Acid-Base Balance

Question 1

summarize the renal contribution to the regulation of acid base balance

Answer 1

1. reabsorption of filtered HCO3−, which occurs fundamentally in the proximal tubule; and ​
2. excretion of acids through the titration of urinary buffers and the excretion of ammonium, which takes place primarily in the distal nephron

Question 2

what largely determines the pH of extracellular fluid? describe

Answer 2

the ratio between bicarbonate (HCO3-) and carbon dioxide (CO2)

if HCO3- increases, so does pH (more alkaline/basic)
if CO2 increases, pH decreases (more acidic)

Question 3

what are the 4 important players in regulation of ECF acid-base balance? describe which is slow and rapid

Answer 3

rapid correction of pH:
1. intracellular (proteins, phosphates) and extracellular buffers (HCO3-)
2. lungs: regulation of CO2

slower correction of pH
1. kidneys: regulate concentration of HCO3- and H+
2. liver: lactic acid metabolism, ketogenesis, protein homeostasis

Question 4

give 3 relevant acid sources

Answer 4

1. metabolism of animal proteins (sulfur containing AAs)
2. metabolism of dietary acids
3. anaerobic metabolism of carbohydrates (lactic acid) and fats (ketone bodies)

Question 5

give a relevant alkali source

Answer 5

metabolism of vegetable proteins (anionic side-chains)

Question 6

what are 2 acid-base neutral processes?

Answer 6

1. normal oxidative phosphorylation of carbohydrates and fat: generates CO2 that is eliminated by lungs and H2O so sum of all rxns is neutral
2. metabolism of some proteins

Question 7

GENERALLY describe renal contribution to acid-base balance

Answer 7

1. reabsorption of filtered HCO3-, mostly in the proximal tubule
2. excretion of acids through titration of urinary buffers and excretion of ammonium, primarily taking place in the distal nephron

Question 8

explain the main functions of the proximal tubule pertaining to acid-base regulation

Answer 8

1. since HCO3- is freely filtered by the kidney, 80% of HCO3- then is reabsorbed in the proximal tubule
2. the Na+/K+ ATPase pump creates the Na+ gradient that drives Na+/H+ exchange (Na+ in H+ out)
3. some of the filtered HCO3- is co-transported from the tubular lumen into the proximal tubule interstitium with Na+
4. most of the filtered HCO3- combines with the H+ that was pumped out of the cell into the tubular lumen to make carbonic acid, which dissociates into water and CO2
5. the CO2 enters proximal tubule cells and recombines with water in the presence of carbonic anhydrase to form carbonic acid, which then dissociates to H+ and HCO3- (now inside the cell), which then leaves to the interstitium also via co-transport with Na+

every H+ moved out of a cell across one membrane is accompanied by the transport of HCO3- out of the cell on the OPPOSITE membrane

Question 9

explain the main functions of the distal nephron pertaining to acid-base balance

Answer 9

1. chloride and bicarbonate concentrations share an inverse reciprocal relationship during either acidosis or alkalosis
   2a. Type A intercalated cells reabsorb HCO3- and K+; secrete H+ and Cl-; are active during acidosis
   2b. Type B intercalated cells reabsorb H+ and Cl-; secrete HCO3- and K+; active during alkalosis
2. proton secretion is gradient-limited: there’s a need to consume these protons in order to keep secreting them (this is where buffers come in)
   3a. in animals under mild acid pressure with normal phosphate intake, there is enough phosphate left in the tubular fluid (after proximal reabsorption) to accept approx half of secreted H+
   3b. ammonia normally accepts the rest of the secreted load of H+, and production can be dramatically upregulated in heavy acid load

Question 10

predict the renal response to acid or alkali loads

Answer 10

under acid pressure, want to excrete acid:
1. freely filter HCO3-
2. reabsorb the majority of HCO3-
3. reabsorb some additional HCO3-
4. secrete H+ and secrete NH4 using Type A intercalated cells
5. excrete acidic urine containing NH4+

under alkaline pressure, want to excrete base:
1. freely filter HCO3-
2. reabsorb the majority of filtered HCO3-
3. reabsorb some additional HCO3-
4. secrete some HCO3- using Type B intercalated cells
5. excrete alkaline urine containing HCO3-

Question 11

predict changes in acid-base balance produced by defects in the proximal tubule or distal nephron

Answer 11

both a proximal tubular defect (impair HCO3- reabsorption) and a distal tubular defect (impair H+ secretion) would result in a type of metabolic acidosis known as renal tubular acidosis