GFR & RBF depend on...
    • Relative resistances at AffAs & EffAs

7

Autoregulation

  • Changes in glomerular pressures & flow can change due to...
  • Autoregulation
  • Predominant regultaory changes in renal vascular resistance under normal conditions

  • Changes in glomerular pressures & flow can change due to...
    • Position changes
    • Ingestion or loss of solute / fluid
  • Autoregulatoin
    • Maintenance of a near normal intrarenal hemodynamic environment (RBF, RPF, & GFR) despite large changes in systemic BP
    • Accomplished by adjusting renal vascular resistances
  • Predominant regultaory changes in renal vascular resistance under normal conditions 
    • Pre-glomerular AffA changes resistance by constricting or dilating to maintain GFR & RBF

8

Structural components of hte glomerulus involved in autoregulation

  • AffA
    • Bottom right vessel
  • EffA
    • Bottom left vessel
  • Macula densa
    • Epithelial lining on the bottom b/n the arterioles
  • Glomerular mesangial cells
    • Black in the mdidle
  • SNS

9

Autoregulation

  • Function
  • Where most reabsorption of salt & water occurs
  • Where final qualitative changes in urinary excretion occur
  • Primary site of qualitative change
  • If delivery to these segments was not closely regulated...
  • Ex. a disparity of 5% difference b/n GFR & reabsorption...
  • Effective circulating volume

  • Function
    • Prevent excess salt & water loss
  • Where most reabsorption of salt & water occurs
    • Proximal tubule & LOH
  • Where final qualitative changes in urinary excretion occur
    • Distal tubules beyond the macula densa
  • Primary site of qualitative change
    • Collecting tubule
  • If delivery to these segments was not closely regulated...
    • Enhanced flow would overwhelm the reabsorptive capacity of distal segments
    • --> life-threatening losses of salt & water
  • Ex. a disparity of 5% difference b/n GFR & reabsorption...
    • --> loss of 1/3 of the extracellulra volume --> vascular collapse
  • Effective circulating volume
    • Volume necessary in the vascular space to ensure adequate vital organ perfusion
    • Maintained by tight control of GFR & reabsorption by the kidney

10

Diseases cuased by autoregultaory failure

  • Acute kidney injury
    • Esp acute tubular necrosis ("vasomotor nephropathy")
  • Diabetic nephropahty
  • Hypertensive nephropathy
  • Progressive renal failure ("hyperfiltration injury")

11

Myogenic hypothesis

  • Intrinsic mechanism of autoregulation
  • Arterial smooth muscle contracts/relaxes when vascular wall tension increases/decreases
    • Increase perfusion pressure --> distend renal arteriolar blood vessel walls --> increase wall tension --> AffA contracts --> decrease perfusion pressure & blood flow back to normal values
  • Vascular response to wall tension is mediated by Ca
  • Properties are confined to the AffA
  • Time < 10 seconds

12

Tubuloglomerular feedback (TGF)

  • General
  • Importance of Cl
  • Increase RBF, GFR, & fluid / solute delivery to the tubule -->
  • Adenosine hypothesis
  • Proposed mechanism

  • General
    • Dependent on the close proximtiy of macula densa cells to the smooth muscle & granular cells of the juxtaglomerular apparatus
    • Macula densa cells detect changes in Cl delivery w/ altered renal tubular flow --> changes in AffA resistance
  • Importance of Cl
    • Cl dependence of hte Na/K/2Cl pump in the luminal membrane of the cortical & medullary thick limbs of the LOH
    • Osmolality of the luminal fluid also plays a role
  • Increase RBF, GFR, & fluid / solute delivery to the tubule -->
    • Macula densa cells sense increased Cl --> AffA constriction --> decrease RBF & GFR to normal
  • Adenosine hypothesis
    • Increase tubular flow --> increase ATP hydrolysis in macula densa cells --> increase local interstitial adenosine
    • AffA has a high conc of type 1 adenosine receptors
    • Adensoine --> AffA constriction --> reduce delivery of solute ot the macula densa
  • Proposed mechanism
    • Increase Na --> Na/K/2Cl works faster --> generate AMP & adenosine --> increase urine output & flow --> vasoconstriction
    • Decrease flow --> vasodilatoin

13

Renin-angiotensin system

  • General
  • Stimulation --> outcome
  • Renin storage & synthesis
  • Renin secretion
  • When renin is released
  • What inhibits renin release

  • General
    • Extrinsic regulation via hormonal mechanisms
  • Stimulation --> outcome
    • Compromised volume homeostasis --> renin secretion stimulation --> AII production --> maintain arterial BP, renal perfusion pressure, preserve GFR, & minimize salt & water loss
  • Renin storage & synthesis
    • In the granular epithelial cells of the AffA in the JG apparatus
  • Renin secretion
    • Decrease intracellular Ca --> increase cytosolic cAMP in JG cells --> renin secretion
  • When renin is released
    • Decreased blood volume or extracellular fluid volume --> decreased renal artery perfusion pressure
      • Volume depletion due to trauma, hemorrhage, inadequate fluid intake, or excess losses from diarrhea, sweating, or vomiting
      • Sensing mechanism: renal vascular baroreceptors in JG cells are sensitive to AffA wall tension
    • Decreased AffA, carotid arterial, & atrial wall tension
      • Vascular baroreceptors --> SNS --> increase catecholamines --> interact w/ AffA adrenergic receptors --> increase renin
    • Decreased Na intake
    • Increased renal SNS activity
  • What inhibits renin release
    • AII, K, ADH, thromboxane A2

