Oxygen transfer and content

1. HEMOGLOBIN (Hb)
 It is the main carrier of oxygen.
 It is a protein made of 4 subunits,each of
which carries a heme moeity attached to a
polypeptide chain.
 Hb contains 2 alpha and 2 beta chains.
 Heme is a complex made up of porphyrin and
one atom of ferrous ion.
 The iron stays in ferrous state,so that the
reaction is OXYGENATION.

2.  In deoxy hbelectrostatic bonds within and
between protein chains are strongHb will be
in tense configurationaffinity of Hb for O2 is
low.
 In oxyHbelectrostatic bonds are
weakerhb adopts its relaxed stateaffinity
of Hb for O2 is high
 Each gram of Hb can carry 1.34 ml of O2.
 So, with a Hb conc of 15g/dl,O2 content is
approximately 20ml/100ml.

3. OXYGEN
 It was first prepared by Joseph Priestly
 Called it as a DEPHLOGISTICATEDAIR.
 It is a tasteless,odourless gas.
 It supports combustion.
 Its critical temp is -118.6degrees cent.
 It is stored in cylinders or bulk supply
systems.

4.  98% of O2 is transported attached to Hb as
Oxyhemoglobin.
 A small amount is carried dissolved in plasma
(nearly 2%).

5. OXYGEN TRANSPORT
 This is discussed under following headings
1. Partial pressures of O2
2. Diffusion from alveoli to blood
3. Transport of O2 in blood

6. Oxygen Mixed venous Arterial
1. Amount of solution in
plasma
0.13 ml% 0.3 ml%
2.Tension 40 mm Hg (5.3k Pa) 100mmHg (13.3 k.pa)
3. Amount combined
with Hb (OxyHb)
14 ml % 19 ml %
4. Saturation 75 % 98 %

8. OXYGEN CASCADE
 It is the process of declining O2 tension from
atmosphere to mitochondria.
 At sea level atm pressure of O2 is 760 mm of
hg.O2 makes 21% of inspired air,so it exerts a
partial pressure of 760 x 0.21=159 mm of hg.
 This is starting point of cascade, and O2 is
diluted down through the body to the cell so
that at cellular level PO2 may be only 3 or 4
mm of hg.

9. KEY STEPS IN OXYGEN CASCADE
Uptake in lungs
Carrying capacity of blood
Delivery to capillaries
Delivery to interstitium
Delivery to individual cells
Cellular use of oxygen

10. Uptake in the lungs from
atmosphere
 The alveolar partial pressure of O2 PAO2 can
be calculated from:
 PAO2=PIO2-PaCO2/R.R is the respiratory
quotient(0.8).
 This is the O2 partial pressure with which
blood in pulmonary capillaries equilibrates
during its rapid transit through the capillary.
 Approx normal value is 104 mm hg.

11. VENTILATION
 It refers to the movement of inspired gas into
and expired gas out of the lungs.
- Alveolar ventilation
- Dead space ventilation

12. Alveolar Ventilation
 The portion of minute ventilation that
reaches the alveoli and respiratory
bronchioles each minute and participates in
gas exchange is called the Alveolar
ventilation.
 It is Approx 5 L/min.
 As blood flow through the lungs is also 5
L/min (CO) the overall alveolar ventilation
perfusion ratio is Approx 1.

13. Dead space ventilation
 It is the portion of tidal volume that remains
in airways and cannot participate in gas
exchange.
 Anatomic dead space
 Physiologic dead space

14. Uptake of O2 by pulmonary
capillary blood
 Alveolar pO2=104 mm hg
 Pulmonary arterial pO2=40 mm hg
 Difference-64 mm hg
 Therefore, along the pressure gradient,O2
diffuses through the alveolar capillary
membrane causing a rapid rise in Po2 as
blood passes through the capillaries and
becomes equal to alveolar PO2.
 Thus pulmonary venous PO2=104 mm hg

15. Transport of oxygen in arterial
blood
 98% of blood enters the left atrium
oxygenated upto a PO2 of about 104 mm hg.
 Another 2 % of blood has passed from aorta
through the bronchial circulation which
supplies mainly the deep tisssues of the lungs
and is not exposed to lung air.
 This blood flow is called “shunt flow”

16. Pulmonary shunting
 Shunting-perfusion without ventilation
 Pulmonary shunt is that portion of cardiac
output that enters left side of heart without
coming in contact with an alveolus
 True shunt-no contact
 Anatomic shunts
 ‘Shunt like’ (relative)shunt

17. Venous admixture
 It is the mixing of shunted,non reoxygenated
blood with reoxygenated blood distal to the
alveoli resulting in a reduction in
Pao2
Sao2
 Normal shunt is 3 to 5 %
 Shunts above 15% are associated with
significant hypoxemia

18. Diffusion of O2 from peripheral
capillaries to cells
 O2 is constantly used by the cells, and
thereby Po2 in peripheral tissue cells remains
lower in peripheral capillaries at venous end.
 The arterial Po2 of 95mm hg is thus reduced
to Po2 of around 40 mmhg at venous end of
capillaries.
 Cellular Po2 ranges between 5-40 mm
hg(average 23mmhg)

19. Pasteur point
 Critical mitochondrial Po2 below which
aerobic metabolism cannot occur.
 Normally it ranges from 1.4 to 2.3 mm hg.

