Acid Base Regulation

Question 1

What is the equation for pH?

Answer 1

ph = -log10 [H+]

Question 2

Give the equation for HCO3- mediated buffering in the circulation.

Which molecule is the base and which is the acid here?

Answer 2

H+ + HCO3- = H2CO3 = H2O + CO2

H2CO3 is the acid and HCO3- is the base.

Question 3

What is the pH of arterial blood?

Answer 3

7.4

Question 4

What is the pH of venous blood?

Answer 4

7.35

Question 5

What is the concentration of HCO3- in arterial blood?

Answer 5

24mM

Question 6

What is the concentration of HCO3- in venous blood?

Answer 6

25mM

Question 7

What is the PCO2 in arterial blood?

Answer 7

40 mmHg

Question 8

What is the PCO2 in venous blood?

Answer 8

46mmHg

Question 9

What is the Henderson-Hasselbalch equation?

Answer 9

pH = pK + log10 [base]/[acid]

Question 10

What is pKa?

Answer 10

The pH at which half of a substance is ionised.

Question 11

How is blood H2CO3 concentration measured?

Answer 11

By multiplying PCO2 (mmHg) by 0.03.

Question 12

What is the equation for blood H+ concentration?

Answer 12

[H+] α [CO2] / [HCO3-]

Question 13

List 4 processes that result in a net hydrogen ion production.

Answer 13

1 - ATP hydrolysis.

2 - Anaerobic respiration.

3 - Production of ketones.

4 - Ingestion of acids.

Question 14

In which condition is ketone production high?

Answer 14

Diabetes mellitus.

Question 15

Why is the kidney implicated in pH regulation?

Answer 15

• Because H+ is removed by combination with HCO3-, which produces excretable H2O and CO2.
• The loss in HCO3- must be restored by the kidney.

Question 16

What is the maximum rate of renal HCO3- reabsorption?

Answer 16

4 mM / min.

Question 17

At which plasma HCO3- concentration do you expect HCO3- reabsorption to reach its maximum rate?

Answer 17

24 - 25mM (the same as the normal blood HCO3- concentration).

Question 18

How is the kidney able to produce HCO3- when the blood concentration of HCO3- is low?

How is H+ buffered in the tubules during HCO3- production?

Answer 18

• When there is not an excess of HCO3- in the tubular lumen (under the maximum filtration rate), the vasa recta may act as a source of CO2.
• HPO4 2- acts as a buffer for H+ in the tubules.

Question 19

List 2 factors that limit the rate of renal HCO3- reabsorption.

Answer 19

1 - H+ concentration in the proximal tubule.

2 - In turn, the concentration of Na+ / H+ exchangers in the proximal tubule.

Question 20

List the two dominant mechanisms for H+ secretion into the tubular lumen.

Answer 20

Primary active transport through:

1 - Apical H+ ATPases.

2 - H+ / K+ ATPases.

Question 21

In which cells does H+ secretion occur in the distal tubule?

Answer 21

Alpha intercalated cells.

Question 22

Give the equation for H2PO4- mediated buffering in the urine.

Answer 22

H2PO4- = HPO4 2- + H+

Question 23

Where and how is ammonia produced in the kidney?

How does this contribute to the production of HCO3-?

Answer 23

• It is produced in the proximal tubule.
• It is produced as a byproduct of conversion of glutamine to glutamic acid and then to alpha-ketoglutarate.
• Alpha ketoglutarate is metabolised to form HCO3-.

Question 24

With which molecule is ammonia in equilibrium in the filtrate?

What is the advantage of having this equilibrium?

Answer 24

• NH4+ is in equilibrium with NH3.

- NH4+ acts as another reservoir for H+.

Question 25

How might ammonia production contribute to Na+ absorption in the proximal tubule?

Answer 25

- NH4+ production in the epithelia will lead to increased H+ and NH3 production. - H+ exits the cell via the Na+ / H+ exchanger. - NH3 freely diffuses across the apical membrane into the filtrate, where it recombines with H+ to form NH4+ (maintaining the concentration gradient).

Question 26

What is the average pH of filtrate at the end of the proximal tubule? How does this change by the end of the nephron?

Answer 26

- pH is 6.9 at the end of the proximal tubule. | - By the end of the nephron, pH is highly variable but falls to about 4.5.

Question 27

On a mixed Davenport diagram (diagram 4 on the lecture slides), what do the horizontal lines represent and what do upward-sloping lines represent?

Answer 27

- The upward-sloping lines represent changing HCO3- concentrations at different set concentrations of pCO2. - The horizontal lines represent changing pCO2 for different set concentrations of HCO3.

Question 28

List 2 causes of respiratory alkalosis.

Answer 28

1 - Hyperventilation. 2 - High altitude.

