Proximal Convoluted Tubule

What are Starling forces?

These are the forces acting on the fluid within the capillary that determine how the fluid itself behaves and the extent to which it either remains within the vessel or leaks out into the interstitium. There are four primary forces of interest:

Capillary hydrostatic pressure and interstitial hydrostatic pressure are the two forces generated by the fluid itself exerting pressure on the walls of the vessel (Unit = Pc and Pi). Capillary oncotic pressure is the pressure required to keep the fluid in the capillary and is generated by the solutes and proteins within the fluid (Unit = πc). This is why people with low albumin become oedematous, as their oncotic pressure is very low and the plasma fluid leaks out into the tissues.

Interstial osmotic pressure is the equivalent force that prevents fluid moving back from the interstitium into the capillary, generated by solutes and proteins in the interstitial fluid.

It’s also important to appreciate the factors that alter these forces, and the resultant net fluid flux:

  • Dehydration increases capillary oncotic pressure, increasing reabsoprtion of fluid back into to the plasma
  • Poor venous drainage causes increased venous capillary hydrostatic pressure, resulting in extravasation of fluid and oedema

What is the formula for net filtration in the bowman’s capsule?

  • This is the balance between the hydrostatic pressure of the plasma against the hydrostatic pressure in the bowman’s capsule, as well as the effect of plasma oncotic pressure which attempts to retain water within the blood vessel
    • Plasma hydrostatic pressure = Pc = 48mmHg due to the presence of the efferent arteriole
    • Interstitial hydrostatic pressure = 10mmHg
    • Plasma oncotic pressure is 25mmHg
  • Net filtration pressure = Pc – Pi – πi
    • NFP = 48mmHg – 10mmHg – 25mmHg
      • NFP = 15mmHg

What are the different ways in which filtered substances can be reabsorbed in the proximal tubule?

Primary active transport

  • ATP is used to drive substrates across the membrane against their concentration gradient
  • Sodium potassium pump
  • Active Calcium reabsorption across the basal membrane
  • Hydrogen ion secretion
  • Hydrogen Potassium exchange on the apical membrane

Secondary active transport

  • Uses the ionic gradients established as a result of primary active transport, to drive a second substrate across the membrane against its concentration gradient
  • Most commonly sodium is used as the driving ion
  • Can either be cotransport or counter transport

Facilitated diffusion

  • Via ion channels and ion transporters down the ion’s concentration gradient
    • E.G. glucose via GLUT transporters

Paracellular transfer

  • Substances can move between the cells within the nephron, usually down a concentration or electrical gradient
  • Solvent drag
  • Water is reabsorbed and can drag solutes with it
  • Water is reabsorbed fastest in the presence of aquaporins

What happens in the proximal convoluted tubule?

  • The vast majority of reabsorption of filtered solute and fluid occurs in the PCT
    • 60% of water
    • 60-70% of sodium, calcium and chloride ions
    • 50-60% of potassium ions
    • 90% of bicarbonate
    • All glucose, assuming Tmax has not been exceeded
      • (plasma concentration <11mmol/litre)
    • The majority of filtered amino acids are reabsorbed

How is sodium reabsorbed in the PCT?

  • 80% undergoes active countertransport using hydrogen ion secretion
  • This also facilitaes chloride and bicarbonate reabsorption
  • This requires carbonic anhydrase
  • Water follows passively, maintaining a constant osmolality
  • Sodium is then pumped out into the blood by Na/K/ATPase
    • The potassium largely then passively diffuses back out

How is chloride reabsorbed in the PCT?

  • Sodium reabsorption requires hydrogen secretion, leading to bicarbonate reabsorption
  • Chloride reabsorbed as it undergoes exchange for formate, bicarbonate, and oxalate
    • This is driven by the sodium/hydrogen antiporter which supplies H+ ions to associate with the oxalate, bicarbonate and formate, to allow them to diffuse back into the cell and repeat the process
  • By the end of the tubule, similar amounts of chloride are reabsorbed as sodium
  • Superficial nephrons are more chloride permeable

How is glucose handled by the kidney?

  • It is freely filtered by the glomerulus, in proportion to plasma concentration
  • Usually completely reabsorbed in the proximal tubule in two steps, with distal segments of the nephron only involved if there is exceptionally large amounts of glucose present as seen in diabetes
    • Step 1
      • Sodium-glucose linked transport (SGLT) co-transporters use the concentration gradient of sodium to actively move glucose up its concentration gradient
    • Step 2
      • GLUT-facilitated diffusion across basolateral membrane into interstitial fluid
      • Sodium is pumped out of the cell into the interstitium by the Na/K ATPase pump to maintain low intracellular sodium and therefore maintain the concentration gradient that drives step 1
  • This process has a maximum absorption rate, which is seen at a plasma concentration of 10-12 mmol/litre
    • The Tm (tubular maximum) rate of absorption of glucose is 300-380mg per minute
      • At 22 mmol/litre plasma concentration, every nephron has maxed out at Tm and so any further glucose is excreted in the urine

Please draw a graph to show how renal excretion of glucose changes with plasma concentration

  • There is a linear, directly proportional relationship between plasma glucose concentration and the amount filtered, because glucose is freely filtered at the glomerulus
  • Reapsorption also increases, initially at the same rate, but then flattens off after 11 mmol/litre plasma concentration as the maximal rate of reabsorption Tmax is reached, which is quoted usually around 300mg/min
  • At 11 mmol/litre glucose begins to be excreted in the kidney, and this increases linearly once Tmax has been reached, and the rate of increase of excretion matches that of filtration

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