Kidney Function II: Production of a Concentrated Urine

• What is haematocrit?

  Ratio of RBC volume to total blood volume
• how to calculate renal blood flow from renal plasma flow

  renal plasma flow = 600 ml/min

  whole blood: 45% cells (haematocrit)

  plasma: 55% of blood volume

  renal blood flow = 600/0.55 = 1100 ml/min
• (applying Fick's principle to the kidney)

  
  

  how do you calculate the amount of substance entering the kidney?

  Amount of substance leaving the kidney

  +

  Amount of substance excreted in the urine
• give an example of a substance that shows net reabsorption but may also be secreted

  potassium (K+)
• what is the equation for renal plasma flow?


  renal plasma flow = (u x v) / (Partery - Pvein)

  
  

  for PAH, vein pressure is assumed to be zero, so:

  renal plasma flow = (u x v) / (Partery)

  = renal clearance for PAH

  
  

  U = concentration in urine

  V = volume of urine/min

  P = concentration in plasma

  Partery = concentration in arterial plasma

  Pvein = concentration in venous plasma
• Therefore, what is clearance of PAH a measure of?

  Effective renal plasma flow
• what does the clearance value more than 120ml/min mean?

  secretion

  
  

  (e.g. PAH)
• what does the clearance value less than 120ml/min mean?

  reabsorption

  
  

  (e.g. most solutes)
• what does the clearance value of 120ml/min mean?

  no reabsorption or secretion

  
  

  (e.g. inulin)
• Why can clearance of inulin be used to accurately measure GFR?

  because it's freely filtered, not reabsorbed, not secreted, not metabolised & easily measured
• what are inulins?

  Inulin's are a group of naturally occurring polysaccharides produced by many types of plants.

  -administered intravenously
• what is creatinine?

  Creatinine is a breakdown product of creatine phosphate from muscle and protein metabolism.

  - it is normally found in the plasma; so patients would not need to undergo an invasive intravenous infusion (like with inulin)
• explain how glomerular filtration rate is measured?

  experimentally:

  - using clearance of inulin

  - very accurate

  
  

  clinically:

  - using clearance of creatinine

  - provides an estimate

  - creatinine is slightly secreted by organic cation transporters in the tubule and so can cause a slight overestimate of GFR
• How can you calculate renal clearance?

  Renal clearance= (U*V)/P

  
  

  U= concentration in urine

  V= volume of urine/min

  P= concentration in plasma
• what is clearance?

  Volume of plasma that is cleared of a substance in a given time
• POTASSIUM

  
  

  What are factors that will affect K+ secretion by the principal cells of the collecting duct?

  1. Anything that will affect Na+ entry through epithelial Na+ channels

  2. Aldosterone stimulates K+ channels, so will increase K+ secretion

  3. Tubular flow rate- high flow rates favour secretion

  4. Acid-base balance: acidosis inhibits it & alkalosis enhances it
• POTASSIUM

  
  

  sodium and potassium are both positively charged ions that move through specific ion channels down their electrochemical gradient.

  what 2 parts does the electrochemical gradient consist of?

  - The chemical gradient, or difference in ion concentration across a membrane

  
  

  - The electrical gradient, or difference in charge across a membrane.
• POTASSIUM

  
  

  How does secretion of K+ ions happen at the principal cells of the collecting duct?

  - The Na+K+ ATPase pump drives K+ secretion by pumping K+ into the cells at the basolateral surface.

  - At the luminal surface, K+ moves into the tubule lumen, via K+ channels or in co-transport with chloride via potassium-chloride cotransporters. The -ve potential in the tubular lumen due to Na+ reabsorption also promotes K+ secretion
• POTASSIUM

  
  

  
  

  What is the potassium reabsorption at the level of the DCT and the collecting duct outweighed by?

  Potassium secretion at the level of the principal cells of the collecting duct
• POTASSIUM

  
  

  How do K+ ions leave the intercalated cell in the collecting duct?

