Acid-Base Balance Flashcards
Metabolic reactions are very sensitive to the pH of the fluid in which they occur, what does this relate to?
The high reactivity of H+ ions with Pr- which causes changes in configuration and function, especially in enzymes
Why is the pH of the ECF very closely regulated?
Because acid/base disturbances lead to lots of metabolic disturbances
What is the normal pH and free H+ ion concentration of arterialised blood?
pH 7.4
Free H+ ion concentration 40 x 10^-9 moles/l or 40 x 10^-6 mmoles
What ions contribute to pH?
Only free H+ ions
What are the sources of H+ ions?
Respiratory acid
Metabolic acid
Why is the formation of carbonic acid not normally a net contributor to increased acid?
Because any increase in production causes an increase in ventilation, problems occur when lung function is impaired
What is the equation for respiratory acid production?
CO2 + H2O H2CO2 H+ + HCO3-
How is metabolic acid produced?
Via metabolism or inorganic and organic acids
What is the oxidation of organic anions a major source of?
Alkali
What is the function of a buffer?
To minimise the changes in pH when H+ ions are added or removed
What is the Henderson-Hasselbach equation?
pH = pK + log [A-] / [HA]
What is the most important extracellular buffer system?
The bicarbonate buffer system,
H2CO3 H+ + HCO3-
pH = pK + log [HCO3-] / [H2CO3]
What is the Henderson-Hasselbach equation for a pH of 7.4 and a pK of 6.1, for the bicarbonate buffer system?
7.4 = 6.1 + log [HCO3-] / [H2CO3]
What does the quantity of carbonic acid depend on?
The amount of CO2 dissolved in the plasma, which depends on the solubility of CO2 and Pco2
What is the solubility of CO2 in blood at 37 degrees?
0.03mmoles/l/mmHg PCO2
or
0.225 mmoles/l/kPa PCO2
What is the normal value of PCO2?
40mmHg or 5.3 kPa
At a normal PCO2, what is the value of [H2CO3]?
40 x 0.03mmoles/l
or
5.3 x 0.225 mmoles/l
= 1.2 mmoles/l
What is the normal value of [HCO3-]?
24mmoles/l
Normal range 22-26
How does the bicarbonate system work as a buffer?
An increase in ECF H+ ion concentration drives the reaction to the right, so that some of the additional H+ ions are removed from solution and so any change in pH is reduced
What happens in an ordinary budder system?
As H+ increases and drives reaction to the right, the increase in products would begin to push the reaction back to reach a new equilibrium position where only some of the additional H+ ions are buffered
What greatly increases the buffering capacity of the bicarbonate?
Ventilation is increased and CO2 is decreased so the reaction is pulled to the right, greatly increasing the buffering capacity of the bicarbonate
When is the aim of the acid/base balance met?
Once arterial pH has been protected
How is H+ eliminated from the body?
By the kidneys
Excretion coupled to the regulation of plasma [HCO3-]
What are the other buffers in the ECF?
Plasma proteins
Dibasic phosphate
What are the primary intracellular buffers?
Proteins
Organic and inorganic phosphates
Haemoglobin
Buffering of H+ ions by ICF buffers causes changes in what?
Plasma electrolytes
To maintain electrochemical neutrality, the movement of H+ must be accompanied by what?
Cl-
or
exchanged for a cation K+
In acidosis, the movement of K+ out of cells into plasma can cause what?
Hyperkalaemia
What does hyperkalaemia cause?
Depolarisation of excitable tissues, leading to ventricular fibrillation and death
What provides an additional store of buffer? When is this important?
Bone carbonate
Important in chronic acid loads, as in chronic renal failure there is wasting of the bones
What is the loading of H+ from the diet?
50-100 mmoles per day
If H+ ions were present as free ions in total body water, what pH would they cause?
1.2-2.4
When does arterial pH remain normal?
As long as the lungs and kidneys are working
What percentage of metabolic acid is buffered in the plasma?
43% buffered in plasma
57% buffered in cells
What percentage of buffering occurs in the cells?
97% of buffering occurs within the cells, the rest occurs with plasma proteins
How does the kidney regulate [HCO3-]?
Reabsorbing filtered HCO3-
Generating new HCO3-
Both of these processes depend on active H+ ion secretion from the tubule cells into the lumen
What is the mechanism for the reabsorption off HCO3-?
Active H+ secretion from the 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 -> CO2 and H2O
CO2 is freely permeable and enters the cell -> H2O in the presence of carbonic anhydrase which then dissociates to form H+ and HCO3-
H+ ions are the source of secreted H+
HCO3- ions pass into the peritubular capillaries with Na+
Where does the bulk of HCO3- reabsorption occur?
In the proximal tubule (> 90%)
What is the normal GFR value?
180l/day
What is the minimum urine pH in humans?
4.5-5
Maximum is around 8
What is the net production of H+ per day?
50-100 mmoles
What molecules are responsible for most buffering?
Dibasic phosphate
Uric acid
Creatinine
Why is the formation of titratable acidity important?
It generates new HCO3- and excretes H+
Where is Na2HPO4?
