Acid-base Balance

Question 1

Decsribe the range of plasma pH

Answer 1

• Plasma pH must be maintained within a tight range
• pH 7.35 – 7.45
• Very low but tightly regulated concentration of H+ ions
– 44.5 – 35.5 nmol.l-1
• Plasma pH greater than 7.45 - Alkalaemia
• Plasma pH less than 7.35 - Acidaemia

Question 2

What is alkalaemia

Answer 2

• Alkalaemia lowers free calcium by causing Ca2+ ions to come out of solution
– Increases neuronal excitability
• pH > 7.45 leads to paraesthesia and tetany
• Alkalaemia can be very serious
• 45% mortality if pH rises to 7.55
• 80% mortality at pH 7.65

Question 3

What is acidaemia

Answer 3

• Increases plasma potassium ion concentration
– Effects excitability (particularly cardiac muscle)
• arrhythmia
• Increasing [H+] affect many enzymes
• Denatures proteins
• Effects muscle contractility, glycolysis, hepatic function
• Effects severe below pH 7.1
• Life threatening below pH 7.0

Question 4

Describe how the kidneys and lungs work together to control plasma pH

Answer 4

Kidneys
• Control pH – variable recovery of hydrogen carbonate and active secretion of hydrogen ions
Lungs
• Alveolar ventilation allows diffusion of O2 into blood and CO2 out of blood – control pO2 and pCO2
• Rate of ventilation controlled by chemoreceptors

Question 5

What is the pH of arterial blood determined and controlled by?

Answer 5

• Determined by:
• Ratio of pCO2 and [HCO3-]
• HCO3- is made in red blood cells
• But the concentration present is CONTROLLED by the kidneys
• Normal concentration in arterial blood ~ 25 mmol/l
– Range 22 – 26 mmol.l-1
– But can be changed to maintain pH

Question 6

What does acid production not deplete HCO3-

Answer 6

• Normally we produce acid due to metabolism
• This does not deplete HCO3- because:
– The kidneys recover all filtered HCO3-
– Proximal tubule makes HCO3- rom amino acids, putting NH4+ into urine
– Distal tubule makes HCO3- from CO2 and H2O; the H+ is buffered by phosphate and ammonia in the urine

Question 7

Describe renal control of HCO3- (recovery)

Answer 7

• HCO3- filtered at the glomerulus
• Mostly recovered in PCT
• H+ excretion linked to Na+ entry in PCT
• H+ reacts with HCO3- in the lumen to form CO2 whic enters cell
• Converted back to HCO3- which enters ECF

Question 8

Describe the creation of HCO3- in the pct

Answer 8

• Glutamine → α- ketoglutarate
– Produces HCO3- and ammonium (NH4+)
– HCO3- enters ECF
- NH4+ enters lumen (urine)

Question 9

Describe the renal control of HCO3-

Answer 9

• Distal tubule and collecting ducts also secrete H+ produced from reaction of CO2 with water
• H+ ions are ACTIVELY secreted
• H+ buffered by ammonia and phosphate (‘titratable’)
– Produce NH 4+ and H2PO4- which are excreted
• No CO2 is formed to re enter cell
• Allows HCO3- to enter plasma

Question 10

Describe the H+ buffering systems in the kidney

Answer 10

See slide

Question 11

Describe ammonium generation

Answer 11

• Excretion of ammonium is the major adaptive response to an increased acid load in healthy individuals
• Ammonium generation from glutamine in proximal tubule can be increased in response to low pH
• NH4+ + —> NH3 + H+
– NH3 freely moves into lumen and throughout interstitium
- H+ actively pumped into lumen in DCT and CT
– H+ combines with NH3 —> NH4+(trapped in lumen)
- NH4+ can also be taken up in TAL and transported to interstitium and dissociates to H+ and NH3 —> lumen of CD

Question 12

Decsribe aci excretion

Answer 12

• The minimum pH of urine is 4.5 (≈ 0.04mmol.l-1 H+)
• No HCO3- - (has all been recovered)
• Some H+ is buffered by phosphate (titratable)
• Some has reacted with ammonia to form ammonium
• Total acid excretion = 50 – 100mmol H+ per day
• This is needed to keep [HCO3-] normal

Question 13

Describe the link between H+ and K+ in distal nephron

Answer 13

• Acidosis  —> hyperkalaemia
– Potassium ions move out of cells 
– Decreased potassium
excretion in distal nephron
More h+. These move into cell.causes outward movement of k+ ions.  Increase in ecf k. Hyper kalaemia. .
• Alkalosis —> hypokalaemia
– Potassium ions move into cells
– Enhanced excretion of
potassium in distal nephron
Alkalaemia. Fewer h_. H+ out of cells. K+ into cells. Hypokalaemia.

Question 14

What is respiratory acidosis

Answer 14

• Hypoventilation -> hypercapnia (pCO2 rises)
• Hypercapnia -> fall in plasma pH
• That is respiratory acidosis (acidaemia)
• Characterised by:
– High pCO2
– Normal HCO3-
– Low pH

Question 15

What is respiratory alkalosis

Answer 15

• Hyperventilation -> hypocapnia (fall in pCO2)
• Hypocapnia -> rise in pH • This is respiratory alkalosis (alkalaemia)
• Characterised by:
– Low pCO2
– Normal HCO3-
– Raised pH

Question 16

How is resp acid/alkalosis compensated for

Answer 16

• Plasma pH depends on ratio of [HCO3-] to pCO2, not on their absolute values
• Changes in pCO2 an be compensated by changes in [HCO3-]
• The kidneys increase [HCO3-] to compensate for respiratory acidosis
• The kidneys decrease [HCO3-] to compensate for rep alkalosis.
• But takes time, 2-3 days
Chronic can be compensated but not acute

