Acid Base Buffers

Acid base buffers     Buffers are primarily weak acids (with salt of its conjugate base), it is able to take up or release H+ so that changes in free H+ concentration are minimised. Buffers are located in the extracellular fluids, intracellular fluids and bone. Intracellular buffers - These include proteins, organic and inorganic phosphate and haemoglobin. The bones are an important site for the buffering of acid and base loads. An acid load, for example, is associated with the uptake of some of the excess H+ ions by bone, resulting in the release of buffer compounds, such as CaCO 3 and CaHPO4, into the extracellular fluid. This is demonstrated by decreased osteoblastic and increased osteoclastic function, resulting in bone loss. Extracellular buffers – These include inorganic phosphates and plasma proteins. Another extracellular buffer is the bicarbonate/carbon dioxide buffer system shown below: HCO3- is the most important buffer in extracellular fluid as it has a relatively high and measurable concentration, and it possesses the ability to vary PCO 2 via changes in alveolar ventilation. Bicarbonate used in the buffering process must be regenerated to maintain normal acid base balance Renal excretion of H+ Reabsorption of bicarbonate (and secretion of H+) 1. Intracellular H2O breaks down into H+ and OH- ions and then the OH- combines with CO2 to form HCO3- via a reaction catalysed by CA 2. In the proximal tubule, H+ ions are secreted into the lumen by the Na-H exchanger and HCO3- ions are returned to systemic circulation by a Na +-3HCO3- cotransporter. In collecting tubules, the processes are mediated by the active H +-ATPase pump and the Cl— HCO3- exchanger. 3. Secreted H+ ions combined with the filtered HCO3- to form H2CO3, and then CO2 and H2O, which are passively reabsorbed and can be used in the first step. The dissociation of carbonic acid is facilitated when luminal carbonic anhydrase is present. Titratable acids  These are H+ excreted with urinary buffers. Inorganic phosphate (H 2PO4- and HPO42-) is the most important of these buffers because of its relatively high concentration in urine. Note in the diagram below that a new HCO3- is absorbed for each secreted H + and that H+ secretion occurs by Na+-H+ exchange in proximal. tubule and by active H +-ATPase pump in collecting tubules Ammonium excretion  Ammonium excretion can occur in three ways: o Ammonium (NH4+) production in the early proximal tubular cells In the proximal tubule, glutamine is taken up by cells and metabolised into NH 4+ and alpha-ketoglutarate. The utilisation of the latter results in the generation of HCO3-, whereas NH4+ substitutes for H+ on the Na+-H+ exchanger and is secreted directly into the lumen. o Medullary recycling of ammonia NH4+ production occurs primarily in the proximal tubule. Most of the NH4+ is then reabsorbed in the thick ascending limb of the loop of Henle, by substitution for K+ on the Na+-K+-2Cl- carrier in the luminal membrane. Partial dissociation into NH3 and H+ occurs in less acidic tubular cells. The NH3 then diffuses into the medullary interstitium where it achieves relatively high concentrations. It then diffuses back into the segments with the lowest pH and a favourable gradient, where the secreted NH3 is trapped as NH4+ and excreted o Medullary interstitial NH3 concentration reaches high concentrations that allow this ammonia to diffuse into the tubular lumen in the medullary collecting tubule, where it is trapped as NH4+ by secreted H+ ions In the collecting tubules, non-polar lipid-soluble NH3 diffuses from the interstitial fluid into the lumen, where it combines with secreted H+ to form NH4+. Ammonium is lipid-insoluble and is unable to diffuse back out of the lumen. It should be noted that each NH4+ ion that is excreted is associated with the generation of a new HCO3- ion that is returned to the peritubular capillary.  THUS, in summary: the ammonium ion is produced from glutamine in the proximal tubule cells and reabsorbed in the thick ascending limb and enters the medullary interstitium. The medullary interstitium is impermeable to ammonium ion but not to ammonia (the dissociation product of ammonium). Ammonia is freely permeable through the epithelial cells and diffuses into the tubular lumen. Once in the lumen, it recombines with hydrogen ion secreted by hydrogen ATPases. Once the ammonia combines with hydrogen ion, the ammonium is trapped in the lumen and is excreted