In the lumen - one Na+ is reabsorbed in exchange for secreted H+
What is the source of new HCO3-?
Indirectly CO2 from the blood - enters tubule cells, combining with water to form carbonic acid in the presence of carbonic anhydrase
Carbonic anhydrase dissociates to yield what?
H+ which is used for secretion and new HCO3-
What happens to phosphate ions not reabsorbed by the proximal tubule Tm?
They become greatly concentrated in the distal tubule because of removal of up to 95% of the initial filtrate
Ammonium excretion is a major adaptive response to what?
An acid load - generates new HCO3- and excretes H+
What is the basis for the mechanism of ammonium excretion?
NH3 is lipid soluble, NH4+ is not
How is NH3 produced?
By deamination of amino acids, primarily glutamine, by the action of renal glutaminase within the renal tubule cells
What happens when NH3 moves out into the tubule lumen?
It combines with secreted H+ ions to form NH4+, which then combines with Cl- ions to form NH4Cl
How is NH4Cl excreted?
Via the distal tubule mechanism
What is the source of secreted H+?
CO2 from the blood
What exchanger is there in the proximal tubule?
NH4+/Na+ exchanger - NH4+ ions formed within the cells pass out into the lumen
What is the activity of renal glutaminase dependent on?
pH
What effect does a fall in intracellular pH have on renal glutaminase?
When intracellular pH falls there is an increase in renal glutaminase and therefore more NH4+ produced and excreted
What is the main adaptive response of the kidney to acid loads?
The ability to augment NH4+ production
Why does it take 4-5 to reach maximum effect of ammonium excretion?
Because of the requirements of increased protein synthesis
How much H+ can be lost as NH4+ in severe acidosis?
Normally only 30-50 mmoles/l H+ per day are lost as NH4+, but this can increase to 250mmoles/l in the presence of severe acidosis
When does a change in pH occur?
If respiratory or renal function is abnormal, or any acid/base load overwhelms the body, a change in pH occurs
Decreased pH - acidosis
Increased pH - alkalosis
What disorders affect PCO2?
Respiratory
What disorders affect [HCO3-]?
Renal
Why does the pH fall in respiratory acidosis?
Due to a respiratory change - so PCO2 must have increased
Respiratory acidosis results from reduced ventilation and therefore retention of CO2
What are the acute causes of respiratory acidosis?
Drugs which depress the medullary respiratory centres e.g. barbiturates and opiates, obstruction of major airways
What are the chronic causes of respiratory acidosis?
Lung disease e.g. bronchitis, emphysema, asthma
Response is to protect pH and so increase [HCO3-]
Acid conditions stimulate what?
Glutaminase - so more NH3 is produced
What is the effect of respiratory acidosis on PCO2, H+ and HCO3-?
PCO2 increased
This causes increased secretion of H+ and increased HCO3-
Increased PCO2 also increases the ability to reabsorb HCO3-
What can be done to remove the primary disturbance causing respiratory acidosis?
What does this mean in chronic respiratory acidosis?
Only restoration of normal ventilation can remove the primary disturbance
Although the renal compensation to increase HCO3- protects the pH, it does not correct the original disturbance
This means that in chronic respiratory acidosis e.g. bronchitis, blood gas values are never normalised
The underlying disease process prevents the correction of ventilation
Patients with lung disease will always have aberrant PCO2 and [HCO3-], but when will pH be maintained at a level compatible with life?
As long as kidney function is not impaired
What is respiratory alkalosis due to?
A fall in PCO2
This can only occur through increased ventilation and CO2 blow-off (alveolar hyperventilation)
What are the acute causes of respiratory alkalosis?
Voluntary hyperventilation
Aspirin
First ascent to altitude
What are the chronic causes of respiratory acidosis?
Long-term residence at altitude
Decreased PO2 to < 60 mmHg (8kPa) which stimulates peripheral chemoreceptors to increase ventilation
How are alkaline conditions dealt with?
HCO3- resorptive mechanism
If PCO2 decreases, less H+ is available for secretion, so less of the filtered load of HCO3- is reabsorbed so HCO3- is lost in the urine
What must be normalised in respiratory alkalosis to correct the disturbance?
Ventilation must be normalised
What is metabolic acidosis due to?
Decreased [HCO3-], either due to an increased buffering of H+ or due to direct loss of HCO3-
What must be done to protect the pH in metabolic acidosis?
PCO2 must be decreased
What are the causes of metabolic acidosis?
Increased H+ production, as in ketoacidosis or lactic acidosis
Failure to excrete normal dietary load of H+ as in renal failure
Loss of HCO3- as in diarrhoea i.e. failure to reabsorb intestinal HCO3-
Metabolic acidosis stimulates ventilation so that
PCO2 falls
In what way is ventilation increased in metabolic acidosis?
In depth rather than in rate - this may be very striking, reaching a maximum of 30 L/min (compared to the normal 5-6 L/min) when the arterial pH falls to 7.0
What is Kussmaul breathing an established clinical sign of?
Renal failure or diabetic ketoacidosis
How do the kidneys normally correct the disturbance caused by metabolic acidosis?
By restoring [HCO3-] and getting rid of H+ ions
What is the source of H+ ions in metabolic acidosis?
