Acid-Base Balance Flashcards
How is pH calculated?
pH = log101/[H+]
Increased [H+] reduces pH
Decreased [H+] increases pH
What is the pH of normal plasma?
~7.4
What is the pH of arterial blood?
~7.45
What is the pH of venous blood?
~7.35
How is the pH of plasma maintained? What is the normal range and what happens outside of this range?
Tight regulation of [H+] input and output.
pH outside 6.8-8.0 is fatal. It causes neuromuscular excitability, cardiac arrhythmias (changes in K+ induced) and enzyme denaturation.
Some H+ can be ingested, but major source is metabolism.
What are the 3 elements which maintain acid-base balance?
- Buffering - the least important mechanism, but closely related to the lungs and kidneys which underlie life.
- Lungs
- Kidneys
Define the bicarbonate buffer system.
CO2+H2O ⇌ H2CO3 ⇌ H+ + HCO3-
In the presence of carbonic anhydrase, this will happen much faster.
To control pH, we must control free [H+].
H+ is produced by metabolism and added to the body through diet.
What are the relative proportions of CO2 and [HCO3-] in arterial blood under normophysiology?
- PCO2 = 40mmHg
- [HCO3-] = 24mM/L
Describe the Henderson-Hasselbalch equation.
pH = 6.1 + log [HCO3-] / PCO2 x 0.03
- 6.1 = pKa for the reaction
- 0.03 = solubility coefficient (mmol/mmHg/L)
What is the relationship of pH with the kidneys and lungs?
- pH is proportional to the bicarbonate ion concentration divided by the partial pressure of carbon dioxide.
- The base is controlled by the kidneys and the acid is controlled by the lungs.
- This means we can control our pH by changes in the renal system and changes in the respiratory system.
Describe how buffering helps to maintain acid-base balance.
- Buffering is the rapid response to change in pH (seconds - few hours):
- Extracellular buffers
- Intracellular buffers
- Bone
Describe the role of extracellular buffers in the maintenance of acid-base balance.
- The most important of these is the bicarbonate buffer system.
- Quite weak - but ubiquitous and CO2 and H2CO3 can be controlled, so other buffering system are needed.
- Phosphate buffer system also, but this is much more important in the kidney and ICF.
Describe the role of intracellular buffers in the maintenance of acid-base balance and give an example.
- CO2 rapidly diffuses from ECF to ICF of all cells and H+ increases (pH changes).
- H+ and HCO3- might also diffuse to a small extent (except in RBC where it is high).
- Buffering by proteins e.g. Hb in RBCs ‘mops-up’ H+
- H+ + Hb ⇌ HHb
- Example: haemoglobin. 4 subunit protein. Like other proteins, it has the capacity to grab ions and take them out of solution. It can take H+ ions out of solution and hold onto them. If they are not free they are not acidic so in the pocket of haemoglobin they are not causing a solution to be acidic.
Describe the role of bone in maintaining acid-base balance.
- In acidosis H+ is buffered by, for example, PO43-, OH- (short-term).
- Note also dissolution of bone mineral by osteoclasts in chronic acidosis.
- Osteoclasts dissolve bone and the products of this dissolution are free to be used in other metabolic processes.
Describe the role of the respiratory system in maintaining acid-base balance.
CO2+H2O ⇌ H2CO3 ⇌ H++HCO3-
- Assuming metabolic CO2 production is constant, the only thing that affects [CO2] is alveolar ventilation.
- Assume normal alveolar ventilation = 1
- By increasing alveolar ventilation or decreasing we can change the pH.
Describe the role of the kidneys in maintaining acid-base balance.
- Kidneys excrete either acidic or basic urine.
- HCO3- is filtered continuously into tubules; if excreted in the urine, this will reduce base from the blood.
- H+ is secreted into tubules, removing acid from the blood.
- More H+ secreted than HCO3- filtered - net loss of acid from ECF.
- More HCO3- filtered than H+ secreted - net loss of base from ECF.
