Session 4 Flashcards
Carbon dioxide in blood
- CO2 is more soluble than oxygen
- CO2 reacts chemically with water
- CO2 also reacts with Hb (but at different site from O2)
Arterial blood
- Has almost 2.5x as much CO2 as O2
- More dissolved and more reacted with water
Carbon dioxide in arterial blood
- Total content of gases (dissolved and reacted)
- Total content CO2 in arterial blood ≈ 21 mmol.l-1
- Total content O2 in arterial blood ≈ 8.9 mmol.l-1
- Why so much CO2 in blood going to the tissues?
- CO2 dissolves in water so can be used to control pH
- [CO2]dissolved = solubility x pCO2 – Solubility factor for CO2 at 37oC = 0.23
- At pCO2 of 5.3 kPa water dissolves 1.2 mmol.l-1 CO2
- Dissolved CO2 reacts with water in plasma and in red blood cells
- CO2 in arterial blood is not there as a waste product
Carbon dioxide in plasma
- Dissolved CO2 reacts with water to form carbonic acid (H2CO3)
- Carbonic acid very quickly dissociates to hydrogen ions (H+) and hydrogen carbonate ions (HCO3-)
- We can effectively ignore the intermediate carbonic acid when we study the reaction
- Dissolved CO2 reacts with water to form hydrogen ions (H+) and hydrogen carbonate ions (HCO3-)
- The reaction is reversible
- The rate of the reaction depends on the reactants and products
Control of blood pH (acid-base balance)
- CO2 has a major role in controlling blood pH
- Controlling CO2 is more important for pH than for transporting it from tissues to the lungs
- Arterial blood pH must be kept within a narrow range (pH 7.35 – pH 7.45)
- First consider CO2 in arterial blood
pH of plasma
•Depends on how much CO2 reacts to form H+
– This in turn depends on [CO2] dissolved which pushes the reaction to the right – And on [HCO3-] which pushes the reaction to the left
CO2 + H2O ⇔ H+ + HCO3
[dissolved CO2] 1.2 mmol.l-1
[HCO3-] 25 mmol.l-1
- Depends on dissolved CO2
- And concentration of hydrogen carbonate
Dissolved CO2
- The amount of CO2 dissolved depends directly on the partial pressure of CO2
- If pCO2 rises plasma pH will fall (becomes more acidic)
- If pCO2 falls plasma pH will rise (becomes more alkaline)
- The pCO2 of alveoli is the determining factor
- This is controlled by altering the rate of breathing
Hydrogen carbonate in plasma
- Plasma contains 25mmol.l-1 HCO3– The cation associated with this is mostly Na+ not H+
- This high [HCO3-] cannot come from CO2 in plasma
- High [HCO3-] prevents nearly all dissolved CO2 from reacting – pH of plasma is alkaline
Henderson-Hasselbalch equation
- Provides a way of calculating pH from pCO2 and [HCO3-]
- pH = pK + Log ([HCO3-] /(pCO2 x 0.23))
- pK is a constant; pK = 6.1 at 37oC
- 20 times as much HCO3-as dissolved CO2
- Log 20 = 1.3
- pH = 6.1 + 1.3 = 7.4
CO2 + H2O ⇔ H+ + HCO3
[dissolved CO2] 1.2 mmol.l-1
[HCO3-] 25 mmol.l-1
pH of arterial blood
- Ratio of [HCO3-] and pCO2 determine pH
- pCO2 determined by alveolar pCO2 – Rate of ventilation
Hydrogen carbonate production in red blood cells
- Reaction is speeded up by the enzyme carbonic anhydrase (CA) in RBCs
- The reaction proceeds in the forward direction because the products are mopped up in the RBC
- H+ ions bind to the negatively charged Hb inside RBCs
- Chloride-bicarbonate exchanger transports HCO3- out of RBCs
- Creates a plasma concentration of 25mmol.l-1 HCO3
slide 14 lec 1
Binding of H+ to haemoglobin
- Haemoglobin has a large capacity for binding H+ ions
- The amount of HCO3- that erythrocytes produce depends on the binding of H+ to haemoglobin
- Erythrocytes produce HCO3- but they don’t control concentration of HCO3- in plasma
Plasma hydrogen carbonate
- [HCO3-] doesn’t change much with pCO2
- HCO3- comes from the RBCs – The reaction is mostly determined by H+ binding to Hb
Role of kidney in controlling [HCO3-]
- Kidney controls amount of HCO3- by varying excretion
- Therefore pH is dependent on how much CO2 is present (controlled by rate of breathing)
- and how much bicarbonate is present (controlled by kidneys)
- pH = pK + Log ([HCO3-] /(pCO2 x 0.23))
Hydrogen carbonate buffers extra acid
- The body produces acids – Lactic acid, keto acids, sulphuric acid
- Acids react with HCO3- to produce CO2
- Therefore [HCO3-] goes down
- The CO2 produced is removed by breathing and pH changes are minimised (buffered)
Arterial and venous pCO2
- Arterial pCO2 is determined by alveolar pCO2
- This determines how much CO2 is dissolved
- And therefore affects pH
- pCO2 is higher in venous blood – Comes from metabolically active tissues
- This means a bit more CO2 will dissolve
- But need to consider how venous blood can transport and give up the correct amount of CO2 to the lungs
