Acid-base regulation L13

Question 1

Define pH.

Answer 1

• log[H+]

Question 2

what is normal arterial pH?

Answer 2

7.4

Question 3

what is normal venous pH?

Answer 3

7.35

Question 4

Do we measure blood pH from the arterial or venous circulation?

Answer 4

arterial as venous can be more variable depending on the tissue bed the blood is coming from (different substances in venous blood)

Question 5

What is arterial HCO3- concentration?

Answer 5

24mM

Question 6

What is venous HCO3- concentration?

Answer 6

25mM

Question 7

why is venous HCO3- concentration slightly higher than arterial?

Answer 7

CO2 produced in tissue bed which reacts with water to form HCO3- (and H+)

Question 8

Normal arterial Pco2 in mmHg and kPa?

Answer 8

40mmHg, 5kPa

Question 9

Normal venous Pco2?

Answer 9

46mmHg

Question 10

What is the Henderson-Hasselbach equation

Answer 10

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

where pK = rate constant

Question 11

What is the normal value of pK (rate constant)?

Answer 11

6.1

Question 12

What does the HH equation tell us about the relationship between HCO3- concentration and pH?

Answer 12

proportional - increase in HCO3- leads to increase in pH

Question 13

what is the relationship between CO2 concentration and pH?

Answer 13

inversely proportional - increase in CO2 leads to decrease in pH

Question 14

What are some of the ways that H+ can be produced in the body?

Answer 14

• hydrolisation of ATP
• production of ketones (high in diabetes)
• ingestion of acids
• production of lactate

Question 15

How is H+ formed in anaerobic respiration?

Answer 15

glucose > lactic acid > dissociation into lactate and H+

Question 16

How is excess H+ removed from the body?

Answer 16

reacts with HCO3- to form CO2 which can be exhaled *however this decreases circulating HCO3- = problem!

Question 17

HCO3- reabsorption occurs in which part of the nephron?

Answer 17

proximal tubule *look back to previous lectures

Question 18

Is HCO3- reabsorption Tm limited?

Answer 18

yes - therefore an excess of HCO3- will not be reabsorbed > can quickly correct HCO3- concentration

Question 19

What is the kidneys response to CO2 entering through the vasa recta rather than the filtrate?

Answer 19

• 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)

Question 20

Describe new HCO3- production in the kidney.

Answer 20

• 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

Question 21

How is H+ secreted into the distal tubule?

Answer 21

primary active transport:

• H+ ATPase
• H+K+ ATPase

*occur in alpha-intercalated cells of distal tubule

Question 22

How are excess H+ ions buffered in the filtrate?

Answer 22

• 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)

Question 23

State the equation for the reaction between H+ and hydrogen phosphate.

Answer 23

H+ + HPO4^2- H2PO4-

Question 24

At blood plasma, what is the predominate form of hydrogen phosphate present in solution?

Answer 24

higher pH (7.4) so HPO4^2- predominates as less H+ reacting with it

Question 25

In acidic urine, what is the predominate form of hydrogen phosphate present in solution?

Answer 25

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.

Question 26

In extreme acidosis, what mechanism can the kidney use to get rid of H+ from the body?

Answer 26

- 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

Question 27

What is the urinary pH at the end of the proximal tubule?

Answer 27

6. 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

Question 28

What is the typical cause of respiratory acidosis?

Answer 28

hypoventilation

Question 29

Describe and explain the presentation of the blood for respiratory acidosis?

Answer 29

- 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.

Question 30

What is the typical cause of respiratory alkalosis?

Answer 30

hyperventilation, high altitude

Question 31

Describe and explain the presentation of the blood for respiratory alkalosis?

Answer 31

- 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.

Question 32

What are typical causes of metabolic acidosis?

Answer 32

renal failure, lactic acidosis, ketoacidosis, poisoning (e.g. aspirin) *many many more!

Question 33

Describe and explain the presentation of the blood for metabolic acidosis?

Answer 33

- 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

Question 34

What are typical causes of metabolic alkalosis?

Answer 34

vomiting, contraction alkalosis (increase in pH due to fluid losses)

Question 35

Describe and explain the presentation of the blood for metabolic alkalosis?

Answer 35

- 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

Question 36

What is the anion gap?

Answer 36

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.

Question 37

What is anion gap usually measured as?

Answer 37

[Na+] - [Cl-] - [HCO3-]

Question 38

What is the normal reference range for the anion gap?

Answer 38

3-11mmol/L *although this tends to vary between laboratories

Question 39

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?

Answer 39

- 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

Question 40

NOTE

Answer 40

look at davenport diagrams on handout