Acid base balance Flashcards
Sources of H+
Respiratory acid - when lung function is impaired production of HCO3- trumps ventilation
Metabolic acid - inorganic and organic acids
Normal pH of arterial blood
7.4 (free [H+] of 40x10^-9 moles/l
only free [H+] ions contribute to pH
What is the major source of alkali for the body?
Oxidation of organic anions such as citrate
Difference between inorganic and organic acids
Inorganic acids: eg S-containing amino acids => H2SO4 and phosphoric acid is produced from phospholipids
Organic acids: fatty acids, lactic acid
Function of buffers
Minimise changes in pH when H+ ions are added or removed
What is Henderson-Hasselbalch equation
𝑝𝐻=𝑝𝐾+log〖([𝐴^−])/([𝐻𝐴])〗
defines the pH in terms of the ratio of [A-]/[HA] NOT the absolute amounts
What is the most important extracellular buffer?
Bicarbonate buffer system
What is the solubility of CO2 in blood at 37 degrees?
0.03 mmoles/L/mmHg
What is the equation for respiratory acid?
CO2 + H2O H2CO3 H+ + HCO3-
What determines the amount of H2CO3?
The amount of CO2 dissolved in plasma
Solubility of CO2 and PCO2
How do you calculcate the concentration of H2CO3 in the blood?
Use the solubility of CO2 in blood multiplied by the the pressure of PCO2
The ratio of bicarbonate to H2CO3 is 20:1 - so the concentration of bicarbonate will be 20 times greater
24 mmoles/l is described as the standard bicarbonate
What is the range of pH compatible with life?
7.0-7.6
What is the effect of adding H+ to the bicarbonate position?
Drives the reaction to the right - the side which favours more production of H2O and CO2
Some of the additional H+ ions are removed from solution and therfore the change in pH is reduced
Ventilation also serves to remove CO2 and water from the RHS of the equation - respiration increases the buffering capacity and H+ ions are prevented from contributing to the pH (pH doesn’t decrease)
A decrease in ventilation and an increase in CO2 will cause the reaction to move in which direction
To the left
There is a decrease in H+ ions
Which organ is responsible for the elimination of H+?
The kidneys
The excretion of H+ is coupled to the regulation of what in the plasma?
HCO3-
What other buffers (other than the bicarbonate buffer system) exist in the ECF?
Plasma proteins
Dibasic phosphate
Equation for plasma buffer
Pr- + H+ HPr
Equation for dibasic phosphate buffer
HPO4^2- + H+ H2PO4-
What is the primary intracellular buffer inside erythrocytes?
Haemoglobin
What are some primary intracellular buffers?
Proteins, organic and inorganic phosphates
What happens with K+ ions in acidosis due to an increase in H+ ions?
K+ ions move out of the cells (in order to maintain electrochemical neutrality) into the plasma which can cause hyperkalaemia => depolarisation of excitable tissues => ventricular fibrillation => death
What provides an additional store of buffer in the body?
Bone
This is important in chronic acid loads (chronic renal failure) => wasting of bones occurs
How does the buffering of H+ ions by ICF buffers affect plasma electrolyte concentrations?
Movement of H+ across cells must be accompanied by Cl- as in red blood cells or exchanged for a cation, K+ to maintain electrochemical neutrality.
How much H+ do we get from out diet everyday?
50-100 mmoles (if this was present as free H+ in total body water the pH would exceed normal values - buffering system ensures this doesn’t happen)
What % of metabolic acid is buffered in plasma vs in cells?
43% in plasma
57% in cells
What % of respiratory acid is buffered within cells?
97% of buffering occurs within cells, Hb particularly important, rest with plasma proteins.
How does the kidney regulate [HCO3-]? (2)
Reabsorbing filtered HCO3-
By generating new HCO3-
Both of these processes depend on active H+ ion secretion from the tubule cells into the lumen.
How is HCO3- reabsorbed?
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 => Makes CO2 and H2O.
CO2 is freely permeable and enters the cell.
Within the cell, CO2 => H2CO3 in the presence of carbonic anhydrase (present in all tubule cells) which then dissociates to form H+ and HCO3-
H+ ions are the source of secreted H+
The HCO3- ions (not the same as filtered ones) pass into the peritubular capillaries with Na+
Bulk of HCO3- reabsorption occurs in the proximal tubule >90% No H+ is excreted
What is the minimum and maximum urine pH in humans?
minimum = 4.5-5.0
maximum = 8.0
The buffering of urine is done most by which substances?