Properties of haemoglobin are important for CO2 transport
- Buffering of H+ by Hb depends on level of oxygenation – Always H+ ions bound to Hb, but amount depends on the state of the Hb molecule
- If more O2 binds Hb → R-state and lessH+ ions bind – As at lungs
- If less O2 binds Hb → T-state and more H+ ions bind – As at tissues
At the tissues
- Less O2 binds to Hb → T-state and more H+ ions bind
- If Hb binds more H+ in RBCs then more HCO3- can be produced
- Therefore more CO2 is present in plasma in venous system –Both in dissolved and reacted form
- Hb has lost O2 and so binds more H+
- This allows more HCO3- to form
- HCO3- is exported to the plasma
Extra CO2 in venous blood
- [Dissolved CO2] increases a little
- Much more converted to HCO3- due to the increased capacity of Hb for H+
– ↑ [HCO3-]
- There is only a very small change in plasma pH because both [HCO3-] and pCO2 have increased
- pH = pK + Log ([HCO3-] /(pCO2 x 0.23))
What happens when venous blood arrives at the lungs
- Hb picks up O2 and goes into R-state
- This causes Hb to give up the extra H+ it took on at the tissues
- H+ reacts with HCO3- to form CO2
- CO2 is breathed out
Formation of carbamino compounds
- CO2 can bind directly to proteins
- Binds directly to amine groups on globin of Hb
- Binding of molecular CO2 onto Hb is not part of acid base balance but contributes to CO2 transport
- More carbamino compounds are formed at the tissues – because PCO2 higher – and unloading of O2 facilitates binding of CO2 to Hb
- This CO2 is given up at the lungs
CO2 transport
•So CO2 is transported in 3 forms
– Dissolved CO2
– As hydrogen carbonate
– As carbamino compounds
Amounts in arterial blood
For these calculations I have assumed plasma accounts for 55% and red blood cells for 45% of whole blood.
Values are expressed as the concentration in whole blood
• Total carbon dioxide in whole arterial blood = 21.5mmol.l-1
add slide from lec 1
Amounts in mixed venous blood
For these calculations I have assumed plasma accounts for 55% and red blood cells for 45% of whole blood. Values are expressed as the concentration in whole blood.
• Total carbon dioxide in whole venous blood = 23.3 mmol.l-1
Transported carbon dioxide
- = Total in venous blood – total in arterial blood
- = 23.3 – 21.5 mmol.l-1 • = 1.8 mmol.l-1
- Therefore only ~ 8% of the total is transported.
- The rest of the carbon dioxide is there as part of the pH buffering system
- Of the 1.8 mmol.l-1 that is transported at rest
- Approximately –
- 60% travels as hydrogen carbonate
- 30% travels as carbamino compounds
- 10% travels as dissolved CO2
Function of the respiratory system
- Maintain oxygen and carbon dioxide partial pressure gradients to optimise transfer
- Regulate pH of extracellular fluid
- Alveolar pO2 and pCO2 need to be kept constant within the normal range
Define hypercapnia, hypocapnia and hypoxia?
- Rise in pCO2 HYPERCAPNIA
- Fall in pCO2 HYPOCAPNIA
- Fall in pO2 HYPOXIA
What happens to partial pressure of oxygen and carbon dioxide during exercise?
- In exercise pO2 drops and pCO2 rises
- Breathing more will restore both
- Hyperventilation - Ventilation increase without change in metabolism
- Hypoventilation - Ventilation decrease without change in metabolism
Hyperventilation
• Hyperventilation • increase ventilation without change in metabolism • pO2 will rise • pCO2 will fall
Hypoventilation
• decrease ventilation without change in metabolism – pO2 will fall – pCO2 will rise
But…. • If pO2 changes without a change in pCO2 correction of pO2 will cause pCO2 to drop – Leading to hypocapnia
Hypoxia
- Oxygen - Haemoglobin dissociation curve
- Sigmoid curve
- Flat from approx. 8kPa
- pO2 can fall considerably before saturation is markedly affected
- Control system needs to avoid marked hypoxia
Carbonic acid-bicarbonate buffer system
- A major buffer system in blood
- Highly effective because the amount of dissolved CO2 is controlled by respiration
- In addition, [HCO3-] is regulated by the kidneys
- pH = pK + log [HCO3-] / [H2CO3-]
- Because H2CO3- is in equilibrium with CO2 so can be substituted for it
The effect of pCO2 on plasma pH
- pH = pK + log ([HCO3-]/(pCO2 x 0.23))
- If [HCO3-] remains unchanged
- If pCO2 increases then pH falls
- If pCO2 decreases then pH rises
- Small changes in pCO2 lead to large changes in pH
Effect of pH disturbances
- Plasma pH is controlled between 7.38 – 7.46
- If pH falls below 7.0 enzymes become denatured
- If pH rises above 7.6 free calcium concentration drops leading to tetany
How does ventilation influence plasma pH?
