0816 - Metabolic Acid-Base Flashcards
What is normal blood pH? When are people considered acidotic and alkalotic?
Normal 7.4 (7.38-7.42)
pH of 7.35 = Acidosis (note that this is still an alkaline pH)
pH of 7.45 = Alkalosis
Ph greater than 8 or less than 6.8 = death.
What are the broad symptoms of acidosis?
pH 7.35 = Acidosis
Depresses CNS, Leads to coma, respiratory failure
What are the broad symptoms of alkalosis
pH 7.45 = Alkalosis
Stimulates CNS, Leads to muscle seizures and convulsions.
What are the 3 levels of protection against pH changes? How does each work?
Chemical buffering - bind H+ to buffer bases, particularly HCO3-
Respiratory - Blow off CO2 (75%)
Renal (later response) - excrete/resorb H+ and synthesise/excrete/resorb HCO3- (25%)
How is net urinary acid excretion calculated?
NAE = Filtered buffers (bound to phosphate, creatinine, uric acid) + Synthesised buffers (bound to ammonia) - filtered HCO3- excretion.
Filtered buffers are present in circulation, filtered into tubule and protons can bind to them.
Synthesised buffers are synthesised in kidney, rather than in circulation.
How can the kidneys minimise alkalosis?
HCO3- transporters get maxed out at levels above normal plasma. Thus, kidneys are well placed to excrete excess HCO3-, minimising alkalosis. HCO3- (in CD) secretion can also occur, but only happens in metabolic alkalosis.
How does acidosis affect transporters in the nephron?
In PT, acidosis increases Na/H antiporter and Na/3HCO3- expression and activity
In CD, acidosis increases H+ ATP-ase expression.
Aklalosis causes reverse effects
HCO3- resorption is regulated by H+ gradient.
What is the primary H+ efflux mechanism in PT?
Na/H+ antiporter.
What does carbonic anhydrase do?
Converts CO2+H2O into H+ and HCO3- (and back). By being present in cytoplasm and on plasmalemma, can control urine and blood pH to maintain appropriate acid-base balance (H+ can be used to titrate urinary buffers).
How does the kidney produce HCO3- in NH4+ synthesis? KEY EXAM CONCEPT
In early PT, glutamine enters cell via Na-linked transporter, and is metabolised in mitochondria to alpha-KG, releasing 2x NH4+ (glutaminase and glutamate dehydrogenase). Alpha-KG reacts with 2 x H+ (from 2x H2O) to form ½ glucose. Remaining 2x OH- react with 2x CO2 on carbonic anhydrase to form 2x HCO3- which is pumped out by Na/3x HCO3- symporter. 2x HCO3- for each Gln.
NH4+ dissociates, with NH3 diffusing across the membrane and H+ being pumped out. Recombine into NH4+ in the lumen.
How is NH4+ handled by the nephron?
Produced from Gln in mitochondria, dissociates, and re-combines in lumen. However, in TAL, it re-enters cells, de-protonate, and enter interstitium (this is bad - trying to excrete NH3/NH4). in CD, NH3 diffuses back into cell, and NH4 re-enters by 2x Na/3x NH4 ATP-ase. Then same process, dissociates, H+ pumped out, and NH3 diffuses into tubule, to recombine again.
What happens to NH4+ excretion in non-renal metabolic acidosis?
Increases to 3x normal level within 1-2 days. This is due to increased hepatic glutamine production (and decreased urea formation) and processing by nephron to produce HCO3-.
Explain the urine Anion Gap
Urine needs to maintain net electroneutrality (Cation charge= anion charge). While some ions (K, Na, Cl) are measured, others are not. Thus, UAG is the balance of Na+K-Cl, and roughly equates to [NH4+]. Not useful in Ketoacidosis due to high excreted anions (ketones).
Zero to positive with normal NH4+ production, but strongly negative with increased NH4+ production (remember - comes from HCO3- synthesis)
How does the anion gap change in ketoacidosis?
Anion gap is high, as the anion involved is not Cl-, thus cannot be measured and is included in the gap.
Anion gap = [Na]-([Cl]+[HCO3-])
It is normal in diarrhea or renal tubule acidosis (as compensated by Cl-, which can be measured so not included in the gap).
