oxygen transport, oxy-hbdissociation curve,carbon di oxide, hypoxia

1. Transport of gases
DR KIRAN KUMAR C
MBBS.,MD.,FAGE.,C DIAB
ASSISTANT PROFESSOR

5. Boyle's law
• Boyle's law shows that, at constant temperature,
the product of an ideal gas's pressure and volume is
always constant
• This is known as Boyle's law which states: the
volume of a given mass of gas is inversely
proportional to its pressure, if the temperature
remains constant
• P=T/V

6. Charles's law
• It says that, for an ideal gas at constant pressure, the volume is
directly proportional to its absolute temperature
V α T

7. DALTON’S LAW
• Total barometric pressure (Pb) is equal to the sum of the partial
pressures of the individual gases.
• Each gas has a partial pressure, which is the pressure the gas
would exert if each gas were present alone in the volume occupied
by the whole mixture at the same temperature.
• Dalton law can be written as follows:
• PB = PN2 + PO2 + PH2O + PCO2
7

9. • The Henry law states that at equilibrium, the
amount of gas dissolved in a liquid at a given
temperature is directly proportional to the
partial pressure and the solubility of the gas.
• The Henry law accounts only for the gas that
is physically dissolved and not for chemically
combined gases

10. Gases move down partial pressure gradients.
• Gas exchange at both the pulmonary capillary and the tissue capillary
levels involves simple passive diffusion of O2 and CO2 down partial
pressure gradients.
• No active transport mechanisms exist for these gases.
• The individual pressure exerted independently by a particular gas
within a mixture of gases is known as its partial pressure, designated
by Pgas
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11. 11

12. PARTIAL PRESSURE GRADIENTS
• A difference in partial pressure between capillary blood
and surrounding structures is known as a partial pressure
gradient.
• Partial pressure gradients exist between the alveolar air
and pulmonary capillary blood. Similarly, partial pressure
gradients exist between systemic capillary blood and
surrounding tissues.
12

13. • A gas always diffuses down its partial pressure gradient from
the area of higher partial pressure to the area of lower partial
pressure, similar to diffusion down a concentration gradient
13

14. Fick’s Law of Diffusion
• Fick's law states that the diffusion of a gas (Vgas) across a sheet
of tissue is directly related to the surface area (A) of the
tissue, the diffusion constant (D) of the specific gas, and the
partial pressure difference (P1 - P2) of the gas on each side of
the tissue and is inversely related to tissue thickness (T)

16. pO2(mmHg) pCO2(mmHg)
Atmospheric air 160 0.23
Alveoli 104 40
Arterial blood 98 35-45
Tissue <40 >46
Venous blood 40 46
16

17. OXYGEN TRANSPORT
• O2 is transported by the blood
either,
• Dissolved in the blood
plasma (<2%). 0.3 ml/100
ml
• Combined with
haemoglobin (Hb) in the
red blood cells (>98%) or,
17

18. • The dissolved oxygen obeys the Henry’s law,
• Amount dissolved is proportional to the pO2.
• There is no limit to the amount of O2 that can be carried in dissolved
form, provided the pO2 is sufficiently high.
• This is a distinct advantage over O2 transport as oxyhaemoglobin
which cannot exceed a certain limit.
18

19. Applied
• Therefore, dissolved O2 at high pO2 (hyperbaric oxygen) is utilized in
clinical practice for the oxygenation of tissues when the haemoglobin
gets denatured in certain types of poisoning, e.g. carbon monoxide
poisoning.

20. • Is such an O2-carrying capacity adequate to supply O2 to
the systemic tissues?
• If these tissues could extract all the O2 dissolved in arterial
blood so that no O2 remained in venous blood, and if
cardiac output were 5000 mL/min,
• According to the Fick principle the delivery of dissolved O2
to the tissues would be
20

21. 21

22. Hemoglobin

23. In combination with Hb
• Most of the O2 that diffuses into the pulmonary capillary blood rapidly
moves into the RBC’s and chemically attaches to the hemoglobin.
• Each RBC contains about 280 million Hb molecules, which are highly
specialized to transport O2 and CO2.
• The normal hemoglobin value for the adult male is 14 to 16 g% and
female is 12 to 15 g%.
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24. 24

25. • Normal adult hemoglobin consists of four haem groups which are the
pigmented, iron-containing non-protein portions
• Four amino chains that collectively constitute globin (a protein)
• At the center of each heme group, the iron molecule can combine
with one O2 molecule for form oxyhemoglobin:
25

