8. Use of Oxygen
Oxygen acts as the electron
acceptor
Oxidative phosphorylation results
in the synthesis of adenosine
triphosphate (ATP).
The coenzyme ATP supplies
energy to all active metabolic
processes.
9. Hypoxic Cell Injury
Depletion of ATP
Development of intracellular acidosis
Increased concentrations of metabolic by-products
Generation of oxygen free radicals
Destruction of membrane phospholipids.
14. Oxygenation
Oxygenation is the process of
oxygen diffusing passively from
the alveolus to the pulmonary
capillary, where it dissolves
into the plasma and binds to
hemoglobin in red blood cells
Insufficient oxygenation is
termed Hypoxemia.
20. Partial pressure
In a mixture of gases, each gas has a partial
pressure which is the Hypothetical Pressure of that gas
if it alone occupied the entire volume of the original
mixture at the same temperature
21. The total pressure of a mixture of gases
The total pressure of a mixture of gases is equal to the sum of the partial
pressures of the individual gases in the mixture
22. Fraction of inspired oxygen (FiO2)
The Fraction or Percentage of oxygen in the space being
measured.
Natural air includes 20.9% oxygen = FiO2 of 0.21.
Oxygen-enriched air has a higher FiO2than 0.21, up to
1.00 =100% oxygen.
23. The oxygen content
The oxygen content of blood is the volume of oxygen
carried in each 100ml blood.
(O2 carried by Hb) + (O2 in solution)
=
(1.34 x Hb x SpO2 x 0.01) + (0.023 x PaO2)
24. Oxygen saturation
The fraction of
Oxygen-saturated hemoglobin
------------------------------------
-----------
Total hemoglobin (unsaturated
+ saturated)
25. Barometric pressure (PB)
Barometric pressure (also known as
atmospheric pressure) is the force
exerted by the atmosphere at a
given point.
The height of the column of mercury
that is supported by air pressure.
Decrease in density
27. Barometric pressure (PB) changes with altitude)
Increasing altitude result
of a fall in barometric
pressure (PB).
The decrease in Po2 with
altitude is caused ENTIRELY
BY A DECREASE IN PB.
Decrease in density
28. FIO2 does not change with altitude
FIO2 does not change with altitude, which means that the
percentage of O2 in the atmosphere is essentially the
same at 30,000 feet (about 9,000 m) as it is as sea level.
Therefore, the decreased PO2 at an altitude that makes it
difficult to breathe is due to a decrease in the PB, not to a
decrease in FIO2
30. PARTIAL PRESSURE OF INSPIRED AIR
0.21 X 760 = 160
PIO2
The fractional concentration of
oxygen in DRY AMBIENT AIR
(FAmbO2) is 0.21
At sea level with a barometric
pressure (Pb) of 760 mm (PAmbO2)
FIO2 X BAROMETRIC PRESSURE
=
PARTIAL PRESSURE [ PO2 ]
31. PARTIAL PRESSURE OF INSPIRED HUMIDIFIED OXYGEN
PIO2
The addition of saturate
(Psvp) by the upper airway
mucosa reduces the tension of
inspired gas (PiO2).
[101.3 - 6.3 ] = 20kPa
[760-47 =713] x 0.21 =149 mm
FIO2 X BAROMETRIC PRESSURE
=
PARTIAL PRESSURE [ PO2 ]
33. The PAO2 is determined
FIO2 =21
PO2 = 150
Some oxygen is absorbed
Alveolar carbon
dioxide tension
34. Alveolar carbon dioxide tension
(PACO2) Alveolar CO2 tension (PACO2) is determined by the
balance between:
1. Rate of delivery of CO2
(V˙Co2) into the alveoli by pulmonary capillary blood.
2. Rate of removal of CO2 by alveolar ventilation
PACO2 can be varied by controlling alveolar
ventilation.
35. The PAO2 is determined :
The rate of delivery of CO2
(V˙Co2) by pulmonary capillary
blood
200 ml
The rate of removal of
oxygen by absorption into
pulmonary capillary blood
250 ML
36. RQ is the respiratory quotient
The ratio
V . CO2 / V . O2
is the respiratory exchange ratio (R)
0.8.
37. The alveolar gas equation PAO2
PiO2 = 20 kPa [150 mm]
PACO2 = 5 kPa [38 mm ]
RQ = 0.8
PAO2 = 150 − (38 ÷ 0.8) = 102 mm
38. Alveolar ventilation VA
A normal tidal volume of 600 ml
results
1. 150 ml to overcome the
dead space of the
tracheobronchial tree.
2. Alveolar ventilation of
450 ml.