  Through the basolateral potassium channels, and so are reabsorbed
• POTASSIUM

  
  

  How are Type A intercalated cells in the collecting duct linked to potassium reabsorption?

  K+ is reabsorbed by the intercalating cells (and distal cells) and is driven by the luminal H+K+ ATPase transporter which actively pumps potassium into the cell
• POTASSIUM

  
  

  What percentage of K+ ions are reabsorbed in the DCT?

  ~5%, mediated by a K+-H+ exchanger
• POTASSIUM

  
  

  What percentage of K+ ions are reabsorbed in the thick ascending limb?

  ~30%, mediated by the Na+:K+:2Cl- cotransporter
• POTASSIUM

  
  

  Is potassium reabsorption linked to sodium reabsorption?

  Yes
• POTASSIUM:

  
  

  What percentage of K+ ions are reabsorbed in the PCT?

  65% are passively reabsorbed
• POTASSIUM:

  
  

  How does the kidney handle potassium?

  It's freely filtered in the renal corpuscle, and 95% of it is reabsorbed before the filtrate reaches the collecting tubules. Potassium that is to be excreted in the urine, is then secreted into the lumen of the collecting duct
• POTASSIUM:

  
  

  What does maintenance of potassium balance involve?

  1. Renal excretion

  2. Gastrointestinal losses

  3. Cellular shifts
• POTASSIUM:

  
  

  what is the mM of potassium in normal plasma, during hypokalaemia and during hyperkalaemia?


  - Normal plasma: 3.5-5.0 mM

  - Hypokalaemia: plasma [K+ ]<3.5mM

  - Hyperkalaemia: plasma [K+ ]>5.5mM
• POTASSIUM:

  
  

  K+ major intracellular cation in the body

  TRUE/FALSE

  TRUE
• ADH

  
  

  what does concentrated urine depend on?

  - Renal medulla interstitial fluid high osmolality

  
  

  - Collecting duct:

  i) passing through concentrated zone.

  ii) being water permeable when ADH present
• ADH

  
  

  When can a concentrated or iso-osmotic urine be generated?

  When ADH is present= it causes water reabsorption

  (so when it's not present, dilute urine is produced)
• ADH

  
  

  What is the effect of ADH binding to V2 receptors?

  It causes insertion of aquaporin-2 into the luminal membrane via a cAMP mediated event
• ADH

  
  

  What does ADH bind to?

  V2 receptors on the collecting duct cells
• ADH

  
  

  What do aquaporins do?

  Facilitate the passive transport of water across a membrane by an osmotic gradient
• ADH

  
  

  What is the key cell type that mediates water permeability?

  Principal cell of the collecting duct, which constituently expresses aquaporin-3 and -4 on the basolateral membrane
• Why is the distal tubule considered a diluting segment?

  Because it has very low water permeability

  i.e. sodium is reabsorbed there but there is no reabsorption of water taking place there
• What does the term 'tonicity' describe?

  The osmolality of a solution relative to plasma

  
  

  same tonicity=isotonic

  greater osmolality=hypertonic

  lesser osmolality=hypotonic
• UREA:

  
  

  what are the functions of the loop of Henle?

  1. To separate sodium and water reabsorption.

  2. To reabsorb more sodium than water.

  3. To create a gradient of increasing osmolality in the medullary interstitial fluid by reabsorbing sodium and recycling urea.
• UREA:

  
  

  What is 'urea recycling'?

  Urea secretion at loop of Henle & urea reabsorption by collecting duct
• UREA:

  
  

  How is urea handled by the kidney?

  1) It is freely filtered by the renal corpuscle

  2) It is passively reabsorbed in PCT

  3) It is secreted via urea transporters in loop of Henle

  4) It is reabsorbed via urea transporters in collecting duct

  5) ~40-60% of the percentage of filtered urea is excreted