Transport of respiratory gas

1. Transport of respiratory gases

2. Gas Laws
Transport of oxygen
Transport of carbon-dioxide

3. DALTON’S LAW
• “States that in a mixture of non
reacting gases the total pressure exerted
is equal to the sum of the partial
pressures of the individual gases “

4. CHARLES LAW
• “States that for an ideal gas at
constant pressure, the volume is directly
proportional to its absolute
temperature”

5. Henry’s Law
States that at a constant temperature, the amount of given gas that dissolve
in a given type and volume of liquid is directly proportional to the partial
pressure of that gas in equilibrium with that liquid

6. BOYLES LAW
• States that the absolute pressure
exerted by a given mass of an ideal gas is
inversely proportional to the volume it
occupies if the temperature and
amount of gas remain unchanged in a
closed system

7. Oxygen transport
● Oxygen is vital for life sustaining aerobic respiration
● Most commonly used drug in anesthesia and critical care
Medicine
1)Transport of o2 from
atmosphere to alveoli
2)Transport of o2 from
alveoli to tissue

8. Transport of
oxygen from
atmosphere
to alveoli
• Breath 21% O2= 760*21%=160mmhg
In
warmed and humidified air in upper
airway (760-47)*21%=150mmhg
In Alveolar gas co2 is added —> PAO2
= PIO2 – (PaCO2 ÷ Respiratory
Quotient)
• PAO2 = 150 – (40 ÷ 0.8) mm Hg
• = 150 – 50 mm Hg
• = 100 mm Hg
• PAO2=100mmhg - driving pressure for
o2 from alveoli to capillary

9. ● Occurs by diffusion and convection
● Diffusion describes passive
movement of Oxygen down a
concentration gradient
● Convection describes movement of
Oxygen within the circulation, occurring
through bulk transport
1. Diffusion of oxygen from alveoli to pulmonary
capillary blood
2. Transport of oxygen in arterial blood
3. Diffusion of oxygen from systemic capillaries
into
tissue fluid
4. Diffusion of oxygen from tissue fluid into cells
Transport of
Oxygen from
alveoli to
body tissue
Transport of
oxygen from
alveoli to cell

10. 1)Diffusion of oxygen from alveoli to
pulmonary capillary blood
• PAO2=100mmHg
pulmonary arterial blood that enter pulmonary capillary
has partial pressure 40mmHg
• Gradient 60mmhg -movement of o2 from alveoli to
arterial end of capillary

12. ● PAO – Driving Pressure for O Diffusion Into Pul Capillary Bed and
2 2
Main Determinant of PaO normally
2
● PAO -PaO reflects overall efficiency of O uptake from alveoli to
2 2 2
arterial blood
• Capillary blood fully oxygenated before traversing 1/3 distance of
alveolo-capillary interface
• 0.75 sec Pulmonary capillary transit time maximum uptake by
0.25sec
● Inadequate oxygenation due to reduced pul capillary time occurs
only with very high C.O. or severe desaturation of mixed pul
arterial blood

13. 2)Transport of oxygen in arterial
blood(Transport by convection)
• 98%-blood pass through pulmonary capillary—>paO2
100mmHg
• 2% from bronchial circulation return to Left atrium not
take part in gas exchange—shunt flow/venous
admixture
• partial pressure of O2 in left atrium 95mmhg

14. 3)Diffusion of O2 from systemic
capillaries into tissue fluid
• Arterial blood in systemic capillary pO2 = 95mmhg
• interstitial fluid surrounding tissue 40mmhg
• gradient 55mmhg
• venous blood leaving tissue equilibrium with interstitial
fluid po2 40mmhg

15. 4)Diffusion of O2 from tissue fluid
into cell
• Tissue continuously utilising o2
• intracellular po2 23mmhg(5-40mmhg)
• intracellular po2 1-3 mmhg sufficient to support
aerobic metabolic activities(pasteur point)
• Diffusion of oxygen depends upon rate of blood flow to the tissue and
metabolic activity

