Acid Base Balance Flashcards
What are metabolic reactions sensitive to?
pH of the fluid in which they occur
Why are metabolic reactions sensitive to pH?
It is due to the high reactivity of the H ions with Pr which can cause changes in configuration and function leading to metabolic disturbance
What is pH very closely related to?
ECF
What is the normal pH of arterialised blood?
- pH 7.4
- Equal to free [H+] of 40 x 10^-9 moles/l or 40 x 10^-6 mmoles/l.
What is the only thing that contributes to pH?
Free H ions
What produces H ions?
The body
How does the levels of H in the blood compare to other plasma constituents?
It is one millionth of other constituents
What are the potential sources of H?
- Respiratory acid
- Metabolic acid
Why is carbonic acid not normally a net contributor to increased acid?
An increase in production usually increases ventilation
When does a build up of respiratory acid occur?
When lung function is impaired
What is the major source of alkali?
Oxidation of organic anions such as citrate
How is metabolic acid gained via inorganic acids?
S-containing amino acids
H2SO4 and phosphoric acid is produced from phospholipids
How is metabolic acid gained via organic acids?
- Fatty acids, lactic acids
- On a normal diet, there is a net gain to the body of 50-100 mmoles H per day
What do buffers do?
Minimise changes in pH when H ions are added or removed
What does the Henderson-Hasselbach equation equal?
It defines the pH in terms of the ratio of [A]/[HA] NOT the absolute amounts
What is the Henderson Hasselbach equation?
pH=pK+ log ( [A]/[HA])
What is the most important extracellular buffer?
Bicarbonate buffer system
What does the quantity of H2CO3 depend on?
The amount of CO2 dissolved in plasma which depends on solubility of CO2 AND Pco2
What is the normal pCO2 and ranges?
- Normal 5.3kPa (40mmHg)
- Range 4.8-5.9 (36-44)
What is the normal bicarbonate and ranges?
- Normal 24mmoles/l
- Range 22-26
What is the normal pH and ranges?
- Normal 7.4
- Range 7.37-7.43
What is a simplified version of the Henderson-Hasselbach equation?
pH= [HCO3]/PCO2
How is the basic mechanism of the bicarbonate buffer system evident?
- As ECF increases, H drives the reaction to the right, so that some of the additional increased H ions are removed from solution and a change in pH is reduced.
- In an ordinary buffer system the increase in products would push the reaction back to a new equilibrium where only some of the additional H ions are buffered
How does bicarbonate prevent H from contributing to the pH?
- H has NOT been eliminated from the body
- instead HCO3- has buffered the H+
- the respiratory compensation has greatly increased the buffering capacity
- free H+ ions are prevented from contributing to the pH.
How is H eliminated from the body?
Elimination of H+ from the body is by the kidneys and this excretion is coupled to the regulation of plasma [HCO3-]
What other buffers are there in the ECF?
Plasma proteins
Pr+ H HPr
Dibasic phosphate to monobasic phosphate
HPO4+H H2PO4
What are primary intracellular buffers?
- proteins
- organic and inorganic phosphates
- erythrocytes, haemoglobin
What does buffering of H ions by ICF buffers cause?
They cause changes in plasma electrolytes, since to maintain electrochemical neutrality, movement of H+ must be accompanied by Cl- as in red cells or exchanged for a cation, K+ .
How does acidosis lead to death?
In acidosis, the movement of K+ out of cells into plasma can cause hyperkalaemia which cause depolarization of excitable tissues leading to ventricular fibrillation and death.
What does bone carbonate provide?
An additional store of buffer
When is bone carbonate very important?
In chronic acid loads such as chronic renal failure which leads to wasting of bones
When does arterial pH remain remarkably constant?
When the lungs and kidneys are working normally
What happens to H gained through diet?
H is buffered until the kidneys can excrete it
What buffering occurs for metabolic acid?
43% buffered in plasma, primarily with HCO3 57% in cells
How does the kidney regulate [HCO3]?
- By reabsorbing filtered HCO3
- By generating new HCO3
What does regulation of [HCO3] by the kidney depend on?
Active H ion secretion from the tubule cells into the lumen
Describe the mechanism for the reabsorption of HCO3.
