Renal control of pH

Question 0

What are the consequences of acidaemia and alklaemia respectively?

Answer 0

ACIDAEMIA (pH 7.38 >) = Kussmaul’s respiration (“air hunger”) results in an attempt to correct acidosis

ALKALAEMIA (pH 7.42

Question 1

What is the Henderson-Hasselbalch equation? What does it demonstrate?

Answer 1

pH = pKa (6.1) + log([HCO3-]/pCO2 x 0.23)

Demonstrates that pH depends on the ratio between [HCO3-] and pCO2

[HCO3-] = controlled by kidneys, disturbed in metabolic/renal disease 
pCO2 = determined by respiration, controlled by chemoreceptors, disturbed in respiratory disease

Question 2

What is the effect of ventilation on the acid base balance?

Answer 2

Hypoventilation: less CO2 breathed out -> increased pCO2 (hypercapnia) -> reduced pH -> respiratory acidaemia

note: acidaemia = change in pH, acidosis = change in [HCO3-] specifically

Hyperventilation: more CO2 breathed out -> reduced pCO2 (hypocapnia) -> increased pH -> respiratory alkalaemia

Question 3

What is the difference between correction of pH and compensation of pH?

Answer 3

Respiratory changes CORRECT respiratory disturbances of pH
Metabolic changes COMPENSATE respiratory disturbances of pH

(and vice versa)

Question 4

What is the effect of changing metabolism on the acid base balance?

Answer 4

Production of H+ causes reduced [HCO3-] -> reduced pH -> metabolic acidosis

(can be compensated by changing respiration rate via peripheral chemoreceptors -> increased respiration -> reduced pCO2 -> ratio of [HCO3-] to pCO2 maintained)

Reduction of H+ causes increased [HCO3-] (less HCO3- required to neutralise stomach acid) -> increased pH -> metabolic alklaosis

(can be partially compensated by changing respiration rate -> reduced respiration -> increased pCO2 -> ratio of [HCO3-] to pCO2 maintained)

Question 5

How do the kidneys increase [HCO3-]?

Answer 5

Must recover ALL filtered HCO3- AND secrete additional HCO3-

Recovery of HCO3-: (80%-90% in PCT, rest in thick ascending limb)

1. H+ exported into lumen up its conc. gradient via NHE
2. H+ combines with HCO3- in the lumen to form CO2 & H2O
3. CO2 & H2O diffuse into tubular cell
4. CO2 & H2O reconverted to H+ & HCO3-
5. HCO3- diffuses into the ECF, H+ exported via NHE

Production of HCO3-: (PCT & DCT)
PCT: glutamine broken down into alpha-ketoglutarate and ammonium (NH3 + H+ from urine)
DCT (alpha-intercalated cells): same as recovery except H+ (generated from CO2 & H2O) exported via H+/K+ antiporter or by proton pump and combines with hydrogen phosphate to form dihydrogen phosphate

Question 6

What is the normal acidic content of urine? How is this controlled?

Answer 6

Minimum pH 4.5

Buffered by phosphate (filtered) & ammonium (excreted) ions

Amount of phosphate controlled by changes in the pH of the DCT (i.e. changes in HCO3- export)

Question 7

What are some of the cellular responses to acidosis?

Answer 7

Increased activity of NHE (all HCO3- recovered)

Increased production of ammonium in PCT

Increased secretion of H+ in DCT

Increased export of HCO3- from tubular cells to ECF

Question 8

What is the anion gap?

Answer 8

Indicates whether any HCO3- has been replaced with something other than Cl- (i.e. what has changed to cause metabolic acidosis)

= ([Na+] + [K+]) - ([Cl-] + [HCO3-])
principal cations in plasma - principal anions in plasma

Increased anion gap when anions from metabolic acid have replaced HCO3- e.g. lactate

note: some renal problems can reduce [HCO3-] without increasing the anion gap (HCO3- replaced by Cl-)