OXYGEN AND CARBON DIOXIDE

TRANSPORT

Dr. Raju JadhavDNB PGT

Dept. Of AnaesthesiologyMedica Superspecialty Hospital

OXYGEN(O2)

• Key factor for aerobic metabolism.

• Substrate used by cells in max quantity.

• No storage system in tissues, therefore continuous supply required.

O2 TRANSPORT• The oxygen transport system comprises the following consecutive

processes:1. Mass transport by active convection of atmospheric air from the

environment to the pulmonary alveolar spaces, powered by the contraction/relaxation cycling of the respiratory muscles whose action is regulated mainly by the medullary and pontine respiratory centers and peripheral chemoreceptors.

2. Passive diffusion occurs across the alveolo-capillary membrane, through the plasma and across the erythrocyte membrane finally binding to hemoglobin (HGb) ‘‘driven’’ by a partial-pressure gradient for oxygen (pAO2 – paO2).

3. Mass transport by active convection of blood from the alveolar capillaries and the left heart through the vascular distribution system to all systemic capillaries,and return to the right heart, powered by the contraction/relaxation cycling of the myocardium, regulated by the autonomic nervous system, various hormones,and other local vascular regulatory functions affecting the distribution of blood flow.

OXYGEN TRANSPORT Carried in bld in 2 forms:1.By red blood cells• Bound to Hb.• 97-98%.

2.Dissolved O2 in plasma• Obeys Henry’s Law (“Amount of gas dissolved in a

solution is directly proprtional to its partial pressure”) PO2 x α = O2 conc in solα = Solubility Coefficient (0.003mL/100mL/mmHg at

37C)• Low capacity to carry O2 i.e <2%.

HAEMOGLOBIN•Iron-Porphyrin compound• Normal adult = HbA =α2β2• Hb F= α2γ2• The γ chains ↑ hb affinityto O2.• Each gm of Hb can carryup to 1.34ml of O2,theoretically up to1.39 ml/gm.

OXYGEN TRANSPORT Oxyhemoglobin Formation:

• Oxygen + Hb Oxyhemoglobin (Reversible)

• When oxygen binds to haemoglobin, it forms OXYHAEMOGLOBIN.

• In the lungs where the partial pressure of oxygen is high, the reaction proceeds to the right forming Oxyhemoglobin.

• In the tissues where the partial pressure of oxygen is low, the reaction reverses. OxyHb will release oxygen, forming deoxyhemoglobin.

HAEMOGLOBIN Haemoglobin molecules can transport up to four O2’s

When 4 O2’s are bound to haemoglobin, it is 100% saturated, with fewer O2’s it is partially saturated.

Oxygen binding occurs in response to the high PO2 in the lungs

Co-operative binding: haemoglobin’s affinity for O2 increases as its saturation increases.

OXYGEN SATURATION & 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 the Oxygen Capacity.

• O2 CONTENT -The sum of O2 carried on Hb and dissolved in plasma.

• CaO2 (ml/dL) = (SaO2 x Hb x 1.34) + (PO2 x0.003)

• O2 content in 100 ml blood (in normal adult with Hb 15 gm/dl) ~ 20 ml/dl

• (19.4 ml as OxyHb + 0.3 ml in plasma)

ARTERIAL O2 CONTENT

Venous O2 content (CvO2)

• CvO2 =(SvO2 x Hb x 1.34) + (PvO2 x 0.003)

• Normally-15ml/dl.• Mixed venous saturation (SvO2 ) measured in

the Pul Artery represents the pooled venous saturation from all organs.

• SvO2 influenced by changes in both DO2 and VO2

• Normally, the SvO2 is about 75%, however, clinically an SvO2 of about 65% is acceptable.

TOTAL O2 DELIVERY• DO2 (ml/min) = Q x CaO2 x 10• DO2 = Q x Hb x SaO2 x 1.34 x 10• Q=Cardiac Output and multiplier of 10 is

used to convert CaO2 from ml/dl to ml/L)• N 900-1,100 ml/min• Decreased oxygen delivery occurs when

there is:• ↓ed cardiac output• ↓ed hemoglobin concentration• ↓ed blood oxygenation

O2 CONSUMPTION• The amount of oxygen extracted by the peripheral

tissues during the period of one minute is called oxygen consumption or VO2.

• (N- 200-300ml/min)• VO2 = Q x (CaO2 - CvO2) x 10• VO2 = Q x 1.34 x Hb x (SaO2-SvO2) x 10• O2 consumption is commonly indexed by the

patients body surface area (BSA) and calculated by:

• VO2 / BSA• Normal VO2 index is between 110-160ml/min/m2.

OXYGEN EXTRACTION RATIO

• The oxygen extraction ratio (O2ER) is the amount of oxygen extracted by the peripheral tissues divided by the amount of O2 delivered to the peripheral cells.

• Also known As: Oxygen coefficient ratio & Oxygen utilization ratio.

• Index of efficiency of O2 transport .

• O2ER = VO2 / DO2• Normally ~ 25% but increases to 70-80% during

maximal exercise in well trained athletes

FACTORS THAT AFFECT O2ER

Increased with:•Decreased CO•Increased VO2•Exercise•Seizures•Shivering•Hyperthermia•Anemia•Low PaO2

Decreased with:•Increased Cardiac Output•Skeletal Muscle Relaxation•Peripheral Shunting•Certain Poisons•Hypothermia•Increased Hemoglobin•Increased PaO2

A reduction below point 'c' in figure cannot becompensated for by an increased oxygen extraction andresults in anaerobic metabolism and lactic acidosis.

