Describe the process reabsorbing and excreting bicarbonate in the kidney.
80% reabsorbed in the proximal tubule
10% reabsorbed in the thick ascending limb
6% reabsorbed in the distal convoluted tubule
4% reabsorbed in the collcecting ducts
excretion of 0.36 mmoles/day
What are the components that contribute to total amount of acid excreted by the kidneys?
acid in the diet
acid produced by metabolism
acid produced when a base is lost in the stools
What are some of the mechanisms of bicarbonate reabsorption in the proximal tubule?
apical membrane has a Na+/H+ antiporter that secretes H+ into the tubular fluid, using the energy in the lumen-t-cell Na+ gradient
a portion of H+ secretion is also mediated by an H+-ATPase
H+ and HCO3- are produced within the cell by carbonic anhydrase
H+ is secreted into the tubular fluid, and HCO3- exits the cell across the basolateral membrane and returns to the peritubular blood
the H+ in the tubular fluid combines with the filtered HCO3- to form H2CO3, which is converted to CO2 and H2O
Describe the mechanisms of HCO3 reabsorption in the TAL.
HCO3- exits the basolateral membrane via a Cl-/HCO3- exchanger
CA activity is not necessary as it is in proximal tubule
Describe the mechanism of HCO3- in the distal tubule and the collecting duct.
mechanisms of reabsorption does not directly depend on Na+ via Na/H exchanger
steps in HCO3 reabsorption:
1) H+ and HCO3 are produced within the cell (CA)
2) H+ is secreted by H+-ATPase and to a lesser extent by H+-K+ ATPase (apical membrane)
3) HCO3 exits the cell by Cl-HCO3 antiporter (basolateral membrane)
Describe the layout of an alpha-intercalated cell.
H+ and HCO3- are produced by the hydration of CO2, catalyzed by CA II
H+ is secreted into the tubular fluid through an H+-ATPase and a K+-H+-ATPase
HCO3- exits the cell across the basolateral membrane in exchange for Cl-
there is also a chloride channel in the apical membrane
Describe the layout of a beta-intercalated cell.
HCO- is secreted into the tubular fluid through a HCO3-/Cl- exchanger
H+-ATPase pushes H+ into the blood
a chloride channel also exists on the basolateral surface
CA in the cell converts CO2 and H2O into HCO3-
activity of these cells is increased during metabolic alkalosis when the kidneys need to excrete excess HCO3-
the name of the transporter in the beta-intercalated cell that pushes bicarb into the tubular lumen in exchange for a chloride ion
Describe the layout of non-alpha non-beta intercalated cells.
a H+-ATPase pumps H+ into the tubular lumen
A HCO3-/Cl- exchanger is also located in the apical membrane
there are no channels on the basolateral membrane
HCO3- is created inside the cell through CA
What is the equation for net acid excretion?
NAE = [(NH4+ + TA)] - [(HCO3- + OA)]
TA = titratable acids
OA = organic anions
Describe the formation of titratable acids.
several weak acids filtered at the glomerulus that can act as buffers in the urine
H2Po4- is the major urinary buffer due to its favorable pKa of 6.80 and its relatively high rate of urinary excretion
creatinine and uric acid are also weak buffers
What are the major steps of ammonium excretion?
1) Nh4 is produced, primarily in the early proximal tubular cells
2) luminal NH4+ is partially reabsorbed in the thick ascending limb and the NH3 then recycled within the renal medulla
3) the medullary interstitial NH3 reaches high concentrations that allow NH3 to diffuse into the tubular lumen in the medullary collecting tubule where it is trapped as NH4+ by secreted H+
What are the reactions in the proximal tubules that lead to generation of ammonium?
Glutamine -> NH4+ + glutamate -> NH4+ + alpha-ketoglutarate2-
function of citrate in the urine
urinary base, main mode of base excretion under normal circumstances
1:1 Ca2+:citrate-3 complex has a very high association constant and solubility
most effective chelator of calcium in the urine to prevent precipitation with phosphate and oxalate
How is citrate handled in the nephron?
proximal tubule cells have a NaDC1 transporter that pushes 3 Na+ and citrate2- from the lumn into the cell
NaDC-3 pushes 3Na and citrate 3- from the interstitium into the cell
they combine and form oxaloacetate and acetyl-CoA with the help of citrate lyase
How are citrate levels adjusted in the case of metabolic acidosis?
there is an adaptive increase in uptake and metabolism of citrate within the proximal tubule
this reduces excretion of base into the urine and helps maintain acid-base status by increasing the net acid excretion
activites of cytoplasmic citrate lyase and mitochondrial aconitase are also increased
What are the two pathways for metabolizing citrate?
cytoplasmic pathway involving citrate lyase
mitochondrial pathway involving the citric acid cycle