16. Transport by convection
❏ Physically dissolved form (2%)
❏ Combined with hemoglobin (98%)

17. Physically dissolved form
● Dissolved state in water present in rbc and plasma
● Henrys law
● Dissolved oxygen =oxygen solubility ×partial pressure of Oxygen in arterial
blood
= 0.003×95mm of Hg
= 0.29ml/dl
so in a normal healthy adult 0.29 ml of Oxygen is transported in dissolved form
in 100 ml of blood
As cardiac output is 5L/mt at rest Oxygen transport in dissolved form at rest is
around 15 ml/mt against the requirement of 250 ml/mt

18. Clinical application
Hyperbaric oxygen therapy increases the tissue oxygenation
● Only 0.3 ml oxygen is transported in dissolved form in Hyperbaric oxygen
therapy it increases to about 6 ml/ dl of blood, that accounts for 300ml/mt
of Oxygen supply which is adequate for tissue oxygenation

19. Structure of hemoglobin
● Each Hb molecule by 4 heme group+4
globin chain
● Heme is an iron containing porphyrin
● Porphyrin nucleus has 4 pyrrole
rings
bonds
● Iron
joined by non covalent
in the ferrous form is
attached to N of each pyrrole
ring and to th N of imidazole
group of globin
O2 bind with fe2+ by coordination
bond
Combination with hemoglobin
● Possible due to binding affinity of hemoglobin for oxygen

20. Formation of oxyhemoglobin
Hb molecule may be represented as Hb4 and it reacts with 4 molecules of
Oxygen to form Hb4O8
Hb4+O2
Hb4O2+O2
Hb4O4+O2
Hb4O6+O2
Hb4O2
Hb4O4
Hb4O6
Hb4O8
● 1 Red blood cell contain 280 million molecules of Hb
● 1 RBC can potentially carry 1 billion molecules of Oxygen

21. R and T forms of hemoglobin
● Quaternary structure of Hb determines it affinity for oxygen
● In deoxyhemoglobin, the globin units are tightly bound in a tense
configuration which reduces affinity for oxygen (T form)
● When first oxygen is bound ,the bonds holding globin units are released,
producing relaxed or R form

22. Relates percentage saturation of Oxygen carrying power of hemoglobin to
partial pressure of Oxygen
Oxygen dissociation curve

23. Significance of steep phase
● Oxygen saturation of Hb is very high
● Even small increase in po2 leads to greater percentage saturation
of Hb and facilitates Oxygen loading
● Even small decrease in po2 in tissues leads to unloading of Oxygen

24. Significance of plateau phase
● ODC Plateaus around 60 mm of Hg and flattens at po2 of 70 mm of
Hg
● Increase in po2 above 60mm of Hg produces only small increase in o2
binding (oxygen saturation and content remain apparently constant)

25. P50
P50 is the level of po2 at which 50%of Hb is saturated with o2
● Assess the binding affinity of Hb
● In adults at sea level P50 occurs at po2 of 27 mm of Hg
● If P50 is high it signifies decrease in affinity for o2, ODC shift to
right
● If P50 is low !ODC shift to left

26. Factors Affecting O2-hb Dissociation Curve
● PH
● PCO2
● 2,3 – Diphosphoglycerate
● Temperature
● Presence/Percentage of fetal Hb

27. Effect Of Ph
● A fall in PH shifts the curve to the right (i.e., reduced affinity
for O to Hb) & a rise shifts to the left. (i.e., increased affinity
2
for O to Hb) also known as “BOHR EFFECT”
2
● The PH changes may be due to either metabolic or
respiratory disturbances or both
● ↓
In PH from 7.4 to 7.2 causes shift of curve to right by 15%
● ↑
In PH by similar value causes shift of curve to left by similar
magnitude

29. Effect Of PCO2
● Shift of O2-Hb dissociation curve to right by ↑
PCO2 - Important to
enhance oxygenation of blood in lungs and to enhance release of O2 in
the tissues
● In the lungs, CO2 diffuses out of the blood (H+ conc also ↓
due to ↓
in
H2CO3 conc) Shift of O2-Hb curve to left & more avid binding of O2 to
Hb ↑
in quantity of O2 bound to Hb ↑
O2 transport to tissues.
● When the blood reaches the tissue capillaries, the opposite occurs (
↑CO2
and ↑
H+) and hence greater release of O2 due to less avid binding of
O2 to Hb.

