Unit I
Oxygen Delivery:
Heart, Lungs and RBCs
Michel Désilets
Objectives

Trace the oxygen delivery system from ambient air to the cellular level.

Define oxygen content, oxygen saturation and partial pressure of
oxygen.

Describe the mechanisms of hypoxemia and relate them to their
position in the alveolar O2 equation.

Compare the effects of methemoglobin and sulfhemoglobin on oxygen
delivery and content as a method to understand oxygen delivery.

Outline the methods of clinical and laboratory assessment of cyanosis,
hypoxemia and tissue hypoxia.
Oxygen delivery system
Inspired
tracheal air
(humidified)
PEO2 = 116
PECO2 = 32
PO2 = 160
PCO2 = 0.3
PIO2 = 150
PICO2 = 0.3
PAO2 = 102
PACO2 = 40
PvO2 = 40
PvCO2 = 45
PaO2 = 95
PaCO2 = 40
Rhoades & Bell. Medical Physiology. Principles for Clinical Medicine, 3rd Ed. , 2009
Symbols
P = partial pressure
(mm Hg)
I = in inspired air
(humidified)
E = in expired air
A = in alveolar air
a = in arterial blood
v = in venous blood
Oxygen delivery system
The oxygen cascade
Symbols
P = partial pressure
(mm Hg)
atm = in atmospheric air
I = in inspired air
(humidified)
E = in expired air
A = in alveolar air
c = in end pulmonary
capillary
a = in arterial blood
v = in venous blood
PatmO2
http://www.prognosis.org/physiology/index.php
(Also, for more details: http://www.altitude.org/oxygen_delivery_model.php)
Oxygen delivery system
1. Pulmonary ventilation: from atmosphere to alveoli
• Dry air in atmosphere (barometric pressure) = 760 mm Hg  PO2 + PN2
PatmO2 = FIO2 x 760 = 0.21 x 760 = 160 mm Hg
(FIO2 = Fraction of O2 in inspired dry air)
• In trachea: air saturated with water vapour: PIO2 = FIO2 x (760 – PH2O) = 0.21 x (760 – 47) = 150 mm Hg
Oxygen delivery system
1. Pulmonary ventilation: from atmosphere to alveoli
• In alveoli: O2 partly absorbed by capillary blood and replaced with CO2
Alveolar gas equation:
PAO2  PIO2 − [PACO2 / RQ]  100 mm Hg
RQ
•
•
= Respiratory quotient = rate of CO2 production (VCO2) / rate of O2 consumption (VO2)
•
•
= VCO2 / VO2  0.8
Symbols
P = partial pressure
(mm Hg)
atm = in atmospheric air
I = in inspired air
(humidified)
E = in expired air
A = in alveolar air
c = in end pulmonary
capillary
a = in arterial blood
v = in venous blood
Oxygen delivery system
2. From alveoli to blood
• In a perfect lung: PaO2 = PAO2
i. Ventilation-perfusion mismatch (50%):
•
•
 Low VA / Q ratio at the base of the lungs
ii. Anatomic shunts (50%):
 Bronchial arteries to pulmonary veins
(1% of cardiac output)
 Coronary venous blood (Thebesian
veins) to left ventricle (<1% of cardiac
output)
iii. Diffusion block (normally small):
 Incomplete equilibrium through the
respiratory membrane
Definitions:
• Physiological shunt: Ventilation-perfusion
mismatch + anatomic shunts
• Venous admixture: Mixing of oxygenated
blood with unoxygenated blood
Partial pressure (mm Hg)
• In practice: PaO2 < PAO2
3 causes:
Oxygen delivery system
2. From alveoli to blood
Alveolar-arterial oxygen gradient (AaDO2):
5% shunt  AaDO2 ≈ 10 mm Hg
AaDO2
PaO2
PatmO2
Oxygen delivery system
Alveolar-arterial oxygen gradient (AaDO2):
• Difference between alveolar (PAO2) and arterial (PaO2) partial pressures of O2
AaDO2 = PAO2 – PaO2
• Normal A-a O2 gradient: 5-15 mm Hg
• A-a O2 gradient increases with age
Quick estimate: AaDO2  (age + 10) / 4
E.g.: AaDO2  10 mm Hg at age 30
• A-a O2 gradient increases with increasing FIO2
