acid-base balance Flashcards
pH range of ECF
7.35 - 7.45
pH of ECF controlled by what 3 systems
-buffering
-resp system (removes CO2 from plasma)
-kidneys (excretes acidic/alkaline urine-> eventually changes pH of blood when parts are reabsorbed)
what is the major buffer system used in the body
CO2 - carbonic acid - bicarbonate buffer system
what is the CO2 - carbonic acid - bicarbonate buffer system; what is it catalyzed by
catalyzed by CA (carbonic anhydrase)- can catalyze 1st rxn in EITHER direction
henderson-hasselback equation for bicarbonate buffers
pH = 6.1 + log ( [HCO3-] / alpha x Pco2)
pKa: 6.1
alpha: 0.03
Pco2: partial pressure of CO2
in an ideal world, what is supposed to be the denominator for the henderson-hasselback equation for bicarbonate buffer, & what is used instead
carbonic acid (but can’t be measured bc it completely dissociates)
so we use->
alpha x Pco2
alpha: permeability coefficient for CO2
what is the normal ratio of bicarbonate to alpha Pco2 at a pH of 7.4
[HCO3-] : alpha Pco2
20 : 1
what is true about the concentrations of bicarbonate & CO2 if the ratio of bicarbonate : alpha Pco2 is 20:1
concentrations don’t matter, as long as ratio is 20:1, then pH = 7.4
normal [HCO3-]
~24 mM
normal (arterial) Pco2
40 mmHg
normal amount of CO2/volatile acid produced per day
15,000 mmol /day
normal amount of fixed acid produced per day
1 mmol / kg /day
(~70 kg man -> makes 70 mmol /day)
what has to happen to all daily acid load, & why
all acid produced must be excreted -> to maintain acid-base homeostasis
(for fixed acid)
intake + production = _____ + _____
excretion + elimination
every day, kidneys must secrete enough H+ to _____ & _____
excrete ~70 mmol fixed acid
&
reabsorb the filtered ~4300 mmol HCO3-
how much HCO3- is filtered & reabsorbed per day
4300 mmol /day
H+ secreted into lumen of nephron is immediately buffered by one of 3 buffer systems:
1) reacts w filtered HCO3-
HCO3- + H+ -> CO2 + H2O
2) produces a titratable acid
B- + H+ -> HB
3) reacts w NH3 (ammonia)
NH3 + H+ -> NH4+
3 bases commonly used in buffer system that produces a titratable acid
HPO42-
creatinine
urate
when is HCO3- indirectly reabsorbed
when it reacts w secreted H+ in the tubular fluid (as one of the buffer systems)
HCO3- (bicarbonate in TF that was filtered across glomerulus) reabsorption mechanism
NHE (apical membrane) secretes H+ into TF
->
H+ + HCO3- react & form H2CO3 (carbonic acid)
->
H2CO3 –(CA)–> CO2 + H2O
->
CO2 crosses apical membrane & goes into cell
->
CO2 + H2O –(CA)–> H2CO3
->
H2CO3 -> H+ + HCO3-
->
HCO3- crosses basolateral membrane & leaves cell
3 steps for how body deals w non-volatile acid
1) ECF buffers immediately neutralize acid
2) if acid is buffered by HCO3-, resulting CO2 is excreted by lungs (this HCO3- needs to be replaced)
3) buffer regenerated by kidneys
2 ways fixed acid (H+) is excreted
buffered by a “titratable acid”
buffered by NH4+ (ammonium)
for every fixed acid (H+) that is buffered, what molecule is produced
HCO3-
equation for net urinary acid excretion (UAE)
UAE = (H+ excreted as titratable acid) + [ammonia in urine] - (excretion of filtered HCO3-)
why can you not just measure pH to get net urinary acid excretion (UAE)
pH is mostly [free H+] (and most of these are still buffered)
3 urinary buffers, & which is most important
HPO42- (phosphate- most important)
urate
creatinine
what is the pH from proximal tubule -> up through distal tubule, & what buffer works best here
tubular fluid pH is ~7
phosphate
how do you know what buffer will work best for a solution
if the pKa of the buffer is within 1 of the solution’s pH
pH > pKa, _____ of the buffer is protonated
less
pH < pKa, _____ of the buffer is protonated
more
when are urate & creatinine good buffers
later in collecting duct as pH begins to fall
what is ammonia’s behavior as a buffer & why
under normal conditions, majority of ammonia is protonated (becomes ammonium) bc it’s pKa is 9.2
ammonia is produced by _____, & then secreted _____
epithelium in PCT cells
secreted into tubular fluid
mechanism of ammonia production
(in PCT cells)
what is the key transporter in the apical membrane of the PCT for H+ secretion, & what is the secondary transporter
NHE3 (Na+/H+ exchanger)
H+ ATPase
what is the key transporter in the basolateral membrane of the PCT for H+ secretion, & what are the other 2
NBCe1 (Na+/HCO3- cotransporter)
AE2 (HCO3-/Cl-)
Na+/K+ ATPase
locations on the nephron where there is NO acid-base handling
thin descending limb (tDLH)
thin ascending limb (tALH)
what % of filtered HCO3- is reabsorbed in TALH
10%
what % of filtered HCO3- is reabsorbed in PCT
80%
what % of fixed acid is excreted in PCT
78% (as NH3 with some TA (titrated acid))
what % of filtered HCO3- is reabsorbed in distal tubule, CCD, & OMCD
10%
what % of fixed acid is reabsorbed in distal tubule, CCD, & OMCD
7% (as TA)
what % of fixed acid is reabsorbed in IMCD