- active H+ secretion from tubule cells coupled to passive Na reabsorption
- filtered HCO3 reacts with the secreted H+ to form H2CO3. In the presence of carbonic anhydrase on the luminal membrane forms CO2 and H2O
- CO2 is freely permeable and enters the cell
- CO2 reacts in the presence of carbonic anhydrase to from H2CO3 which then dissociates to form H and HCO3
- H ions are the source of the secreted H
- HCO3 ions pass into the peritubular capillaries with Na
- bulk of HCO3 reabsorption occurs in the proximal tubule >90%
What is the importance of HCO3 reabsorption?
HCO3 must be reabsorbed as failure to do so would mean that H would be added to the ECF
When is there no excretion of H ions?
During HCO3 reabsorption
Why is it efficient to convert HCO3 to CO2?
Although the HCO3- reabsorbed is not the same ion as was filtered, the net effect is the same. HCO3- is a large charged molecule, by converting it to CO2 it is much easier to save this valuable buffer.
What is the minimum urine pH in humans?
4.5-5
What is the maximum urine pH in humans?
8
What is the usual net production of H per day?
50-100 mmoles
What would happen is H ions were free in urine?
pH would be very low and result in stinging hence why H is buffered in urine
What acts as buffers?
Several weak acids and bases act as buffers. Most is done by dibasic phosphate, HPO4, also uric acid and creatinine.
Why is the process of buffering urine called titratable acidity?
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 24hour urine sample.
What is the importance of the formation of titratable acidity?
It generate new HCO3 and excretes H
What is titratable acidtiy only used for?
Acid loads
What is the process of titratable acidity dependent on?
Pco2 of the blood
Describe the process of titratable acidity.
- Na2HPO4 in the lumen. One Na+ is reabsorbed in exchange for secreted H+. This monobasic 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 H2O 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 is the site of formation of titratable acidity?
Distal tubule
Why is the distal tubule the site of titratable acidity?
Because un-reabsorbed dibasic phosphate becomes highly concentrated by the removal of volume of filtrate.
What does a major adaptive response to an acid load cause?
Generation of new HCO3 and excretion of H
What is the basis of the mechanism of ammonium excretion?
NH3 is lipid soluble. NH4 is not. This differential solubility is basis for mechanism
How is NH3 produced?
NH3 is produced by deamination of amino acids, primarily glutamine, by the action of renal glutaminase within the renal tubule cells
What happens to NH3 once it is formed?
NH3 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. (Distal tubule mechanism)
What is the source of secreted H ions in ammonium excretion?
CO2 from the blood
What happens to new formed HCO3 in ammonium excretion?
The new HCO3- passes with Na+ ions into the peritubular capillaries
What exchanger is there in the proximal tubule which allows NH4 ions formed within cells to pass out into the lumen?
NH4/Na exchanger
What is renal glutaminase exquisitely dependent on?
pH
What happens to renal glutaminase activity when intracellular pH falls?
There is an increase in renal glutaminase activity and therefore more NH4 is produced and excreted
What is the main adaptive response of the kidney to acid loads?
The ability to augment NH4+ production
How long does it take kidney augmentation of NH4 production to reach maximal effect?
It takes 4-5 days to reach maximal effect because of the requirements of increased protein synthesis.
How can the amount of H lost ad NH4 differ?
Normally only 30-50 mmoles H+ per day are lost as NH4+ , but this can increase to 250 mmoles/l in the presence of severe acidosis
How quickly can the ability to make NH4 be switched off when there is excess alkali?
It takes time
When does a change in pH occur?
- renal or respiratory function is abnormal
- acid or base load overwhelms the body
What is a decreased pH known as?
Acidosis
What is an increased pH known as?
Alkalosis
What do respiratory disorders affect?
Pco2
What do renal disorders affect?
[HCO3]
What is respiratory acidosis?
pH has fallen and it is due to a respiratory change, so Pco2 must have increased. Respiratory acidosis results from reduced ventilation and therefore retention of CO2.
What acute causes of respiratory acidosis are there?
- Drugs which depress the medullary respiratory centres, such as barbiturates and opiates.
- Obstructions of major airways
What chronic causes of respiratory acidosis are there?
Lung disease e.g.
- Bronchitis
- Emphysema
- Asthma
What is the response to respiratory acidosis?
