Acid-Base regulation

Question 1

What blood pHs would result in death?

Answer 1

pH <6.8

pH >8

Question 2

Describe the pathological formation of acid.

Answer 2

1. Methanol poisoning - forms formic acid
2. Ethylene glycol poisoning - forms glycolic acid, glyoxylic acid, oxalic acid
3. Drugs/toxins:
   - inhibition of oxidative phosphorylation –> anaerobic metabolism –> lactic acid
   - Liver disease –> impaired lactate clearance –> lactic acid
4. CO:
   - inhibition of oxidative phosphorylation –> anaerobic metabolism –> lactic acid
   - impaired O2 delivery –> anaerobic metabolism –> lactic acid
5. Hypotension/hypoxia:
   - impaired O2 delivery –> anaerobic metabolism –> lactic acid
6. uncontrolled diabetes/starvation - forms acetoacetate and beta-hydroxybutyrate

Question 3

What are the different mechanisms that limit changes in pH? How long does each one take?

Answer 3

1. chemical buffer systems in blood (immediate)
2. respiratory centre in brainstem (1-3 minutes)
3. renal mechanisms (hours to days)

Question 4

What are the 3 chemical buffers in the body?

Answer 4

1. bicarbonate
2. proteins (haemoglobin, albumin)
3. phosphate

Question 5

What % of body weight is made up by:

• Plasma (ECF)
• Interstitial fluid (ECF)
• Intracellular fluid (ICF)

Answer 5

• Plasma (ECF): 5%
• Interstitial fluid (ECF): 15%
• Intracellular fluid (ICF):40%

Question 6

What effect does acid-base disturbance have on blood [K+]?

Answer 6

Acidaemia = HYPERkalaemia 
Alkalaemia = HYPOkalaemia

Question 7

What are the main cations and anions forming the plasma?

Answer 7

Cations:

• Na+
• K+

Anions:

• HCO3-
• Cl-
• Protein anions

Question 8

What are the main cations and anions forming the interstitial fluid?

Answer 8

Cations:

• Na+
• K+

Anions:

• HCO3-
• Cl-

Question 9

What are the main cations and anions forming the intracellular fluid?

Answer 9

Cations:

• K+
• Na+

Anions:

• PO4 3-
• Protein anions

Question 10

What ions usually make up the unmeasured cations and anions in the ECF and ICF?

Answer 10

Cations:

• calcium
• magnesium
• proteins (unless plasma)

Anions:

• phosphates (unless ICF)
• sulfates
• proteins

Question 11

How can the anion gap be calculated? what is the normal range?

Answer 11

([Na+] + [K+]) - ([Cl-] + [HCO3-]) = 12-16 mEq/L

([Na+] + [K+]) - ([Cl-] + [HCO3-]) = 8-12 mEq/L

Question 12

What are the causes of loss of bicarbonate? What acid-base change does this lead to?

Answer 12

• severe diarrhoea
• chronic laxative abuse
• villous adenoma
• external drainage of pancreatic/biliary secretions (fistulas)
• loss via NG tube
• urinary diversions
• administration of acidifying salts

Causes NORMAL GAP ACIDOSIS

Question 13

What other situations (apart from loss of bicarbonate) can cause normal gap acidosis?

Answer 13

Reduced kidney excretion of H+
- more bicarbonate is needed to help buffer excess H+ = reduced HCO3-
(no compensation from Cl-)

Question 14

What can cause reduced kidney H+ excretion (resulting in normal gap acidosis)?

Answer 14

• ketoacidosis
• lactic acidosis
• renal failure
• toxic ingestions

Question 15

What acid-base change does hypoalbuminaemia result in? What are the potential causes?

Answer 15

Low gap acidosis
(reduced albumin = increased bicarbonate and Cl-)

Causes:

• haemorrhage
• nephrotic syndrome
• intestinal obstruction
• liver cirrhosis

Question 16

By how much does the anion gap change in metabolic alkalosis?

Answer 16

Small increase of ~4-6 mEq/L

Question 17

In the kidneys, where is most of the bicarbonate reabsorbed?

Answer 17

Proximal convoluted tubule (70-90%)

DCT (10-30%)

Question 18

What is secreted and reabsorbed by the alpha-intercalated cells? What channels are used to secrete/reabsorb?

Answer 18

secreted:
- acid (via H+ ATPase and H+/K+ exchanger), in the form of H+

reabsorbed:
- bicarbonate (via basolateral Cl-/HCO3- exchanger)

Question 19

What is secreted and reabsorbed by the beta-intercalated cells? What channels are used to secrete/reabsorb?

Answer 19

Secreted:
- bicarbonate (via pendrin - specialised apical Cl-/HCO3-)

Reabsorbed:
- acid (via basal H+ - ATPase)

Question 20

How do renal tubular cells control pH in acidosis?

Answer 20

1. Kidney wants to excrete H+
   - -> upregulation of Na+/H+ transporter on luminal surface of cells
   - -> glutamine anf glutamate are deaminated to excrete ammonia (NH3) into the urine – neutralises the urine
   - -> phosphate is also present to reduce the acidity of the urine
2. Kidney wants to secrete bicarbonate into the blood
   - -> will help reduce the acidity of the blood

Question 21

How do renal tubular cells control pH in alkalosis?

Answer 21

1. H2CO3 dissociates into HCO3- and H+
2. HCO3- is excreted via the urine by upregulation of a HCO3-/Cl- exchanger (pendrin)
3. H+ is secreted/reabsorbed into the blood via H+-ATPase

Question 22

What is the main reason behind respiratory acidosis occurring? Give examples of situations in which it occurs. What is the compensation for this acid-base change?

Answer 22

Reason: CO2 retention
Situation: hypoventilation (COPD)
Compensation: Renal –> H+ excretion and HCO3- gain

Question 23

What is the main reason behind respiratory alkalosis occurring? Give examples of situations in which it occurs. What is the compensation for this acid-base change?

Answer 23

Reason: CO2 loss
Situation: hyperventilation (anxiety or altitude)
Compensation: Renal –> H+ retention and HCO3- loss

Question 24

What is the main reason behind metabolic acidosis occurring? Give examples of situations in which it occurs. What is the compensation for this acid-base change?

Answer 24

Reason: gain of acid, loss of base
Situation: diarrhoea, keto-acidosis, lactic acidosis
Compensation: Respiratory –> CO2 loss and HCO3- falls

Question 25

What is the main reason behind metabolic alkalosis occurring? Give examples of situations in which it occurs. What is the compensation for this acid-base change?

Answer 25

Reason: loss of acid, gain of base
Situation: vomiting, hypokalaemia, ingestion of HCO3-
Compensation: Respiratory –> CO2 and HCO3- rise