Oxygen cascade

JOSEPH PREISTLY ANTONIE LAVOISIER

o2
• Stephen hale – prepared oxygen along with many other gases- 1727
• Priestly- o2 component of air-1777
• Lavoiser- 1780-1789
o2 absorbed by lungs and after metabolism eliminated as co2+ h2o
properties
• 21%
• Solidifies @ -218 c < Pale blue liquid < Boiling point @ 1atm is -183 c
• Critical tempertature -118 c- above which exist as gas
• Aids combustion- energy needed to start it is very less- grease on
cylinder valves- explosion.
• Preparation of oxygen
Liquefaction of air – joule Thomson effect
Distillation of liquid air nitrogen-more volatile- boiling point -196 c,
drawn off from top o2 from below.
Stored at high pressue 2000psig.
Oxygen is the ultimate electron acceptor
1. Abundant in atmosphere in gaseous form

2. It is hydrophobic
(this allows it to easily enter cells by diffusing across phospholipid membranes)

3. It is extremely electronegative
(it has a very high affinity for electrons, therefore it can forcefully pull electrons
through the ETC)

4. Non Toxic end product

Oxygen in biological system
• Substrate used by cells in maximum quantity
• Key factor for aerobic metabolism and cell integrity
• No storage system in tissues - continuous supply
• Tissue hypoxia  anaerobic metabolism→ death
• Cascade – oxygen transport from environmental air to
mitochondria
Ultimate need of 02: electron acceptor

Acetyl coA

Energy substrates – Glucose, fatty acids, amino acids

6co2+6 h2o+sun energy- c6h12o6+ 6o2
FLOW OF OXYGEN IN BIOLOGICAL SYSTEM

• Convective - bulk movement

• Active energy dependant process
• Tracheobronchial tree and circulation

• Diffusive
• passive movement down concentration gradient
• Alveolo-capillary membrane and capillary-tissue transport
CONVECTIVE FLOW

Patm O2
Pi O2

PA O2
Inspired oxygen
• 21% of the mixture
• Partial pressure: Patm O2
• Patm × 0.21
• 760 × 0.21 = 159.6 mmHg (dry gas)
• As the air enters nose, 6% water vapor is added
• (Patm – 47)
• (760 – 47 ) = 713 mmHg
• Pi02 = (Patm – 47) × Fio2
• = 713 × 0.21 =149.7mmHg
Factors influencing inspired oxygen partial pressure:
1. Atmospheric Pressure
• Partial pressure = Patm × 0.21
• Ascending to High Altitudes produces linear reduction in
partial pressure of inspired oxygen
• Hyper Baric Oxygen therapy:
1. Carbon Mono oxide poisoning 7. Crush injury
2. Cyanide Poisoning 8. Compartment syndrome
3. Gas Embolism 9. Severe Osteomyelitits
4. Decompression sickness 10. Radiation injury
5. Severe Anemia / blood loss 11. CNS abscess
6. Clostridial Myonecrosis 12. Skin graft / Flap

MECHANISM OF O2 DELIVERY: DISSOLVE OXYGEN IN PLASMA INCREASES

Factors influencing alveolar oxygen partial pressure:
2. Inspired oxygen concentration
Partial pressure = Patm × 0.21

FLOW 2 4 6 8 10 15
RATE
FiO2 0.24 0.28 0.31 0.35 0.40 0.60
Factors influencing alveolar oxygen partial pressure:
1. oxygen consumed , 2.alveolar ventilation
• Alveolar O2 (PAO2) = Inspired Oxygen - Oxygen consumed
ALVEOLAR GAS EQUATION (Comroe)
• Alveolar O2 (PAO2) = Inspired Oxygen - Oxygen consumed
PAO2 = PIO2 - Oxygen consumed

• Oxygen consumed is not measurable

• Carbon di oxide produced can be measured
R = V CO2/ VO2
VO2 = PaCO2/R
• PAO2 = PIO2 - [40 mm Hg /0.8]
= PIO2 - [50]
PAO2 = 149.7- [50]
PAO2 = 99.7 mm Hg
CALCULATE
• What is the PiO2 & PAO2 at FiO2 1?
• PiO2 = ( Patm – 47)× FiO2
• (760 – 47 ) × 1 = 713
• PAO2 = PiO2 – ( VCO2/RQ)
• = 713 – 50 = 663 mmHg
PaO2 in Systemic circulation