39. Alveolar ventilation affects PAO2.
At very low tidal volumes
the dead space
alone may be
ventilated even
though the minute volume
(rate x tidal volume) is
normal due to a high
respiratory rate.
40. Alveolar ventilation affects PAO2.
PAO2 will fall rapidly if alveolar
ventilation levels falls assuming
normal oxygen consumption
(about 250 ml min−1).
41. The importance of PAO2
102 mm
Determines the partial Pressure Gradient
driving oxygen across the alveolar–
capillary membrane.
42. To summarise:
PAO2 is intermediate between
the inspired oxygen tension (PiO2)
the arterial oxygen tension (PaO2), due to oxygen being absorbed
and CO2 exhaled.
43. The movement of respiratory gases across
The Alveolar-capillary Membrane
Pao2 is dependent on this movement
44. Oxygen uptake is determined by .
1. The diffusion properties of
the alveolar-capillary
membrane.
2. Pulmonary capillary blood
flow.
45. Fick’s law
DIRECTLY PROPORTIONAL to
1. The membrane surface area (As).
2. The diffusion coefficient of the gas (D).
3. The partial pressure difference( P) of the gas.
INVERSELY PROPORTIONAL to
4. Membrane thickness (T)
The diffusion
46. Pulmonary capillary blood flow.
The transit time at rest = 0.75 sec
The transit time : during which capillary oxygen tension
equilibrates with alveolar oxygen tension.
Ordinarily this process takes only about one third of the
available time,[0.25 sec ] leaving A WIDE SAFETY
MARGIN to ensure that
“The End-capillary PO2 Is Equilibrated With Alveolar
PO2”.
47. PAo2- Pao2 (Aa) gradient
102-95 =7.5mm
The PAo2- Pao2 (Aa) gradient
describes the overall efficiency of
oxygen uptake from alveolar gas
to arterial blood in the lungs.
It is normally less than 1 kPa
[7.5mm] but may exceed 60 kPa
[40mm] in severe respiratory
failure.
50. Normal Venous admixture
Venous admixture is normally
less than 5% of the cardiac
output and is reflected by a low
Aa gradient.
51. Pathological shunts
“True” Shunt (mixed venous blood that completely
bypasses the pulmonary capillary bed)
and
“Effective” shunt due to ventilation perfusion
mismatch.
52. “True” Shunt
Hypoxia is therefore not corrected by
increasing oxygen .
A shunt represents blood that does
not come into contact with ventilated
alveoli therefore remaining
deoxygenated.
53. “Effective” shunt
“Effective” shunt due to ventilation -
perfusion mismatch.
Consolidation
pulmonary contusion
Atelectasis
pulmonary oedema
extra pulmonary shunts such as
congenital heart disease.
54. Dead space ventilation
Dead space refers to the
proportion of the tidal volume
that does not take part in gas
exchange.
55. Anatomical dead space
the volume of the
conducting air passages
that does not reach alveoli.
It is increased by
bronchodilator use.
56. Increased Apparatus Dead Space
“Dead space is increased
when ventilation is
performed through a
mouthpiece and a valve or
through a facemask.
This “apparatus dead
space” is something
between 25 and a few
hundred mL.
57. Alveolar dead space –
The gas that reaches alveoli but does not take part in gas exchange.
58. PAo2- Pao2 (Aa) gradient
102-95 =7.5mm
The PAo2- Pao2 (Aa) gradient
describes the overall efficiency of
oxygen uptake from alveolar gas
to arterial blood in the lungs.
It is normally less than 1 kPa
[7.5mm] but may exceed 60 kPa
[40mm] in severe respiratory
failure.
59. Rule of thumb
A-a gradient
A-a gradient = (Age/4) + 4
Increased age affects A-a gradient (at sea level on room
air)
1. Age 20 years: 4 to 17 mmHg
2. Age 40 years: 10 to 24 mmHg
3. Age 60 years: 17 to 31 mmHg
4. Age 80 years: 25 to 38 mmHg
62. Oxygen Is Transported in Two Forms
Physically dissolved in the blood.
2% is carried in the physically dissolved form.
Combined with hemoglobin (Hb) in
the red cell .
98% of the oxygen is carried by haemoglobin.
63. Physically dissolved oxygen
Henry’s law states that at
equilibrium, the amount of gas
dissolved in a liquid at a given
temperature is
Directly proportional to
The partial pressure of the gas.
The solubility of the gas.
64. The arterial Partial Pressure of oxygen
PaO2
Only gases that are free in
solution will contribute to the
partial pressure of that gas
65. The arterial Partial Pressure of oxygen
PaO2
O2 bound to Hemoglobin will
not increase the partial
pressure of that gas
66. The amount of physically dissolved oxygen
If PaO2 equals 100 mm Hg, then dissolved O2 = 0.3 mL/dL.
