Session 4 Flashcards

1
Q

Carbon dioxide in blood

A
  • 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
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2
Q

Control of blood pH (acid-base balance)

A
  • 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
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3
Q

pH of plasma

A

•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
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4
Q

Dissolved CO2

A
  • 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
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5
Q

Hydrogen carbonate in plasma

A
  • 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
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6
Q

Henderson-Hasselbalch equation

A
  • 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

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7
Q

pH of arterial blood

A
  • Ratio of [HCO3-] and pCO2 determine pH
  • pCO2 determined by alveolar pCO2 – Rate of ventilation
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8
Q

Hydrogen carbonate production in red blood cells

A
  • 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

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9
Q

Binding of H+ to haemoglobin

A
  • 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
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10
Q

Plasma hydrogen carbonate

A
  • [HCO3-] doesn’t change much with pCO2
  • HCO3- comes from the RBCs – The reaction is mostly determined by H+ binding to Hb
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11
Q

Role of kidney in controlling [HCO3-]

A
  • 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))
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12
Q

Hydrogen carbonate buffers extra acid

A
  • 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)
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13
Q

Arterial and venous pCO2

A
  • 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
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14
Q

Properties of haemoglobin are important for CO2 transport

A
  • 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
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15
Q

Extra CO2 in venous blood

A
  • [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))
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16
Q

What happens when venous blood arrives at the lungs

A
  • 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
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17
Q

Formation of carbamino compounds

A
  • 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
18
Q

CO2 transport

A

•So CO2 is transported in 3 forms

– Dissolved CO2

– As hydrogen carbonate

– As carbamino compounds

19
Q

Amounts in arterial blood

A

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

20
Q

Amounts in mixed venous blood

A

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

21
Q

Transported carbon dioxide

A
  • = 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
22
Q

Function of the respiratory system

A
  • 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
23
Q

Define hypercapnia, hypocapnia and hypoxia?

A
  • Rise in pCO2 HYPERCAPNIA
  • Fall in pCO2 HYPOCAPNIA
  • Fall in pO2 HYPOXIA
24
Q

What happens to partial pressure of oxygen and carbon dioxide during exercise?

A
  • 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
25
Q

Hyperventilation

A

• Hyperventilation • increase ventilation without change in metabolism • pO2 will rise • pCO2 will fall

26
Q

Hypoventilation

A

• 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

27
Q

Hypoxia

A
  • 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
28
Q

Carbonic acid-bicarbonate buffer system

A
  • 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
29
Q

The effect of pCO2 on plasma pH

A
  • 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
30
Q

How does ventilation influence plasma pH?

A
  • 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
31
Q

Kidney response to change in plasma pH

A
  • 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
32
Q

Metabolic acid effect

A
  • 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
33
Q

Metabolic alkali

A
  • if plasma [HCO3-] rises (e.g. after vomiting)
  • plasma pH rises

metabolic alkalosis

• can be compensated to a degree by decreasing ventilation

34
Q

Summarise which condition is assigned to varying pH,pCO2,HCO3-

A

slide 21 lec 2

35
Q

Control of breathing

A
  • 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
36
Q

Respiratory control pathways

A
  • 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

37
Q

Feedback control of breathing by pCO2

A

slide 27 lec 2

38
Q

Central chemoreceptor physiology

A
  • 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
39
Q

CSF pH

A
  • 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
40
Q

Choroid plexus

A
  • 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-]
41
Q

Persisting hypoxia effect on CSF

A
  • 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
42
Q

Persisting hypercapnia

A
  • 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