26. • The most important factor determining the % Hb saturation is the PO2 of
the blood, which in turn is related to the concentration of O2 physically
dissolved in the blood
• According to the law of mass action, if the concentration of one
substance involved in a reversible reaction is increased, the reaction is
driven toward the opposite side. Conversely, if the concentration of one
substance is decreased, the reaction is driven toward that side.
26

27. • Applying this law to the reversible reaction involving Hb and O2 (Hb +
O2 = HbO2), when blood PO2 increases, as in the pulmonary
capillaries, the reaction is driven toward the right side of the equation,
increasing formation of HbO2 (increased % Hb saturation).
• When blood PO2 decreases, as in the systemic capillaries, the reaction
is driven toward the left side of the equation and oxygen is released
from Hb as HbO2 dissociates (decreased % Hb saturation)
27

28. O2 carrying capacity of hemoglobin
• Each g% of Hb is capable of carrying approximately 1.34 ml of O2
thus:-
• O2 bound to Hb = 1.34 ml O2 x g% Hb
• 1.34 x15 =20.1 ml
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29. Oxygen Hb dissociation curve
• Its a curve obtained when the
relation between PO2 and Hb
saturation is plotted.
• It is a sigmoid/ S shaped curve.
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30. Zones of O2-Hb dissociation
curve:
• Loading Zone (association) –
upper flat part, related to O2
uptake in lungs, shows
“margin of safety” for Hb
saturation even when
external O2 is decreased.
• Unloading Zone
(dissociation) – steep portion
of curve seen below PO2
below 60 mm/hg, concerned
with O2 delivery to tissue
30

32. The Oxygen Disassociation Curve
Haemoglobin saturation is
determined by the partial pressure of
oxygen. When these values are
graphed they produce the Oxygen
Disassociation Curve
In the lungs the partial
pressure is
approximately 100mm
Hg at this Partial
Pressure haemoglobin
has a high affinity to 02
and is 98% saturated.
In the tissues of other
organs a typical PO2 is
40 mmHg here
haemoglobin has a
lower affinity for O2
and releases some but
not all of its O2 to the
tissues. When
haemoglobin leaves the
tissues it is still 75%
saturated.

33. Haemoglobin Saturation at High Values
Lungs at sea level:
PO2 of 100mmHg
haemoglobin is
98% SATURATED
Lungs at high
elevations: PO2
of 80mmHg,
haemoglobin 95
% saturated
Even though PO2
differs by 20
mmHg there is
almost no
difference in
haemoglobin
saturation.
When the PO2 in the
lungs declines below
typical sea level
values, haemoglobin
still has a high
affinity for O2 and
remains almost fully
saturated.

34. Haemoglobin Saturation at Low Values

35. Factors Altering Haemoglobin Saturation

37. Factors Altering Haemoglobin Saturation (Exercise)

38. Factors Affecting Haemoglobin Saturation
• Blood acidity…
• Blood temperature…
• Carbon Dioxide concentration

39. Factors affecting Disassociation – Right Shift
BLOOD TEMPERATURE
• increased blood temperature
• reduces haemoglobin affinity
for O2
• hence more O2 is delivered to
warmed-up tissue

42. 2, 3 Di-phosphoglycerate.
• Produced during Embden Meyerhof pathway
• It is highly charged anion, binds to B-chain of deoxygenated blood.
• Increase in 2,3 DPG decreases the affinity for O2 shifting the curve to
right.
• Causes: chronic hypoxia (high altitude) and anaemia
Advantages/ disadvantage:
• Advantageous to tissue as greater O2 is released.
• Disadvantageous for lungs as at same PO2, blood takes up less O2.

44. Left Shift
BLOOD TEMPERATURE
• Decreased blood temperature
• increases haemoglobin affinity for O2
• hence less O2 is delivered to cooled-up tissue
BLOOD Ph
• increase of blood pH (making blood
more basic)
• caused by decrease in H+ ions
• increases affinity of Hb for O2
• and less O2 is delivered to tissue
CARBON DIOXIDE CONCENTRATION
• the lower CO2 concentration in tissue
• the higher the affinity of Hb for O2

45. 2, 3 Di-phosphoglycerate.
• Decrease in 2,3 DPG increases the affinity for O2 shifting the curve to left.
• Causes: chronic hypoxia (high altitude) and anaemia
Fetal Hb:
• Its affinity to 2,3 DPG is less than HbA
• Can take higher volume of O2 when compared to HbA
Advantages/ disadvantage:
• Disadvantageous to tissue due to lesser O2 release.
• Limited Advantage for lungs as greater uptake of O2 takes place.