- The body produces ~80mEq of ‘non-volatile acids’ per day (not H2CO3 so can’t be lost through ventilation). The kidney must remove these.
- Kidney must also coneserve bicarbonate levels.
Which 3 processes are used by the kidney to maintain acid-base balance?
- Secretion of H+
- Reabsorption of filtered HCO3-
- Production of new HCO3-
What are the 4 categories of possible acid-base balance disturbance?
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
What causes the initial respiratory acid-base balance disturbance?
Initial disturbance results from increased or decreased PCO2
What causes the initial metabolic acid-base balance disturbance?
Initial disturbance results from increased or decreased [HCO3-].
This is unrelated to PCO2.
What happens to pH, H+ concentration, PCO2 and HCO3- concentration in respiratory acidosis?
- Increased PCO2 is the primary event.
- The secondary events are:
- Decreased pH
- Increased H+ concentration
- Increased HCO3- concentration
What happens to pH, H+ concentration, PCO2 and HCO3- concentration in respiratory alkalosis?
- Decreased PCO2 is the primary event.
- The secondary events are:
- Increased pH
- Decreased H+ concentration
- Decreased HCO3- concentration
What happens to pH, H+ concentration, PCO2 and HCO3- concentration in metabolic acidosis?
- Decreased HCO3- is the primary event.
- The secondary events are:
- Decreased pH
- Increased H+ concentration
- Decreased PCO2
What happens to pH, H+ concentration, PCO2 and HCO3- concentration in metabolic alkalosis?
- Increased HCO3- is the primary event.
- The secondary events are:
- Increased pH
- Decreased H+ concentration
- Increased PCO2
What are the common causes of respiratory acidosis?
- Respiratory depression
- Emphysema
- Chest injury
- Chronic bronchitis
What are the common causes of respiratory alkalosis?
- Excessive ventilation (voluntary or ‘panic’)
- Blows off CO2
- High altitude - reduced PO2 (hypoxia) stimulates ventilation via peripheral chemoreceptor response.
What are the common causes of metabolic acidosis?
- May be due to:
- Failure of the kidneys to secrete metabolic acids normally fromed in the body.
- Formation of excess metabolic acids.
- Addition of excess acidss to th body via ingestion or infusion.
- Loss of base from the body.
- Unmanaged type 1 diabetes mellitus.
Describe the mechanism by which type 1 diabetes mellitus can cause metabolic acidosis?
- Type 1 diabetes is a common cause of matabolic acidosis if it is not managed.
- In the absence of insulin, fats are metabolised instead of glucose.
- Acetoacetic acid (ketoacid) is formed and blood levels rise.
- This can be severe and the kidneys excrete a large amount in the urine.
What are the common causes of metabolic alkalosis?
- Excess retention of HCO3- or loss of H+
- Vomiting - loss of H+ from the stomach results in an imbalance.
- (Vomiting the contents of the duodenum which is rich in bicarbonate can result in metabolic acidosis)
How is acid-base balance maintained following an assault?
- Buffering
- Compensation
- Correction
Describe the ‘compensation’ which occurs if normal acid-base balance is disrupted.
- Compensation is the restoration of pH irrespective of what happens to [HCO3-]p and PCO2.
- The first priority is to restore the pH to 7.4 as soon as possible.
- Physiologically, the focus is on H+ concentration - this can be at the expense of bicarbonate ion concentration and PCO2.
Describe the ‘correction’ which occurs if normal acid-base balance is disrupted.
- This strictly only applies to processes in non-nephrogenic metabolic acidosis, resulting in restoration of pH, [HCO3-]p and PCO2 to normal.
- Normalisation is not always possible without intervention as it can rely on the underlying cause being eliminated.
- But, for example, correction normalisation would be possible in the case of an asthma attack that has subsided.
How does a blood-gas analyser work?
- Blood-gas analyser can measure pH and PCO2.
- [HCO3-] can be calculated.
- These variables can then be plotted on a davenport diagram.
