Acid-base regulation L13 Flashcards
Define pH.
- log[H+]
what is normal arterial pH?
7.4
what is normal venous pH?
7.35
Do we measure blood pH from the arterial or venous circulation?
arterial as venous can be more variable depending on the tissue bed the blood is coming from (different substances in venous blood)
What is arterial HCO3- concentration?
24mM
What is venous HCO3- concentration?
25mM
why is venous HCO3- concentration slightly higher than arterial?
CO2 produced in tissue bed which reacts with water to form HCO3- (and H+)
Normal arterial Pco2 in mmHg and kPa?
40mmHg, 5kPa
Normal venous Pco2?
46mmHg
What is the Henderson-Hasselbach equation
pH = pK + log[base]/[acid]
where pK = rate constant
What is the normal value of pK (rate constant)?
6.1
What does the HH equation tell us about the relationship between HCO3- concentration and pH?
proportional - increase in HCO3- leads to increase in pH
what is the relationship between CO2 concentration and pH?
inversely proportional - increase in CO2 leads to decrease in pH
What are some of the ways that H+ can be produced in the body?
- hydrolisation of ATP
- production of ketones (high in diabetes)
- ingestion of acids
- production of lactate
How is H+ formed in anaerobic respiration?
glucose > lactic acid > dissociation into lactate and H+
How is excess H+ removed from the body?
reacts with HCO3- to form CO2 which can be exhaled *however this decreases circulating HCO3- = problem!
HCO3- reabsorption occurs in which part of the nephron?
proximal tubule *look back to previous lectures
Is HCO3- reabsorption Tm limited?
yes - therefore an excess of HCO3- will not be reabsorbed > can quickly correct HCO3- concentration
What is the kidneys response to CO2 entering through the vasa recta rather than the filtrate?
- this suggests an excess of H+ in blood which reacts with HCO3- to produce CO2. This results in a lower concentration of HCO3- in the blood.
- the kidney responds by ‘de novo’ HCO3- production i.e. production of new HCO3- within the kidney
- this replaces HCO3- lost elsewhere in the body
- H+ in circulation is also buffered by HPO42- to stop it from reacting with HCO3- to form more CO2 (and H2O)
Describe new HCO3- production in the kidney.
- CO2 enters epithelial cells of proximal tubule from interstitium (from vasa recta)
- CO2 combines with H2O to form HCO3- and H+ using CA.
- H+ is removed through Na+/H+ pump to stop it reacting
- HCO3- moves into interstitium through 3HCO3-/Na+ co-transporter
- increase in HCO3- in body
How is H+ secreted into the distal tubule?
primary active transport:
- H+ ATPase
- H+K+ ATPase
*occur in alpha-intercalated cells of distal tubule
How are excess H+ ions buffered in the filtrate?
- No HCO3- to react with H+ as most is reabsorbed in proximal tubule
- H+ buffered using hydrogen phosphate instead
- helps to keep urinary H+ low (urine is not too acidic)
State the equation for the reaction between H+ and hydrogen phosphate.
H+ + HPO4^2- H2PO4-
At blood plasma, what is the predominate form of hydrogen phosphate present in solution?
higher pH (7.4) so HPO4^2- predominates as less H+ reacting with it
In acidic urine, what is the predominate form of hydrogen phosphate present in solution?
lower pH (5) so H2PO4- predominates as excess H+ reacts with HPO4^2- –> buffering the pH.
*can maintain an only slightly acidic pH urine as H+ ions are removed by buffer, don’t need to have very low urinary pH to remove H+ ions.
In extreme acidosis, what mechanism can the kidney use to get rid of H+ from the body?
- in PT, glutamine converted into glutamic acid and then alpha-ketoglutarate
- at each conversion stage, NH4+ is produced.
- in cell, NH4+ is in equilibrium with NH3
- NH3 can cross apical membrane into filtrate
- the H+ ions (from NH4+ > NH3 + H+) pass into filtrate through Na+/H+ antiporter
- NH4+ reforms in filtrate
- this mechanism helps to remove some of excess H+
*this is not the main mechanism and only happens in extreme acidosis
What is the urinary pH at the end of the proximal tubule?
- 9
* later down the nephron pH can be variable depending on how much acid is in the body, can get as low as 4.5
What is the typical cause of respiratory acidosis?
hypoventilation
Describe and explain the presentation of the blood for respiratory acidosis?
- low pH and high HCO3-
- low pH due to decreased respiratory rate > high CO2 in circulation
- high CO2 leads to high H+, reaction favours:
CO2 + H2O –> HCO3- + H+
Kidney produces MORE HCO3- in compensation, thereby returning pH towards normal.
What is the typical cause of respiratory alkalosis?
hyperventilation, high altitude
Describe and explain the presentation of the blood for respiratory alkalosis?
- high pH and low HCO3-
- high pH due to increase in respiratory rate > low CO2 in circulation
- low CO2 leads to low H+, reaction favours:
H+ + HCO3- –> CO2 + H2O
Kidney decreases production or recovery of HCO3- in compensation, thereby returning pH towards normal.
What are typical causes of metabolic acidosis?
renal failure, lactic acidosis, ketoacidosis, poisoning (e.g. aspirin) *many many more!
Describe and explain the presentation of the blood for metabolic acidosis?
- low pH and low HCO3-
- low pH due to increase in H+ in circulation
- increase in H+ leads to decrease in HCO3-, reaction favours:
H+ + HCO3- –> CO2 + H2O
*can be vice versa i.e. decrease in HCO3- leads to increase in H+ > same result, low pH
H2O + CO2 –> H+ + HCO3-
CNS increases ventilation rate in compensation > decrease CO2, returning pH to normal
What are typical causes of metabolic alkalosis?
vomiting, contraction alkalosis (increase in pH due to fluid losses)
Describe and explain the presentation of the blood for metabolic alkalosis?
- high pH and high HCO3-
- high pH due to decrease in H+ in circulation
- decrease in H+ leads to increase in HCO3-, reaction favours:
H2O + CO2 –> H+ + HCO3-
*can be vice versa i.e. increase in HCO3- leads to decrease in H+ > same result, high pH
H+ + HCO3- –> CO2 + H2O
CNS decreases ventilation rate in compensation > increase CO2, returning pH to normal
What is the anion gap?
The measured difference between positive (cations) and negative (anions) charges in our bodies. The difference is due to anions that are not analysed in testing. There is a normal range for the anion gap and if the value is higher than the normal range (in serum), this can suggest metabolic acidosis.
What is anion gap usually measured as?
[Na+] - [Cl-] - [HCO3-]
What is the normal reference range for the anion gap?
3-11mmol/L *although this tends to vary between laboratories
A higher-than-normal anion gap can be due to a high concentration of ions that are not being tested in sample. Which anions might they be?
- lactate - anaerobic metabolism - lactic acidosis
- ketones - diabetes or alcohol toxicity
- sulfates, phosphates, urate and hippurate - renal failure
- aspirin overdoes
*therefore causes of metabolic acidosis can change the anion gap
NOTE
look at davenport diagrams on handout
