Acid Base Balance

Question 1

Define acid-base control

Answer 1

Control of H⁺ concentrations

Question 2

Why is the regulation of H⁺ ions more important than other ions?

Answer 2

Due to their effects on protein function:

• Alteration of protein activity (esp enzymes)
• Alteration of binding of other ions (e.g. decreased H⁺ → increased Ca²⁺ binding to albumin

Question 3

Define acid and base

Answer 3

Acid: Any chemical that can donate a proton

Base: Any chemical that can accept a proton

Question 4

Describe the relationship between H⁺and pH

Answer 4

Inverse relationship between H⁺ and pH

1 unit change in pH represents a 10 fold change in H⁺

Question 5

What are the 3 main mechanisms that control H⁺ concentrations?

Answer 5

Buffer systems

• Minimise sudden changes in H⁺- unable to change overall body pH

Lungs

• Rapid adjustment of CO₂ excretion

Kidneys

• Slow adjustment of H⁺ excretion in urine and adjust body HCO₃^- levels.

Question 6

Define buffer

Answer 6

Any substance that can reversibly bind H⁺

Question 7

What are the 3 main buffer systems in the body?

Where are they found?

Answer 7

Bicarbonate buffer system

• Extracellular
• HCO₃^- + H⁺ ⇔ H₂CO₃ (carbonic acid)

Phosphate buffer system

• Intracellular and urine
• HPO₄^2- + H⁺ ⇔ H₂PO₄^-

Protein buffer system

• Mainly intracellular
• Pr^- + H⁺ ⇔ HPr

Question 8

What are the main intracellular buffer systems?

Answer 8

PO₄ (phosphate) buffer systems

Haemoglobin buffer system

Question 9

What are the main extracellular fluid buffer systems?

Answer 9

Bicarbonate buffer system

Plasma protein buffers

Question 10

What is the most important extracellular buffer?

What is its role?

Answer 10

Bicarbonate buffer system

• Connects the control of CO₂ by the lungs to the control of HCO₃^- by the kidneys allowing the systems to compensate for eachother.

HCO₃^- + H⁺ ⇔ H₂CO₃ ⇔ (CA) H₂O + CO₂

Question 11

Which enzyme allows carbonic acid to dissociate to H₂O and CO₂?

Answer 11

Carbonic anhydrase (carbonic dehydratase)

Question 12

What is the ratio of HCO₃^- : CO₂ that is necessary to keep pH at roughly 7.4?

Answer 12

20 : 1

Question 13

What is necessary for the maintenance of pH?

Answer 13

Functioning lungs for excretion of CO₂ (increase or decrease in ventilation)

Functioning kidneys for excretion of H⁺ and production of HCO₃^-

Question 14

How do the kidneys control extracellular fluid pH?

What are both of these processes dependent on?

Answer 14

• By controlling the amount of H⁺ excreted in urine
• By reabsorbing filtered HCO₃^-

Both of these processes dependent on the ability of the kidneys to secrete H⁺

Question 15

How much HCO₃^- is normally in urine?

Answer 15

None- usually all reabsorbed in the kidneys

Question 16

Where does the majority of renal reabsorption of HCO₃^- occur?

Answer 16

Proximal convoluted tubule

Question 17

How is HCO₃^- reabsorbed in the kidney?

Answer 17

Proximal convoluted tubule:

• HCO₃^- cannot be reabsorbed alone as it cannot cross the luminal membrane.
• Na⁺/H⁺ exchangers in the luminal membrane absorb Na⁺ and secrete H⁺ which reacts with HCO₃^- to form H₂CO₃ (carbonic acid)
• H₂CO₃ is converted to H₂O and CO₂ in the presence of carbonic anhydrase- CO₂ diffuses into the cell.

Luminal epithelial cell:

• CO₂ reacts with H₂O inside the cell and is converted back to H₂CO₃ by carbonic anhydrase.
• H₂CO₃ rapidly dissociates to HCO₃^- and H⁺
• HCO₃^- moves across the basolateral membrane into the blood via HCO₃^-/ Na⁺ symporter
• H⁺ is re-secreted back into the luminal membrane to be used again.

Question 18

How is H⁺ secreted in the late distal and collecting tubules?

What stimulates this activity?

