Renal blood flow, glomerular filtration

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Renal blood flow and glomerular filtration

Data for a resting, young adult, 70 kg man

  • A healthy man's blood flow distribution is like this:
    • 1200 ml / min to the liver
    • 1200 ml / min to the kidneys
    • 750 ml / min to the brain
    • 250 ml / min to the heart
  • Note that the kidneys receive 25% of the cardiac output and the highest proportion of blood flow by weight.
  • Also note that the kidneys use 20 ml of Oxygen / min.
    • This is mostly to drive ATP production for active Na reabsorption.
    • The kidneys have low oxygen extraction from their blood supply.

Blood flow rate of the kidney

  • The blood flow rate can be described by the number of ml of blood that flow in a certain time (min) to a certain mass of tissue (g).
    • ml / min / g
  • The flow rate within the kidney is highest in the cortex (good for inducing filtration) and lowest in the medulla (good for preventing "washout" of solutes in the interstitium).
What is washout?

Autoregulation of renal blood flow and GFR

  • The kidney is engineered to have autoregulation of RBF and GFR.
  • This autoregulation keeps small, normal changes in arterial blood pressure from changing the GFR.
    • This is important because Na and H20 loss are a function of GFR (recall that as GFR increases, there is less time in the tubule to reabsorb Na and therefore less absorption of H20).
    • So we don't want GFR to be changing all the time.
  • There are two mechanisms by which GFR is regulated: myogenic and tubuloglomerular feedback.


  • Myogenic GFR regulation
    • This mechanism is not unique to the kidney, many vascular beds use it, including the brain.
    • Recall that the point is to keep GFR at some constant levels and that an increased arterial blood pressure would increase GFR.
    • So as arterial blood pressure increases, we want to myogenically decrease the blood pressure to maintain the same GFR.
    • As arterial blood pressure increases, the vascular endothelial wall is stretched, stretch sensors on vascular smooth muscle cells open Ca channels, Ca enters the smooth muscle, muscle contracts, the lumen diameter decreases, and the vascular resistance increases.
    • By this Stretch-Ca-based contraction of vascular smooth muscle and increased resistance, the renal blood flow (RBF) remains constant even when systemic blood pressure is elevated.


  • Tubuloglomerular feedback
    • Recall that the point is to keep GFR at some constant level because we don't want to lose too much Na or too much water (occurs when GFR is too high--not enough time in tubule to reabsorb the Na and H20).
    • Note that there can be multiple afferent arterioles for a single glomerulus.
    • The macula densa detects when NaCl levels in the filtrate are elevated.
    • When filtrate NaCl levels are elevated, the macula densa cells release ATP which causes constriction of the afferent arterioles.
    • Constriction of the afferent arterioles leads to decreased glomerular capillary hydrostatic pressure (PGC to that nephron) and therefore decreased GFR (in that nephron).
    • Note that ATP is metabolized to adenosine in the interstitial fluid space between the macula densa and the smooth muscle cells of the afferent arteriole.
    • Adenosine binds the A1 receptor on the afferent arteriole.

Renal sympathetic nerves and RBF control

  • The two autoregulation control mechanisms for GFR are myogenic and tubuloglomerular; however, the body has a third for emergent situations: sympathetic nervous control.
    • So, in these emergent situations, the blood pressure has drastically dropped for some very bad reason (trauma, et cetera).
  • Sympathetic nervous control of the renal blood flow works by rapidly, temporarily constricting the afferent arterioles.
    • This is a prioritization of water retention and continued blood flow to other organs over the proper function of the kidneys.
  • Sympathetic nervous control is achieved through renin and catecholamines (epinephrine and norepinephrine).
    • Renin starts the angiotensin pathway which leads to angiotensin 2 and thus vasoconstriction, aldosterone release, and AVP release (all of which elevate blood pressure).
    • Epinpehrine and norepi bind the a1-adrenoreceptors to directly cause vasoconstriction of the vascular smooth muscle.

