Acid-Base Balance

Question 1

How is pH calculated?

Answer 1

pH = log₁₀1/[H⁺]

Increased [H⁺] reduces pH

Decreased [H⁺] increases pH

Question 2

What is the pH of normal plasma?

Answer 2

~7.4

Question 3

What is the pH of arterial blood?

Answer 3

~7.45

Question 4

What is the pH of venous blood?

Answer 4

~7.35

Question 5

How is the pH of plasma maintained? What is the normal range and what happens outside of this range?

Answer 5

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.

Question 6

What are the 3 elements which maintain acid-base balance?

Answer 6

1. Buffering - the least important mechanism, but closely related to the lungs and kidneys which underlie life.
2. Lungs
3. Kidneys

Question 7

Define the bicarbonate buffer system.

Answer 7

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.

Question 8

What are the relative proportions of CO₂ and [HCO₃^-] in arterial blood under normophysiology?

Answer 8

• PCO₂ = 40mmHg
• [HCO₃^-] = 24mM/L

Question 9

Describe the Henderson-Hasselbalch equation.

Answer 9

pH = 6.1 + log [HCO₃^-] / PCO₂ x 0.03

• 6.1 = pKa for the reaction
• 0.03 = solubility coefficient (mmol/mmHg/L)

Question 10

What is the relationship of pH with the kidneys and lungs?

Answer 10

• 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.

Question 11

Describe how buffering helps to maintain acid-base balance.

Answer 11

• Buffering is the rapid response to change in pH (seconds - few hours):
  
  • Extracellular buffers
  • Intracellular buffers
  • Bone

Question 12

Describe the role of extracellular buffers in the maintenance of acid-base balance.

Answer 12

• 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.

Question 13

Describe the role of intracellular buffers in the maintenance of acid-base balance and give an example.

Answer 13

• 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.

Question 14

Describe the role of bone in maintaining acid-base balance.

Answer 14

• In acidosis H⁺ is buffered by, for example, PO₄^3-, 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.

Question 15

Describe the role of the respiratory system in maintaining acid-base balance.

Answer 15

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.

Question 16

Describe the role of the kidneys in maintaining acid-base balance.

Answer 16

• 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.

Question 17

Which 3 processes are used by the kidney to maintain acid-base balance?

Answer 17

• Secretion of H⁺
• Reabsorption of filtered HCO₃^-
• Production of new HCO₃^-

Question 18

What are the 4 categories of possible acid-base balance disturbance?

Answer 18

• Respiratory acidosis
• Respiratory alkalosis
• Metabolic acidosis
• Metabolic alkalosis

Question 19

What causes the initial respiratory acid-base balance disturbance?

Answer 19

Initial disturbance results from increased or decreased PCO₂

Question 20

What causes the initial metabolic acid-base balance disturbance?

Answer 20

Initial disturbance results from increased or decreased [HCO₃^-].

This is unrelated to PCO₂.

Question 21

What happens to pH, H⁺ concentration, PCO₂ and HCO₃^- concentration in respiratory acidosis?

Answer 21

• Increased PCO₂ is the primary event.
• The secondary events are:
  
  • Decreased pH
  • Increased H⁺ concentration
  • Increased HCO₃^- concentration

Question 22

What happens to pH, H⁺ concentration, PCO₂ and HCO₃^- concentration in respiratory alkalosis?

Answer 22

• Decreased PCO₂ is the primary event.
• The secondary events are:
  
  • Increased pH
  • Decreased H⁺ concentration
  • Decreased HCO₃^- concentration

Question 23

What happens to pH, H⁺ concentration, PCO₂ and HCO₃^- concentration in metabolic acidosis?

Answer 23

• Decreased HCO₃^- is the primary event.
• The secondary events are:
  
  • Decreased pH
  • Increased H⁺ concentration
  • Decreased PCO₂

Question 24

What happens to pH, H⁺ concentration, PCO₂ and HCO₃^- concentration in metabolic alkalosis?

Answer 24

• Increased HCO₃^- is the primary event.
• The secondary events are:
  
  • Increased pH
  • Decreased H⁺ concentration
  • Increased PCO₂

Question 25

What are the common causes of respiratory acidosis?

Answer 25

* Respiratory depression * Emphysema * Chest injury * Chronic bronchitis

Question 26

What are the common causes of respiratory alkalosis?

Answer 26

* Excessive ventilation (voluntary or 'panic') * Blows off CO₂ * High altitude - reduced PO₂ (hypoxia) stimulates ventilation via peripheral chemoreceptor response.

Question 27

What are the common causes of metabolic acidosis?

Answer 27

* 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.

Question 28

Describe the mechanism by which type 1 diabetes mellitus can cause metabolic acidosis?

Answer 28

* 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.

Question 29

What are the common causes of metabolic alkalosis?

Answer 29

* 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)

Question 30

How is acid-base balance maintained following an assault?

Answer 30

1. Buffering 2. Compensation 3. Correction

Question 31

Describe the 'compensation' which occurs if normal acid-base balance is disrupted.

Answer 31

* **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.

Question 32

Describe the 'correction' which occurs if normal acid-base balance is disrupted.

Answer 32

* 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.

Question 33

How does a blood-gas analyser work?

Answer 33

* Blood-gas analyser can measure pH and PCO₂. * [HCO₃^-] can be calculated. * These variables can then be plotted on a davenport diagram.

Question 34

What happens during respiratory acidosis?

Answer 34

* 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.

Question 35

What happens during respiratory alkalosis?

Answer 35

* 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

Question 36

What happens during metabolic acidosis?

Answer 36

* [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.

Question 37

How is acid-base balance regulated in metabolic acidosis due to diabetic ketoacidosis?

Answer 37

* **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.

Question 38

What is the first line of defence against acid-base disturbance in metabolic acidosis due to diabetic ketoacidosis?

Answer 38

* 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.

Question 39

What is the second line of defence against metabolic acidosis due to diabetic ketoacidosis?

Answer 39

* 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.

Question 40

What is the third line of defence against metabolic acidosis due to diabetic ketoacidosis?

Answer 40

* 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.

Question 41

What happens during metabolic alkalosis?

Answer 41

* 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.

Question 42

Why would a patient with diabetic ketoacidosis be thirsty?

Answer 42

* 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.