67. Rule of thumb for PaO2
Normal Pao2 at sea level (in mm hg).
Breathing room air at 21% oxygen
should have a pao2 of about 100
100 minus the number of years over age 40.
68. Rule of thumb : FIO2 vs PaO2
Multiply FIO2 by 5
Breathing 50%, we know that
his pao2 should be about
250.
69. Binding Affinity of Hemoglobin for Oxygen
Oxygen binds rapidly and reversibly to hemoglobin:
70. Hemoglobin (Hb)
1. The O2-carrying
protein of red blood
cells (RBCs)
2. Hb is also involved in
CO2 transport.
3. Hb is an important
blood pH buffer
71. The Haemoglobin molecule
Has four polypeptide chains
(two α and two β chains)
Each has a covalently
bound to haem group
consisting of a porphyrin
ring with a central iron atom
.
Iron is in the FERROUS
(Fe2+) state.
72. Haem
A single oxygen molecule
can bind to the central
iron atom of each haem
group.
73. Hb & oxygen
One Hb can bind to Four O2
molecules.
Hemoglobin tends to combine
with either four oxygen
molecules or none
Less than 0.01 sec required for
oxygenation
74. Binding Affinity of Hemoglobin for
Oxygen
Hemoglobin bound with oxygen, it is
called oxyhemoglobin (HbO2).
The hemoglobin not bound with O2 is
called deoxyhemoglobin (Hb).
75. Oxygen saturation
The fraction of
Oxygen-saturated hemoglobin
----------------------------------
-------------
Total hemoglobin (unsaturated
+ saturated)
76. Oxygen Saturation
SpO2 = oxygen saturation as measured
by pulse oximeter
SaO2 = oxygen saturation as measured
by arterial blood analysis (e.g. a blood
gas)
ScvO2 = oxygen saturation as measured
by CVP Cath.
SvO2 = oxygen saturation as measured
by swan ganz cath
77. Each gram of hemoglobin
can bind with 1.34 mL of
oxygen.
79. P 50
Binding of one molecule facilitate the
second molecule binding
P 50 (partial pressure of O2 at which Hb
is half saturated with O2) 26.6mmHg
81. An S-shaped curve
The shape of the curve results
because the hemoglobin affinity for
oxygen INCREASES progressively as
blood PO2 increases.
82. Physiological advantages due to the “S”shape
The plateau region of the curve :
The loading phase :
Oxygen is loaded onto hemoglobin to form
oxyhemoglobin in the pulmonary capillaries.
83. The plateau region illustrates how oxygen
saturation remain fairly constant despite wide
fluctuations in alveolar PO2.
For example, if PAO2 were to rise from 100 to
120 mm Hg, hemoglobin would become only
slightly more saturated (97 to 98%).
84. Oxyhemoglobin dissociation Curve.
The steep unloading phase:
large quantities of oxygen released or unloaded
from hemoglobin in to the tissue capillaries where a
lower capillary PO2 prevails.
85. P50 :
Assess The Binding Affinity of hemoglobin for oxygen.
The P50—the PO2 at which 50% of
the hemoglobin is saturated
The normal P50 for arterial blood
is 26 to 28 mm Hg.
86. Factors that affect the binding affinity of hemoglobin for O2:
1. Temperature
2. Arterial carbon dioxide tension
3. Arterial pH.
87. Shift to the right [A high P50 ].
A rise in PCO2.
A rise in H+ IONS,
Acidosis
A rise in temperature.
Increase in 2,3-DPG
A high P50 signifies a
decrease in hemoglobin’s
affinity for oxygen
89. 2,3-diphosphoglycerate {2,3-DPG}
An increase in 2,3-DPG facilitates
unloading of oxygen from the red cell
at the tissue level
(shifts the curve to the right).
An increase in red cell 2,3- DPG occurs with
exercise and with hypoxia (e.g., high altitude,
chronic lung disease).
90. Shift to the LEFT [A LOW P50 ].
A fall in PCO2.
A fall in H+ ions alkalosis.
A fall in temperature.
A low P50 signifies an increase in
hemoglobin’s affinity for oxygen
91. Bohr effect
The effect of carbon dioxide and
hydrogen ions on the affinity of
hemoglobin for oxygen .
92. Stored blood
Part of the ‘storage lesion’ of blood for transfusion is a
fall in 2,3-DPG levels to about 30% of normal after
3 weeks storage in whole blood in CPD-A medium
(citrate phosphate- dextrose-adenine).
