SM_200a: Acid Base Integration I

Question 1

Describe the schematic for integration of acid-base balance

Answer 1

Question 2

Blood pH lines of defense include _____, _____, and _____

Answer 2

Blood pH lines of defense include buffering systems, alveolar ventilation to regulate PCO₂, and regulation of plasma bicarbonate by the kidneys

Question 3

Describe the defense against an acute acid load

Answer 3

Defense against an acute acid load

• Extracellular buffering of the excess H⁺ by HCO₃^- (almost immediately)
• Respiratory compensation decreases PCO₂ (within several minutes)
• Intracellular buffers such as proteins and organic phosphates (within hours)
• Renal excretion of acid load (complete within 4-6 days)

Question 4

Components of cellular buffering (60% of a H⁺ load) are ______, ______, and ______

Answer 4

Components of cellular buffering (60% of a H⁺ load) are imidazole ring in histidine (pK 7.0), HCO₃^- (pK 6.1), and phosphate (pK 6.8)

Question 5

Intracellular pH is _____

Answer 5

Intracellular pH is 7.10-7.30

Question 6

_____ transporters in cell membrane protect the cell against changes in pH

Answer 6

Acid-base transporters in cell membrane protect the cell against changes in pH

• Na⁺/H⁺ antiporter
• Na⁺ dependent Cl^-/HCO₃^- exchanger
• Na⁺ independent Cl^-/HCO₃^- exchanger

Question 7

Amiloride blocks the _____

Answer 7

Amiloride blocks the Na⁺/H⁺ antiporter

Question 8

If cell loaded with acid, pH ____ then ____

Answer 8

If cell loaded with acid, pH decreases then recovers (cell quickly recovers)

Question 9

If person loads up on base, pH ____ then ____

Answer 9

If cell loaded with base, pH rises then falls (cell recovers spontaneously)

Question 10

Kidneys can excrete either ____ or ____, but they typically excrete ____ because Western diet is heavy in ____

Answer 10

Kidneys can excrete either acid or base, but they typically excrete acid because Western diet is heavy in acid

Question 11

80% of HCO₃^- is absorbed in the ____

Answer 11

80% of HCO₃^- is absorbed in the PCT

Question 12

Describe HCO₃^- reabsorption in the nephron

Answer 12

HCO₃^-​ reabsorption in the nephron

• Essentially all filtered HCO₃^-​ is reabsorbed
• 80% is reabsorbed in PCT
• 15% reabsorbed in loop of Henle
• 5% reabsorbed in distal tubule and collecting duct (fine regulation)

Question 13

Renal acid-base transporters involved in bicarbonate reabsorption that are in the apical membrane include _____, _____, _____, and _____

Answer 13

Renal acid-base transporters involved in bicarbonate reabsorption that are in the apical membrane include Na⁺/H⁺ antiporter, H⁺ ATPase, H⁺/K⁺ ATPase, and pendrin (Cl^-/HCO₃^-)

Question 14

Renal acid-base transporters involved in bicarbonate reabsorption that are in the basolateral membrane are _____ or _____

Answer 14

Renal acid-base transporters involved in bicarbonate reabsorption that are in the basolateral membrane are Na⁺/HCO₃^- and Cl^-/HCO₃^-

Question 15

NHE3 is the main enabler of _____ formation in the proximal tubule

Answer 15

NHE3 is the main enabler of bicarbonate formation in the proximal tubule

(Na⁺/3HCO₃^- transporter allows reabsorption of bicarbonate in PCT)

Question 16

Describe mechanism of HCO₃^- reabsorption in the PCT

Answer 16

Mechanism of HCO₃^- reabsorption in the PCT

1. H⁺ and HCO₃^- production within the cell via carbonic anhydrase
2. H⁺ is secreted into tubular fluid using Na⁺/H⁺ antiporter and H⁺ ATPase
3. H⁺ secreted, combined with filtered HCO₃^- to form H₂CO₃ and then CO₂ + H₂O via carbonic anhydrase
4. CO₂ + H₂O are rapidly reabsorbed
5. CO₂ + H₂O comnine within cell to form H⁺ and HCO₃^-
6. HCO₃^- moves out of cell across basolateral membrane

Question 17

In the PCT, for every H⁺ secreted, there is _____ removed from the tubular lumen and reabsorbed in the peritubular blood

Answer 17

In the PCT, for every H⁺ secreted, there is a HCO₃^- removed from the tubular lumen and reabsorbed in the peritubular blood

Question 18

The two differences between HCO₃^- reabsorption in the TAL and the PCT are that in the TAL ______ and _______

Answer 18

The two differences between HCO₃^- reabsorption in the TAL and the PCT are that in the TAL a Cl^-/HCO₃^- exchanger is present and carbonic anhydrase is absent

Question 19

Describe HCO₃^- reabsorption in the TAL

Answer 19

HCO₃^- reabsorption in the TAL

• 10-15% of filtered HCO₃^- reabsorbed in TAL
• HCO₃^- exits basolateral membrane via Cl^-/HCO₃^- exchanger
• Carbonic anhydrase activity not necessary because it is in the brush border of the proximal tubule