- Hypoventilation leads to an increase in pCO2
- Hypercapnia leads to a fall in plasma pH – Respiratory acidosis
- Hyperventilation leads to a decrease in pCO2
- Hypocapnia leads to a rise in plasma pH – Respiratory alkalosis
Kidney response to change in plasma pH
- plasma pH depends on the ratio of [HCO3-] to pCO2, not on their absolute values
- changes in pCO2 can be compensated by changes in [HCO3-]
- the kidney controls [HCO3-]
- respiratory acidosis is compensated by the kidneys increasing [HCO3-]
- respiratory alkalosis is compensated by the kidneys decreasing [HCO3-]
- this takes 2-3 days
Metabolic acid effect
- if the tissues produce acid, this reacts with HCO3
- the fall in [HCO3-] leads to a fall in pH
- metabolic acidosis
- this can be compensated by changing ventilation
- increased ventilation lowers pCO2
- restores pH towards normal
Metabolic alkali
- if plasma [HCO3-] rises (e.g. after vomiting)
- plasma pH rises
metabolic alkalosis
• can be compensated to a degree by decreasing ventilation
Summarise which condition is assigned to varying pH,pCO2,HCO3-
slide 21 lec 2
Control of breathing
- Control of two partial pressures
- No need for precise control of pO2 as long as it stays above 8kPa
- Control of pCO2 much more critical
- Changes in ventilation can correct metabolic disturbances of pH
Respiratory control pathways
- Sensors located in CNS and the periphery feed information back to the control centre for processing
- Ventilation is adjusted as necessary
Peripheral chemoreceptors
- Carotid and aortic bodies
- large falls in pO2 stimulate – increased breathing – changes in heart rate – Changes in blood flow distribution
- i.e. increasing flow to brain and kidneys
Central chemoreceptors
- peripheral chemoreceptors will detect changes but are relatively insensitive to pCO2
- central chemoreceptors in the medulla of the brain are much more sensitive to pCO2
- detect changes in arterial pCO2
- small rises in pCO2 increase ventilation
- small falls in pCO2 decrease ventilation
- the basis of negative feedback control of breathing
Blood brain barrier prevents H+ and HCO3- from affecting brain or CSF
Feedback control of breathing by pCO2
slide 27 lec 2
Central chemoreceptor physiology
- respond to changes in the pH of cerebro-spinal fluid (CSF)
- CSF separated from blood by the blood-brain barrier
- CSF [HCO3-] controlled by choroid plexus cells
- CSF pCO2 determined by arterial pCO2
CSF pH
- determined by ratio of [HCO3-] to pCO2
- [HCO3-] fixed in short term – BBB impermeable to HCO3
- so falls in pCO2 lead to rises in CSF pH
- rises in pCO2 lead to falls in CSF pH
- but persisting changes in pH corrected by choroid plexus cells which change [HCO3-]
- Elevated pCO2 drives CO2 into CSF across blood brain barrier
- CSF [HCO3-] initially constant
- So CSF pH falls
- Fall in CSF pH detected by central chemoreceptors
- Drives increased ventilation
- Increased ventilation
- Lowers pCO2 and restores CSF pH
Choroid plexus
- CSF [HCO3-] determines which pCO2 is associated with ‘normal’ CSF pH
- CSF [HCO3-] therefore ‘sets’ the control system to a particular pCO2
- It can be ‘reset’ by changing CSF [HCO3-]
Persisting hypoxia effect on CSF
- Example – pO2 = 8.6 kPa – pCO2 = 3.9 kPa – pH = 7.47
- Hypoxia detected by peripheral chemoreceptors – Increase ventilation
- BUT pCO2 will fall further – Decrease ventilation
- SO: CSF composition compensates for the altered pCO2
- Choroid plexus cells selectively add H+ or HCO3- into CSF
- Central chemoreceptors “accept” the pCO2 as normal
Persisting hypercapnia
- Hypoxia and hypercapnia
- Respiratory acidosis
- Decreased pH of CSF
- Peripheral and central chemoreceptors stimulates breathing
- But acidic pH undesirable for neurons
- Therefore choroid plexus needs to adjust pH of CSF
- Addition of HCO3
- Central chemoreceptors “accept” the high pCO2 as normal
