The Nephron

The nephron is most basic functional unit of the kidney.
There are about 1 million nephrons in each kidney.
The main purpose of the nephron is to regulate the concentration of water, solutes and pH by filtering the blood by reabsorping what's needed and eliminating waste.

Anatomy and Physiology of The Nephron

  1. Afferent Arteriole - Brings unfiltered blood to the nephrons. The kidney filters 1.2L of blood per minute
  2. Renal Corpuscle - The initial nephron filtering component. Only plasma makes it through.
    • Glomerulus - A network of capillaries allowing increased surface area to facilitate in ultrafiltration.
    • Bowman's Capsule - A cup-like sac at the beginning of tubule. Collects plasma, electrolytes and other small molecules (e.g. Glucose, Amino Acids, Urea).
  3. Efferent Arteriole - Vessel diameter is less than the afferent arteriole causing greater hydrostatic pressure in the glomerulus, assistining in ultrafiltration.
  4. Proximal Convoluted Tubule (PCT) - Beginning portion of the nephron inbetween Bowman's capsule and the Loop of Henle. This is where a majority (65%) of reabsorbtion takes place.
  5. Loop of Henle - "U" shaped structure starting at the distal portion of PCT and ending at the proximal portion of the Distal Convoluted Tubule.
    • Descending Limb - Water permeable. The osmolarity starts at 300mOsm/L in the tubule and the surrounding interstitial space. As the tubule descends from the renal cortex toward the medulla, the osmolarity increases and more water leaves the tubule through osmosis. The concentration can increase up to 1200mOsm/L at the bend or bottom of the Loop of Henle.
    • Ascending Limb - Water impermeable. As the Loop Henle ascends back towards the renal cortex from the medulla, the outside osmolarity decreases. However, the tubule is now water impermeable, causing the diffusion of ions from the tubule to the interstitial space. Osmolarity can be as low as 100mOsm/L at the end of this limb.
  6. Distal Convoluted Tubule (DCT) - Water impermeable. Responsible for reabsorbing ions, especially Ca++(Calcium).
  7. Connecting Tubule - Most distal portion of the anatomyphysiology/nephron. Water reabsorption is dependent on if Antidiuretic Hormone is present or not. Home of principal cells where aldosterone controlled secretion of K+ takes place.

Carbonic Anhydrase in the Proximal Convoluted Tubule

This process will explain the reabsorption of HCO3-(Bicarb) in the Proximal Convoluted Tubule. This will be important to know when understanding the mechanism of action of Carbonic Anhydrase Inhibitors, such as Acetazolamide (Diamox).

  1. In this area, Na+(Sodium)-K+(Potassium) Adenosinetriphosphatase (ATPase) along the basilar cell wall, pump 3 sodium ions out the cell, and in return take 2 potassium ions into the cell, making the cell poor in Na+.
  2. The low intracellular Na+ level and high Na+ levels within the tubule allow a shift along the luminal cell wall. This causes Na+ to shift into the cell and moving H+(Hydrogen) out of the cell into the PCT by the Na+/H+ Pump.
  3. The H+ now combines with HCO3- forming H2CO3(Carbonic Acid).
  4. The H2CO3 is then converted in the tubule by Carbonic Anhydrase into H2O(Water) and CO2(Carbon Dioxide).
  5. CO2 diffuses into cell and is reformed into H2CO3 again.
  6. H2CO3 dissociates into HCO3- and releases a H+. The HCO3- leaves the cell, and the H+ is pushed out of the cell and into the tubule by the Na+/H+ Pump.

NKCC2 in The Thick Afferent Limb of The Loop of Henle

This next process will explain the action of the Na+-K+-2Cl- cotransporter (NKCC2) protein located in the Thick Ascending Loop of Henle, the reabsorption of Ca++ (Calcium) and Mg++ (Magnesium).
  1. Na+, K+ and 2Cl- ions move from the luminal side into the cell through active transport protein, NKCC2.
  2. K+ shifts from the cell back into the lumen through renal outer medullary potassium channels (ROMK) or "leaky channels". This generates a shift in the electrochemical gradient causing the reabsorption of other cations such as Mg++ and Ca++.

Na+-Cl- Symporter in The Distal Convoluted Tubule

The important point to remember in this process is that Ca++ is being reabsorbed into the cell and the rest of the body.
  1. Na+/K+ ATPase on basolateral membrane side make cells poor in Na+.
  2. The Na+-Cl- Symporter takes in Na+ and Cl- ions into the cell.
  3. Ca++ enters cells through channels on luminal side of the cell.
  4. Ca++ actively transported out of cell due to Ca++ ATPase and Na+/Ca++ exchanger located on the basolateral membrane. This keeps intracellular Ca++ levels low.

Principal Cells in the Collecting Tubule

The Principal Cells are mainly influenced by Aldosterone and ADH. The more aldosterone present the more intake of Na+ and Cl-, therefore reabsorption of water too, and the excretion of K+ and causing a concentrated filtrate. When there is less aldosterone, the opposite effect takes place causing less activity of the Na+/K+ ATPases, thus less Na+ and water is reabsorbed. When ADH is present, aquaporin channels reabsorb water causing a more concentrated filtrate. When ADH is not present the aquaporin will not allow water to be reaborbed causing diuresis and a diluted filtrate.