Presented by: DR Rony Mathew Department Of Anaesthesiology

1. Presented By:Dr. Rony Mathew
Moderators:Dr. Basheer, Dr. Krishnadas

2.  Pressure = nRT
V
 Diffusion of gases
 Gases in contact with a liquid
 Partial pressure

3.  Total pressure exerted by a gaseous mixture
is equal to the sum of the partial pressures of
individual component in a gas mixture
 Individual partial pressure exerted by a
component gas in a mixture α volume
fraction of that gas component in that gas
mixture

4. Composition of Dry Air
20.98% O2
78.06% N2
0.04% CO2
0.92% Other inert gases
Barometric Pressure at sea level = 1Atm = 760 mmHg
P O2 = 0.21X760 = 160 mmHg
P CO2 = 0.004X760 = 0.3mmHg

5. Atmospheric air
↓
Alveoli
↓
Arterial blood
↓
Tissue capillaries
↓
Mitochondria
OXYGEN CASCADE
It describes the process of decreasing oxygen
tension from atmosphere to mitochondria.

6.  Water vapour pressure at body temp =
47mmHg
 Thus, Pressure exerted by gas in saturated
moist air = 760-47 = 713mmHg
 => Partial pressure of O2 in saturated moist
air = 713 x 0.21 = 149 mmHg
 This is the starting point of O2 cascade.

7.  Down the respiratory tree, O2 tension is
further diluted by the alveolar CO2.
 The partial pressure of alveolar oxygen(PAO2 )
is calculated by alveolar gas equation
PAO2= PiO2-PACO2/R
PaCO₂ = PACO₂ ( 40mmHg ) as CO₂ is
freely diffusible.

8.  R is RESPIRATORY QUOTIENT(RQ) , the ratio
of rate of CO₂ produced to the rate of
oxygen uptake.
 RQ=VCO₂/VO₂
 200/250=0.8
 RQ depends on the metabolic substrate
ie,carbohydrate only diet =1. Protein
&fat=0.8
 So PAO2 =149-(40/0.8)~100mmHg.

9.  Alveolar PAO2 is 100mmHg. Blood returning
from tissues to heart has low PO2 (40mmHg).
 So oxygen diffuses from alveoli to
pulmonary capillaries.
 After oxygenation,blood moves to pulm.
veins→left side of heart→ arterial system →
systemic tissues.
 In a perfect lung pO₂ of pulm. Venous blood
would be equal to pO₂ in the alveolus.

10. = [(1.34 x HbxSaO2)+(0.003xPaO2)] x Q
 O2 delivery to tissues depends on
Hb concentration
O2 binding capacity of Hb
saturation of Hb
amount of dissolved O2
cardiac output (Q)

11.  Initially the dissolved O2 is consumed.
 Then the sequential unloading of Hb bound O2
occurs.
 Transport of O2 from the capillaries to tissues is
by simple diffusion.
 Pasteur point is the critical PO2 at which
delivered O2 is utilised by the tissue & below
which the O2 delivery is unable to meet the
tissue demands.

15. FACTORS AFFECTING O2 CASCADE AT EACH
LEVEL

16. Atmosphere to alveolus
High altitude.
 At high altitude, the barometric pressure is
less than that at sea level, and thus, even
though the FiO2 is 21%,the piO2 is
decreased.
Water vapour
 Higher the water vapour lesser will be the
PiO2 . Upper resp. tract, humidifies inspired
air , depends upon temp.

17. In the alveolus
 Amount of CO2 in the alveolus depends on
the metabolism & degree of hypoventilation.
 Fever,sepsis,malignant hyperthermia
increases CO2 production.

18. Alveous to capillaries
• Ventilation/perfusion mismatch
• Shunt
• Slow diffusion.

19. VENTILATION /PERFUSION MISMATCH
• in normal lung itself upper zones are over
ventilated while lower zones are relatively
overperfused and under ventilated.
• pulmonary venous blood is a mixture of
pulmonary capillary blood from all the
alveoli,hence a lower PO2 than PAO2

20. SHUNTS
 Occur when deoxygenated blood passes
unventilated alveoli , without getting oxygenated ,
to enter the systemic arterial system .
examples of shunts :
atelectasis
consolidation of lung
small airway closure.
 These effects are overcome by a
compensatory mechanism termed HYPOXIC
PULMONARY VASOCONSTRICTION ( HPV ).

21. SLOW DIFFUSION
 Normally diffusion is very rapid and is
completed by the time the blood has passed
about 1/3 of the way along the pulm.
capillary.
 Diffusion is affected in pulmonary diseases.

23. ALVEOLAR ARTERIOLAR GRADIENT :
P( A – a )O2
 Partial pr of Oxygen in Arterial blood is
given by
PaO2=102-age/3
 Normal Aa gradient is 5-15mmHg.
 AA gradient ↑ due to:
slow diffusion.
atelectasis
pulm. Edema
congenital heart disease(right to left
shunt)

24.  Aa gradient depends upon:
shunt
ventilation/perfusion mismatch
mixed venous O2 tension
 Aa gradient directly proportional to shunt
and inversely proportional to mixed venous
O2 tension.