Question 20

Describe HCO₃^- in the distal tubule and collecting duct

Answer 20

HCO₃^- in the distal tubule and collecting duct

• 5-10% of filtered load is reabsorbed
• Reabsorption NOT mediated by Na⁺/H⁺ exchanger
• Alpha-intercalated cells secrete H⁺
• Beta-intercalated cells secrete HCO₃^-: H⁺ ATPase located in the basolateral membrane and pendrin (Cl^-/HCO₃^-) is in apical membrane, activity increased during metabolic aklalosis
• Normally, H⁺ secretion via alpha-intercalated cells predominates over HCO₃^- secretion via beta-intercalated cells

Question 21

The cell types in the collecting tubule are _____, _____, and _____

Answer 21

The cell types in the collecting tubule are principal cells, alpha-intercalated cells, and beta-intercalated cells

Question 22

Priniciple cells in the collecting tubule ____ and _____

Answer 22

Priniciple cells in the collecting tubule retain Na⁺ through ENaC and secrete K⁺ via ROMK

Question 23

Alpha-intercalated cells in the collecting tubule _____

Answer 23

Alpha-intercalated cells in the collecting tubule secrete acid primarily via the H⁺ ATPase

Question 24

Beta-intercalated cells in the collecting tubule _____ via the _____

Answer 24

Beta-intercalated cells in the collecting tubule secrete base via the HCO₃^-/Cl^- antiporter

Question 25

Normally, \_\_\_-intercalated cells predominate

Answer 25

Normally, alpha-intercalated cells predominate (programmed to secrete acid)

Question 26

In alpha-intercalated cells, H⁺ leaves the cell primarily through _____ and interacts with _____ to form \_\_\_\_\_, while HCO₃^- leaves through the _____ transporter

Answer 26

In alpha-intercalated cells, H⁺ leaves the cell primarily through H⁺ ATPase and interacts with NH₃ to form NH₄⁺, while HCO₃^- leaves through the Cl^-/HCO₃^- transporter

Question 27

In beta-intercalated cells, _____ allows secretion of bicarbonate into tubule lumen

Answer 27

In beta-intercalated cells, pendrin allows secretion of bicarbonate into tubule lumen

Question 28

Urine buffers are _____ and \_\_\_\_\_

Answer 28

Urine buffers are phosphate and ammonia (titratable acids)

Question 29

Describe titratable acidity

Answer 29

Titratable acidity * Weak acids filtered at the glomerulus that act as buffers * Effectiveness of buffer depends on the quantity of the buffer and its pKa * Phosphate is the major urinary buffer that contributes to TA, uric acid and creatinine also contribute

Question 30

\_\_\_\_\_ is the major urinary buffer that contributes to titratable acidity because its pKa is closest to urine pH

Answer 30

Phosphate is the major urinary buffer that contributes to titratable acidity because its pKa is closest to urine pH

Question 31

Net acid excretion = \_\_\_\_\_\_

Answer 31

Net acid excretion = (NH₄⁺ + TA) - HCO₃^-

Question 32

Describe the process of ammonium (NH₄⁺) formation and excretion

Answer 32

Ammonium (NH₄⁺) formation and excretion 1. NH₄⁺ formation from glutamine in proximal tubule 2. NH₄⁺ reabsorption in the loop of Henle and NH₃ recycling within the kidney medulla 3. NH₃ diffusion into the medullary collecting duct and trapping as NH₄⁺ by secreted H⁺

Question 33

Ammonia is produced from _____ in the PCT

Answer 33

Ammonia is produced from glutamine in the PCT (NH₃ is for diffusion whereas NH₄⁺ is active)

Question 34

NH₄⁺ is reabsorbed in the loop of Henle via the _____ transporter

Answer 34

NH₄⁺ is reabsorbed in the loop of Henle via the Na⁺/K⁺/2Cl^- transporter

Question 35

NAE = \_\_\_\_\_

Answer 35

NAE = (NH₄⁺ + TA) - HCO₃^-

Question 36

Citrate is _____ in PCT

Answer 36

Citrate is reabsorbed in PCT

Question 37

Factors affecting HCO₃^- reabsorption and acid excretion are \_\_\_\_\_, \_\_\_\_\_, \_\_\_\_\_, and \_\_\_\_\_

Answer 37

Factors affecting HCO₃^- reabsorption and acid excretion are acid-base alteration, volume, mineralocorticoid (aldosterone), hypokalemia, and angiotensin II

Question 38

Acids are mainly excreted in a ______ called \_\_\_\_\_\_

Answer 38

Acids are mainly excreted in a buffered form called titratable acids (NH₄⁺ and others)

Question 39

Metabolic acidosis stimulates \_\_\_\_\_\_

Answer 39

Metabolic acidosis stimulates HCO₃^- reabsorption

Question 40

Metabolic alkalosis ____ HCO₃^- reabsorption

Answer 40

Metabolic alkalosis inhibits HCO₃^- reabsorption