Hormomal control of RBF

  • In addition to autoregulation and sympathetic emergent control of RBF, there is long-term control via endogenous hormones.
  • Renal vasodilators:
    • Recall that vasodilation increases RBF, increases GFR, and increases loss of Na and H20.
    • Prostaglandins, NO, dopamine, atrial natriuretic peptide
  • Renal vasoconstrictors:
    • Recall that vasoconstriction decreases RBF, decreases GFR, and decreases loss of Na and H20.
    • Angiotensin 2, epi, norepi, throboxane A2, adenosine
      • Thromboxane makes sense because it is activated when bleeding / clotting which is a good time to conserve water.
      • Angiotensin 2 makes sense because it generally serves to conserve and reabsorb water, and decreasing RBF will slow filtrate flow and thus allow the tubule cells to reabsorb more of the H20.

Dampening effect of prostaglandins on renal vasoconstriction

  • We have seen that sympathetic nerves cause vasoconstriction at the kidney (renin + epi / norepi -> vasoconstriction of the afferent arteriole).
  • We have also seen that prostaglandins cause vasodilation at the kidney (vasodilation of the afferent arteriole).
  • Finally, we know that NSAIDs decrease prostaglandin synthesis systemically.
  • So, it makes sense that giving NSAIDs to a pt who is volume depleted (or otherwise has poor kidney function) is bad because it will reduce prostaglandin synthesis, therefore reduce the amount of vasodilation force on the afferent arteriole, and result in lower RBF, lower GFR, and less filtration.
Where do the prostaglandins come from?  Is there a local, renal source?

Hallmark of glomerular disease

  • The hallmark of damage to the glomeruli is protein in the urine (proteinuria).
  • Measuring protein in the urine underestimates the amount that is let into the filtrate at the glomerulus.
    • This is because much of the filtered protein is metabolized or endocytized while it is part of the filtrate in the tubule.

Glomerular filtration occurs over 3 layers

  • There are three major layers in the glomerulus through which a molecule must pass to get from the blood to the filtrate.
  • The first layer is the capillary's endothelium.
    • There are fenestrae through which most anything except cells can pass.
    • However, we don't want proteins to pass through the endothelial barrier b/c they are large and will clog the glomerulus.
    • The fenestrations of the endothelial cells are negatively charged to repel proteins (which are generally negatively charged).
    • The fenestrae are about 70nm in diameter.
  • The second filtration level is the basement membrane
    • The endothelial cells of the arteriole sit on the basement membrane.
  • The last specialization are the podocytes.
    • Podocytes sit on the outside of the basement membrane and send out feet from their cell body.
    • The feet of neighboring podocytes rest very near to one another to form small slits through which only small molecules can pass.
    • The slits formed by the podocytes are called filtration slits or slit pores.
    • The filtration slits are about 4-14 nm in diameter.
    • NEPHRIN is a critical structural protein for filtration slits.
      • We believe NEPHRIN is a critical protein for proper filtration because when it is mutated, massive proteinuria occurs.

Factors affecting filterability

  • Size, shape, deformability, and electrical charge are the major factors in deformability.
  • Size: Albumin and hemoglobin rarely make it into the filtrate but myoglobin does readily enter the filtrate.
  • Charge: albumin has a mass very similar to Hb but is found much less in the filtrate, probably due to albumin's negative charge.

GFR is determined by Starling forces

  • Recall Starling forces which apply to all capillary beds of the body, including the renal capillaries and the glomeruli:
    • There are four forces affecting flow from blood to interstitial fluid and vice versa.
    • In the case of GFR, the competing fluids are capillary blood and the filtrate, not blood and interstitial fluid.
    • Blood colloid pressure (PiGC) wants to keep stuff in the blood.
      • Note that the blood colloid pressure (PGC) increases proximal to distal in the capillary as water is filtered out.
    • Filtrate colloid pressure (PFC) wants to keep stuff in the interstitial fluid.
    • Capillary hydrostatic pressure (PGC) wants to force stuff out of the capillary.
    • Filtrate hydrostatic pressure (PBSwants to force fluid into the blood.
      • PBS is negligible.
  • There is a constant called the glomerular ultrafiltration coefficient (Kf) that accounts for the normal surface area and capillary permeability.
    • If there is vascular damage, the glomerular ultrafiltration coefficient may decrease.
  • GFR = Kf * (PGC - PBS - PiGC)
    • That is GFR = ultrafiltration coefficient * (capillary hydrostatic pressure - filtrate hydrostatic pressure - blood colloid pressure).

Force differences along systemic capillaries and renal capillaries

  • There is a distinct difference between....
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