1. VENTILATION PERFUSION MISMATCH

2. DEFECTS IN DIFFUSION
1.DIFFUSION DEFECTS

• High cardiac output, tachycardia

• ARDS, Hyaline membrane disease
LOADING OF OXYGEN IN PULMONARY CAPILLARY

• Right shift of ODC • Release of CO2 when O2

binds to Hb
• Unloading of oxygen at
tissue level due to • Deoxygenated Hb favors
acidosis CO2 transport
 2.VENTILATION / PERFUSION mismatch

Anatomical shunts Apparatus dead space

Physiological shunts Anatomical dead space
Pathological Shunts Alveolar Dead spaces
DEAD SPACES
•  dead space is the volume of air which is inhaled that
does not take part in the gas exchange
APPARATUS DEAD SPACE

VOLUME OF THE BREATHING SYSTEM FROM THE

PATIENT-END TO THE POINT UP TO WHICH, TO
AND FRO MOVEMENT OF EXPIRED GAS TAKES PLACE
 In an afferent reservoir system with adequate FGF, the apparatus dead space
extends up to the expiratory valve positioned near the patient 
 In an efferent reservoir system, the dead space extends upto the point of FG
entry
  In Circle systems  where inspiratory and expiratory limbs are separate, it
extends upto the point of bifurcation
ANATOMIC DEAD SPACE
• Measured by FOWLERS technique
• AKA - single breath nitrogen test
• What are the other parameters deduced from fowlers
test?
ALVEOLAR DEAD SPACE
• Ideally D alv must be zero
• V/Q mismatch
Under / Un perfused , Well ventilated Alveoli
Ex . Pulmonary emboli

• WHAT IS THE V/Q RATIO OF ALVEOLAR DEAD SPACE?

• Q = 0 , V/Q = INFINITY
• ALVEOLAR DEAD SPACE CORRESPONDS TO WEST ZONE _____
•1
 DEAD SPACE ESTIMATION : CO2 eliminatiom

P ET CO2
PECO2 ↓PECO2 PaCO2

PaCO2 PACO2 NO BLOOD

FLOW

WELL PERFUSED ALVEOLI UNDER- PERFUSED ALVEOLI

PaCO2 = PACO2 = PECO2 PaCO2 > PECO2
Venous Admixture
Calculated amount of venous blood that is required to reduce
the partial pressure of oxygen from pulmonary capillary end
to arterial circulation
Types of Venous Admixture
• Anatomical shunts
• Bronchial veins
• Thebesian veins
• Pleural veins
• Pathological shunts
• Atelectasis, bronchial obstruction, ARDS
• Right to left shunts
• Alveolar dead spaces
• Perfusion greater than ventilation
• Low ventilation areas
• Low transit times
SHUNT FRACTION

• “WHAT IS LOST OUT OF WHAT WAS GAINED”

• Qs/Qt= (CcO2-PaO2) / (CcO2 – PvO2)
• (100 – 90) / (100 – 50) = 10/50 = 0.20
ISOSHUNT CURVES

Increasing FiO2 has flatter response curve as the shunt

increases.
Quantification of shunt : A-a, A/a,P/F
1. A- a gradient
• PAO2 – PaO2 = {FiO2 (Patm – 47) – (PaCO2/RQ)} – PaO2
• ={0.21(760-47) - (40/0.8) – 90
• = 10 mmHg
• Is it the best way to quantify diffusion gradient?
• Effect of age
• Effect of FIO2
• Influence of Hypocarbia / Hypercarbia
EVERY DECADE A-a WIDENS BY 1 mmHg
[AGE/ 4}+ 4 is a rough estimate formula
A – a gradient in clinical states
PAO2 – PaO2 = {FiO2 (Patm – 47) – (PaCO2/RQ)} – PaO2

 Diffusion defect: PaO2 decreases , A-a widens

Hyper ventilation: PaCO2 decreases (eg.20 mmHg)
 [{0.21(760-47) - (20/0.8)] – 90 = [150 – 25] – 90 = 35
 GRADIENT WIDENS EVEN THOUGH PaO2 IS NORMAL