20. Oxygen utilization
 Arterial blood
 100 ml of blood combines with 19.4 ml of o2
 PO2 95 mm hg
 Hb saturation 97%
 Venous blood
 100 ml of blood combines with 14.4 ml of o2
 Po2 40 mm hg
 Hb saturation 75%
 Thus 5 ml of o2 is transported by each 100 ml of
blood through tissues per cycle(250ml/5ml/min)

21. STRENUOUS EXERCISE
 The muscle cells use O2 at a rapid rate,can
cause muscle interstitial fluid PO2 to fall from
40 to 15 mm hg.
 At this low pressure,only 4.4 ml of O2 remain
bound to Hb in each 100 ml of blood.
 So O2 delivery rate is increased by 3 times.
 Cardiac output increases by 6 to 7
fold.Therefore upto 20 fold increase in O2
transport is present.
 Utilization coeffiecient is increased 75-80%.

22. ODC CURVE
 It is a sigmoid shaped curve
 The amount of oxygen that is saturated on
the hb(So2) is dependent on the amount
dissolved(Po2).
 Amount of O2 carried by hb raises rapidly up
to Po2 of 60 mm hg(steep slope)but above
that curve becomes flatter(flat slope).
 Combination of 1st heme with O2 increases
affinity of 2nd heme for 2nd O2 and so on.it is
known as positive cooperativity.

23. Significance of shifts in ODC
curve
 Shifts in ODC curve are usually presented as
changes in P50 value.
 P50 is defined as Po2 at which Hb is 50% saturated.
 Normal P50 value is 27 mmHg(3.6kPa).
 Shift to Left Lowers and shift to Right Raises P50
value.
 Changes in P50 have only modest effect on O2
uptake in lungs but have significant effect on release
of O2 to the tissues.
 A low P50 decreases O2 availability to tissues and
lead to cellular hypoxia.

24.  Characteristic points on the curve:
1. The arterial point
Po2=100mm hg % So2=97.5%
2. The mixed venous point
Po2=40 mmhg % So2=75%
3. The P50
Po2=27 mm hg % So2=50%

25.  The steep lower part of the curve means
peripheral tissues can withdraw large
amounts of O2 for only a small drop in
capillary PO2.
 This maintenance of blood PO2 assists
diffusion of O2 into tissue cells.

26. Po2 mmHg Hb
saturation
%
O2 content
of blood
100  80
(20)
97.5  96
(1.5)
19.2  18.9
(0.3)
60  40 (20) 91  74 (17) 17.9  14.5
(3.4)
 Similar reduction (20
mmHg) in different
positions of curve have
different effects.
 Po2 from 60 – 40 mmHg
causes 10 times greater fall
in blood O2 content.

27. Fetal haemoglobin
 It has no beta chain
 It has more affinity to oxygen than the adult
haemoglobin.
 This helps the fetus to extract oxygen from
maternal blood

28. 2,3-DPG
 It is an organic phosphate normally found in
RBC.
 It is produced during anaerobic glycolysis.
 It has a tendency to bind to beta chains of Hb
and thereby decrease the affinity of Hb for o2.
 Hbo2 + 2,3-DPG=Hb-2,3 DPG+O2.
 It promotes a rightward shift and enhances
oxygen unloading at tissues.
 This shift is longer in duration than that due to
[h+] or PCO2 or temperature.

29. Role of 2,3-DPG
 The levels increase with
 cellular hypoxia
 anaemia
 hypoxemia secondary to copd
 congenital heart disease
 ascent to high altitudes

30.  The levels decrease with
 Septic shock
 Acidemia
 Stored blood has no DPG after 2 weeks of
storage

31. CO POISONING
 CO binds to Hb with far greater avidity than
molecular O2(over 200 fold),resulting in two
main effects.
 Formation of CO-Hb results in fewer sites
available for O2 binding,reducing the blood
O2 content.
 Causes conformational changes in
Hb,reducing the tendency to release bound
O2.

32. Methemoglobinemia
 The binding of O2 to Hb is a complex,allosteric
mechanism.
 In conditions like Methemoglobinemia, MetHb is
formed by oxidation of ferric ion instead of
ferrous,which is less able to bind O2,resulting in
diminished O2 content and less O2 delivery.
 In severe cases,lactic acidosis develops because
of impaired O2 delivery.
 It occurs due to
- Hereditary metemoglobinemia
- Excessive production like NO poisoning.