30. Effect Of 2,3 - DPG
● This substance combines with globin & modifies O2
access to the haem chain, i.e., a rise in 2,3 DPG being
associated with a reduction in the affinity of Hb for O2
● Therefore high concentration of 2,3 DPG shifts the curve
to the right & a low concentration shifts it to the left

31. ● It Increases in several conditions in the presence of diminished
peripheral tissue O availability, such as hypoxaemia, chronic
2
lung disease, anaemia, and congestive heart failure.
● Decreases in septic shock and hypophosphataemia.
Effect Of 2,3 - DPG - cont’d

32. Effect Of Temperature
● ↑ Temp ↓ affinity of O2 to Hb and hence shift of curve to right
and more release of O2 at a given PO2. Opposite changes occur
with ↓ temp
● But however there is no evidence that the tissues suffer from
hypoxia because there is a coincidental fall in O2 demand

34. Factors affecting odc
Shift to left
1. Dec temperature
2. Dec Pco2
3. Dec 2,3DPG
4. Inc ph
Shift to right (decreased affinity)
1. Inc temperature
2. Inc Pco2
3. Inc 2,3DPG
4. Dec ph

35. Fetal Haemoglobin
● Fetal haemoglobin (HbF) is structurally different from normal
haemoglobin (Hb).
● The fetal dissociation curve is shifted to the left relative to the
curve for the normal adult.
● Typically, fetal arterial oxygen pressures are low, and hence the
leftward shift enhances the placental uptake of oxygen.

36. ● At the placenta there is a higher concentration of 2,3-DPG
formed. This binds more readily to adult haemoglobin but not to
fetal haemoglobin. This causes the adult Hb to release more
oxygen at the placenta to be taken up by the fetus. Fetal Hb is
made up of gamma chains not beta ones, and 2,3-DPG does not
bind readily to gamma chains, hence it does not give up its
oxygen.
Fetal Haemoglobin -cont’d

38. Double Bohr effect
● Described by Hauge, it happens in pregnancy
● The transfer of acids from the fetal blood into the maternal
intervillous spaces causes the fetal PH to rise & increases the affinity
of blood to O2. i.e., ODC shift to left
● At the same time the acids passing to maternal circulation cause the
maternal PH to fall thereby reducing the affinity of maternal blood for
O2. i.e., ODC shift to right, so further O2 is released to the fetus
● This accounts for 2-8% of transplacental transfer of O2

39. Double Haldane effect
● The materno-fetal transfer of O2 produces deoxy-Hb in the
maternal blood, that has a greater affinity for CO2
● As the fetal blood takes up O2, it enhances CO2 release, which
diffuses in to the maternal blood, thus further increasing the
CO2 content of maternal blood
● This may account for 46% of transplacental transfer of CO2

40. Effects Of Carbon Monoxide
● Haemoglobin binds with carbon monoxide 240 times more readily
than with oxygen. The presence of carbon monoxide on one of the 4
haem sites causes the oxygen on the other haem sites to bind with
greater affinity. This makes it difficult for the haemoglobin to release
oxygen to the tissues and has the effect of shifting the curve to the left
(as well as downward, due to direct competitive effects of carbon
monoxide). With an increased level of carbon monoxide, a person can
suffer from severe tissue hypoxia while maintaining a normal pO2

41. Methaemoglobinemia
● Methaemoglobinaemia is a form of abnormal haemoglobin
where ferrous (Fe2+), which is normally found in haemoglobin, is
converted to the ferric (Fe3+) state. This causes a leftward shift in
the curve as methaemoglobin does not unload O2 from Hb.
However, methaemoglobin has increased affinity for cyanide,
and is therefore useful in the treatment of cyanide poisoning.