46. P50 and its significance
• A common point of reference on the oxygen
dissociation curve is the P50.
• The P50 represents the partial pressure at
which the hemoglobin is 50% saturated with
oxygen, typically 26.6 mm Hg in adults.
• The P50 is a conventional measure of
hemoglobin affinity for oxygen.
• Hb affinity for O2 is inversely related to P50
value.

47. • In the presence of disease or other conditions that change the
hemoglobin’s oxygen affinity and, consequently, shift the curve to the
right or left, the P50 changes accordingly.
• An increased P50 indicates a rightward shift of the standard curve,
which means that a larger partial pressure is necessary to maintain a
50% oxygen saturation, indicating a decreased affinity.
• Conversely, a lower P50 indicates a leftward shift and a higher
affinity.
47

48. O2 dissociation curve for Myoglobin
• Specialized muscle protein which is required for
sustained contraction (heart and muscles of leg)
• Curve is rectangular hyperbola, as myoglobin’s
association with O2 even at low concentration is very
fast.
• Does not show Bohr’s effect.
• At PO2 40 mm/hg, myoglobin is 95% saturated, even at
PO2 5 mm/hg, myoglobin is around 60% saturated.
• Hence act as temporary store house for O2

49. Effect of CO on O2 transport
• CO has 200 times the affinity for Hb.
• Forms carboxyhaemoglobin.
• Binds to same site where O2 binds.
• P50 for CO is only 0.5 mm/hg.
• CO lowers the tissue O2 tension.
• Therefore, a PCO only a little greater than
0.4 mmHg can be lethal.

50. O2 Release in Tissues
O2 release at Rest:
• O2 delivery: amount of O2 presented to body cells per minute =
arterial O2 content X by cardiac output
20 ml X 5 L/min = 1 L/min
• O2 consumption: about 5 ml O2 diffuses from blood to tissue due to pressure
gradient every minute, thus O2 consumption at rest is:
5 X 5000/ 100 or 250 ml of O2 per minute.

51. • Utilization coefficient: % of O2 consumed out of delivered
O2 to the tissue
= O2 consumed/min X 100
O2 delivered/min
=250 ml/min x 100
1000 ml/ min
= 25%
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52. TRANSPORT OF CO2

53. Carbon Dioxide Transport
• Carbon dioxide also relies on the blood for transportation.
Once carbon dioxide is released from the cells, it is carried in
the blood primarily in three ways…
• Dissolved in plasma, (7%)
• As bicarbonate ions resulting from the dissociation of
carbonic acid, (70%)
• Bound to haemoglobin. (23%)

54. pO2(mmHg) pCO2(mmHg)
Atmospheric air 160 0.23
Alveoli 104 40
Arterial blood 98 35-45
Tissue Less than 40 More than 46
Venous blood 40 46
54

55. Dissolved Carbon Dioxide
• Part of the carbon dioxide released from the tissues is dissolved in plasma.
But only a small amount, typically just 7 – 10%, is transported this way.
(venous blood has 2.7 ml/100 ml)
• This dissolved carbon dioxide comes out of solution where the PCO2 is low,
such as in the lungs.
• There it diffuses out of the capillaries into the alveoli to be exhaled.
• The arterial blood has 2.4 ml/100 ml of CO2 in dissolved state.

56. CO2 transport in bicarbonate form
At tissue level – Cl- shift of Hamburger effect

57. CO2 transport in bicarbonate form cont..
In lungs

58. CO2 transport in Carbamino Form
• Approximately 30% of RBC contents is Hb
• CO2 forms carbamino hemoglobin
• Released H+ is buffered by histidine residues (imidazole group)
• CO2 formation in plasma:
CO2 binds the amine groups of plasma proteins to form carbamino
compounds.
•
Percent of the total PaCO2: 23 %

 HCOONHRCONHR 22

59. CO2 transport in Carbamino Form cont..
Carbino-Hb formation at tissue

60. CO2 transport in Carbamino Form cont..
Release of CO2 from carbimino-Hb at lungs

61. The CO2 Dissociation Curve
• Its obtained by plotting relationship
between PCO2 and total CO2
content in blood.
• Shows relationship between two
nearly linear over wider range of
PCO2

62. Factors affecting CO2 Dissociation Curve
1. Oxygen: Deoxygenation of the blood increases
its ability to carry carbon dioxide.
• Haldane Effect: Increasing O2-saturation
reduces CO2 content and shifts the CO2
dissociation curve to right.