Question 29

How does the kidney respond to respiratory alkalosis?

Answer 29

- With respiratory alkalosis, CO2 concentration decreases, so the equilibrium shifts towards CO2 according to the HCO3- buffering equation (H+ is lost). - In order to restore the pH, the kidney reduces production of HCO3- to shift the equilibrium back towards H+ (produces H+).

Question 30

What might you expect to see on a Davenport diagram for respiratory alkalosis?

Answer 30

- The initial loss of pCO2 will follow the horizontal line (pCO2 for a defined [HCO3-]) downwards and to the right (as pH increases). - Where horizontal line intersects the upward-sloping line ([HCO3-] for a defined pCO2), the decrease in HCO3- production will follow the upward-sloping line downwards and to the left (as pH decreases again).

Question 31

Give an example of a cause of respiratory acidosis.

Answer 31

Hypoventilation.

Question 32

How does the kidney respond to respiratory acidosis?

Answer 32

- With respiratory acidosis, CO2 concentration increases, so the equilibrium shifts towards H+ according to the HCO3- buffering equation (H+ is produced). - In order to restore pH, the kidney increases production of HCO3- to shift the equilibrium back towards CO2 (removes H+).

Question 33

What might you expect to see on a Davenport diagram for respiratory acidosis?

Answer 33

- The initial gain of pCO2 will follow the horizontal line (pCO2 for a defined [HCO3-]) upwards and to the left (as pH decreases). - Where the horizontal line intersects the upward-sloping line ([HCO3-] for a defined pCO2), the increase in HCO3- production will follow the upward-sloping line upwards and to the right (as pH increases again).

Question 34

List 4 causes of metabolic acidosis.

Answer 34

1 - Renal failure. 2 - Lactic acidosis. 3 - Ketoacidosis. 4 - Poisoning (e.g. aspirin).

Question 35

How does the body respond to metabolic acidosis?

Answer 35

- With metabolic acidosis, H+ goes up, which causes HCO3- to go down OR HCO3- goes down, which causes H+ to go up. - In order to restore pH, the CNS increases the ventilation to decrease CO2, returning the pH towards normal (kind of like inducing respiratory alkalosis).

Question 36

What might you expect to see on a Davenport diagram for metabolic acidosis?

Answer 36

- The initial loss of HCO3- will follow the upward-sloping line ([HCO3-] for a defined pCO2) downwards and to the left (as pH decreases). - Where the upward-sloping line intersects the horizontal line (pCO2 for a defined [HCO3-]), the decrease in pCO2 will follow the horizontal line downwards and to the right (as pH increases again).

Question 37

List 2 causes of metabolic alkalosis.

Answer 37

1 - Vomiting. 2 - Contraction alkalosis.

Question 38

How does the body respond to metabolic alkalosis?

Answer 38

- With metabolic alkalosis, H+ goes down, which causes HCO3- to go up OR HCO3- goes up, which causes H+ to go down. - In order to restore pH, the CNS decreases the ventilation to increase CO2, returning the pH towards normal (kind of like inducing respiratory acidosis).

Question 39

What might you expect to see on a Davenport diagram for metabolic alkalosis?

Answer 39

- The initial increase of HCO3- will follow the upward-sloping line ([HCO3-] for a defined pCO2) upwards and to the right (as pH increases). - Where the upward-sloping line intersects the horizontal line (pCO2 for a defined [HCO3-]), the increase in pCO2 will follow the horizontal line upwards and to the left (as pH decreases again).

Question 40

If a Davenport diagram is divided into 4 equal quadrants, which conditions are represented by each quadrant and why?

Answer 40

- The top left quadrant represents respiratory acidosis as it is the area where pCO2 is high. - The bottom right quadrant represents respiratory alkalosis as it is the area where pCO2 is low. - The top right quadrant represents metabolic alkalosis as it is the area where [HCO3-] is high. - The bottom left quadrant represents metabolic acidosis as it is the area where [HCO3-] is low.

Question 41

What is the anion gap? What is the average range for the anion gap? What does an increase in the anion gap suggest?

Answer 41

- The imbalance in measured bodily anions compared to cations, such that there is a relative excess of cations. - The average range for the anion gap is 3-11 mmol/L. - An increase in the anion gap suggests that there is a high concentration of anions that are not being accounted for.

Question 42

List 7 causes of an increased anion gap.

Answer 42

Generally, causes of acidosis increase the anion gap: 1 - Lactate produced during anaerobic metabolism. 2 - Ketones, especially in diabetes or alcohol toxicity. 3 - Sulfates which accumulate during renal failure. 4 - Phosphates which accumulate during renal failure. 5 - Urate, which accumulates during renal failure. 6 - Hippurate, which accumulates during renal failure. 7 - Aspirin overdose.