Acid Base Balance I Flashcards
Why is pH important?
Metabolic reactions are exquisitely sensitive to the pH of the fluid in which they occur.
Relates to the high reactivity of H+ ions with negatively charges proteins -> changes in configuration and function, especially enzymes.
Therefore Acid/Base disturbances -> all sorts of metabolic disturbances
pH of ECF is very closely regulated
What does pH mean?
The free [H+] in that fluid
Only free H+ ins contribute to pH
What is the [H+] like compared to concentration of other plasma constituents?
Other plasma constituents are present in mmoles
(e.g. Na+, K+, Cl-, glucose etc)
So [H+] is 1 millionth that of other plasma constituents
(40x10-6mmoles/l for pH 7.4)
What produces H+?
The body
What are the sources of H+?
Respiratory acid
Metabolic acid
How is respiratory acid a source of H+?
CO2 + H2O H2CO3
H+ + HCO3-
Formation of carbonic acid is not normally a net contributor to increased acid because any increase in production -> increase in ventilation
How is metabolic acid (non-respiratory acid) a source of H+?
via metabolism
- Inorganic acids: e.g. S-containing amino acids -> H2SO4 and phosphoric acid is produced from phospholipids
- Organic acids: fatty acids, lactic acid
- On a normal diet there is a net gain to the body of 50-100 moles H+ per day.
Wht is the major source of alkali in the body?
Oxidation of organic anions such as citrate
What do buffers do?
Why are they so important?
Minimize changes in pH when H+ ions are added or removed
Way too many H+ per day from diet. If present as free H+ in total body water -> pH of 1.2-2.4
As long as kidneys and lungs are working this can be dealt with.
H+ is successfully buffered until it can be excreted by the kidneys
What is the Henderson-Hasselbalch equation?
Defines the pH in terms of the ratio of [A-]/[HA] NOT the absolute amounts
pH = pK + log [A-]/[HA]
What is the most important extracellular buffer?
Bicarbonate buffer system
H2CO3 H+ +HCO3-
What is the ratio of
[HCO3-]/[H2CO3] in the blood?
pK of bicarbonate buffer system = 6.1
So in plasma at pH 7.4…
7.4 = 6.1 + log [HCO3-]/
[H2CO3]
1.3 = log 20, so the ratio at pH 7.4 is 20:1
What does the quantity of H2CO3 in plasma depend on?
The amount of CO2 dissolved in plasma
Which depends on the solubility of CO2 and Pco2
What is the normal pCO2?
pCO2
=5.3kPa = 40mmHg
Range
4.8-5.9kPa = 36-44mmHg
What is the normal pH?
7.4
Range = 7.37-7.43
What is the normal
[HCO3-]?
24mmoles
Range = 22-26mmoles
What is the basic mechanism of the bicarbonate buffer system (assuming its a closed system)?
H+ + HCO3- H2CO3
H2O +CO2
Increase in ECF [H+] drives the reaction to the right, so that some of the additional increase H+ ions are removed from solution and therefore a change in pH is reduced.
However if this is a closed system when equilibrium is established the [H+] will not return to the original level as everything in the system will be slightly raised
Therefore only some of the additional H+ ions are buffered
How does the respiratory system work with the bicarbonate buffer system to return an increased ECF [H+] to its original level?
Once the bicarbonate buffer system equilibriates CO2 will be raised
This causes an increase in ventilation to burn off this excess CO2.
Since CO2 lowers, the bicarbonate buffer system shifts even further to the right alowing H+ to return to its original level
What should be remember about the how the respiratory system controls pH?
H+ has NOT been eliminated from the body.
Instead the HCO3- has buffered the H+ and the respiratory compensation has greatly increased the buffering capacity so that free H+ ions are prevented from contricuting to the pH
What eliminates H+ from the body?
Kidneys
How do the kidneys control the Acid/base balance of the body?
Elimination of H+ from the body is by the kidneys and this excretion is coupled to the regulation of plasma [HCO3-]
How do the kidneys and respiratory system work together to control pH?
Demonstrate this through the Henderson-Hasselbach equation
pH = pK + log [HCO3-]
/Pco2
[HCO3-] = renal regulation Pco2 = respiratory regulation
This “independent” regulation of these factors determining pH is the basis of compensatory mechanisms
Appart from the bicarbonate buffer system what other buffers in the EFC exist?
Plasma proteins
Pr- + H+ HPr
Dibasic phosphate
HPO4(2-) + H+ H2PO4-
(monobasic phosphate)
What are the primary intracellular buffers?
Proteins, organic and inorganic phosphates and, in the erythrocytes, haemoglobin.
How does buffering of H+ ions by ICF buffers cause changes in plasma erythrocytes?
To maintain electrochemical neutrality, movement of H+ must be accompanied by Cl- as in red blood cells or exchanged for a cation, K+.
How does acidosis effect K+?
In acidosis, the movement of K+ out of cells into the plasma can cause hyperkalaemia -> depolarisation of excitable tissues -> ventricular fibrillation and death.
