acid-base balance and the kidney Flashcards
pH equation
-log10[H+]
normal pH of arterial blood
7.4
what is pH regulation dominated by?
HCO3-/CO2 buffering system
what is the henderson-hasselbalch equation?
what causes a resp acidosis/alkalosis?
acidosis = inceasesd CO2 eg poor gas exchange in lungs
alkalosis = decreased CO2 eg hyperventilation
what causes a metabolic acidosis/alkalosis?
- acidosis = decreases HCO3-
- alkalosis = increased HCO3- = RARE
what is normal HCO3- is mM?
24 mM
what is normal CO2 in mM?
1.2 mM = 40mmHg
how many mmol of CO2 is produced a day?
15 000
metabolism produced __ mmol H+ a day
40
— non-volatile acids = sulphyric, phosphoric, organic acids
net uptake of __mmol H+ a day by GIT
30
kidney has to excrete __mmol H+ a day and reabsorb all the filtered ____ (equivalent to 4000 mmol H+ a day)
- 70
- HCO3-
typical urine output a day
1.5 litres
what are the 3 mechanism of acid-base balance in the kidney?
- reabsorption of filtered bicarbonate
- excretion of H+ as titration acid
- excretion of H+ as NH4+ (ammonium)
describe reabsorption of filtered HCO3-
- H+ secretion at apical membrane reclaims HCO3- as Co2 + H2O
- HCO3- extruded at basolateral membrane
- net transfer of HCO3- from lumen to blood
- involves carbonic anhydrase was II and IV
carbonic anhydrase II vs IV
II = intracellular in cytoplasm
IV = expressed in apical membrane
describe excretion of H+ as ‘titratable acid’ TA
- H+ and HCO3- generated from CO2 and H20 in cell
- secreted H+ is mostly buffered by filtered phosphate - also creatinine, urate etc
- new HCO3- enters circulation and neutralises acidity
describe excretion of H+ as NH4+ (ammonium)
- NH4+ synthesised by the kidney
- comes from glutamine metabolism
- new HCo3- enters circulation and neutralises acidity
what are the sites of HCO3- reabsorption?
- most is reabsorbed in the PCT
- small amounts in TAL (10%), DCT (6%) and CD (4%)
- very little excreted : <0.01%
where is most of the NH4+ secreted?
PCT
what mmol of acid are excreted by kidneys?
70mmol
= 40mmol NH4+ + 30mmol TA
kidneys excrete additional H+ as what?
- titratable acid using filtered buffers like phosphate
- NH4+ = synthesised
when does renal tubule acidosis occur and what are the different types?
- occurs when there are defects in HCO3- reabsorption and H+ excretion
4 types:
- 1 = distal RTA
- 2 = proximal RTA
- 3 = mixed (1+2)
- 4 = hyperkalaemia RTA (hypoaldosteronism)
what is the dominant transporter in the PCT?
NHE3
what predominates later in the tubule?
H+ ATPase
in the PCT, HCO3- in tubular fluid is converted to CO2 and OH- as a result of what? what happens to the products?
carbonic anhydrase IV
- CO2 diffuses into cell and combines with OH- (via CA II) to form HCO3-
- OH- combines with H+ in tubular fluid to form water — diffuses into cell via osmosis, then breaks down into H+ and OH-
in the PCT, how does HCO3- leave the cell on the basolateral side?
kNBCe1
describe kNMCe1
- how HCO3- crosses basolateral membrane in early PCT
- electrogenic with a net transport of 2 -ve charges
- 1 Na+ for every 3 HCO3-
- membrane potential helps drive HCO3- exit
NHE3 vs H+ ATPase gradient
- NHE3 = large capacity but limited gradient
- H+ ATPase = can generate a larger capacity
what transporters are present in the apical membrane of the TAL and DCT?
same as PCT
NHE3 and H+ ATPase
what is used instead of kNBCe1 on the basolateral side of the cell for HCO3- reabsorption in TAL and DT?
AE2 = HCO3-/Cl- exchanger
where is the majority of the V-type H+ ATPase activity?
later on in tubule — a-intercalated cells of collecting tubule and duct cells
what is the main function of the H+/K+ ATPase in the a-intercalated cells of the CD?
K+ reabsorption
what is on the basolateral membrane to reabsorb HCO3- in the a-intercalated cells?
kAE1 (HCO3- Cl- exchanger)
where are the V-type H+ ATPase cells in the collecting dyct?
apical membrnae of a-intercalated cells — NOT on principal cells
where and how is NH4+ produced?
by glutamine metabolism in PCT
NH4+ is secreted as ____ which passively diffuses across ___ membrane. NH4+ then reformed by combining with __ (which is excreted in exchange for __)
- NH3
- apical
- H+
- Na+
what does glutamine metabolism produce?
NH4+ and OH-
what happens to the OH- produced in glutamine metabolism in the PCT?
combine with CO2 via CA II to form HCO3- — this can then enter blood across basolateral membrane via NMB
what happens to NH4+ in the TAL?
- reabsorbed via ROMK2 chanel and NKCC1 (NH4+ in oak e of usual K+_
- low permeability at apical membrane, so it leaves across basolateral membrane
what happens to NH4+ in the collecting duct?
- re-secreted
- most crosses epithelium as NH3 (can freely diffuse across membrane)
- maybe some NH4+ carried by NaK ATPase
describe type 1 — distal renal tubular acidosis
- defective H+ excretion by distal segment of nephron
- inability to acidify urine — serious systemic consequences = metabolic acidosis
- may be incomplete — compensatory mechansims of PCT
- but treatable by HCO3- supplementation
- several transproter mutiatons — mainly affected the a-intercalated cells : kAE1, V-type H+ ATPase, CAII (proximal affects too)
describe type 2 — proximal RTA
- rare autosomal recessive disease
- impaired HCO3- reabsorption in PCT
- severe metabolic acidosis
- not treatable by HCO3- supplementation (80% f bicarbonate is reabsorbed in PCT)
- attributed to mutations in kNBCe1
- ocular abnormalities too because of kNMCe1 and pNBCe1 expression there too
resp/metaoblic acidosis :
an increase in PCO2 (resp) or decrease in HCO3- btoh directly stimulate what?
an increase in H+ secretion and increase in NH4+ synthesis by proximal tubule
chronic resp/metabolic acidosis leads to an increased expression of what?
NHE3 and kNMCe1
resp/metabolic alkalosis — chronic leads to more what?
more B-intercalated cells (HCO3- secreting) in collecting tubule