This is improved with storage in plasma-reduced blood
in SAGM (saline-adenine glucose- mannitol).
94. The oxygen content of blood
Is the volume of oxygen carried in each 100 ml blood.
(O2 carried by Hb)
= (SaO2 × 1.34 × Hb × 0.01)
+
(O2 in solution)
= ( 0.003 × PO2)
95. Oxygen content of arterial blood (CaO2)
oxygen content of arterial blood can be calculated.
(SaO2) = 100%, Hb = 15 g dl−1, (PaO2) = 100 mm of Hg
O2 carried by Hb =
( 100 x 1.34 mL O2 /g Hb X 15 g Hb/dL blood = 20.1 mL
O2/dL blood)
Dissolved oxygen (0.003 × PO2). = 0.3
then oxygen content of arterial blood
CaO2 = 20.1 + 0.3 = 20.4
ml per 100 ml
96. Oxygen content of mixed venous blood (CvO2 )
oxygen content of arterial blood can be calculated.
(SvO2) = 75%, Hb = 15 g dl−1, (PaO2) = 45 mm of Hg]
O2 carried by Hb =
( 75 x 1.34 mL O2 /g Hb X 15 g Hb/dL blood = 15.0 mL
O2/dL blood)
Dissolved oxygen (0.003 × PO2). = 0.3
then oxygen content of mixed venous blood
CvO2 = 15.0 + 0.3 = 15.3
ml per 100 ml
97. The oxygen content of blood
(CaO2)
(100 x 1.34 mL O2 /g Hb X 15 g
Hb/dL blood
= 20.1 mL O2/dL blood
Dissolved oxygen
(0.023 × PO2)= 0.3
20.1 + 0.3= 20.4 ml
(CvO2 )
(75 x 1.34 mL O2 /g Hb X 15 g
Hb/dL blood
= 15 mL O2/dL blood
Dissolved oxygen
(0.023 × PO2) = 0.3
15 + 0.3= 15.3 ml
99. Oxygen delivery (DO2) or flux
Amount of oxygen delivered to the
peripheral tissues per minute.
Cardiac Output X Arterial Oxygen Content
DO2 is approximately 1000 mL/min
100. DO2 during exercise
O2 requirement may be increased by 20 times.
Blood remains in capillary blood < ½ N time , but saturation
not affected
101. During exercise
FULL SATURATION IN FIRST ⅓ OF N TIME
INCREASED DIFFUSION CAPACITY
Additional capillaries open up
V/Q ratio improves
Dilatation of both alveoli and capillaries
102. Oxygen Return
The oxygen return is the product of mixed
venous oxygen content (C¯vO2) and cardiac
output.
C¯vO2 = 15.2 ml per 100 ml and ˙Q = 5 litres
per minute
oxygen return = 760 ml min−1
103. Oxygen consumption
Oxygen consumption
(VO2) is the amount of
oxygen consumed by the
tissues per minute and can
be using Fick’s principle, by
measuring the oxygen
content of mixed venous
blood.
The oxygen content of the pulmonary arterial
circulation .
Mixed Venous Oxygen Content =
Arterial Oxygen content - Oxygen consumption
------------------------------
Cardiac output.
104. Oxygen consumption
DIFFERENCE BETWEEN OXYGEN DELIVERY AND THE OXYGEN
RETURNED to the lungs in the mixed venous blood.
(oxygen delivery) −(oxygen return)
=
1000 − 760 = 240 ml min−1
106. OXYGEN EXTRACTION RATIO
Normally the extraction ratio is about 25%
This is the fraction of
oxygen delivered via the
cardiovascular system that
is actually utilized by the
tissues.
108. OXYGEN EXTRACTION RATIO
in a normal 75 kg adult undertaking routine activities:
VO2 is approximately 250 ml/min
DO2 is approx 1000 ml /min
O2ER is 25%
(Increases to ~70% during maximal exercise in an athlete)
110. RELATIONSHIP BETWEEN VO2 and DO2
At rest, VO2 remains constant over
a wide range of oxygen delivery
(DO2) because changes in DO2 are
balanced by reciprocal changes in
oxygen extraction
111. changes in DO2 are
balanced by reciprocal
changes in oxygen
extraction
extraction
112. When cardiac output is acutely
reduced by acute blood withdrawal,
tamponade, anemia, or hypoxemia,
O2ER increases (SvO2
decreases) and VO2 remains quite
quite stable, until DO2 falls below a
critically low threshold (DO2crit), when
VO2 starts to fall.
An abrupt increase in blood lactate
concentrations then occurs, indicating
the development of anaerobic
metabolism.