Dibasic phosphate
HPO42-
Uric acid
Creatinine
What is titratable acidity?
A non-bicarbonate buffer excreted in the urine. HCO3- is produced and H+ is excreted.
The amount of strong base (NaOH) needed to titrate the pH of urine back to pH 7.4 for a 24 hour urine sample
What is the process of titratable acidity?
The dibasic phosphate is present in the lumen of the tubule - Na2 HPO4. One sodium is reabsorbed in exchange for secreted H+. This monobasic phosphate removes H+ from the body.
CO2 from the blood enters the tubule cells and forms H+ and HCO3-. The H+ formed here is the source of H+ that is exchanged for sodium in the previous step. HCO3 - here re enters the blood
the process occurs primarily 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 process of titratable acidity dependant on?
Dependant on PCO2 of the blood
Where is the site of formation of titratable acidity? And why?
Distal tubule
Because removal of volumes of fluid in the proximal tubule and the loop of henle causes the conc of un-reabsorbed dibasic phosphate to become highly concentrated
How is ammonium produced?
Deamination of amino acids, primarily gluatmine - by the action of renal glutaminase within the renal tubule cells
Which is lipid soluble NH3 or NH4+?
NH3 is lipid soluble
NH4+ is not
In an acid load what happens to NH3 after it is produced?
NH3 moves out into the tubule lumen, where it combines with secreted H+ ions to form NH4+
NH4+ combines with Cl- ions (from NaCl) to form NH4Cl which is excreted. (Distal tubule mechanism)
How does NH4+ leave the proximal tubule
There is an NH4+/Na+ exchanger so NH4+ ions formed within the cells pass out into the lumen. Net effect is the same).
What is the source of H+ in ammonium excretion?
CO2 from the blood
What is the activity of renal glutaminase when intracellular pH falls?
Renal glutaminase activity increases and therefore more ammonium is produced and excreted
This results in net excretion of H+ and generation of new HCO3-
This ability to augment ammonium production is the main adaptive mechanism of the kidney to acid loads
A decrease in pH puts the body into what state?
Acidosis
An increase in pH puts the body into what state?
Alkalosis
What do respiratory disorders affect?
PCO2
What do renal disorders affect?
[HCO3-]
Describe 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 therefor retention of CO2.
Acute causes of respiratory acidosis (2)
Drugs which depress the medullary respiratory centres, such as barbiturates and opiates.
Obstructions of major airways.
Chronic causes of respiratory acidosis
Lung diseases eg bronchitis, emphysema, asthma, COPD
What is the body’s response to a prolonged increase in PCO2 due to respiratory acidosis?
Want to protect the pH by increasing HCO3- (renal compensation).
Increased PCO2 will cause increased secretion of H+ and higher levels of
HCO3-.
When you generate more HCO3-, the PCO2 will also increase the ability to reabsorb it. (need CO2 to make HCO3-)
What is the only thing that can remove the primary disturbance to body pH?
What does this mean in chronic respiratory acidosis?
Restoration of normal ventilation
In chronic respiratory acidosis blood gas values are never normalised. The underlying disease process prevents the correction of ventilation, but because the kidney maintains high [HCO3-], the pH is protected.
Look
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 major problems arise in those with lung disease?
When they develop renal dysfunction too
Describe what respiratory alkalosis is
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.
Acute causes of respiratory alkalosis (3)
Voluntary hyperventilation
Aspirin
First ascent to altitude
Chronic causes of respiratory alkalosis (2)
Long term residence at altitude
Decrease in Po2 to < 60mmHg (8kPa) stimulates peripheral chemoreceptors to increase ventilation.
How is body pH protected in respiratory alkalosis?
Need to decrease [HCO3-] - HCO3- reabsorptive mechanism kicks in
How is HCO3- lost in the urine in chronic respiratory alkalosis
A decrease in PCO2 means less H+ is available for secretion therefor less of the filtered load of HCO3- is reabsorbed so HCO3- is lost in the urine
An acidosis of metabolic origin must be due to what?
a decrease in [HCO3- due to either increased buffering of H+ or a direct loss of HCO3-
How must the pH be protected in metabolic acidosis?