25. Arterial blood to tissue
 Serum Hb level.
 Percentage of Hb saturated with O2.
 Cardiac output.
 Amount of dissolved oxygen.

26.  In two ways
 Dissolved in serum.(5%)
 Combination with Hb(95%)

27. OXYHEMOGLOBIN
 One Hb molecule with its 4 heme group is
capable of binding 4 molecules of O2.
 1gm of fully oxygenated Hb contains 1.34ml
of O2 (vary depending on Fe content)
 At an arterial PO2 of 100mmHg,Hb is 98%
saturated,thus 15gm of Hb in 100ml blood
will carry about 20ml of O2
 =1.34ml x 15gm x 98/100=20

28. • Henry’s law :states that the concentration
of any gas in a solution is proportional to its
partial pressure
• Gas concentration= x partial pressure
 is the gas solubility coefficient
=0.003ml/dl(100ml of blood)/mmHg
for O2
• Dissolved O2 in arterial blood is thus
0.3ml/dl (0.003ml/dl x100mmHg).

29.  Venous blood have an O2 partial pressure of
40mmHg and Hb is 75% saturated.thus it
contains about 15ml of O2/100ml
 1.34x15x75/100=15
 Thus every 100ml of blood passing through
the lungs will take up 5ml of O2

30.  Total O2 content of blood is the sum of O2
in the solution & that carried by Hb.
O2 content
=0.003ml O2/dl x PaO2 + 1.34 x Hb x %
saturation of Hb

31.  Amount of O2 leaving the left ventricle per
minute in the arterial blood .
 O2 content of arterial blood X cardiac output
 O2 content of arterial blood = (O2 bound to
Hb + dissolved O2)
 i.e 20ml+0.3ml=20.3ml/dl(20.3ml/100ml)
 So O2 flux=20.3ml/100ml X
5000ml=1000ml

32.  Hb : Anaemic Hypoxia
 O2 saturation : Hypoxic Hypoxia
 Cardiac output : Stagnant Hypoxia

33.  Relates saturation of Hemoglobin (Y axis) to
partial pressure of O2 (X axis)
 It’s a sigmoid shaped curve with a steep
lower portion and flat upper portion
 Describes the nonlinear tendency for O2 to
bind to Hb.

35.  Ferrous iron in each heme binds with one O2
 One Hb molecule can bind 4 molecules of O2
 Deoxy Hb : globin units are tightly bound in a
tense configuration (T state)
 As first molecule of O2 binds, it goes into a
relaxed configuration (R state) thus exposing
more O2 binding sites  500 times increase in
02 affinity  characteristic sigmoid shape of
ODC

36. CHARACTERISTICS OF THE CURVE

37.  Characteristic sigmoid shape which offers
many physiological advantages
 It reflects the physiological adaptation of Hb
to take up O2 at higher partial pressures
(alveoli) and release oxygen at lower partial
pressures (tissues )

38.  The flat upper portion means that even if PO2
falls somewhat, loading of O2 wont be
affected much.
 Even when red cells take up most of the O2
from alveoli , PO2 drop is less compared to
gain in saturation  a large PO2 difference
still exists for diffusion of O2 to continue

39.  The steep lower part of the curve means
peripheral tissues can withdraw large
amounts of 02 for only a small drop in
capillary PO2.
 This maintenance of blood PO2 assists
diffusion of 02 into tissue cells

40. The characteristic points on the curve are:
 1) The arterial point
PO2=100mmHg and SO2=97.5%
 2) The mixed venous point
PO2=40mmHg and SO2=75%
 3) The P50
PO2=27mmHg and SO2=50%

42.  It is the partial pressure at which 50% of Hb is
saturated.
 At a pH of 7.4 , temp 37C , the PO2 at which
the Hb is 50% saturated (P50) is 27mmHg
 When affinity of Hb for 02 is increased , P50
decreases : shift to left in ODC
 When affinity is reduced , P50 increases : shift
to right in ODC

44. SHIFT OF ODC

45. Right shift - High P50 (>27mmHg)
 Hb has decreased affinity for O2
 O2 delivery facilitated at tissue level
Causes:
 Increase in H+
 Increase in temperature
 Increase in 2,3 DPG
 Increase in PCO2
 Exercise
 Anaemia
 Drugs : propranalol , digoxin etc

46. Left shift - Low P50 (<27mmHg)
 Hb has ↑ed affinity for O2
 O2 delivery at tissues is decreased
Causes:
 Low H+
 Low temperature
 Low 2,3 DPG
 Low PCO2
 Variants of normal Hb (fetal Hb, carboxy Hb,
met Hb)

