Acid Base Regulation Flashcards
What is the equation for pH?
ph = -log10 [H+]
Give the equation for HCO3- mediated buffering in the circulation.
Which molecule is the base and which is the acid here?
H+ + HCO3- = H2CO3 = H2O + CO2
H2CO3 is the acid and HCO3- is the base.
What is the pH of arterial blood?
7.4
What is the pH of venous blood?
7.35
What is the concentration of HCO3- in arterial blood?
24mM
What is the concentration of HCO3- in venous blood?
25mM
What is the PCO2 in arterial blood?
40 mmHg
What is the PCO2 in venous blood?
46mmHg
What is the Henderson-Hasselbalch equation?
pH = pK + log10 [base]/[acid]
What is pKa?
The pH at which half of a substance is ionised.
How is blood H2CO3 concentration measured?
By multiplying PCO2 (mmHg) by 0.03.
What is the equation for blood H+ concentration?
[H+] α [CO2] / [HCO3-]
List 4 processes that result in a net hydrogen ion production.
1 - ATP hydrolysis.
2 - Anaerobic respiration.
3 - Production of ketones.
4 - Ingestion of acids.
In which condition is ketone production high?
Diabetes mellitus.
Why is the kidney implicated in pH regulation?
- Because H+ is removed by combination with HCO3-, which produces excretable H2O and CO2.
- The loss in HCO3- must be restored by the kidney.
What is the maximum rate of renal HCO3- reabsorption?
4 mM / min.
At which plasma HCO3- concentration do you expect HCO3- reabsorption to reach its maximum rate?
24 - 25mM (the same as the normal blood HCO3- concentration).
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?
- 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.
List 2 factors that limit the rate of renal HCO3- reabsorption.
1 - H+ concentration in the proximal tubule.
2 - In turn, the concentration of Na+ / H+ exchangers in the proximal tubule.
List the two dominant mechanisms for H+ secretion into the tubular lumen.
Primary active transport through:
1 - Apical H+ ATPases.
2 - H+ / K+ ATPases.
In which cells does H+ secretion occur in the distal tubule?
Alpha intercalated cells.
Give the equation for H2PO4- mediated buffering in the urine.
H2PO4- = HPO4 2- + H+
Where and how is ammonia produced in the kidney?
How does this contribute to the production of HCO3-?
- 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-.
With which molecule is ammonia in equilibrium in the filtrate?
What is the advantage of having this equilibrium?
- NH4+ is in equilibrium with NH3.
- NH4+ acts as another reservoir for H+.
How might ammonia production contribute to Na+ absorption in the proximal tubule?
- 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).
What is the average pH of filtrate at the end of the proximal tubule?
How does this change by the end of the nephron?
- 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.
On a mixed Davenport diagram (diagram 4 on the lecture slides), what do the horizontal lines represent and what do upward-sloping lines represent?
- 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.
List 2 causes of respiratory alkalosis.
1 - Hyperventilation.
2 - High altitude.
How does the kidney respond to respiratory alkalosis?
- 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+).
What might you expect to see on a Davenport diagram for respiratory alkalosis?
- 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).
Give an example of a cause of respiratory acidosis.
Hypoventilation.
How does the kidney respond to respiratory acidosis?
- 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+).
What might you expect to see on a Davenport diagram for respiratory acidosis?
- 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).
List 4 causes of metabolic acidosis.
1 - Renal failure.
2 - Lactic acidosis.
3 - Ketoacidosis.
4 - Poisoning (e.g. aspirin).
How does the body respond to metabolic acidosis?
- 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).
What might you expect to see on a Davenport diagram for metabolic acidosis?
- 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).
List 2 causes of metabolic alkalosis.
1 - Vomiting.
2 - Contraction alkalosis.
How does the body respond to metabolic alkalosis?
- 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).
What might you expect to see on a Davenport diagram for metabolic alkalosis?
- 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).
If a Davenport diagram is divided into 4 equal quadrants, which conditions are represented by each quadrant and why?
- 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.
What is the anion gap?
What is the average range for the anion gap?
What does an increase in the anion gap suggest?
- 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.
List 7 causes of an increased anion gap.
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.
