5. Acid base physiology

Question 1

which reaction determines plasma pH

Answer 1

CO2 + H2O HCO3- + H+

Question 2

state the normal plasma pH range

Answer 2

7.35-7.45

Question 3

which control systems are used for medium and long term plasma pH regulation

Answer 3

• Medium: respiratory control - changing rate of alveolar ventilation (not long term as requisite changes in resp. cannot be maintained without consequences)
• Long: renal control - variable production of novel HCO3- and definite acid elimination without consumption of physiological buffers

Question 4

how are changes in plasma pH detected by resp. system

Answer 4

Peripheral and central chemoRs detect ECF pH changes… afferent impulses to brainstem resp. centres… change in muscles of breathing… change in alveolar ventilation rate.

1. peripheral chemoRs in carotid and aortic bodies - detect changes in pO2 and pH
2. central chemoRs in brain medulla - detect changes in pCO2

Question 5

why can central chemoRs detect changes in plasma pCO2 but not plasma pH

Answer 5

Blood-brain barrier is impermeable to H+ and HCO3- : central chemoRs cannot respond quickly to changes in blood pH.

But chemoRs can sense CSF pH which is closely associated with arterial pCO2 (which can cross the BBB). E.g. increased arterial CO2 diffuses across BBB into CSF… converted by CA to HCO3 + H+ … increased H+ causes decreased CSF pH… chemoRs cause increased resp. to eliminate accumulated CO2. And vice-versa for decreased pCO2.

Question 6

what is the effect of chronic pCO2 changes on central chemoR control

Answer 6

• CSF pH determined by pCO2 : HCO3- ratio.
• BBB is impermeable to HCO3- so its conc. is relatively fixed - [HCO3-] controlled by metabolism of choroid plexus cells. This set CSF [HCO3-] determines which pCO2 is associated with ‘normal’ CSF pH.
• However, longer term changes to CSF pCO2 (eg in chronic hypoxia: peripheral chemoRs detect decreased pO2… decrease RR… increase pCO2) cause choroid plexus cells to compensate (as acidic pH undesirable for neurons) and selectively add HCO3- into CSF (import from blood across BBB) to balance pH.
• Causes central chemoRs to accept altered pCO2 as normal so will no longer act to increase resp. rate and depth.

Question 7

suggest 2 reasons why T2RF Ps should not be given uncontrolled O2 therapy

Answer 7

Can lead to worsening of hypercapnia:

1. persisting hypercapnia causes ‘re-setting’ of central chemoRs (due to choroid plexus cell import of HCO3- to normalise CSF pH)… unresponsive to high pCO2… no longer act to increase RR and depth. So it is hypoxic stimulus which is now keeping increased resp. effort going via peripheral chemoRs. O2 therapy corrects hypoxia, removing stimulus… decreased ventilation… worsened hypercapnia despite improved hypoxia.
2. Oxygen therapy removes hypoxia-induced vasoconstriction of poorly ventilated alveoli… increased perfusion of these alveoli, diverting blood away from better ventilated alveoli… worsening of V/Q mismatch.

Question 8

how should Ps with T2RF be treated with O2

Answer 8

Controlled O2 therapy (24 or 28% O2), aiming for target saturation of 88-92%

Question 9

why does normal metabolic acid production (e.g. protein breakdown) not deplete HCO3-

Answer 9

1. kidneys recover all filtered HCO3- in PCT
2. PCT produces HCO3- from amino acids, excreting H+ in form of NH4+ into urine
3. DCT and CD produces HCO3- from CO2 and H2O, with H+ buffered by phosphate and ammonia in urine

Question 10

How does the PCT recover filtered HCO3-

Answer 10

• HCO3- diffuses from lumen into cell as CO2… in cell, CO2 reacts with H2O (via CA) to reform HCO3 + H+… HCO3- transported into ECF via basolateral HCO3-/Na+ symporter.
• System depends on presence of H+ in nephron lumen to form the CO2 - provided by CO2 breakdown in cell by CA. The H+ is transported back to lumen by NHE (requires basolateral Na/K ATPase). In lumen, reacts with HCO3- to form CO2 which diffuses, etc.

Question 11

describe how HCO3- is produced and H+ is excreted in the PCT

Answer 11

metabolism of glutamine to a-ketoglutarate in PCT cell results in production of 2 HCO3- and 2 ammonia (NH3+):

• 2 HCO3- are transported to ECF via HCO3-/Na+ symporter (requires basolateral Na/K ATPase)
• 2 NH3+ are loaded with free H+ to form NH4+ (ammonium) which is secreted into tubule by Na+/NH4+ antiporter

Question 12

describe how HCO3- is produced and H+ is excreted in the DCT and CD

Answer 12

In DCT and CD cells, CO2 reacts with H2O to form HCO3- and H+. This H+ is then buffered in filtrate by:

1. inorganic phosphate (HPO4^2-) - reacts with H+ to form H2PO4-. Critical urinary buffer as its conc. progressively increases as fluid is reabsorbed in tubule
2. NH3+ (produced in PCT but freely moves into DCT and CDs which are highly permeable) - reacts with H+ to form NH4+, to which DCT and CD cells are impermeable, so is secreted in urine

Question 13

what is the major adaptive response to an increased acid load in healthy individuals

Answer 13

excretion of ammonium (NH4+) from NH3+ generated in PCT and H+ actively pumped into lumen in DCT and CD