Role of Kidney in Acid/Base Flashcards
Normal pH =
< 7.35 = ___
> 7.45 = ___
7.35-7.45
acidemia
alkalemia
A 70 kg person will produce about ___ /day of nonvolatile acids (___)
this means that every ___ mmol of H+ are added to the ECF every day from nonvolatile acids
we only have 300 mEq/mole of HCO3- so at max, we can neutralize ___ days worth of H+ and need to keep replacing that 60 mmol/day
60 mEq; sulfuric/phosphoric acid
60 mmol of H+
5 days worth (20 mmol/L * 15L = 300 mmol HCO3-)
Major acid buffering mechanisms in ECF
major buffering proteins involved
H+ + HCO3- –> H2CO3 –> CO2 + H2O
(convert nonvolatile acid into volatile CO2 that can be eliminated rather than simply buffered)
proteins = albumin, Hb, gammaglobulins
how is bicarb regulated in the kidney
rate limiting step
key to making rxn fast? where is it located
85% reabsoption in prox tubule + synthesis of bicarb
H2CO3 dissolution
carbonic anhydrase is key; located in brush border membranes and in cell
Reabsorption of bicarb is ___
acid/base neutral with respect to ECF (NO CHANGE IN PH) to make sure don’t lose HCO3-
Taking bicarb from lumen to serosa (no net gain of H+ = cycled from cell into lumen and back)
Amount HCO3- reabsorbed daily
100% of filtered is reabsorbed = [20 mM] x 190L/day = 3800 mmol HCO3- reabsorbed per day
Reabsorption of bicarb in proximal tubule process
1) secretion of H+ from inside of cell into lumen via Na-H exchanger (NHE) in apical (electro neutral)
2) H+ in lumen combine with bicarb to form H2CO3 –> CO2 + H2O
3) CO2 highly permeable to apical membrane and diffuse into cell
4) in cell CO2 + H2O –> H2CO3 (highly reversible)
5) H2CO3–> H+ + HCO3- due to low bicarb and H+ in cell
6) bicarb reabsorb across basolateral membrane via sodium-bicarb co-transporter (NBC) (electro neutral)
Bicarbonate synthesis mechanism
1) in DT/CD in intercalated cells, CO2 go from ECF into cell
2) CO2 + H2O –> H2CO3 –> H+ + HCO3-
3) H+ pumped into lumen for excretion in urine via H+ ATPase (to pump H+ against gradient) and HCO3- transported passively across serosal
4) URINE BECOMES ACIDIC
5) neutralize with buffers (titratable acids = HPO4-, creatinine, urate) and ammonia trapping
How does body neutralize urine from bicarb synthesis
neutralize with buffers (titratable acids = HPO4- - , creatinine, urate) and ammonia trapping
Titratable acids = acid anions from desorption of bone (HPO4- -)
combine with H+ to form H2PO4- (still charged so won’t cross apical) and urinate H2PO4-
Describe ammonia trapping
glutamine broken down by glutaminase in cells
–> release NH3 –> diffuse into tubule and binds H+
NH4+ can’t diffuse back –> excreted (60-200 mmol synth per day)
ammonia trapped into tubular fluid because becomes charged NH4+ and cannot be reabsorbed
2 rules of HCO3- regulation
1) no bicarb synthesis is possible until bicarb reabosprtion complete (100% of filtered load)
if secreted H+ during synthesis, combine with HCO3- and becomes CO2 and then added back into ECF so don’t get secretion of H+
CO2 that enters back into cell will inhib CO2 across basolateral for synthesis
2) H+ secretion is limited and depends on:
a) pCO2, # of H+ ion secretion mechanisms (NHE in prox tubule and H+ ATPase in DT/CD)
Renal response to metabolic acidosis
1) metabolic acidosis, incr H+ produced
2) incr buffering with HCO3- AND incr apical H+ pumps
3) INCR CO2 PRODUCTION (but ELIM via resp compensation), destroy HCO3-
4) decr filtered load of HCO3- (based on [HCO3-[ * GFR) so rate of synth HCO3- incr (partial renal compensation never able to replace loss of HCO3- entirely) = ACUTE
5) decr H+ secretion required for HCO3- reabsorption
6) incr H+ secretion capacity for HCO3- synth (regulated by incr # H+ transporters, incr # NHE and #ATPase so rate of H+ will incr) = CHRONIC
7) incr HCO3- synth, replenish lost HCO3-
Long term effects of changes in ECF potassium levels on plasma pH
with hyperkalemia
with hypokalemia
1) Hyperkalemia –> decr rate of H+ secretion and excretion so H+ retained in ECF –> acidosis
2) therefore, hypokalemia induced shift of H+ into tubular cells –> incr H+ secretion and excretion –> alkalsosi
Mechanism of diamox (acetazolamide)
Diamox inhibit carbonic anhydrase
slow reabsorption of HCo3- (more bicarbonate stays in tubule with Na+ and becomes diuretic)
why doesn’t synthesis occur in reabsorption (prox tubule) if have same channels?
Compare activity of reabsorption and synthesis
1) Reabosrption just so much more in prox tubule (100% reabsorption by time you leave prox tubule) so by the time in DT/CD it is purely synthesis
2)
In reabsorption = secretes 3800 mmol HCO3- per day (much more active than synthesis)
In synthesis = secrete 60 mmol HCO3-/day
Rate of HCo3- synthesis equation
Rate of HCo3- synthesis = (Rate of H+ secretion) - (rate of HCO3- Filtration)
Rate of H+ secretion depends on pCO2 and # H+ transported
Rate of HCO3- filtration = [HCO3-] x GFR
ACUTE COMPENSATION mechanism for metabolic acidosis
CHRONIC COMPENSATION for metabolic acidosis
decr filtered load of HCO3- (based on [HCO3-[ * GFR) so rate of synth HCO3- incr (partial renal compensation never able to replace loss of HCO3- entirely)
less H+ secretion for reabsorb HCO3- and excess secretory capacity for incr HCO3- synthesis
incr H+ secretion capacity for HCO3- synth (regulated by incr # H+ transporters, incr # NHE and #ATPase so rate of H+ will incr) = CHRONIC
Reaction of H2CO3 has 2 problmes
1) elim acid anions that produced H+ ions in first place (HSO4-, H2PO4-)
filtered at glomerulus and excreted in urine
2) elim of each H+ requires destruction of HCO3-
in what situation is ammonia trapping incr
metabolic acidosis
upregul glutaminase
differences btwn reabs and synth of HCO3-
reabs = CO2 from lumen, neutral
synthesis = CO2 from serosa, not neutral because pump H+ into lumen
similarities = apical H+ secretion and basolateral reabs of HCO3- from cell interior
Regulation
Severe metab acidosis
Sever metab alkalosis
1) > 200 mmol/day H+ from nonvolatile acid so need to incr HCO3-
2) excreting up to 80 mmol of HCO3 per day
what are the rate limiting step for bicarb homeostasis
apical secretion of H+ ions
basolateral extrusion of bicarbonate
rates of apical H+ secretion and basolateral HCO3- extrusion depend on
CO2 and H+ in resp acidosis and metab acidosis cause cell
ECF pH and CO2 levels
to insert more transporters into apical and basolateral
