Acid-Base Biochemistry Flashcards
What is pH?
- The concentration of hydrogen ions in a solution
What is the expression for pH?
pH = -log[H+]
What is the importance of H+ ions?
- Reactive and readily combine with negative charges and proteins
- Alter conformational shape
- Disrupt tertiary structure, disrupt active sites, disrupts subsequent function
What is the optimal pH range for most enzymes?
- 35-7.45 [H+]= 25-45 nmol/L
- Not true for all enzymes, e.f. pepsin and trypsin
When does acidosis occur (in terms of pH)?
- Falls below reference
- pH= 6.9-7.35
[H+] = 46-125 nmol/L
When does alkalosis occur (in terms of pH)?
- Rises above reference range
- pH = 7.45-7.8
- [H+] = 16-34 nmol
Define an acid
- Compounds which form H+ in solution
- Proton donors
Define a base
- Compounds that bind H+
- Proton acceptors
What is a strong acid/base?
- Dissociates completely in solution
What are weak acids/bases?
- Only partially ionised in solution
- Exists in equilibrium with ions
What is the Henderson-Hasselbalch equation?
HA H+ + A-
What is the principle behind the Henderson-Hasselbach equation?
- For any weak acid/base, the pH of the solution is determined by the ratio of dissociated base to undissociated acid
- pH is dependent on amount of acid and amount of conjugate base as well as the extent to which they dissolve
Describe a buffer
- Weak acid/base
- Accepts H+ when concentration of acid increases
- Releases H+ when concentration of acid decreases
What is meant by buffer capacity?
- Buffers are only effective within a certain range of [H+]
- Once capacity is exceeded buffer will no longer be able to maintain pH
How does a buffer affect the Henderson-Hasselbalch equation?
HA H+ + A-
- Adding acid (H+) drives reaction to left
- Adding alkali removed H+ and drives reaction to the right
What is the bicarbonate buffer?
CO₂+H₂O H₂CO₃ H⁺+HCO₃⁻
- Components can be regulated
- CO₂ by the lungs and bicarbonate by the kidneys
Describe proteins as buffers
- Most abundant buffers but are not modifiable
- Carry net negative charge at physiological pH so can absorb H+
- Haemoglobin has the highest concentration in the blood
Describe phosphate buffer
HPO₄²⁻ + H⁺ H₂PO₄
- Important in urine
- Concentration too low in blood to be an effective buffer
What is the significance of acid-base balance?
- Maintaining pH within these limits is vital
- Acid produced by the body is dealt with by a 2-step process
- H+ buffered by physiological buffers
- Acid products are eliminated via lungs and kidneys
- i.e. acid base balance is the process which maintains [H+] within normal limits
What are the sources of acid?
- Acid constantly produced in body
- Metabolism
- Ingestion of external acid (aside from overdose) generally has little effect on pH
How is acid excreted?
- Metabolic acid by kidneys
- Carbon dioxide removed through lungs
How is sulphuric acid produced in the body?
- From oxidation of sulphur-containing amino acids such as cysteine
How is phosphoric acid produced in the body?
- From dietary phosphate
How is lactic acid produced in the body?
- From anaerobic respiration
How are ketone bodies produced in the body?
- β-hydroxybutyric acid + oxaloacetic acid
- High in type 1 diabetes
- Ketoacidosis
What enzyme catalyses the reaction producing bicarbonate ions?
Carbonic anhdydrase
Which organ is more effective at removing acid?
Lungs, kidneys are slow
- Average person generates around 13 moles of CO₂ a day
How is H+ produced and how is it buffered?
- Produced from respiration
- Buffered by bicarbonate and Hb
How does the addition of carbon dioxide affect oxygen delivery?
- Drives it
What is respiratory acidosis?
- Increase PaCO₂ and H+ in hypoventilation
- Carbon dioxide is not released which leads to acidity
What is respiratory alkalosis?
- Decrease PaCO₂ and H+ hyperventilation
What is metabolic acidosis?
- Non-respiratory acidosis, increase in H+ and decrease in bicarbonate
What is metabolic alkalosis?
- Non-respiratory decrease in H+ and increase in bicarbonate
What do clinical acid base machines measure?
- Arterial blood gas
- Direct PaCO₂, PaO₂ and pH (via an electrode)
How is [HCO₃⁻] measured?
- Derived from pH and PaCO₂ using the Henderson-Hasselbalch equation
What measurements can be estimated from the bicarbonate concentration?
- Standard bicarbonate
- Base excess
What controls ventilation?
Carbon dioxide
What is the normal range for PaCO₂?
- 4.8 - 6.1kPa
> 6.1 is respiratory acidosis
<4.8 is respiratory alkalosis
Why is the pH not the most reliable indicator of respiratory acidosis/alkalosis?
- pH may be within normal range as a result of metabolic compensation
- However, if PaCO₂ is outside normal range, respiratory acidosis/alkalosis still exists
How much of carbon dioxide is carried as the bicarbonate ion?
- 80%
- Each kPa of carbon dioxide will increase bicarbonate by around 1mmol/L
- Determined by respiratory rate
Why is bicarbonate not a very important measurement?
Ambiguous
What does a proportionate change in PaCO₂ and HCO₃⁻ suggest?
Respiratory acid base imbalance
What does a disproportionate change in PaCO₂ and HCO₃⁻ suggest?
Metabolic acid base imbalance
What is the base excess?
Change in bicarbonate concentration produced by the metabolic component of an acid-base disturbance
- Deviation away from what normal bicarbonate should be
What would the base excess be in metabolic acidosis?
Base excess is negative because there is not enough bicarbonate
What would the base excess be in metabolic alkalosis?
Base excess is positive because there is too much bicarbonate
What is the standard bicarbonate?
- It is in estimate of what the HCO₃⁻ would be if PaCO₂ was normal
- Value removes the respiratory influence on the buffer capacity
SB= normal bicarbonate +/- base excess HCO₃⁻
What is the normal range for the anion gap?
10-18 mmol/l
Diagnostic and plasma must be neutral
What is the most common cause of increased anion gap (with examples)?
- Metabolic acidosis, e.g.
- Drug toxicity- salicylates (Acetosalicylate)
- Alcohol- methanol generated formate
- Diabetic ketoacidosis (acetoacetate)
What type of metabolic acidosis does not increase anion gap?
- Tubular acidosis
- Increases Cl- accompanies the HCO₃⁻ loss anion gap is retained
Why is a normal HCO₃⁻ not necessarily indicative of no acid base disorder?
- In a double (respiratory + metabolic) acidosis, respiratory acidosis increases bicarbonate while metabolic acidosis will decrease
- Two effects then cancel out
- But base excess will still be difference
