Renal Transport Of HCO3- And H+ And Acid-Base Disorders

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5/4/10 9 Am

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What is the normal pattern of acid-base balance?
CO2 + nonvolatile acids are the acids you haveHCO3 - is the base
CO2 is blown off by the lungs, so you don't have to worry about itHCO3- is filtered by the kidneys and reabsorbedNonvolatile acids have to be excreted
What are the 3 systems that control plasma pH?
1. Lungs2. Kidneys3. Buffers
What is the role of a proton buffer?
To minimize changes in pH
What is the equation for acid dissociation/formation?
HA <----> H+ + A-
What is the equation for pH?
pH = - log [H+]
WHat is the equation for pK?
pK = - log [K]
What is the Henderson-Hasslebach equation?
pH = pKa + log ([A-])/[HA]
What is the most important buffer in the body?
serum bicarbonate
What are the 2 roles of the kidneys in acid-base balance?
1.  Secrete H+ to reabsorb almost all of the filtered HCO3-2.  Secrete daily net production of nonvolatile acids, with accompanying equal production of HCO3-
Net urinary acid excretion has 2 parts.  What are they?
1. H+ excretion requires binding of H+ to buffers (ex: phosphate, creatinine, urea) to produce a titratable acid2. H+ can bind to ammonia to form NH4+ to be excreted
What is the equation for net urinary acid excretion?
Net urinary acid excretion = titratable acids + ammonium - (excretion of filtered HCO3-)
Why does the excretion of filtered HCO3- have to be subtracted from acid excretion to get the net urianry acid excretion
Because the reabsorption of HCO3- requires the secretion of H+.  So if some of the HCO3- is not reabsorbed and is excreted, this represents H+ that was not exchanged and secreted, so it's like your adding acid back int othe system.
How is an acid challenge handled?
3 steps are involved:1. HCO3- and non-HCO3- buffers in the plasma neutralize most of the H+B- + H --> BHHCO3 + H --> H2CO3 --> CO2 + H2O2. CO2 is blown off by the lungs3. The kidneys produce new HCO3- to replace the HCO3- lost and to regenerate the non-bicarbonate buffersBH + HCO3 --> H2CO3 + B --> H2O + CO2 + B
HCO3- reabsorption requires __________
H+ secretion (NOT excretion!)
Describe HCO3- reabsorption.
HCO3- is converted by a luminal membrane CA to CO2 + OH-, and secreted H+ combines with the OH to form H2O.  H2O and CO2 freely diffuse into the cell, where an intracellular carbonic anhydrase combines then to re-form HCO3-.
Describe excretion as a titratable acid.
For every H+ that is secreted, a new HCO3- is produced (by the intracellular carbonic anhydrase) and transported to the plasma.  THe H+ in the lumen combines with a non-bicarb buffer (like HPO4) to form a titratable acid that can be excreted with its buffer.
Where is NH4+ secreted in the nephron?
Proximal tubule
Where is NH4+ reabsorbed in the nephron?
Describe NH4+ reabsorption by the TAL.
Apical membrane = NH4+ channels, Na/2Cl/NH4 cotransporterNH4 is broken down into H+ and NH3 inside the cellNH3 diffuses back into the plasma, reforms NH4+
Describe NH4+ recycling in the LoH.
NH4+ reabsorbed by the TAL is broken down into NH3 and H+ in the interstitium.1) NH3 diffuses back into the PCT and tDLH, where it can bind more H+ and form more titratable acid2) NH3 is secreted further downstream in the collecting ducts3) can re-combine in plasma as NH4 and go to the liver to form urea.
Describe the role of urea and glutamine metabolism in acid/bases.
Proteins and amino acid breakdown produces nitrogenous waste, which has to be converted to urea in the liver.  Urea formation in the liver consumes HCO3-.  Glutamine breakdown in the proximal tubule forms NH4+, and the NH4+ excretion forms new HCO3- that would hve otherwise been lost during the formation of urea.  
What are the effects of respiratory acidosis on H+ secretion?
Respiratory acidosis (i.e. increased PCO2) increases H+ secretion by an unknown mechanism
What are the effects of metabolic acidosis on H+ secretion?
Metabolic acidosis increases H+ secretion by increasing HCO3- uptake and reducing HCO3- backleak.
What are the effects of chronic metabolic acidosis on H+ secretion?
stimulates H+ secretion by increasing the activities of transporters and NH3 synthesis.
Name the 5 factors that increase HCO3- reabsorption
1. Respiratory acidosis (increased PCO2)2. Metabolic acidosis (decreased HCO3-)3. Hypokalemia 4. Decreased ECF volume with Cl- depletion (PT only)5. Mineralocorticoid excess (distal tubule only)
Why does hypokalemia increase HCO3- reabsorption?
H/K pump on the a-intercalated cell, which is responsible for increasing K+ reabsorption.  Pumps one K+ in for each H+ out.  So in hypokalemia, want to have increased activity of the pump to get more K+ into the plasma.  H+ secretion is necessary for HCO- reabsorption, so when this pump is more active, you get more HCO3- reabsorption.