Define acid-base control
Control of H+ concentrations
Why is the regulation of H+ ions more important than other ions?
Due to their effects on protein function:
- Alteration of protein activity (esp enzymes)
- Alteration of binding of other ions (e.g. decreased H+ → increased Ca2+ binding to albumin
Define acid and base
Acid: Any chemical that can donate a proton
Base: Any chemical that can accept a proton
Describe the relationship between H+and pH
Inverse relationship between H+ and pH
1 unit change in pH represents a 10 fold change in H+
What are the 3 main mechanisms that control H+ concentrations?
- Minimise sudden changes in H+- unable to change overall body pH
- Rapid adjustment of CO2 excretion
- Slow adjustment of H+ excretion in urine and adjust body HCO3- levels.
Any substance that can reversibly bind H+
What are the 3 main buffer systems in the body?
Where are they found?
Bicarbonate buffer system
- HCO3- + H+ ⇔ H2CO3 (carbonic acid)
Phosphate buffer system
- Intracellular and urine
- HPO42- + H+ ⇔ H2PO4-
Protein buffer system
- Mainly intracellular
- Pr- + H+ ⇔ HPr
What are the main intracellular buffer systems?
PO4 (phosphate) buffer systems
Haemoglobin buffer system
What are the main extracellular fluid buffer systems?
Bicarbonate buffer system
Plasma protein buffers
What is the most important extracellular buffer?
What is its role?
Bicarbonate buffer system
- Connects the control of CO2 by the lungs to the control of HCO3- by the kidneys allowing the systems to compensate for eachother.
HCO3- + H+ ⇔ H2CO3 ⇔ (CA) H2O + CO2
Which enzyme allows carbonic acid to dissociate to H2O and CO2?
Carbonic anhydrase (carbonic dehydratase)
What is the ratio of HCO3- : CO2 that is necessary to keep pH at roughly 7.4?
20 : 1
What is necessary for the maintenance of pH?
Functioning lungs for excretion of CO2 (increase or decrease in ventilation)
Functioning kidneys for excretion of H+ and production of HCO3-
How do the kidneys control extracellular fluid pH?
What are both of these processes dependent on?
- By controlling the amount of H+ excreted in urine
- By reabsorbing filtered HCO3-
Both of these processes dependent on the ability of the kidneys to secrete H+
How much HCO3- is normally in urine?
None- usually all reabsorbed in the kidneys
Where does the majority of renal reabsorption of HCO3- occur?
Proximal convoluted tubule
How is HCO3- reabsorbed in the kidney?
Proximal convoluted tubule:
- HCO3- cannot be reabsorbed alone as it cannot cross the luminal membrane.
- Na+/H+ exchangers in the luminal membrane absorb Na+ and secrete H+ which reacts with HCO3- to form H2CO3 (carbonic acid)
- H2CO3 is converted to H2O and CO2 in the presence of carbonic anhydrase- CO2 diffuses into the cell.
Luminal epithelial cell:
- CO2 reacts with H2O inside the cell and is converted back to H2CO3 by carbonic anhydrase.
- H2CO3 rapidly dissociates to HCO3- and H+
- HCO3- moves across the basolateral membrane into the blood via HCO3-/ Na+ symporter
- H+ is re-secreted back into the luminal membrane to be used again.
How is H+ secreted in the late distal and collecting tubules?
What stimulates this activity?
Secreted into the tubular lumen by H+ATPase or H+/K+ATPase in type A intercalating cells
Stimulated by aldosterone and by hypokalaemia
How is H+ excreted
Secreted in late distal and collecting tubules by H+ATPase and H+/K+ATPase however this is limited as high concentratins of H+ in the lumen inhibits these transporters. Does not excrete enough H+ on its own.
- Urinary phosphate and ammonia buffers reduce the amount of H+ in the lumen, preventing the high concentrations from inhibiting H+ATPase and H+/K+ATPase.
What is generated by the excretion of H+?
Why is this important?
New HCO3- is generated by the excretion of H+
This is important as some is consumed buffering the non-volatile acids in the body that are produced each day.
Describe the urinary phosphate buffer
2 forms of filtered phosphate:
- Monoprotic: HPO42-
- Diprotic: H2PO4-
These create a buffer pair in tubular fluid:
HPO42- + H+ ⇔ H2PO4-
There is a relative excess of the monoprotic form which is able to buffer excess secreted H+ in the lumen and excrete it in urine as the diprotic form.
How does the urinary phosphate buffer cause production of new HCO3-?
Inside the cell, H2O and CO2 are converted by carbonic anhydrase to H2CO3 which rapidly dissociates to HCO3- and H+.
H+ is pumped out of the cell into the tubular lumen whilst the HCO3- is pumped across the basolateral membrane into the blood.
Describe the urinary ammonia buffer
How does it produce new HCO3-?
Ammonium (NH4+) synthesised from glutamate in the PCT and secreted.
Ammonia (NH3) secreted mainly in the collecting duct.
Form a buffer pair:
NH3 + H+ ⇔ NH4+
NH3 picks up excess H+ and is excreted in the urine as ammonium
New HCO3- is produced in the tubular cells via the same process as with the urinary phosphate buffer.
How does the urinary ammonia buffer respond to the body's acid-base status?
Why is this response slower than the lungs?
Decrease in pH stimulates renal glutamine metabolism which increases activity of glutaminase and increased secretion of H+ and vice versa.
Slower than the lungs as this process requires the synthesis/breakdown of proteins
What is H+ secretion stimulated by?
Increase in extracellular pCO2
Decreased extracellular pH
Also increased aldosterone levels and hypokalaemia
Any process which results in the pH of the blood becoming more acidic
Caused by excess acid and/or loss of alkali
Any process which causes the blood pH to become more basic (alkaline) than normal
Caused by loss of acid and/or excess alkali
What are respiratory and metabolic acidosis/alkalosis
- Primary problem is respiratory (problem with CO2 excretion)
- Primary problem is renal (problem with H+ excretion and/or HCO3- reabsorption or production)
In compensated acidotic or alkalotic conditions, which paramaters will be outside their normal range?
Both CO2 and HCO3- are abnormal but in the same direction (i.e. both raised or both lowered)
What are the causes of respiratory acidosis and alkalosis?
- Low pH due to high CO2
- E.g. hypoventilation
- Compensation: Increased HCO3- production
- High pH due to low CO2
- E.g. hyperventilation- anxiety, high altitude
- Compensation: Reduced HCO3- production