Quick estimate: about 5 to 7 mm Hg per 10% increase ( 6 mm Hg / 10%)
Oxygen delivery system
A-a O2 gradient increases with shunt
AaDO2
Oxygen delivery system
A-a O2 gradient increases with diffusion block
90% block
Oxygen delivery system
A-a O2 gradient increases with increasing FIO2
(FIO2 = Fraction of O2 in inspired dry air)
FIO2 = 0.5
Oxygen delivery system
3. From blood to cells
PatmO2
Oxygen delivery system
CaO2
% Hb saturation (SO2)
O2 content (mL/ dL blood)
PvO2
PaO2
CvO2
Oxygen delivery system
3. From blood to cells
O2 content
(mL O2 / dL blood)
C(a-v)O2
PatmO2
CaO2
CvO2
Oxygen delivery system
3. From blood to cells: Transport of oxygen
O2 content (mL O2 /dL blood) = O2 bound to Hb + O2 dissolved
O2 bound to Hb = O2 capacity of Hb x Hb content x % Hb saturation
(mL O2 /g Hb) x (g Hb/dL blood) x %
• In arterial blood: 1.34 x 15 x 97.5% = 19.6 mL O2 /dL blood
• In mixed venous blood: 1.34 x 15 x 75% = 15.1 mL O2/dL blood
O2 dissolved = Solubility of O2 x PO2
(mL O2 / dL blood • mm Hg) x (mm Hg)
• In arterial blood: 0.003 x 100 = 0.3 mL O2 /dL blood
• In mixed venous blood: 0.003 x 40 = 0.1 mL O2 /dL blood
CaO2 = Arterial blood oxygen content = 19.6 + 0.3  20 mL O2 /dL blood
CvO2 = Venous blood oxygen content = 15.1 + 0.1  15 mL O2 /dL blood
O2 delivery (mL O2 / min): amount of oxygen delivered to the tissues per minute
•
DO2 = Cardiac Output x CaO2 = 5 L/min x 20 mL O2/dL x 10 dL/L = 1000 mL O2 / min
A decrease of O2 delivery could be caused by a decrease in:
1) cardiac output, 2) Hb content, 3) % Hb saturation
Oxygen delivery system
3. From blood to cells: Oxygen extraction
C(a-v)O2 = (CaO2 – CvO2) = (20 – 15) = 5 mL O2/dL
O2 extraction: fraction of O2 removed from the blood
O2 extraction = (CaO2 – CvO2) / CaO2 = 5 / 20 = 0.25
O2 consumption (mL O2 / min): amount of oxygen consumed by the tissues per minute
•
VO2 = Cardiac Output x (CaO2 – CvO2) = 5 L/min x (5 mL O2/dL) x 10 dL/L
= 250 mL O2 / min
An increase in O2 consumption would lead to one or more of the following :
1) A decrease in CvO2 (i.e. an increase in O2 extraction)
2) An increase in cardiac output
3) An increase in CaO2 (long term adaptation)
Oxygen delivery system
Example 1. Cardiogenic shock
A decrease in cardiac output increases C(a-v)O2 gradient,
with little effect on CaO2
Cardiac Output
O2 content (mL/dL blood)
Oxygen delivery system
Example 2. Anemia
A decrease in Hb reduces CaO2 with little effect on C(a-v)O2
gradient
O2 content (mL/dL blood)
CaO2
CvO2
Mechanisms of hypoxia and hypoxemia
• Hypoxia:
Inadequate oxygen delivery
to the tissues
• Hypoxemia:
Reduced PaO2
Mechanisms of hypoxia and hypoxemia
• Hypoxemic hypoxia
I. Oxygen deficit in inspired air
(e.g. high altitude)
II. Alveolar hypoventilation
(e.g. neuromuscular disease)
III. Ventilation/perfusion
mismatch
(e.g. severe asthma, COPD)
IV. Problems with diffusion
(e.g. interstitial lung disease)
V. Right to left shunt
(e.g. cyanotic congenital heart
defects)
Mechanisms of hypoxia and hypoxemia
• Hypoxia without hypoxemia
VI.
Hypoxia of transport (anemia)
(e.g. anemia, CO poisoning, MetHb)
VII.
Ischemic hypoxia (stagnant)
circulatory shock
(e.g. CV Collapse)
VIII. Troubles with diffusion at the
interstitial level
(e.g. interstitial oedema)
IX.
Histotoxic hypoxia
(e.g. cyanide poisoning)
X.
Cellular overuse of oxygen
(e.g. muscular rigidity, fever, chills,
intense exercise)
Mechanisms of hypoxia and hypoxemia