HYPERCARBIA CAN PRODUCE A

NORMAL GRADIENT EVEN IF THERE IS HYPOXIA
 2. a/A ratio

• The influence of FiO2 is mathematically neglected

• Normal value – 0.74 - 0.80
3. PaO2/FiO2 RATIO
• Indirect estimate of shunt fraction
• 100/0.21 = 476
• 90/0.21 = 428
• 80/0.21 = 381
• 50/0.21 =238
• 100/0.5= 200
• 640/1 = 640
• 200/1 =200
• P/F ratio < 200, shunt > 20%
• P/F ratio > 200 , shunt < 20%
DISSOLVED VOLUME IN PLASMA
• Proportional to partial pressure of oxygen in alveolocapillary
membrane : HENRY ‘S LAW
• Oxygen dissolved in plasma = 0.003 × PaO2 /dL
• At an PaO2 100 mmHg
• 100 ml blood will contain 0.3 ml
• 1 litre blood will contain 3 ml
• 5 Lits blood will contain 15 ml (1.5% of total O2 carried)
• Tissue requirement is 250 ml/min
• SOME OTHER EFFECTIVE FORM OF TRANSPORT IS NEEDED
HAEMOGLOBIN
2.BOUND FORM
• Oxygen is insoluble in water phase
• So the maximum o2 content of plasma is 3ml/L
• Oxygen consumption in adult is 250 ml/min
• So cardiac output has to be 83 l/min to meet the
metabolic requirements

IS IT POSSIBLE???
WE CAN LIVE LIKE THIS SITUATION IN 3 ATM PRESSURE
WONDER MOLECULE - HAEMOGLOBIN
COOPERATIVE BINDING

One oxygen molecule binding to Hb changes the

conformation from tensed state to relaxed state and
favours the binding of three oxygen molecules to the
heme binding sites
 Wonder molecule - hemoglobin

• WHAT ARE THE 2 EFFECTS OF OXYGEN BINDING TO

HAEMOGLOBIN?
• ODC
• HALDANE EFFECT
Huffners constant
• Oxygen binding capacity of hemoglobin
• 1 mole Hb can carry 4 moles of oxygen
• 1 mole of Hb = 64458 grams
• 1 mole oxygen = 32 grams = 22.4 litres = 22,400 ml
• 64,458 grams Hb carry 89,600 ml of oxygen
• 1 gram carries 1.37 ml of oxygen
TOTAL OXYGEN IN BLOOD
Each gram of Hb can carry 1.34 ml Of oxygen
Oxygen Content bound to Hb = 1.34 × Hb × SO2
= 1.34 × 14 × 1
= 19.7 ml/ Dl
= 197 ml/L
Dissolved in plasma = PaO2 × solubility constant
= 100 × 0.003
= 0.3 ml /dL
= 3 ml /L
Total content of oxygen = 200 ml/L
PaO2 , SaO2,FnSaO2, SpO2, CaO2
• PaO2 – partial pressure of oxygen in plasma- ABG
• SaO2 – HbO2/ (HbO2 + Hb + met Hb + CO Hb)- ODC
• Also called “fractional saturation”
• Measured by MULTIWAVELENGTH COXIMETER
• fnSaO2 – HbO2/ (HbO2 +Hb)
• “functional saturation”
• Measured by ABG & calculated from ODC
• SpO2 – Saturation expressed as percentage
• Cao2 – total content of O2 in plasma and Hb
Oxygen haemoglobin –
Association – Dissociation curve

PaO2 20 – 25 %
PaO2 27 – 50%
PaO2 40 - 75%
PaO2 60 – 91 %
PaO2 100 – 98 %
PaO2 150 – 99%
 BOHR
EFFECT
Acidosis reduces the affinity
of hemoglobin for oxygen
Blood becomes acidic as it
passes through systemic
capillaries due to CO2 take up
from tissues
So H b unloads O2 at tissues
At lungs blood becomes
alkaline due to CO2 blow off
Hb develops higher affinity for
O2 and becomes easily
saturated
RIGHT SHIFT: REDUCED AFFINITY
Fetal Haemoglobin: LEFT SHIFT:
• HbA: 2 α + 2 β
• HbF : 2α + 2ϒ
• 2,3 DPG can bind to β chain ONLY
• So fetal Hb has high O2

affinity (P50 =
19)
• Umblical vein PaO2 = 28 mmHg
• SaO2 = 70%
Oxygen reserves
Breathing room air Breathing 100 % o2