42. O2 Delivery During Exercise
● During strenuous exercise O2 demand may ↑ to 20 times
Normal
● Blood also remains in the capillary for <1/2 Normal time due to
↑ C.O.
O2 Sat not affected
● Blood fully saturated in first 1/3 of Normal time available
to pass through pulmonary circulation

43. ● Diffusion capacity ↑ upto 3 fold since:
1.Additional capillaries open up ↑ no of capillaries participating in
diffusion process
2. Dilatation of both alveoli and capillaries
↓ alveolo-capillary distance
3.Improved V/Q ratio in upper part of lungs due to ↑ blood flow
to upper part of lungs
O2 Delivery During Exercise -cont'd.

44. Oxygen flux
• Refers to amount of o2 leaving the left
ventricle per mnt
• Also is the amount of O2 delivered to
peripheral tissue

45. Volume of oxygen carried in each 100 ml blood
Sum of O2 bound to Hb and O2 dissolved in plasma
Arterial O2 content(CaO2 )= O2 carried by Hb) + (O2 in solution)
= (k x Hb x SpO2 x 0.01) + (0.023 x PaO2)
=19.95ml/mnt
Sp02 is percentage saturation of Hb with oxygen
Hb is haemoglobin concentration in grams per 100ml of blood
PaO2 is partial pressure of oxygen
K Huffners constant-amount of o2 carried by 1 gm of Hb=
1.31ml/100 ml

46. Oxygen delivery
Oxygen delivery (Do2) = cardiac output ×arterial Oxygen content
= 5 L×19.95
= 997.5ml/mt

47. Oxygen consumption
Oxygen consumed by tissue per minute
■ Vo2=CO ×(Cao2 _CVo2)
=254.5 ml/mt

48. Factors affecting oxygen flux
Factors increasing o2 demand Factors affecting O2 carrying capacity
1. Trauma (surgery, burns)
2. Inflammation/sepsis/pyrexia/shivering
3. Pain
4. Agitation
5. Physiotherapy
6. Thyrotoxicosis
7. Halothane shake
1. Anaemia
2. CCF
3. Acidosis
4. Reduced alveolar ventilation

49. Oxygen extraction ratio
Fraction of Oxygen delivered via cardiovascular system that is actually used
by the tissues
O2ER=Vo2÷Do2
=0.26 at rest

50. Oxygen cascade
• Steps by which partial pressure of o2 decreases
from a higher level in inspired gas to lower level in
mitochondria

51. Steps
• Uptake in lung
• Transport in blood
• Global delivery to tissue
• Regional distribution of O2 delivery
• Diffusion from capillary to cell
• Cellular utilisation of O2

53. Causes of failure of cascade
• Stagnant hypoxia -low cardiac output,vascular
occlusion
• Anaemic hypoxia
• Hypoxic hypoxia-inadequate ventilation,VQ
mismatch,low fio2
• Shunt hypoxia congenital cardiac ds,AV shunt

54. 3
Carbon Dioxide Transport

55. Carbon dioxide
production
● By cell metabolism in mitochondria
● Depends on rate of metabolism and relative amounts of
carbohydrates fat and protein
● 200ml / minute when at rest on eating a mixed diet.
○ Respiratory quotient = 0.8
○ Carbohydrate diet respiratory quotient = 1.0
○ Fat diet respiratory quotient = 0.7

56. Picked up by tissue capillary
Transported in venous blood
Expelled in lung
• Tranfer
• Transport
• Expulsion

57. Carbon dioxide transfer
• By difusion through interstitial fluid
• Pco2 in cell 46mmhg
• Interstitial fluid 45mmhg
• Arterial blood 40mmhg
• Venous blood 45mmhg

58. Carbon dioxide
transport in blood
Transported in blood from tissue to lungs in three ways
● Dissolved in solution
● Buffered with water as carbonic acid(as
bicarbonate)
● Bound to protein particularly
haemoglobin(carbamino compound)

