Hypoxia vs Hypoxaemia

• Hypoxaemia: Abnormally low level of oxygen

in the blood, usually defined as PaO2
<60mmHg
• Dysoxia: Nutrient metabolism is limited by
supply/utilization of oxygen
– Tissue hypoxia: insufficient supply
– Cytopathic hypoxia: defective oxygen utilization in
mitochondria
 Dysoxia

• DO2 rate of O2 delivery to metabolizing tissue

– DO2 = cardiac output x (1.34 x [Hb] x SaO2)

• VO2 defined as the rate of O2 uptake into

metabolizing tissue
– VO2 = cardiac output x 1.34 x [Hb] x (SaO2 – SvO2)
• Fick Method
– VO2 = minute ventilation x (FiO2 – FeO2)
 Abnormal Low VO2
• 2 conditions result in Low VO2 - <200ml/min
– Hypometabolic state >unlikely in ICU patients
– Inadequate tissue oxygenation resulting in
anaerobic respiration

• Low VO2 more sensitive than clinical markers

like lactate
• Oxygen debt correlates with risk of multiorgan
dysfunction
 Oxygen extraction
• O2ER = VO2/DO2 which is (SaO2 – SvO2)/(SaO2)

• If we assume that SaO2 >0.9 to 1…

• O2ER = 1-SvO2
– O2ER is inversely proportional to SvO2

• VO2 is normally 0.25 of DO2 , therefore O2ER is

normally 25%
– Ie. 25% of O2 delivered is used for metabolism
 Homeostasis of oxygenation
• Body attempts to maintain VO2 constant
– VO2 = DO2 x O2ER
• Therefore a decrease in DO2 will result in
increase is O2ER to maintain constant VO2

• Normal O2ER (SaO2 – SvO2) = 20-30%

– If >30%: anemia/low cardiac output state
– IF <20%: defective O2 utilization
 Chemical Markers
• Lactate
– By-product of anaerobic respiration
– However negative charge hinders diffusion across cell
membrane and delayed detection in blood
– Survival is related to initial lactate and rate of lactate
clearance
– Lactate in sepsis not a result of inadequate O2 supply
• Endotoxins etc. inhibit pyruvate dehydrogenase and result in
accumulation of pyruvate (defect in O2 utilization)
 Chemical Markers
• Base Excess
– More specific marker of metabolic acidosis than
serum bicarbonate
• Amount of base that must be added to revert to neutral
pH
– Not specific to lactic acidosis
• Ketosis, DKA, ureamia
 Mechanism of Hypoxaemia
Normal A-a gradient
1. Hypoventilation
2. Reduced inspired oxygen tension

Increased A-a gradient

1. Ventilation-Perfusion Mismatch
2. Right-to-left shunting
3. Diffusion Impairment
 Hypoventilation
• Mechanism
– Alveoli space is made up of ratio of various gases
– PaCO2 and PACO2 increases in hypoventilation
– Results in reduction in PAO2 and subsequently
PaO2
• Characteristics
– Readily corrects with increase in FiO2
– PaCO2 is elevated
– A-a gradient is normal
 Hypoventilation
• Causes of Hypoventilation
– Neuromuscular causes
• Central: Drugs (eg.Opioid/barbiturates),
structural/ischemic CNS lesions affecting respiratory
centres in medulla oblongata
• Peripheral: High C-spine injury, phrenic nerve injury,
GBS,MG, ALS, muscular dystrophy
– Thoracic Cage abnormalities
• Kyphoscoliosis, ankylosing spondylitis, pectus
excavatum
 Reduced Inspired Oxygen Fraction
• Reduction in FiO2 will reduce PAO2
• This reduces the oxygen diffusion gradient and thus
result in hypoxaemia.

• Causes:
– High altitude
– Accidental delivery of low FiO2, disruption is O2 supply to
patient

• Characteristic
– A-a gradient is normal
– PaCO2 is reduced due to hyperventilation
 Ventilation-Perfusion Mismatch
• Normal physiology
– Perfusion and ventilation is greater at lung bases
as compared to apices
– However, difference in ventilation is smaller than
difference in perfusion
– Therefore, V/Q ratio is higher in apices than base
• Ie. Apices relatively better ventilated than bases
 Ventilation-Perfusion Mismatch
• In diseased lung, V/Q mismatch is exacerbated by
disease process increasing dead space/shunting
– Increasing dead space: emphysema, pulmonary
embolism
– Increasing shunt: pneumonia, APO, asthma

• Characteristic:
– Corrected easily with supplemental O2
– Increased A-a gradient
– PaCO2 is normal
 Right-to-left Shunts
• Blood enters systemic circulation and bypasses
lungs without being oxygenated
• 2 types of shunts
– Anatomical (Alveoli bypassed):
• Eg. intracardiac shunts, pulmonary AVMs/fistulas
– Physiological (ventilated alveoli not perfused)
• Eg. pneumonia, APO, ARDS
• Characteristic
– A-a gradient is increased
– PaCO2 is normal
– Difficult to correct with supplemental O2
 Diffusion Limitation
• Occurs due to limitation of movement of oxygen
from alveolus to pulmonary capillaries
• Causes
– Alveolar/interstitial inflammation and fibrosis Eg.
Interstitial lung disease
– Reduction in lung volume:
lobectomy/pneumonectomy
• Characteristic:
– Exercise induced/exacerbated hypoxaemia
– PaCO2 normal
 Summary Slide
Causes pO2 pCO2 A-a gradient Improvement
with increasing
FiO2
Hypoventilation Decreased Increased Normal Yes
Low FiO2 Decreased Decreased Normal Yes
V/Q mismatch Decreased Normal Increased Yes
Shunt Decreased Normal Increased No
Diffusion Decreased Normal Normal/ Yes
limitation Increased
 Measures of oxygenation
• Arterial oxygen
saturation (SaO2):
Proportion of RBCs in
which Hb is bound to O2
via pulse oximetry

• In general SpO2 >95% in

normal individuals
 Measures of oxygenation
• Arterial oxygen tension
(PaO2): Amount of
oxygen dissolved into
plasma
 Measures of oxygenation
• A-a oxygen gradient:
Difference between
PAO2 and PaO2

• Normal A-a gradient

varies with age and also
FiO2
 Measures of oxygenation
• PaO2/FiO2 Ratio:
– Normal PF ratio 300-500 mmHg
– Abnormal <300 mmHg