PCO2 must be decreased
Causes of metabolic acidosis (3)
Increased H+ production, as in ketoacidosis of a diabetic (acetoacetic acid, beta- 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?
Increased ventilation of deeper breaths but normal rate - reaching a maximum of 30 litres per minute rather than 5-6 litres per minute.
This degree of ventilation is an established clinical sign of renal failure or diabetic ketoacidosis. Very serious.
How does kussmaul breathing present a problem for the kidneys?
Kidneys use CO2 to free up hydrogen ions - these hydrogen ions are used to reabsorb bicarbonate and are sometimes excreted (titratable acidity and ammonium excretion)
Respiratory compensation however lowers the PCO2 to protect the pH
However: the amount of H+ secreted is less than normal due to decrease in PCO2. The bicarbonate is reduced moreso. A smaller fraction of H+ is needed for HCO3 reabsorption - greater proportion is available for excretion in the form of titratable acid and ammonium
Body’s response to metabolic acidosis
ECF and ICF buffer
Respiratory compensation
Renal compensation (takes a while to reach maximum activity - renal glutaminase is responsible for deamination - increasing H + excretion and HCO3 reabsorption)
Metabolic alkalosis
Causes of metabolic alkalosis
- Increase in H+ ion loss- vomiting loss of gastric secretions
- renal H+ loss- aldosterone excess, excess liquorice ingestion
- Excess administration of HCO3- is unlikely to produce a metabolic alkalosis in subjects with normal renal function, but may do so if renal function impaired.
- 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 metabolic alkalosis corrected?
Too much H+ for HCO3 to reabsorb - even in th presence of increased PCO2 - excess is lost in the urine - respiratory compensation delays renal correction but protects the pH
What is blood pH defined as?
The ratio of bicarbonate to PCO2
Therefore a decrease in pH is caused by either a decrease in HCO3- OR increased PCO2
An increase in pH (alkalosis) is CAUSED by either:
increased HCO3+ OR decreased PCO2
How long does ammonia production take to be fully turned on?
4-5 days
In the case where a patient has a haemorrhage and also has metabolic acidosis (diabetic ketoacidosis) and respiratory acidosis (chronic bronchitis) what should you do?
High acidity causes hyperkalaemia because hydrogen ions are buffered intracellularly in exchange for potassium ions - danger of centricular fibrillation
(cells soak up hydrogen and expel potassium)
TREATMENT:
Insulin or increase glucose if non-diabetic, stimulates cellular uptake of potassim - make sure not to overcompensate and cause hypokalaemia Calcium resonium - exchanges calcium ions for potassium ions Calcium gluconate (iv) - decreases the excitability of the heart and stabilizes cardiac muscle cell membranes
What are the effects on the blood after episodes of severe vomiting?
Loss of sodium chloride and water - hypovolaemia
Loss of HCL - metabolic acidosis
In metabolic alkalosis as a result of vomiting - what is the effect of hypovolaemia on aldosterone, sodium and H+?
Stimulates aldosterone - increases sodium reabsorption in the distal tubule
Main exchange for sodium is hydrogen (chlorine is low due to loss of NaCl from vomiting)
Respiratory compensation is said to exacerbate metabolic alkalosis
Restoration of volume takes precedence over correction of metabolic alkalosis
Why do you become alkalotic in vomiting and diarrhoea (cause of metabolic acidosis)?
Decrease in ECF volume results in aldosterone production and results in ‘contraction alkalosis’
Alkalosis is corrected by giving sodium chloride and restoring volume
Why does liquorice cause metabolic alkalosis?
Contains glycyrrhizic acid - very similar to aldosterone
What is the anion gap?
The difference between the sum of the principle cations (sodium and potassium) and the principle anions in the plasma (Chlorine and HCO3-)
Normally 14-18 mmoles/l
How does the anion gap change 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 does the anion gap stay the same in acidosis and when does it change?
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. Chloride is included in the principle anions.
However in eg lactic or diabetic acidosis, the reduction in bicarbonate is made up by other anions such as lactate, acetoacetate, b-OH butyrate and so the anion gap is increased.
These are not included in the principle anions so the gap between cations and anions increases