14

Renin-angiotensin system

  • Renin -->
  • Angiotensin converting enzyme (ACE) -->
  • Where ACE & AII are found
  • Most effects of AII are mediated by...
  • AII arrival
  • AII types of functions
  • AII functions
  • Primary function of RAAS

  • Renin -->
    • Angiotensinogen (formed in the liver) --> inactive angiotensin I
  • Angiotensin converting enzyme (ACE) -->
    • Inactive angiotensin I --> active angiotensin II (AII)
  • Where ACE & AII are found
    • Both: most tissues
    • AII: lungs
    • ACE: kidney
  • Most effects of AII are mediated by...
    • The AII receptor subtype AT1
  • AII arrival
    • Arrives at renal vascular receptors via circulation or local cleavage by ACE
  • AII types of functions
    • Circulating endocrine substance w/ systemic effects
    • Paracrine/autocrine/intracrine substance w/ local effects
  • AII functions
    • Systemic vasoconstriction --> increases BP & renal perfusion pressure
    • AffA & EffA constriction --> decreases RBF (& GFR) --> increases FF
      • Constriction is greater in the EffA than the AffA
    • Glomerular mesangial cell contraction --> alter Kf
    • Stimulates aldosterone release --> increases proximal tubular Na absorption --> stimulates thirst, ADH release, & SNS activity
  • Primary function of RAAS
    • Preserve GFR during low perfusion states when RBF can't be maintained

15

Prostaglandins

  • General
  • Synth & release are stimulated by...
  • Release is stimulated by...
  • Endogenous prostaglandins
  • When RAAS & SNS are activated by actual or perceived ("effective") volume depletion
  • Prostaglandin synth inhibition by aspirin or NSADs in effective volume depletion

  • General
    • Local vasodilators of renal vasculature (autocoids)
    • FA products of arachidonic acid synth'd in the kidney
    • Ex. PGE2, PGI2, & PGF2
  • Synth & release are stimulated by...
    • Renal vasoconstriction, volume depletion, & renal hypoperfusion
  • Release is stimulated by...
    • AII, bradykinin, catecholamiens, ADH, & glucocorticoids
  • Endogenous prostaglandins
    • Regulate GFR & RBF.
      • Directly: AffA smooth muscle action
      • Indirectly: altering the action of neural & hormonal influences
    • Vasodilation --> preserve RBF in the presence of vasoconstrictors (ex. AII, SNS)
  • When RAAS & SNS are activated by actual or perceived ("effective") volume depletion
    • Decrease GFR & RBF --> prostaglandin release --> AffA dilation --> increased RBF (& GFR)
    • Actual volume depletion: hemorrhage
    • Perceived ("effective") volume depletion: decreased renal perfusion from advanced CHF or liver disease
  • Prostaglandin synth inhibition by aspirin or NSADs in effective volume depletion
    • Vasoconstriction will be unopposed
    • Renal function (waste removal, salt & water homeostasis) will be compromised as GFR & RBF fall
    • --> severe clinical consequences

16

Extrinsic regulation: neural mechanisms

  • Renal vasculature innervation
  • Renal nerve stimulation -->
  • Renal efferent nerve stimulation ->
  • Necessity of renal nerves
  • Role of SNS in renal vascular resistance regulation

  • Renal vasculature innervation
    • Adrenergic fibers of the SNS
    • Vasoconstriciton dependent on alpha1-adrenergic receptors
  • Renal nerve stimulation -->
    • Increased renal vascular resistance due to AffA & EffA vasoconstriction --> decrease RBF & GFR
    • More stimulation --> AffA vasoconstriction (predominantly) --> decreased glomerular capillayr pressure
  • Renal efferent nerve stimulation -->
    • Increased renin release from JG cells --> increased AII produciton --> AffA & EffA vasoconstriction
    • Prostaglandin stimulation
  • Necessity of renal nerves
    • Not necessary for efficient autoregulation of renal hemodynamics or for the tubuloglomerular feedback mechanism
  • Role of SNS in renal vascular resistance regulation
    • Little role in the normal unstressed organism
    • Stress (ex. hemorrhage, severe volume depletion, CHF, hypoxemia) --> nerual stimulation --> vasoconstriction

17

Summary

  • Dominant regultaors of RBF & GFR in the Na replete state & normal BP range
  • W/ volume contraciton & Na depletion...
  • Cascade during decreased renal perfusion

  • Dominant regultaors of RBF & GFR in the Na replete state & normal BP range
    • Intrinsic mechanisms of autoregulation
      • Myogenic responses
      • Tubuloglomerular feedback
  • W/ volume contraciton & Na depletion...
    • Neural & hormonal mechanisms play a greater role as the decrease in renal perfusion worsens
  • Cascade during decreased renal perfusion
    • See diagram