B5.041 Renal Physiology IV: Control of Acid-Base Equilibrium Flashcards
what is the kidney’s primary function in the acid-base balance of the body
excretion of 70 mmoles H+ per day
nonvolatile acids that cant be breathed off
examples of nonvolatile acids
phosphoric and organic acids
renal mechanisms involved in pH regulation
- bicarb reabsorption / H+ secretion
- urine acidification (H+ titration using bicarb or phosphate)
- ammonium production
discuss the bicarb reabsorption/ H+ secretion mechanism in the proximal tubule
apical membrane: Na+/H+ antiporter that expels H+ into the tubular fluid
BM: Na+/HCO3- symport transfers HCO3- into interstitial space and circulation
both driven by electrical gradient generated by NaKATPase
ratio of H+ secreted to HCO3- reabsorbed in proximal tubule
1:1
discuss the bicarb reabsorption/ H+ secretion mechanism in the a intercalated cells in the distal and collecting tubule
apical: proton pump and H+K+ pump both are ATPases that secrete H+ against the gradient
BM: Cl-/HCO3- exchanger moves bicarb to the interstitium
discuss the bicarb reabsorption/ H+ secretion mechanism in the B intercalated cells in the distal and collecting tubule
reverse of a intercalated cells
apical: HCO3-/Cl- symport
BM: proton pump and H+K+ ATPase
when do the B intercalated cells become important?
when there is an excess of bicarb in the blood
move bicarb back into lumen
summary of bicarb handling in the nephron
proximal loop: 80% bicarb reabsorbed via Na+/HCO3- on BM
distal tubule: 6% bicarb reabsorbed via Cl-/HCO3- on BM
collecting tubule: 4% bicarb reabsorbed via Cl-/3HCO3- on BM….or secreted depending on need via same transporter on apical membrane
0.01% excreted
rest in loop of henle, not clinically significant
summary of proton handling in the nephron
proximal tubule: Na-H antiporter on apical membrane
distal tubule: Na-H antiporter and H ATPase on apical membrane
collecting tubule: H-ATPase and H,K-ATPase on apical (a cells) or BM (B cells)
discuss the process of urine acidification using a phosphate buffer
pH of urine can range from 4.5-7.9 depending on needs
the main buffer in the filtrate is HPO4–/H2PO4-
normal ratio is 4:1, but as more H+ is excreted, ratio can move towards 1:1
at pH 4.8 nearly all phosphate is H2PO4-
discuss the process of urine acidification using a bicarb buffer
carbonic anhydrase present at brush border and cytoplasm of tubular epithelial cells generates H2CO3 and H+
discuss ammonium production in the renal tubules
capacity to excrete H+ with phosphate or other weak acids is limited
ammonium excretion is also used to neutralize the acid load
NH3 easily and rapidly diffuses into tubular fluid and reacts with H+ to form NH4+ which cannot return into cell
NH4+ within cell can also be secreted through Na+/NH4+ antiporter
production of NH3
produced in the tubular cells by deamidation of glutamine catalyzed by glutaminase
1 glutamine = 2 NH3
3 indexes of renal acid-base efficiency
- net acid excretion
- urine anion gap
- plasma anion gap
net acid excretion
= (titratable acidity + [NH4+]) - [HCO3-]
what is the urine anion gap
UAG = ([Na+] + [K+]) - [Cl-]
normal NH4+, UAG negative
low NH4+, UAG zero or positive
why is the UAG negative when NH4+ production is normal
gap for the anions is due to the presence of non-determined cations in urine, primarily NH4+
gives appearance of excess [Cl-]
what is the plasma anion cap
PAG = [Na+] - ([Cl-]+[HCO3-])
normal between 8-16
increases when blood pH is reduced
why does anion gap increase when pH is reduced?
HCO3- concentration lower bc it is being used to buffer H+
other anions that balance Na+ that aren’t counted, giving the appearance of the gap
keto acids
phosphoric acids
acidosis
increased H+ gradient between cells and tubular lumen
alkalosis
decreased H+ gradient between cells and tubular lumen (H+ is retained)
low pH
high PCO2
increased function of exchangers via direct activation and insertion of more exchangers in membranes
buffer systems in tubule
increase gradient for H+ secretion
NH4 production
increases H+ secretion
2 mechanisms for metabolic acidosis
gain of acid
loss of HCO3-
ways to gain acid in the body
more endogenous H+ production
more exogenous H+ intake
less renal H+ excretion
ways to lose HCO3- in body
less renal HCO3- reabsorption
more GI loss
what does it mean to have metabolic acidosis with a normal plasma ion gap
HCO3- is lost, but it is lost with Na+
proximal renal tubular acidosis
bicarb loss with normal PAG
normally 60-70% of bicarb is reabsorbed here, losing this if the proximal tubule isn’t working right
distal renal tubular acidosis
decreased H+ secretion the primary issue
treatment of metabolic acidosis
attack the underlying cause
2 mechanisms for metabolic alkalosis
loss of H+- vomiting, diuretics
gain of HCO3- ingestions of antacids
how is metabolic alkalosis maintained
renal HCO3- retention (hyperaldosteronism, Gitelman’s syndrome, Bartters syndrome)
treatment of metabolic alkalosis
treat underlying cause
