Glomerular Filtration and Tubular Function

Describe glomerular filtration and tubular function.

Glomerulus

  • The glomerulus is a set of capillaries which invaginate Bowman's capsule
  • Fluid filters out of the capillary bed into Bowman's space based on Starling forces:
    • Membrane permeability
    • Hydrostatic pressure gradients
    • Oncotic pressure gradient
      • Reflection coefficient

Glomerular Filtration Rate

Glomerular Filtration Rate is:

  • The volume of plasma filtered by the glomerulus each minute
    Normal renal blood flow is 1.1 L.min-1, however renal plasma flow is less (600 ml.min-1 for a normal haematocrit). Therefore, the normal filtration fraction (proportion of renal blood flow which is filtered) is ~20%.
  • Typically 125ml.min-1
    • Decreases with age (partially due to loss of nephron number)

GFR can be expressed as the product of Net Filtration Pressure and the combination of membrane permeability and membrane surface area, designated Kf (the filtration coefficient):

  • Net Filtration Pressure is given by opposing Starling Forces across the glomerular membrane:
    As protein is not filtered in normal states, the oncotic pressure in Bowman's Space is usually assumed to be 0mmHg.
    • The average capillary NFP is ~17mmHg
    • Hydrostatic pressure
      Determined by renal blood flow and the relative constriction of the afferent and efferent arterioles. Hydrostatic pressure decreases along the capillary. Affected by:
      • MAP
        • Catecholamines
        • Local autoregulation
          • Myogenic
          • Tubuloglomerular Feedback
          • Hormones
            • Angiotensin II constricts the efferent arteriole more than the afferent arteriole, causing an increase in renal resistance with only a small decrease in GFR.
            • Prostaglandin E2 dilates the afferent arteriole, increasing GFR

    • Osmotic pressure
      Increases along the capillary, as protein free-fluid is filtered leaving a higher concentration of protein within the capillary. This change in capillary oncotic pressure is proportional to the filtration fraction - a greater filtration fraction will cause a higher oncotic pressure of fluid in the capillary.
  • Membrane permeability
    Overall permeability is:
    • A function of:
      • Membrane permeability, in turn affected by:
        • Capillary endothelium
        • Basement membrane
          Negatively charged molecules have reduced filtration as the basement membrane is also negatively charged which opposes movement out of the capillary.
        • Foot processes of podocytes
          Molecules less than 7000 Dalton are freely filtered, whilst larger molecules are filtered less.
      • Membrane Surface Area
        Typically very high for water and solutes.
      • Affected by:
        • Glomerulonephritis
          • Change in basement membrane or podocyte foot processes
        • Angiotensin II causing contraction of mesangial cells

Tubular Function

Proximal Tubule

The proximal tubule reaborbs 60% of glomerular filtrate. It reabsorbs basically everything, including protein, and secretes H+, organic ions (such as uric acid and salicylates), ammonium, and up to 60% of filtered urea load.

Loop of Henle

The loop of Henle consists of a thin descending limb and a thick ascending limb;

  • The descending limb reabsorbs water only
  • The thick ascending limb:
    • Reabsorbs common ions (Na+, K+, Cl-) and HCO3-
    • Excretes H+
  • The function of the loop is to concentrate urine in states of water deprivation
    This is done via the countercurrent mechanism.

Countercurrent Multiplier

The countercurrent concentrating system is:

  • Formed from the loop of Henle and collecting ducts
  • Driven entirely by the removal of NaCl from the ascending limb
  • Most easily understood in stages:
    • NaCl is actively transported out of the thick ascending limb, increasing interstitial osmolality at that level
    • Increased interstitial osmolality results in water reabsorption from the descending limb, increasing tubular osmolality at that level
    • This more concentrated tubular fluid then flows to a deeper, more concentrated level, and more water is reabsorbed
    • The effect is progressive concentration of tubular and interstitial fluid, but with a low and stable energy cost as the relative gradients that each transport pump works against is small
    • The end result is a dilute urine leaving the ascending limb, but a highly concentrated medullary interstitium

Countercurrent Exchange

The vasa recta are peritubular capillaries that:

  • Surround the loop of Henle of juxtamedullary nephrons
  • Follow the loop into the medulla
  • Have typically low blood flow
    This prevents "washout" of the countercurrent multiplier, as the slow blood flow allows solute concentrations to equalise at each level of the loop.
    • In hypovolaemic situations, renal blood flow falls and vasa recta flow decreases, further reducing washout
    • When renal blood flow is high, vasa recta flow increases
      This washes out part of the medullary concentration gradient and reduces the concentrating ability of the kidney.

Distal tubules

Fluid entering the distal tubule has about one-third the osmolarity of plasma. The distal tubule:

  • Reabsorbs: Na+, Cl-, HCO3-, Ca2+
  • Secretes: K+, H+

Collecting Ducts

  • The collecting ducts lie in the interstitium (concentrated by the loop of Henle)
  • In the absence of aquaporins, the collecting ducts are impermeable to water
    • Osmolality can fall as low as 50 mmol.L-1 due to continued reabsorption of solute
    • In the presence of aquaporins, water flows down the osmotic gradient into the concentrated interstitium, resulting in a highly concentrated urine
    • ADH also increases collecting duct permeability of urea
      • Urea moves via solvent drag with water

References

  1. Kam P, Power I. Principles of Physiology for the Anaesthetist. 3rd Ed. Hodder Education. 2012.
  2. Greger R, Windhorst U. Comprehensive Human Physiology: From Cellular Mechanisms to Integration. Springer-Verlag Berlin Heidelberg. 1996.
  3. CICM March/May 2010
Last updated 2018-09-21

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