15% (as TA)
what 2 molecules are reabsorbed at TALH
HCO3-
NH4+
at TALH
-intracellular production of _____
-apical secretion of _____
-basolateral efflux of _____
-production of H+ & HCO3- (from CO2 using CA)
-apical secretion of H+ via NHE3
-basolateral efflux of HCO3- via AE2
in TALH, what can NH4+ be mistaken as & what happens bc of this
NH4+ can be mistaken as K+
-> & enter cell via ROMK or NKCC by posing as K+
->
then becomes NH3 in cell
->
diffuses across basolateral membrane as NH3 into ECF
possible fates of NH3 after diffusing across basolateral membrane into ECF from TALH
1) diffuse into tDLH (passive secretion)
2) picked up by vasa recta & “washed out” into systemic circulation
3) secreted into MCD (medullary collecting duct) & titrated by H+ -> becomes NH4+ again & is excreted
(most common route)
where does the greatest degree of acidification of TF occur in the nephron, & why is this surprising
in the collecting duct
surprising bc most H+ secretion occurs in PCT (but pH doesn’t change much bc H+ immediately taken care of)
why does most acidification occur in collecting duct
bc not much buffer is left to deal w H+
decreases in ratio
[HCO3-] : alpha Pco2, _____ pH
decreases
increases in ratio
[HCO3-] : alpha Pco2, _____ pH
increases
a change in arterial pH due to change in Pco2, is what kind of acid-base disturbance
respiratory
respiratory acid-base disturbances are usually caused by _____
changes in rate of CO2 exhalation (pulmonary CO2 excretion rate)
hypoventilation leads to _____
respiratory acidosis (retaining CO2)
hyperventilation leads to _____
respiratory alkalosis (expelling CO2)
normal range for arterial Pco2
35 - 45 mmHg
2 ways that kidneys respond to respiratory acidosis
-increase [HCO3- in ECF]
(by increasing amount of filtered HCO3- that is reabsorbed)
-increase new HCO3- production (by increasing rate of H+ secretion)
mechanism of kidney response to ACUTE respiratory acidosis
CO2 diffuses into cells from ECF
->
lowers intracellular pH
->
increases H+ (& HCO3-) secretion
mechanism of kidney response to CHRONIC respiratory acidosis
same effects as acute &…
upregulates gene expression of transporters -> increases maximum rate of transport & HCO3- reabsorption
a change in arterial pH due to change in [HCO3-], is what kind of acid-base disturbance
metabolic
normal range of arterial [HCO3-]
22 - 28 mEq/L
diarrhea can cause _____ bc _____
metabolic acidosis
loss of HCO3- in diarrhea
vomiting can cause _____ bc _____
metabolic alkalosis
loss of H+ in vomit
mechanism of kidney response to ACUTE metabolic acidosis
(same as response to acute respiratory acidosis)
CO2 diffuses into cells from ECF
->
lowers intracellular pH
->
increases H+ (& HCO3-) secretion
general kidney response to CHRONIC metabolic acidosis
makes new HCO3- (primarily through ammonia production)
mechanism of kidney response to CHRONIC metabolic acidosis
decreased ECF pH
->
decreased ICF pH
->
induces 2+ intra-cellular pathways
1) protein kinase C
2) tyrosine kinase
->
signals go to nucleus
->
increased expression of NHE3, NBC, ammoniagenic enzymes
what is the primary way the body gets rid of excess acid & makes new bicarbonate
production of ammonia
more urinary NH3/NH4+ = _____ new HCO3- produced
more
what is “volume contraction”
a decrease in effective circulating volume (ECV)
what do the compensatory responses to a decreased ECV lead to
secondary metabolic alkalemia
mechanism of secondary metabolic alkalemia
decreased ECV (volume contraction)
->
RAAS system stimulated (goal = to bring more salt/water into body)
->
increases angiotensin II & aldosterone
->
angiotensin II increases H+ secretion via NHE (which increases HCO3- reabsorption & new HCO3- production)
->
aldosterone stimulates:
1) H-ATPase in alpha-intercalated cells = H+ secretion (& HCO3- production)
2) K+ secretion = hypokalemia
(interrelationship between [H+ in ECF] & hyper-/hypokalemia)
acidosis in ECF may induce a _____ in ECF
secondary hyperkalemia
H+ in ECF < H+ in cell
->
K+ in ECF > K+ in cell
(interrelationship between [H+ in ECF] & hyper-/hypokalemia)
alkalosis in ECF may induce a _____ in ECF
secondary hypokalemia
H+ in ECF > H+ in cell
->
K+ in ECF < K+ in cell
why does the interrelationship between [H+ in ECF] & hyper-/hypokalemia exist
bc the cell is unintentionally trying to remain balanced with its + charges
(interrelationship between [H+ in ECF] & hyper-/hypokalemia)
hypokalemia in cell may induce a _____ in cell, bc of _____
secondary alkalosis
bc of H+ influx into cell
K+ in cell < K+ in ECF
->
H+ in cell > H+ in ECF
(interrelationship between [H+ in ECF] & hyper-/hypokalemia)
hyperkalemia in cell may induce a _____ in cell, bc of _____
secondary acidosis
bc of H+ efflux out of cell
K+ in cell > K+ in ECF
->
H+ in cell < H+ in ECF
interrelationship between [H+ in ECF] & hyper-/hypokalemia occurs in what cells
all cells of the body (systemic AND renal)