What happens during respiratory acidosis?
- CO2 retention drives equilibrium to the right.
- Therefore, both [H+]p and [HCO3-]p rise.
- The increased [H+]p results in acidosis (remember pH is a measure of free [H+]).
- Uncompensated respiratory acidosis is indicated if approximate pH <7.35 and PCO2 >45mmHg.
What happens during respiratory alkalosis?
- Excessive CO2 removal drives equilibrium to the left.
- Therefore, both [H+]p and [HCO3-]p fall.
- The decreased [H+]p results in alkalosis.
- Uncompensated respiratory alkalosis is indicated is approximate pH >7.45 and PCO2 <35mmHg
What happens during metabolic acidosis?
- [HCO3-]p is depleted as a result of buffering excess H+ or loss of HCO3- from the body, or increase in H+.
- Uncompensated metabolic acidosis is indicated by approximate pH<7.35, [HCO3-]p is low.
How is acid-base balance regulated in metabolic acidosis due to diabetic ketoacidosis?
- Disruption to homeostasis is in the form of elevated free H+ ions in extracellular fluid (decreased pH).
- Return to homeostasis via:
- Compensation is the first priority; restoring pH as soon as possible, irrespective of [HCO3-] and PCO2.
- Correction is the second priority; restoring [HCO3-] and PCO2.
-
Reduction of free [H+] in solution by:
- Chemical buffers
- Ventilation changes (PCO2)
- Renal system changes.
What is the first line of defence against acid-base disturbance in metabolic acidosis due to diabetic ketoacidosis?
- Excess ketoacids form and their dissociation increases plasma [H+].
- First line - buffers sequester increased [H+].
- Result: [H+] is lowered, but [HCO3-] is also lowered.
- Response takes seconds.
- Low impact (system is quickly overwhelmed).
- We can rely on the buffers as the very immediate (within seconds) response to this disruption. It is a weak response but it is immediate. The H+ ions are filled in by any free bicarbonate ions but very soon these are used up so the resolution has to shift to other mechanisms of greater efficacy.
What is the second line of defence against metabolic acidosis due to diabetic ketoacidosis?
- Respiratory compensation
- Increase ventilation - blowing-off the CO2 at the lungs and draging the reaction even more to the left, provided we have bicarbonate ions, enables more buffering.
- Respiratory centres trigger an increase in ventilation, therefore more CO2 is eliminated.
- Result: [H+] decreases, pH returns towards normal, but [HCO3-] is lowered further still.
- Response takes minutes.
- Effective compensation (ECF pH in normal range) but [HCO3-] (already low due to disturbance) is now lowered even further.
What is the third line of defence against metabolic acidosis due to diabetic ketoacidosis?
- Renal system correction.
- Reabsorption of [HCO3-] from tubular fluid coupled with secretion of [HCO3-] into plasma.
- Increased excretion of H+ as H2PO4- (acid phosphate) coupled with secretion of [HCO3-] into plasma.
- Increased excretion of H+ as NH4+ (ammonium ion) coupled with secretion of [HCO3-] into plasma.
- Response takes days.
- Eventual return of ECF to normal [HCO3-] range.
What happens during metabolic alkalosis?
- As a result of loss of H+ or addition of base, [HCO3-]p rises.
- Uncompensated metabolic alkalosis indicated by approximate pH >7.45, [HCO3-]p is high.
Why would a patient with diabetic ketoacidosis be thirsty?
- Defect in insulin secretion leads to:
- Glucose not being metabolised.
- Fats metabolised as fuel, forming ketoacids.
- Blood becomes acidotic.
- Kidneys eliminate ketoacids in urine.
- High glucose concentration in ECF dehydrates ICF via osmosis.
- High glucose concentration in urine causes osmotic diuresis (i.e. glucose in tubules causes reduction in resorption of fluid → high volume of dilute urine).
- Water is eliminated which decreases the concentraion of water in body fluids, which increases the concentration of solutes in body fluids.