47. Temperature
 Increase in temperature decreases Hb-O2
affinity and curve is shifted to right
 Decrease in temperature increases affinity
and curve shifted to left  decreased release
of O2
 But this wont cause hypoxia because in
hypothermia body O2 demand is also less

48. Hydrogen ions
 Acidosis decreases Hb-O2 affinity and curve
is shifted to right
 Deoxy Hb binds with H+ more actively than
does oxy Hb
 H
+
+ HbO2  H.Hb +O2
 Advantageous at tissue level

49.  Acute conditions : 0.1 unit Ph change causes
3mm Hg change in P50
 Chronic (>2-3 hrs) : depends on
compensatory changes in organic phosphate
synthesis (2,3 DPG, ATP)

50. Carbon dioxide
 Effects attributed to changes in pH
 CO2 + H2O  H2CO3 H + HCO3
 Increase in CO2 shifts curve to right causing
more release of O2
 BOHR EFFECT

52. 2,3 DPG
 Produced in red cells by Embden meyerhof shunt
pathway of glycolysis
 Normal concentration : 4mmol/l
 Binds to deoxyHb and reduces its affinity for O2
 ODC is shifted to right
 Fetal erythrocytes have lower concn of 2,3 DPG
and hence HbF has a higher affinity for O2

54. FACTORS INCREASING 2,3 DPG
 Anaemia
 Hypoxemia
 Cardiac failure
 Chronic acidosis
 Hyperthyroidism
 Uremia
 Cirrhosis liver

55. FACTORS DECREASING 2,3 DPG
 Polycythemia
 Hyperoxia
 Chronic alkalosis
 Hypothyroidism
 Blood storage
NB: blood stored with ACD anticoagulant loses
2,3 DPG faster (6-7 days) than CPD blood.
Effect starts immediately after transfusion
and may last for 2-3 days

56. Physiological situations
(1) Exercise
 ODC for skeletal muscles shifted to right
 This ensures max O2 delivery for exercising
muscles
 Factors : Increased CO2 production
Increased Temperature
Presence of myoglobin
(higher O2 affnity)

57. (2) High Altitude
 A s distance from sea level increases , partial
pressure of gases in atmosphere decreases
 But, volume remains constant eg: 21% for O2
 Leads to a progressive reduction in ambient
O2  Hypoxia
 Compensatory mechanisms  net effect is
right shift of ODC

58.  Increased alveolar ventilation
 Increased Hb production
 Increase in 2,3 DPG
 Increase in diffusing capacity of lungs
 Increase in vascularity of tissues
 Increase cellullar use of 02

59. Congenital Abnormalities
 Hemoglobinopathies: ODC shifted to right or left
depending on affinity of abnormal Hb to O2
 Deficiency of red cell metabolism
Pyruvate kinase deficiency : shift to right
d/t elevated 2,3 DPG levels

60. Carbon Monoxide Poisoning
 Hb has 200 times higher affinity for CO than
O2  50% saturated at 0.4mmhg
 Displaces O2 from Hb
 Increases O2 affinity of those hemoglobin
unbound to CO
 Together it produces a shift to left in ODC
and over all decrease in 02 delivery

61. Chronic disease states
 Cardiopulmonary disease : decreased cardiac
output  O2 extraction more  increased
deoxyHb  stimultes 2, 3 DPG production 
shift to right
 Anaemia : 2 important compensatory
mechanisms
1)increase in CO and oxygen delivery
2)right shift of ODC – increase in 2,3DPG

62. Acute disease states
 Shock: Net effect on ODC involves interaction
of pH , PCO2, temperature and many other
factors.
 2,3DPG & P50 were lower in patients with
septic shock.
 Shift to left  massive transfusions , a/c
alkalosis (hyperventilation , bicarbonate
administration) , hypothermia ,
hypophosphatemia etc

63.  A/c MI: right shift with an elevated P50
 Hypophosphataemia as occurs in starvation,
vomiting, malabsorption etc causes increased
Hb-O2 affinity and shift ODC to left

64.  Occurs at feto-maternal interface.
 CO2 & other metabolic products from the
fetal blood diffuses into maternal blood
making maternal blood more acidic & fetal
blood more alkaline.

65.  In maternal side ODC is shifted to right with
↓ed O2 affinity, causing ↑ed O2 release to
fetus
 In fetal side , there is left shift of ODC, ↑ing
O2 affinity
 Thus Bohr effect acting in two different
directions having a beneficial effect

68. ODC AND THE ANAESTHESIOLOGIST

69.  ODC helps us to relate PO2 and Hb saturation
 A left shift gives a warning that tissue oxygen
delivery may be compromised even when
there is not much drop in PO2
 All inhalational agents including N2O causes
shift to right
 Intravenous agents have no demonstrable
effect on ODC

70.  Among other drugs : propranalol , steroids
have been found to be associated with shift
to right and improved tissue oxygenation
 Blood transfusion : whenever possible, ACD
anticoagulated fresh blood (<5-7 days old)
should be used and avoid massive
transfusions.

71. Thank you
Thank you