FRC 450 2750

BLOOD 750 950

TISSUE FLUIDS 50 ?100

MYOGLOBIN 200 200

TOTAL 1450 4000

 O2 DELIVER AND CONSUMPTION

• CaO2 = (1.34 × Hb × SaO2) + (0.003 × PaO2)

CvO2 = (1.34 × Hb × SvO2) + (0.003 × PvO2)

DO2 = Q × CaO2 × 10
= 5 × 20 × 10
= 1000 ml/min (oxygen flux)
VO2 = Q × (CaO2 – CvO2) × 10
= 5 × 5 × 10
= 250 ml/min
 Atmosphere O2
159 mmHg
End Tidal CO2
35 mmHg
Inspired O2
PiO2 = 150 mmHg
Expired O2
Alveolar O2 PEO2 = 120 mmHg
PAO2 = 110 mmHg PACO2 40 mmHg

Pulmonary Vein Pulmonary Artery

PaO2 = 104 mmHg SvO2 = 75%

Arterial blood Interstitium O2 Venous blood

PaO2 =95 mmHg 45 mmHg PvO2 =45 mmHg
SaO2 = 97% SCvO2 = 70%
Ca02 = 20 ml/ dL Cytoplasm O2 Ca02 = 15 ml/ dL
PaC02 = 40 mmHg 15 mmHg PaC02 = 46 mmHg
CaCO2 =48 ml/dL CaCO2 = 52 ml/dL
Mitochondria O2
5 mmHg
 Total = 250 ml/min
3.5 – 5 ml / kg/min
= 1 MET

• Calorimetry - heat release per unit oxygen consumed

is 13.1 kJ/g of oxygen
• Ficks equation
• Indirect :
• Venous Oxygen Saturation
• Blood lactate level
• Constant flow of o2 to tissues in various supply states
• This is possible by changing the ER
• NORMAL EXTRACTION RATIO = 0.25
• O2ER upto 0.5 – 0.6 is well tolerated
• Below this critical point, O2 utilisation is supply dependant
• shock, hypoxia, ATP depletion, multiorgan failure occurs
• Maintain DO2 : VO2 ratio of 4:1 in critically ill patients
 Mixed Venous Oxygen Saturation
• High SvO2, Normal Lactate
• increased O2 delivery (increased FiO2, hyperbaric oxygen)
• decreased O2 demand (hypothermia, Anaesthesia, NMB)
• High SvO2, High Lactate
• Sepsis , microvascular shunting
• high flow states: sepsis, hyperthyroidism, severe liver disease
• ETC toxins- Cyanide, Di nitro phenol
• Low SvO2
• decreased O2 delivery:
• 1. decreased Hb (anaemia, haemorrhage, dilution)
• 2. decreased SaO2 (hypoxaemia)
• 3. decreased Cardiac output (any form of shock, arrhythmia)
• increased O2 demand (hyperthermia, shivering, pain, seizures)
MIXED VENOUS OXYGEN SATURATION
Why so little oxygen?
• Total body O2 content is 800 ml
• O2 Consumption is 250 ml / min
• Stores will be depleted in 3 minutes
• Anaerobic metabolism will start

• The 2 electrons in outermost orbit of O2 have

opposite spin and cannot participate in
reactions in single step (PAULI principle)
• So to accept electrons and get reduced to
water occurs in steps that generate powerful
FREE RADICALS
THE ANTI OXIDANT SYSTEM

• WHAT IS THE MAXIMUM NON TOXIC FiO2?

APNEIC OXYGENATION
• Diffusion respiration – Draper & Whitehead
• Mass movement oxygenation
• Lungs are denitrogenated and continous o2 insufflation is done
• 250 ml O2 is removed from alveoli
• Out of 200 ml CO2 produced, only 20 ml enters alveolus
• Net suction effect takes 230 ml/min O2 in.
• Pa CO2 increases by 3-6 mmHg / min
• Severe respiratory acidosis will develop before hypoxia occurs
• Air + apnea+ airway obstruction = 90 seconds
• Air + apnea + patent airway = 2 minutes
• 02 + apnea + airway obstruction = 6 minutes
• Apneic insufflation – 100 minutes