63. Factors affecting CO2 Dissociation Curve cont..
2. 2,3 – DPG – It decreases the formation of carbamino-Hb, as it
competes with CO2 for the same sites on Hb especially in case
of reduced blood. Thus causing right shift of the CO2
dissociation curve (decrease in CO2 carrying capacity).
3. Increase in Body temperature: release of O2 from blood,
causes left shift of CO2 dissociation curve (larger amount of
CO2 can be taken of a given PCO2)

64. Rate of Total CO2 transport
• In resting condition: 100 ml of blood transports about 4 ml of CO2 from tissue
to lungs. Hence with average cardiac output of 5L/min, a total of
(4 X 5000)/ 100
= 200 ml of CO2 is transported.
• During exercise: depends on the severity of the exercise. In severe exercise as
much as 4 L of CO2 may be transported/ min. Because of
• Greater solubility and transport in different forms
• Conversion of CO2 into bi-carbonate ions prevents any significant changes
in pH of blood

65. Respiratory Quotient (RQ)
Def: The ratio of the rate of CO2 excretion and rate of O2 consumption per
minute.
Also called as respiratory exchange ratio.
Normal value –
• Rate of CO2 excretion is 4 ml/100 ml/min
• Rate of O2 excretion is 5 ml/100 ml/min
• RQ = 4/5 = 0.8.
• Factors effecting:
• Person utilizing carbohydrate as entire source RQ = 1
• RQ is < 1.0 for proteins and fats.
• RQ < 0.7 for only fats.
Inference: lower RQ suggests catabolic activity, which can be estimated by
amount of O2 removed from air and CO2 released in air.

66. Tissue Hypoxia
• Tissue hypoxia means that the amount of oxygen available
for cellular metabolism is inadequate.
• There are four main types of hypoxia:
• hypoxic hypoxia - circulatory hypoxia
• anemic hypoxia - histotoxic hypoxia
• Hypoxia leads to anaerobic mechanisms that eventually
produces lactic acid and cause the blood pH to decrease.
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67. Hypoxic Hypoxia
• Hypoxic hypoxia or hypoxemic hypoxia refers to the
condition in which the PaO2 and CaO2 are abnormally low.
• This form of hypoxia is better known as hypoxemia (low
oxygen concentration in the blood).
• This form of hypoxia can develop from:
• pulmonary shunting - low alveolar PO2
• diffusion impairment - V/Q mismatch
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68. Anemic Hypoxia
• Anemic hypoxia is when the oxygen tension in the arterial
blood is normal, but the oxygen-carrying capacity of the
blood is inadequate.
• This form of hypoxia can develop from:
• a low amount of Hb in the blood
• a deficiency in the ability of Hb to carry O2
• Increased cardiac output is the main compensatory
mechanism for anemic hypoxia.
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69. Circulatory Hypoxia
• In circulatory hypoxia, the arterial blood that reaches the
tissue cells may have a normal O2 tension and content, but
the amount of of blood--and therefore the amount of O2--
is not adequate to meet tissue needs.
• The two main causes of circulating hypoxia are:
• stagnant hypoxia
• arterial-venous shunting
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70. Histotoxic Hypoxia
• Histotoxic hypoxia develops in any condition that impairs
the ability of tissue cells to utilize oxygen.
• Clinically, the PaO2 and CaO2 in the blood are normal, but
the tissue cells are extremely hypoxic.
• The PvO2, CvO2 and SvO2 are elevated because oxygen is
not utilized.
• One cause of this type of hypoxia is cyanide poisoning.
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71. Cyanosis
• When hypoxemia is severe, signs of cyanosis may develop.
• Cyanosis is the term used to describe the blue-gray or
purplish discoloration seen on the mucous membranes,
fingertips, and toes whenever the blood in these areas is
hypoxemic.
• The recognition of cyanosis depends on the acuity of the
observer, on the lighting conditions, and skin pigmentation.
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72. Polycythemia
• When pulmonary disorders produce chronic hypoxemia,
the hormone erythropoietin responds by stimulating the
bone marrow to increase RBC production.
• An increased level of RBC’s is called polycythemia.
• The polycythemia that results from hypoxemia is an
adaptive mechanism designed to increase the oxygen-
carrying capacity of the blood.
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