Answer 18

Secreted into the tubular lumen by H⁺ATPase or H⁺/K⁺ATPase in type A intercalating cells

Stimulated by aldosterone and by hypokalaemia

Question 19

How is H⁺ excreted

Answer 19

Secreted in late distal and collecting tubules by H⁺ATPase and H⁺/K⁺ATPase however this is limited as high concentratins of H⁺ in the lumen inhibits these transporters. Does not excrete enough H⁺ on its own.

• Urinary phosphate and ammonia buffers reduce the amount of H⁺ in the lumen, preventing the high concentrations from inhibiting H⁺ATPase and H⁺/K⁺ATPase.

Question 20

What is generated by the excretion of H⁺?

Why is this important?

Answer 20

New HCO₃^- is generated by the excretion of H⁺

This is important as some is consumed buffering the non-volatile acids in the body that are produced each day.

Question 21

Describe the urinary phosphate buffer

Answer 21

2 forms of filtered phosphate:

• Monoprotic: HPO₄^2-
• Diprotic: H₂PO₄^-

These create a buffer pair in tubular fluid:

HPO₄^2- + H⁺ ⇔ H₂PO₄^-

There is a relative excess of the monoprotic form which is able to buffer excess secreted H⁺ in the lumen and excrete it in urine as the diprotic form.

Question 22

How does the urinary phosphate buffer cause production of new HCO₃^-?

Answer 22

Inside the cell, H₂O and CO₂ are converted by carbonic anhydrase to H₂CO₃ which rapidly dissociates to HCO₃^- and H⁺.

H⁺ is pumped out of the cell into the tubular lumen whilst the HCO₃^- is pumped across the basolateral membrane into the blood.

Question 23

Describe the urinary ammonia buffer

How does it produce new HCO₃^-?

Answer 23

Ammonium (NH₄⁺) synthesised from glutamate in the PCT and secreted.

Ammonia (NH₃) secreted mainly in the collecting duct.

Form a buffer pair:

NH₃ + H⁺ ⇔ NH₄⁺

NH₃ picks up excess H⁺ and is excreted in the urine as ammonium

New HCO₃^- is produced in the tubular cells via the same process as with the urinary phosphate buffer.

Question 24

How does the urinary ammonia buffer respond to the body’s acid-base status?

Why is this response slower than the lungs?

Answer 24

Decrease in pH stimulates renal glutamine metabolism which increases activity of glutaminase and increased secretion of H⁺ and vice versa.

Slower than the lungs as this process requires the synthesis/breakdown of proteins

Question 25

What is H⁺ secretion stimulated by?

Answer 25

Increase in extracellular pCO₂ Decreased extracellular pH Also increased aldosterone levels and hypokalaemia

Question 26

Define acidosis

Answer 26

Any process which results in the pH of the blood becoming more acidic Caused by excess acid and/or loss of alkali

Question 27

Define alkalosis

Answer 27

Any process which causes the blood pH to become more basic (alkaline) than normal Caused by loss of acid and/or excess alkali

Question 28

What are respiratory and metabolic acidosis/alkalosis

Answer 28

Respiratory: * Primary problem is respiratory (problem with CO₂ excretion) Metabolic: * Primary problem is renal (problem with H⁺ excretion and/or HCO₃^- reabsorption or production)

Question 29

In compensated acidotic or alkalotic conditions, which paramaters will be outside their normal range?

Answer 29

Both CO₂ and HCO₃^- are abnormal but in the same direction (i.e. both raised or both lowered)

Question 30

What are the causes of respiratory acidosis and alkalosis?

Answer 30

**Respiratory acidosis:** * Low pH due to high CO₂ * E.g. hypoventilation * Compensation: Increased HCO₃^- production **Respiratory alkalosis:** * High pH due to low CO₂ * E.g. hyperventilation- anxiety, high altitude * Compensation: Reduced HCO₃^- production

Question 31

What are the causes of metabolic acidosis and alkalosis? What can be done to compensate?

Answer 31

**Metabolic acidosis:** * Low pH due to low HCO₃^- or high H⁺ * E.g excess acid (e.g. lactic), failure of H⁺ excretion or HCO₃^- loss (e.g. severe diarrhoea) * Compensation: Reduced CO₂ (hyperventilation) **Metabolic alkalosis:** * High pH due to high HCO₃^- or low H⁺ * E.g. excess vomiting (acid loss), excess aldosterone * Compensation: Increased CO₂ (hypoventilation)

Question 32

How are ABGs interpreted?

Answer 32

pH: acidosis or alkalosis? If due to CO₂ = primary respiratory problem If due to HCO₃^- = primary metabolic problem Evidence of compensation?