33. Cont..
 Because MetHb has a blue brown colour,the
patient will appear blue.
 The apparent cyanosis is not responsive to
supplemental O2,and therapy involves
converting MetHb to Hb like by using
methylene blue.
 Important medical causes include
benzocaine,dapsone,inhaled NO,etc.,

34. During exercise
 Factors shifting curve to right
 decreased pH
 increased temp
 increased pco2
 increased 2,3-DPG

35. ODC AND ANAESTHESIA
 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.

36. BOHR EFFECT
 A shift of ODC curve to the right in response
to increases in blood CO2 and hydrogen ion,
thus enhancing release of O2 from blood in
tissues and enhancing oxygenation of blood
in lungs- BOHR EFFECT.
 It is the effect by which presence of CO2
decreases the affinity of Hb for O2.

37. DOUBLE BOHR EFFECT
 Occurs at feto maternal interface
 CO2 & other metabolic products from the
fetal blood diffuses into maternal blood
making blood more acidic and fetal blood
more alkaline.
 In maternal side ODC is shifted to right with
decreased O2 affinity,causing increased O2
release to fetus.

38.  In fetal side,there is left shift of
ODC,increasing O2 affinity.
 Thus BOHR effect in two different directions
having a beneficial effect.

39. HALDANE EFFECT
 It occurs in Lungs.
 The amount of CO2 transported is markedly
affected by Po2.
 Increasing O2 saturation reduces CO2
content as it leads to
- Decrease in the formation of Carbamino
compound.
- Release of H+ ions from Hb, leads to H2O
and CO2 formation.

40. CHLORIDE SHIFT
 Also called a HAMBURGER EFFECT.
 In tissues Chloride ions move into RBCs in
exchange for bicarbonate ions to maintain
electrical neutrality.
 The excess H+ ions bind to deoxyHb.

41. REVERSE CHLORIDE SHIFT
 In lung, binding of O2 to Hb decreases its
affinity for H+.
 Then H+ combines with HCO3- forming H2O
and CO2.
 The CO2 thus formed is breathed out from
lungs.
 Chloride diffuses down the conc and charge
gradient out of RBC.

42. OXYGEN SATURATION AND CAPACITY
 Ratio of oxygen bound to Hb compared to
total amount that can be bound is oxygen
saturation.
 Maximal amount of O2 bound to Hb is defined
as oxygen capacity.

43. ARTERIAL O2 CONTENT (CaO2)
 O2 CONTENT-
The sum of O2 carried on Hb and dissolved
in plasma.
 CaO2 (ml/dl)=(SaO2 x Hb x 1.34 mL/dL
blood)+(PO2 x0.003 mL O2/dL blood per mm
Hg).
 O2 content in 100ml blood(in normal adult
with Hb 15gm/dl) is approx 20.3 ml/dl.

44. VENOUS O2 CONTENT (CVO2)
 CvO2 =(SvO2 xHbx1.34)+(PvO2 x0.003)
 Normally-15ml/dl.
 Mixed venous saturation(svO2) measured in
pulmonary artery represents the pooled
venous saturation from all organs.

45. TOTAL O2 DELIVERY (DO2)
 D02(ml/min)=CO X Cao2 x 10
 Normally-900-1100ml/min.
 Decreased O2 delivery occurs when there is
decreased Cardiac Output
decreased Hb conc
decreased blood oxygenation

46. O2 CONSUMPTION(VO2)
 The amount of O2 extracted by the peripheral
tissues during the period of one minute is
called O2 consumption orVO2.
 N-200-300ml/min
 VO2=CO x (Cao2-Cvo2)x 10.
 When DO2 is even moderately reduced,VO2
usually remains normal because of increased
O2 extraction, upto a critical point below
which cellular hypoxia starts.

47. Oxygen Flux
 Amount of oxygen leaving the left ventricle
per minute in the arterial blood.
 = Cardiac output x Arterial O2 saturation x Hb
conc x 1.31
 = 5000ml/min x 98/100 x 15.6/100 g/ml = 1000
ml/min.
 1.31 is the volume of O2 which combines with
1g Hb.
 25 % of this O2 is used up in cellular
metabolism.

48. OXYGEN EXTRACTION RATIO
 The O2 extraction ratio is the amount of O2
extracted by the peripheral tissues ( 5 ml
O2/dl blood)divided by the amount of O2
delivered to the peripheral cells(20 ml O2 /dl
blood).
 Also known as O2 coefficient ratio & O2
utilization ratio.
 Normally-25% but increases to 70-80% during
maximal exercise in well trained athletes. And
decreases when O2 supply exceeds demand.

49. Factors that affect O2ER
Increased with
 DecreasedCO
 IncreasedVO2
 Exercise
 Seizures
 Hyperthermia
 Anaemia
 low pao2
Decreased with
 Increased CO
 Skeletal muscle
relaxation
 Peripheral shunting
 Certain poisons
 Hypothermia
 Increased Pao2.

50. THANK YOU