59. 1)Dissolved
carbon dioxide
● 20 times more soluble than oxygen
● Henry’s law
● Solubility coefficient is 0.0308 mmol/ltr per mm of Hg
● PC02 is 5.3 kpa in arterial blood and 6.1 kpa in mixed venous blood
● Dissolved carbon dioxide in
○ arterial blood is equal to 2.5ml/100ml &
○ venous blood is 3ml/100ml
● With cardiac output of 5 ltr/minute 150ml of carbon dioxide ( dissolved) carried
to lung of which 25ml is exhaled
● 10% of total tranport

60. 2)As bicarbonate
• 70% total transport of co2
• Tissue to plasma to rbc. By pco2 gradient
• Co2+h2o carbonic acid by CA
• H+,hco3- dissociate
• Hco3 – diffuse out due to con.gradient
• H+ partly buffered by hb patly by plasma protein
• Rbc memb impermeable to cation —>passive shift cl- to rbc
• Eflux of hco3- & influx of cl- facilitated by carrier protein

62. Chloride shift / Gibbs - donnan equilib
Hamburger effect
● Anion exchanger ( chloride bicarbonate exchanger )
● Chloride accumulated inside the red cell and buffering of H+ ions on to
reduced haemoglobin -> cellular osmolarity increases -> water enters ->cells
swell -> MCV increases -> hematocrit of venous blood increases by 3%.
● Reverse occurs in lungs

63. Bound to Hemoglobin and
other proteins
● Carbon dioxide combines rapidly with terminal uncharged amino groups (
R-NH2) to form carbamino compounds
R-NH2 + CO2 = RNH-CO2 + H+
● Reduced hemoglobin is the only effective protein buffer of hydrogen ions at
physiological pH -because of the amino acid histidine (each tetramer of
hemoglobin contains 38 histidine residues )
● Different hemoglobin vary in their affinity for C02 , CO and O2
● 20% of transport

64. Carbon dioxide
transport in tissue In the tissues, the acidic form
of the imidazole group of
histidine weakens the strength
of O2 bond and at the same
ions
more
are
basic
time hydrogen
buffered by
hemoglobin

65. Carbon dioxide
transport in lungs The
hemoglobin is facilitated
combination of O2 with
by
histidine group becoming more
basic -> increases affinity for
O2 as CO2 is lost

66. Changes in RBC during passage
through Lungs
In Pulmonary capillary blood
RBC releases CO2 -> Hemoglobin affinity for O2 increases -> Oxygenated
hemoglobin binds fewer hydrogen ions -> more acidic
But the fall in PCO2 shift in chloride and bicarbonate ions makes the RBC less
acidic
Outward shift of water -> smaller MCV -> reduced hematocrit

67. CO2 dissociation
curves
• It relates the CO2 content of blood to the PCO2
• The position of this curve depends on the degree of oxygenation of the
blood
• more deoxygenated the blood —the more CO2 it carries @ a given
PCO2. this is called “HALDANE EFFECT”
• Due to this effect, the uptake of CO2 by blood is facilitated. When this
blood reaches the lungs & becomes oxygenated, elimination of CO2 is
facilitated

68. Carbon dioxide dissociation
curve - cont’d

69. Carbon dioxide dissociation
curve - cont’d
The upper curve is the curve for fully deoxygenated blood & the lower curve
for fully oxygenated or arterial blood
The part of the curve below the arterial point approximate to a straight line, it is
for this reason that blood from zones of lung with high VA/VQ ratios can partly
compensate for blood from zones with low VA/VQ ratios

70. Distribution of CO2 in arterial
and venous blood

71. Summary

72. Oxygenation of Hb
↑ acidity of Hb
↓tendency to combine
with co2
Displacement of CO2
from Hb
↓H+ binding to Hb
↑ Release of H+ from Hb
↑ Formation of Carbonic acid
↑ Release of CO2
LUNGS

73. Reduction of Hb (↓ oxygenation of heme)
↑ basicity of Hb
↑ H+ binding to reduced Hb
↑ dissociation of
carbonic acid
↑ carriage of CO2
as HCO3
TISSUES

74. Previous questions
• Describe odc,oxygen cascade
• Bohr effect,Haldane effect and their role in co2 transp

75. Reference
• Ganongs medical physiology 26th edition
• Paul G Barash 8th edition
• Bja education 2016