Role of Kidney in Acid/Base

Question 1

Normal pH =

< 7.35 = ___

> 7.45 = ___

Answer 1

7.35-7.45

acidemia

alkalemia

Question 2

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

Answer 2

60 mEq; sulfuric/phosphoric acid

60 mmol of H+

5 days worth (20 mmol/L * 15L = 300 mmol HCO3-)

Question 3

Major acid buffering mechanisms in ECF

major buffering proteins involved

Answer 3

H+ + HCO3- –> H2CO3 –> CO2 + H2O

(convert nonvolatile acid into volatile CO2 that can be eliminated rather than simply buffered)

proteins = albumin, Hb, gammaglobulins

Question 4

how is bicarb regulated in the kidney

rate limiting step

key to making rxn fast? where is it located

Answer 4

85% reabsoption in prox tubule + synthesis of bicarb

H2CO3 dissolution

carbonic anhydrase is key; located in brush border membranes and in cell

Question 5

Reabsorption of bicarb is ___

Answer 5

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)

Question 6

Amount HCO3- reabsorbed daily

Answer 6

100% of filtered is reabsorbed = [20 mM] x 190L/day = 3800 mmol HCO3- reabsorbed per day

Question 7

Reabsorption of bicarb in proximal tubule process

Answer 7

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)

Question 8

Bicarbonate synthesis mechanism

Answer 8

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

Question 9

How does body neutralize urine from bicarb synthesis

Answer 9

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-

Question 10

Describe ammonia trapping

Answer 10

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

Question 11

2 rules of HCO3- regulation

Answer 11

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)

Question 12

Renal response to metabolic acidosis

Answer 12

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-

Question 13

Long term effects of changes in ECF potassium levels on plasma pH

with hyperkalemia

with hypokalemia

Answer 13

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

Question 14

Mechanism of diamox (acetazolamide)

Answer 14

Diamox inhibit carbonic anhydrase

slow reabsorption of HCo3- (more bicarbonate stays in tubule with Na+ and becomes diuretic)

Question 16

why doesn’t synthesis occur in reabsorption (prox tubule) if have same channels?

Compare activity of reabsorption and synthesis

Answer 16

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

Question 17

Rate of HCo3- synthesis equation

Answer 17

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

Question 18

ACUTE COMPENSATION mechanism for metabolic acidosis

CHRONIC COMPENSATION for metabolic acidosis

Answer 18

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

Question 19

Reaction of H2CO3 has 2 problmes

Answer 19

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-

Question 20

in what situation is ammonia trapping incr

Answer 20

metabolic acidosis

upregul glutaminase

Question 21

differences btwn reabs and synth of HCO3-

Answer 21

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

Question 22

Regulation

Severe metab acidosis

Sever metab alkalosis

Answer 22

1) > 200 mmol/day H+ from nonvolatile acid so need to incr HCO3-
2) excreting up to 80 mmol of HCO3 per day

Question 23

what are the rate limiting step for bicarb homeostasis

Answer 23

apical secretion of H+ ions

basolateral extrusion of bicarbonate

Question 24

rates of apical H+ secretion and basolateral HCO3- extrusion depend on

CO2 and H+ in resp acidosis and metab acidosis cause cell

Answer 24

ECF pH and CO2 levels

to insert more transporters into apical and basolateral