Need to protect pH so need to increase [HCO3]
How is [HCO3] increased in respiratory acidosis?
- The increased Pco2 will lead to increased secretion of H+ and increased HCO3. Acid conditions stimulate renal glutaminase so get more NH3 produced, BUT, it takes time.
- So there is increased generation of new HCO3- as well as increased reabsorption, because having generated more HCO3- , the increased Pco2 will also increase the ability to reabsorb it.
What is the problem with renal compensation to increase HCO3 in respiratory acidosis?
It protects the pH, it does not correct the original disturbance
What is the only way to ‘cure’ respiratory acidosis?
Only restoration of normal ventilation can remove the primary disturbance.
Why do blood gas values never normalise in chronic respiratory acidosis?
- The underlying disease process prevents the correction of ventilation, but because the kidney maintains high [HCO3], the pH is protected
- Patients with lung disease will always have aberrant Pco2 and [HCO3-], but as long as kidney function is not impaired pH can be maintained at a level compatible with life.
When do problems arise for patients with lung disease?
When they develop renal dysfunction
What is respiratory alkalosis?
Alkalosis of respiratory origin so must be due to a fall in Pco2 and this can only occur through increased ventilation and CO2 blow-off
What are acute causes of respiratory alkalosis?
- Voluntary hyperventilation
- Aspirin
- First ascent to altitude
What are chronic causes of respiratory alkalosis?
Long term residence at altitude,
-Decreased Po2 to <60mmHg (8kPa) stimulates peripheral chemoreceptors to increase ventilation.
What should happen to protect pH in respiratory alkalosis?
[HCO3] should decrease
How are alkaline conditions dealt with?
By the HCO3- reabsorptive mechanism.
What must be normalised to correct the disturbance in respiratory alkalosis?
Ventilation
What is the HCO3 reabsorptive mechanism in the correction of respiratory alkalosis?
If decreased Pco2 , less H+ is available for secretion, therefore less of the filtered load of HCO3- is reabsorbed so HCO3- is lost in the urine
What is metabolic acidosis?
- An acidosis of metabolic origin must be due to a decreased[HCO3-].
- So decreased [HCO3], either due to increased buffering of H+ or direct loss of HCO3
What must happen to protect pH in metabolic acidosis?
-Pco2 must be decreased
What are the causes of metabolic acidosis?
- H+ production, as in ketoacidosis of a diabetic (acetoacetic acid, B-hydroxybutyric acid) or in lactic acidosis.
- Failure to excrete the normal dietary load of H+ as in renal failure.
- Loss of HCO3- as in diarrhoea ie failure to reabsorb intestinal HCO3- .
What is Kussmaul breathing an established clinical sign of?
Renal failure or diabetic ketoacidosis
What is Kussmaul breathing?
- Degree of hyperventilation.
- Increase in ventilation depth rather than rate, which may be very striking, reaching a maximum of 30 l/min cf normal 5-6 l/min when the arterial pH falls to 7.0.
What does metabolic acidosis stimulate?
Ventilation so that PCco2 will fall
How do the kidneys normally correct metabolic acidosis?
Normally the kidneys correct the disturbance by restoring [HCO3-] and getting rid of H+ ions.
What is the problem with the kidneys correcting metabolic acidosis?
Source of H+ ions is the carbonic acid from CO2, but the respiratory compensation lowers the Pco2 to protect the pH
What would complete compensation of disturbance do?
Complete compensation would remove the drive to correct the original disturbance. Survival value of this is that if there were no pressure to correct initial disturbance, a further perturbation may push the system so far that compensation can no longer be effective.
In the correction of metabolic acidosis, how do the kidneys get around the fact that there is less Pco2?
Because of the decreased Pco2, the total amount of H+ secreted by the renal tubule will be less than normal BUT because the plasma [HCO3-] and therefore filtered load of HCO3- is reduced to an even greater extent , a smaller fraction of total H+ is needed for HCO3- reabsorption and therefore a greater proportion is available for excretion in the form of titratable acid and NH4+.
What is very important in the correction of metabolic acidosis?
Time
What does increased metabolic H within the body lead to?
- Immediate buffering in ECF and then ICF.
- Respiratory compensation within minutes.