How does bone carbonate effect Acid/Base balance?
What is the clinical significance?
Provides an additional store of buffer, very important in chronic acid loads as in chronic renal failure -> wasting of bones
How much metabolic acid is buffered in ICF compared with ECF?
43% buffered in plasma
57% in cells
Where is respiratory acid buffered?
97% of buffering within cells, Hb particularly important, rest with plasma proteins
How does the kidney regulate [bicarbonate]?
- Reabsorbing filtered bicarbonate
- By generating new bicarbonate
Both of these processes depend on active H+ ion secretion from the tubule cells into the lumen
What is the mechanism for reabsorption of HCO3-?
Active H+ secretion from tubule cells coupled to passive Na+ reabsorption
Filtered bicarbonate reacts with the secreted H+ to form H2CO3.
In the presence of carbonic anhydrase on the luminal membrane -> CO2 and H2O
CO2 is freely permeable and enters the cell.
Within the cell, CO2 -> H2CO3 (carbonic anhydrase in all tubule cells) which then dissociates to H+ and HCO3-
The H+ ions are the source of the secreted H+
The HCO3 ions pass into the peritubular capillaries with Na+
Where does the bulk of bicarbonate reabsorption occur?
Proximal tubule >90%
Why does bicarbonate have to go through so many reactions to be reabsorbed?
Although the HCO3- reabsorbed is not the same ion as was filtered, the NET effect is the same.
HCO3- is a lrage charged molecule, by converting it to CO2 it is much easier to save this valuable buffer
Why is reabsorption of bicarbonate important?
GFR = 4320mmoles HCO3- filtered per day.
Must be reabsorbed, since failure to do so would be the same as adding H+ to the ECF
What happens to H+ ions during HCO3- reabsorption?
There is no excretion of H+ ions during HCO3- reabsorption
What is the minimum and maximum pH of urine in humans?
Minimum = pH 4.5-5.0
Maximum = pH around 8.0
Why cant we have pH 1 urine?
How do we solve this?
This would cause stinging and be intensely painful -> damage
Several weak acids and bases act as buffers.
Most done by dibasic phosphate, HPO4(2-), also urine acid and creatinine.
The process is called “titratable acidity” because its extent is measured by the amount of NaOH needed to titrate urine pH back to 7.4 for a 24 hour urine same
What is the importance of the formation of titratable acidity?
Genrated new HCO3- AND excreted H+
Only used for acid loads
How does the secretion of H+ work?
- Na2HPO4 in the lumen. One Na+ is reabsorbed for secreted H+. This mono basic phosphate removes H+ from the body
- The source of the new HCO3- is indirectly CO2 from the blood. It enters the tubule cells, combining with water to form carbonic acid in the presence of carbonic anhydrase, which then dissociates to yield H+, used for secretion, and new HCO3-, which passes with Na+ into the peritubular capillaries.
- Occurs principally in the distal tubule, This is where phosphate ions, not reabsorbed by the proximal tubule Tm mechanism, become greatly concentrated because of removal of up to 95% of the initial filtrate.
What does the production of new bicarbonate in the tubule cells depend on?
Pco2 of the blood.
Why is the distal tubule the site of formation of titratable acidity?
Because un-reabsorbed dibasic phosphate becomes highly concentrated by the removal of volume of filtrate
Why do we excrete ammonium?
Major adaptive response to an acid load
Generates new HCO3- AND excretes H+
When is Ammonium excreted?
Only used for acid loads
What is the difference in solubility between NH3 and NH4+?
Why is this important?
NH3 is lipid soluble
NH4+ is not
Differential solubility is basis for mechanism of ammonium excretion.
How is NH3 produced by renal tubule cells?
Produced by deamination of amino acids, primarily glutamine, by the action of renal glutaminase within the renal tubule cells.
What happens to NH3 produced by renal tubule cells?
Moves out into the tubule lumen where it combines with secreted H+ ions to form NH4+ which combines with Cl- ions (from NaCl) to form NH4Cl which is excreted.
Secreted H+ from CO2 in blood
NEW HCO3- passes with Na+ ions into peritubular capillaries
Distal tubule mechanism
How is the ammonium excretion mechanism in the distal tubule different from the proximal tubule?
Distal Tubule Mechanism:
- NH3 moves into lumen
- Combines with H+
- NH4+ formed and excreted
Proximal tubule mechanism:
- NH3 combines with H+ from H2CO3 breakdown
- NH4+ exchanged for Na+ and pumped into lumen
How is renal glutaminase effected by pH?
Exquisitely pH dependent
When intracellular pH falls renal glutaminase activity increases and therefore more NH4+ produced and excreted.
This ability to augment NH4+ production is the main adaptive response of the kidney to acid loads.
How long does the kedney adaptive response through renal glutaminase take to kick in?
It takes 4-5 DAYS to reach maximal effect because of the requirement of increased protein synthesis.
Also takes time to switch off the ability to make NH4+, when there is excess alkali
