B5.041 Renal Physiology IV: Control of Acid-Base Equilibrium

Question 1

what is the kidney’s primary function in the acid-base balance of the body

Answer 1

excretion of 70 mmoles H+ per day

nonvolatile acids that cant be breathed off

Question 2

examples of nonvolatile acids

Answer 2

phosphoric and organic acids

Question 3

renal mechanisms involved in pH regulation

Answer 3

1. bicarb reabsorption / H+ secretion
2. urine acidification (H+ titration using bicarb or phosphate)
3. ammonium production

Question 4

discuss the bicarb reabsorption/ H+ secretion mechanism in the proximal tubule

Answer 4

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

Question 5

ratio of H+ secreted to HCO3- reabsorbed in proximal tubule

Answer 5

1:1

Question 6

discuss the bicarb reabsorption/ H+ secretion mechanism in the a intercalated cells in the distal and collecting tubule

Answer 6

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

Question 7

discuss the bicarb reabsorption/ H+ secretion mechanism in the B intercalated cells in the distal and collecting tubule

Answer 7

reverse of a intercalated cells
apical: HCO3-/Cl- symport
BM: proton pump and H+K+ ATPase

Question 8

when do the B intercalated cells become important?

Answer 8

when there is an excess of bicarb in the blood

move bicarb back into lumen

Question 9

summary of bicarb handling in the nephron

Answer 9

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

Question 10

summary of proton handling in the nephron

Answer 10

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)

Question 11

discuss the process of urine acidification using a phosphate buffer

Answer 11

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-

Question 12

discuss the process of urine acidification using a bicarb buffer

Answer 12

carbonic anhydrase present at brush border and cytoplasm of tubular epithelial cells generates H2CO3 and H+

Question 13

discuss ammonium production in the renal tubules

Answer 13

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

Question 14

production of NH3

Answer 14

produced in the tubular cells by deamidation of glutamine catalyzed by glutaminase
1 glutamine = 2 NH3

Question 15

3 indexes of renal acid-base efficiency

Answer 15

1. net acid excretion
2. urine anion gap
3. plasma anion gap

Question 16

net acid excretion

Answer 16

= (titratable acidity + [NH4+]) - [HCO3-]

Question 17

what is the urine anion gap

Answer 17

UAG = ([Na+] + [K+]) - [Cl-]
normal NH4+, UAG negative
low NH4+, UAG zero or positive

Question 18

why is the UAG negative when NH4+ production is normal

Answer 18

gap for the anions is due to the presence of non-determined cations in urine, primarily NH4+
gives appearance of excess [Cl-]

Question 19

what is the plasma anion cap

Answer 19

PAG = [Na+] - ([Cl-]+[HCO3-])
normal between 8-16
increases when blood pH is reduced

Question 20

why does anion gap increase when pH is reduced?

Answer 20

HCO3- concentration lower bc it is being used to buffer H+

Question 21

other anions that balance Na+ that aren’t counted, giving the appearance of the gap

Answer 21

keto acids

phosphoric acids

Question 22

acidosis

Answer 22

increased H+ gradient between cells and tubular lumen

Question 23

alkalosis

Answer 23

decreased H+ gradient between cells and tubular lumen (H+ is retained)

Question 24

low pH

high PCO2

Answer 24

increased function of exchangers via direct activation and insertion of more exchangers in membranes

Question 25

buffer systems in tubule

Answer 25

increase gradient for H+ secretion

Question 26

NH4 production

Answer 26

increases H+ secretion

Question 27

2 mechanisms for metabolic acidosis

Answer 27

gain of acid

loss of HCO3-

Question 28

ways to gain acid in the body

Answer 28

more endogenous H+ production
more exogenous H+ intake
less renal H+ excretion

Question 29

ways to lose HCO3- in body

Answer 29

less renal HCO3- reabsorption

more GI loss

Question 30

what does it mean to have metabolic acidosis with a normal plasma ion gap

Answer 30

HCO3- is lost, but it is lost with Na+

Question 31

proximal renal tubular acidosis

Answer 31

bicarb loss with normal PAG

normally 60-70% of bicarb is reabsorbed here, losing this if the proximal tubule isn’t working right

Question 32

distal renal tubular acidosis

Answer 32

decreased H+ secretion the primary issue

Question 33

treatment of metabolic acidosis

Answer 33

attack the underlying cause

Question 34

2 mechanisms for metabolic alkalosis

Answer 34

loss of H+- vomiting, diuretics

gain of HCO3- ingestions of antacids

Question 35

how is metabolic alkalosis maintained

Answer 35

renal HCO3- retention (hyperaldosteronism, Gitelman’s syndrome, Bartters syndrome)

Question 36

treatment of metabolic alkalosis

Answer 36

treat underlying cause