Question 17

What is ompensated resp acidosis characterised by

Answer 17

High pCO2, raised [HCO3-], relatively normal pH

Question 18

What is compensated respiratory alkalosis characterised by

Answer 18

Low pco2, lowered [HCO3-], relatively normal pH

Question 19

What happens if the tissues produce acid

Answer 19

• If the tissues produce acid, this reacts with and removes HCO3-
• There is a fall in [HCO3-] -> fall in pH bc ratio changed
• This is metabolic acidosis -> tissues produce more acid, produces H20 ad CO2
• Note the extra CO2 produced is breathed off at the lungs so there is
no increase in arterial pCO2

Question 20

What is the anion gap

Answer 20

The anion gap
• Difference between measured cations and anions
• ([Na+] + [K+]) – ([Cl-] + [HCO3-]
• Normally 10 – 18 mmol.l-1
– Due to other anions that are not measured
• This gap is increased if HCO3- is replaced by other anions
• If a metabolic acid (such as lactic acid) reacts with HCO3- the anion of the acid replaces HCO3-
- is replaced by other anions
• In renal causes of acidosis anion gap will be unchanged
– Not making enough HCO3- but this is replaced by Cl-
When sample results come back from lab. Decide if acidosis from metabolic cause, or renal cause, respiratory acidosis?
We measure conc of sodium one potassium. Anions are chloride and hco3
Gap bc there are anions that are not measured. Most cation are measures
If hco3- conc reduced and replaced by another anion that’s NOT chloride, the gap is increased bc more anion that is not measured
I some1 excercides - produces lactating aid. Reacts with hco3-. Acid anion replaces hco3-

Question 21

What is metabolic acidosis initially characterised by

Answer 21

Normal pCO2, low HCO3-, low pH, increased anion gap is HCO3- is replaced byy another organic anion from an acid. Normal anion gap is HCO3- is replaced by Cl-

Question 22

How is metabolic acidosis compensated

Answer 22

• Peripheral chemoreceptor (carotid bodies) detect pH drop
– Stimulate ventilation
– Leading to decrease pCO2
• Compensated metabolic acidosis is characterised by:
– Low HCO3-
– Lowered pCO2
– Nearer normal pH

Question 23

What is metabolic alkalosis

Answer 23

[HCO3-] increase
Normal pCO2,
Raised HCO3-,
Increased pH (decreased h+ bc increased HCO3-, ratio changed)
Cannot normally be compensated by reduced breathing - need to maintain pO2, but kidney can correct in most cases by retaining less HCO3- (except in excessive fluid loss where Na+ needs to be retained )

Question 24

What leads to respiratory acidosis

Answer 24

Type 2 respiratory failure
- low pO2 and high pCO2
- the alveoli cannot be properly ventilated
– Severe COPD, severe asthma, drug overdose, neuromuscular disease
• Can be compensated for by increase in [HCO3-]
• Chronic conditions can be well compensated such that pH near normal bc kidneys take time, acute is harder to compensate for

Question 25

What conditions lead o metabolic acidosis

Answer 25

• If anion gap is INCREASED – indicates a metabolic production
of an acid
– Keto-acidosis
• diabetes 
– Lactic acidosis
• Exercising to exhaustion
• Poor tissue perfusion 
– Uraemic acidosis
• Advanced renal failure – reduced acid secretion, build up of
phosphate, sulphate, urate in blood

Question 26

Describe conditions leading to metabolic acidosis with a normal anion gap

Answer 26

• If anion gap is normal HCO3- is replaced by Cl-
• Renal tubular acidosis (This is a rare condition)
– Problems with transport mechanisms in the tubules
– Type 1 (distal) RTA – inability to pump out H+
– Type 2 (proximal) RTA (very rare) – problems with HCO3- reabsorption
• Severe persistent diarrhoea can also lead to metabolic acidosis due to loss of HCO3-
– Replaced by Cl-
– Therefore anion gap unaltered

Question 27

Describe metabolic acidosis and potassium

Answer 27

• Non-renal causes of metabolic acidosis cause
increased reabsorption of K+ by kidneys
• And movement of K+ out of cells
• -> hyperkalaemia
• However in diabetic ketoacidosis may be a total body depletion of K+
– K+ moves out of cells (due to acidosis and lack of insulin)
– But osmotic diuresis means K+ lost in urine

Question 28

What are conditions leading to metabolic alkalosis

Answer 28

• In metabolic alkalosis HCO3 is retained in place of Cl-
• Stomach is a major site of HCO3- production
– By-product of H+ secretion
– Severe prolonged vomiting - loss of H+
– Or mechanical drainage of stomach
• Other causes:
– Potassium depletion / mineralocorticoid excess
– Certain diuretics (loop and thiazide)

Question 29

In what situation can meta alkalosis not be compensated

Answer 29

• [HCO3-] increase eg after persistent vomiting
– This should be very easy to correct
– HCO3- can be excreted very rapidly following infusion of HCO3-
• Corrected by:
• Rise in pH of tubular cells leads to fall in H+ excretion and reduction in HCO3-
recovery
• BUT
• Problem if there is also volume depletion
– Capacity to loose HCO 3- is reduced because of high rate of Na+ recovery
– Recovering Na+ favours H+ excretion and HCO3- recovery

Question 30

How can metabolic alkalosis affect potassium levels

Answer 30

• Less H+ excretion in nephron leads to more K+ excreted • Alkalosis also causes movement of K+ ions into cells • This leads to hypokalaemia

Question 31

How can values be interpreted

Answer 31

See slide