The source of H+ ions is the carbonic acid from CO2, but the respiratory compensation lowers the PCO2 to protect the pH
Compensations for acid/base disturbances are always in what direction?
Always in the same direction as the initial disturbance i.e. increased CO2 -> increased carbonic acid
What would complete compensation remove?
The drive to correct the original disturbance
What is the survival value of compensation?
If there was no pressure to correct the original disturbance, a further perturbation may push the system so far that the compensation can no longer be effective
Why is the total amount o H+ secreted by the renal tubule in metabolic acidosis less than normal?
Because of the decrease in PCO2
Why is a smaller fraction of total H+ needed for HCO3- reabsorption (and therefore a greater proportion is available for excretion) in metabolic acidosis?
Because the plasma [HCO3-] and the filtered load of [HCO3-] is reduced to an even greater extent
What effect does decreased H+ secretion have on HCO3-?
HCO3- reabsorption greatly decreased
Increase in new HCO3- generated
What effect does increased metabolic H+ within the body have?
Immediate buffering in the ECF and then ICF
Respiratory compensation within minutes
Why does renal correction of metabolic acidosis take longer to develop the full response to increased H+ excretion and to generate new HCO3-?
Because renal glutaminase takes 4-5 days to reach maximum
What does respiratory compensation delay?
Renal correction, but protects the pH which is more important
What needs to happen in metabolic alkalosis to protect the pH?
[HCO3-] has to increase and PCO2 increase
What are the causes of metabolic alkalosis?
Increased H+ ion loss e.g. vomiting, loss of gastric secretions
Increased renal H+ loss e.g. aldosterone excess, excess liquorice ingestion
Excess administration of HCO3- in patients with impaired renal function (unlikely to cause metabolic alkalosis in patients with normal renal function)
Massive blood transfusions, at least 8 units required to have this effect
In metabolic alkalosis, the greatly increased filtered load of HCO3- exceeds what?
The level of H+ secretion to reabsorb it, even in the presence of increased PCO2
For a given increase in PCO2, is there a smaller decrease in pH in chronic or acute respiratory acidosis?
Chronic respiratory acidosis
How long does NH3 production take to be fully turned on?
4-5 days to be fully turned on, so initially [HCO3-] can only be raised by titratable acid
When do acid/base disturbance not occur in isolation?
Acid/base disturbances do not occur in isolation in otherwise healthy individuals
What should be considered in diabetic patients with ketoacidosis?
Badly controlled diabetes (metabolic acidosis)
What kind of acid/base disturbance is likely in a patient who is a long-term smoker and has chronic bronchitis?
Respiratory acidosis
What kind of acid/base disturbance is likely in a patient with a haemorrhage?
Lactic acidosis (combined metabolic and respirator acidosis)
What does high acidity also cause, other than acidosis?
Hyperkalaemia as H+ ions are buffered intracellularly in exchange for K+ ions - danger of ventricular fibrillation
What is the treatment of hyperkalaemia?
Insulin if diabetic, glucose if non-diabetic (stimulates cellular uptake of K+)
Calcium resonium either orally or rectally - exchanges Ca2+ ions for K+ ions
Ca gluconate (IV) - reduces excitability of the heart and stabilised the cardiac muscle membranes
What effect does vomiting have on acid/base balance?
Loss of NaCl and H2O causes hypovolaemia
Loss of HCl causes metabolic alkalosis
Hypovolaemia stimulates aldosterone to increase distal tubule Na+ reabsorption
Respiratory compensation for metabolic alkalosis helps drive H+ secretion and exacerbates metabolic alkalosis by adding more HCO3- to the plasma
Under conditions of avid Na+ reabsorption, what is the main ion exchanged for Na+?
H+
What takes precedence over the correction of metabolic alkalosis following vomiting?
Restoration of volume
What will giving a patient NaCl following vomiting achieve?
Restoration of volume, alkalosis will be corrected
What happens to acid/base balance in vomiting and diarrhoea?
The patient becomes alkalotic despite acid and alkaline loss, because the decreased ECF volume causes an increase in aldosterone resulting in contraction alkalosis
How does excess liquorice ingestion cause metabolic alkalosis?
It contains glycyrrhizic acid which is very similar to aldosterone - causes contraction alkalosis
The anion gap is the difference between the sum of the principle cations (Na+ and K+) and the principle anions in the plasma (Cl- and HCO3-), what is the normal value of this?
14-18mmoles/l
Why can it be useful to measure the anion hap in metabolic acidosis?
It can help determine the cause of 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
If the acidosis is due to e.g. 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 the anion gap
In lactic or diabetic acidosis, the reduction in bicarbonate is made up by other anions such as lactate, and so the anion gap is increased
What is used to measure real plasma flow?
The organic anion para-amino-hippuric (PAH) acid
How is PAH filtered?
Freely filtered at the glomerulus, and then PAH remaining in the plasma is actively secreted into the tubule
> 90% of plasma is cleared of its PAH content in one transit of the kidney
What is PAH clearance a measurement of?
All the plasma flowing through the kidneys at a given time - renal plasma flow, 660ml/min