Hypoxia
PaO2
AaDO2
CaO2
C(a-v)O2
A
Low PIO2
(low inspired O2)
Low
N
Low
N
B
Hypoventilation
Low
N
Low
N
C
V/Q mismatch
Low
High
Low
N
D
Decreased
diffusion
Low
High
Low
N
E
Cardiovascular
(stagnant)
N
N
N
High
F
Anemia
N
N
Low
N
G
Histotoxic
N
N
N
Low
Symbols
PAO2 = partial pressure of
O2 in alveolar air
PaO2 = partial pressure of
O2 in arterial blood
AaDO2 = PAO2 – PaO2
CaO2 = total content of O2
in arterial blood
CvO2 = total content of O2
in venous blood
C(a-v)O2 = CaO2 - CvO2
Mechanisms of hypoxia and hypoxemia
Condition
PaO2
AaDO2
CaO2
C(a-v)O2
E
Cardiogenic shock
N
N
N
High
PAO2 = partial pressure of
O2 in alveolar air
C
Severe asthma
Low
High
Low
N
A
High altitude
Low
N
Low
N
PaO2 = partial pressure of
O2 in arterial blood
B
Hypoventilation
Low
N
Low
N
C
Tetralogy of Fallot
Low
High
Low
N
D
Pulmonary
fibrosis
Low
High
Low
N
G
CN- toxicity
N
N
N
Low
F
CO poisoning
N
N
Low
N
Would hypoventilation and tetralogy of Fallot respond the same to O2 therapy?
Symbols
AaDO2 = PAO2 – PaO2
CaO2 = total content of O2
in arterial blood
CvO2 = total content of O2
in venous blood
C(a-v)O2 = CaO2 - CvO2
Hypoventilation (50% VT) and O2 therapy (FIO2 = 0.9)
O2
O2 content (mL/dL blood)
Shunt (50%) and O2 therapy (FIO2 = 0.9)
O2
O2 content (mL/dL blood)
Effects of methemoglobin and sulfhemoglobin on O2 delivery and content
- Methemoglobin (metHb): Oxidation of the iron ions in hemoglobin.
Oxidant
Hb (Fe2+)  metHb (Fe3+)
metHb reductase
(Treatment: methylene blue, a “redox dye”)
- Sulfhemoglobin (sulfHb): addition of a sulfur following oxidation of the
porphyrin ring in hemoglobin
Hb + -S  sulfHb
(irreversible)
• The affinity of Hb for O2 (left and right shifts) directly affects oxygen extraction by altering CvO2
 affinity   O2 extraction
 affinity   O2 extraction
Effects of methemoglobin and sulfhemoglobin on O2 delivery and content
Properties of metHb:
• Decreased O2 binding capacity (mimics anemia)
• Increased affinity for O2 (left shift)
 May lead to severe decrease in O2 delivery and extraction
Normal
blood
60% metHb
Anemia (40% of normal)
Effects of methemoglobin and sulfhemoglobin on O2 delivery and content
Properties of sulfHb:
• Decreased O2 binding capacity (mimics anemia)
• Decreased affinity for O2 (right shift)  Effects much less severe than metHb
Normal
blood
60% metHb
Anemia (40% of normal)
60% sulfHb
Clinical and laboratory assessment of cyanosis, hypoxemia and tissue hypoxia.
Main laboratory assessments:
• Pulse oximetry
• Measures Hb saturation (not PaO2)
• Inaccurate in the presence of abnormal Hb or dyshemoglobins (carboxyHb,
metHb, sulfHb)
• Arterial blood gases:
• Measures of PaO2, PaCO2, pH
• From calculation, allow estimates of AaDO2 , CaO2 (with Hb measurement)
CBC News
08/06/2007
[SHb]: 2g/L
Drug used: Sumatriptan
(a sulfonamide)
Clinical and laboratory assessment of cyanosis, hypoxemia and tissue hypoxia.
Main clinical assessments of cyanosis:
Cyanosis: blue coloration of the skin as a result of poor saturation of hemoglobin
(detectable with deoxyhemoglobin > 40 g/L)
Assessment:
Cyanosis
Yes
• Respiratory disease
• Heart failure
Response to O2
No
Continued cyanosis
• Pulmonary shunt (ARDS)
• Cyanotic heart defect
(newborn)
Low
• Exposure to oxidants (drugs,
nitrates)
• Severe acidosis
• Hereditary defects
Yes
PaO2
High
metHb level high, response to methylene blue
No
• SulfHb
• Methylene blue overdose