- Renal correction of the disturbance takes longer to develop the full response to increase H+ excretion and generate new HCO3- because renal glutaminase takes 4-5 days to reach maximum. As HCO3- starts to increase , respiratory compensation begins to wear off until eventually get rid of all excess H+ .
What is the disadvantage of respiratory compensation in metabolic disturbance?
So, respiratory compensation delays the renal correction, but protects the pH, much more important.
What is metabolic alkalosis?
[HCO3-] must have increased and Pco2 will increase to protect the pH
What are the causes of metabolic alkalosis?
- Increased H+ ion loss- vomiting loss of gastric secretions
- Increased renal H+ loss- aldosterone excess, excess liquorice ingestion
- Excess administration of HCO3 in those with renal impairment
- Massive blood transfusions
Why can massive blood transfusions cause metabolic alkalsosis?
Massive blood transfusions can lead to metabolic alkalosis because bank blood contains citrate to prevent coagulation, which is converted to HCO3-, but need at least 8 units to have this effect.
How is excess HCO3 lost in metabolic alkalosis?
In the urine
What is the primary disturbance in respiratory acidosis?
Increased Pco2
What is the primary disturbance in respiratory alkalosis?
Decreased Pco2
What is the primary disturbance in metabolic acidosis?
Decreased HCO3
What is the primary disturbance in metabolic alkalosis?
Increased HCO3
What is the compensation in respiratory acidosis?
Increased [HCO3]
What is the compensation in respiratory alkalosis?
Decreased [HCO3]
What is the compensation in metabolic acidosis?
Decreased Pco2
What is the compensation in metabolic alkalosis?
Increased Pco2
What happens to the pH in respiratory acidosis?
Decreased
What happens to the pH in respiratory alkalosis?
Increased
What happens to the pH in metabolic acidosis?
Decreased
What happens to the pH in metabolic alkalosis?
Increased
What happens to H ion in respiratory acidosis?
Increased
What happens to H ion in respiratory alkalosis?
Decreased
What happens to H ion in metabolic acidosis?
Increased
What happens to H ion in metabolic alkalosis?
Decreased
What is a decrease in pH caused by?
Either
Decreased HCO3
or
Increased Pco2
What is an increase in pH caused by?
Either
Increased HCO3
or
Decreased Pco2
How does the decrease in pH differ between chronic and acute respiratory acidosis?
For a given increase in Pco2, there is a smaller decrease in pH in chronic respiratory acidosis than in acute respiratory acidosis
Why is there a small decrease in pH for chronic respiratory acidosis compared to acute?
Answer lies in mechanisms used to raise [HCO3-]. NH3 production takes 4-5 days to be fully turned on. So initially can only raise [HCO3-] by titratable acid, so limited. With time, can use NH3 production which has a considerable capacity to raise [HCO3-].
Why can high acidity lead to ventricular fibrillation?
High acidity will cause Hyperkalaemia as H+ ions are buffered intracellularly in exchange for K+ ions
When there is ECF volume deficit and acid/base disturbance what happens?
Restoration of volume takes precedence over acid/base disturbance
Why can excess ingestion of liquorice cause metabolic alkalosis?
Liquorice contains glycyrrhizic acid, which is very similar to aldosterone
Why does alkalosis occur in vomiting/diarrhoea even though acid and alkali are lost?
Decreased ECF, increases aldosterone which causes contraction alkalosis
What is the anion gap?
- The difference between the sum of the principal cations (Na+ and K+) and the principal anions in the plasma (Cl- and HCO3).
- Normally 14-18mmoles/L
What can the anion gap be useful to measure?
It can be useful to measure the anion gap in metabolic acidosis.
There are 2 patterns of metabolic acidosis in terms of anion gap, in one there is no change from normal and in the other the anion gap increases.
When is there no change in the anion gap in metabolic acidosis?
If the acidosis is due for example to a loss of bicarbonate from the gut, then the reduction of bicarbonate is compensated by an increase in chloride and so there is no change in anion gap.
When does the anion gap increase in metabolic acidosis?
However in eg lactic or diabetic acidosis, the reduction in bicarbonate is made up by other anions such as lactate, acetoacetate, -OH butyrate and so the anion gap is increased.