•In general, DO2 >>VO2.•When oxygenconsumption is high(exercise) the ↑ed O2requirement is usuallyprovided by an ↑ed CO.•Alternatively, if oxygendelivery falls relative tooxygen consumption thetissues extract moreoxygen from the Hb (thesaturation of mixedvenous blood fallsbelow 70%) (a-b )

O2 DELIVERY DURING EXERCISE• During strenuous exercise VO2 may increase to 20 times

Normal• Blood also remains in the capillary for <1/2 Normal time due

to increased C.O.• O2 Sat not affected as blood is fully saturated in first 1/3 of

Normal time available to pass through pulmonary circulation.

• Diffusion capacity increases upto 3 fold since:1. Additional capillaries open up .So increase in no of

capillaries participating in diffusion process.2. Dilatation of both alveoli and capillaries causing decrease in

alveolo capillary distance.3. Improved V/Q ratio in upper part of lungs due to increase

blood flow to upper part of lungs.

THE EFFECTS OF ANAESTHESIA• The normal protective response to hypoxia is reduced by

anaesthetic drugs and this effect extends into the post-operative period.

Following induction of anaesthesia : • FRC ↓• V/Q mismatch is ↑ed• Atelectasis develops rapidly• This 'venous admixture' increases from N 1% to around 10%

following induction of anaesthesia.• Volatile anaesthetic agents suppress hypoxic pulmonary

vasoconstriction.• Many anaesthetic agents depress CO and therefore ↓ O2 delivery.• Anaesthesia causes a 15% ↓ in metabolic rate and therefore a

reduction in oxygen requirements.• Artificial ventilation causes a further 6% ↓ in oxygen requirements as

the work of breathing is removed.

OXYGEN CASCADE

KEY STEPS IN OXYGEN CASCADE

• Uptake in the lungs• Carrying capacity of blood• Delivery to capillaries• Delivery to interstitium• Delivery to individual cells• Cellular use of oxygen

UPTAKE IN THE LUNGS FROM ATMOSPHERE

• PO2 = FiO2 * Barometric Pressure.• So with FiO2 of 21% , PO2 in the atmospheric air is 160mmHg.

• pAO2 = FiO2 * (PB-PH20) – PaC02/R.Q

• The Alveolar Air Equation,represents the partial pressure of oxygen in alveolar air at the prevailing barometric pressure after accounting for the vapor pressure of water with which tracheal air becomes saturated at body temperature.

• It defines the oxygen partial pressure in the steady state accounting for oxygen extracted and CO2 added by the respiratory gas exchange. This is the oxygen partial pressure with which blood in the pulmonary capillaries equilibrates during its rapid transit through the capillary.

• Approximate normal value of pAO2 is 104 mm Hg.

• The Fick equation of diffusion of a gas in a liquid medium describes the determinants of the oxygen flux as V = A * D * P1-P2/d

where,• A is the area available for diffusion; • D is the diffusion constant for the gas( D= 1 for

O2 and D = 20 for CO2) ; • P1-P2 is the gas partial pressure difference; • d is the diffusion distance, • Thus DP/d is the partial pressure gradient.• Normal O2 diffusion capacity at alveolo-capillary

membrane is 25 ml/min/mmHg.

GAS DIFFUSION PRINCIPLE

UPTAKE OF O2 BY PULMONARY CAPILLARY BLOOD

• Alveolar PO2 = 104 mmHg• Pulmonary Arterial PO2 = 40 mmHg• Difference => 104-40 = 64 mmHg• Therefore, along the Pressure Gradient,

O2 diffuses through the Alveolo-Capillary Membrane causing a rapid rise in PO2 as blood passes through the capillaries and becomes equal to alveolar PO2.

• Thus,Pulmonary Venous PO2 =104mmHg

TRANSPORT OF OXYGEN IN THE ARTERIAL BLOOD

• 98% of blood enters the left Atrium Oxygenated up to a PO2 of about 104 mmHg

• Shunt Flow: 2 percent Shunt Flow

• Venous admixture of blood PO2 change 104 to 95 mmHg

PULMONARY SHUNTING• SHUNTING = PERFUSION WITHOUT VENTILATION.• Pulmonary shunt is that portion of the cardiac

output that enters the left side of the heart without coming in contact with an alveolus.

“True” Shunt – No contact• Anatomic shunts (Thebesian, Pleural, and

Bronchial Veins) • Cardiac anomalies“Shunt-Like” (Relative) Shunt• Some ventilation, but not enough to allow for

complete equilibration between alveolar gas and perfusion.

Shunts are refractory to oxygen therapy

VENOUS ADMIXTURE

• Venous admixture is the mixing of shunted,non-reoxygenated blood with reoxygenated blood distal to the alveoli resulting in a reduction in:

– PaO2– SaO2• Normal Shunt: 3 to 5%• Shunts above 15% are associated with

significant hypoxemia.

EFFECT OF VENOUS ADMIXTURE

DIFFUSION OF O2 FROM PERIPHERAL CAPILLARIES TO THE CELLS

• O2 is contantly used by the cells,and thereby PO2 in peripheral tissue cells remains lower in the peripheral capillaries at the venous end.The arterial PO2 of 95 mmHg is thus reduced to PO2 of around 40mmHg at the venous end of the capillaries.

• There is considerable distance between capillaries and cells . Therefore, cellular PO2 ranges b/w 5-40mmHg (average 23mmHg).

• Only 1-3mmHg of O2 pressure normally required for full support of chemical processes that incorporates O2 in the cell.{PASTEUR POINT – Critical mitochondrial PO2 below which aerobic metabolism cannot occur.Normally it ranges from 1.4 to 2.3 mm Hg}

• Low intracellular PO2 of 23 mmHg is enough and provides large safety factor.

DIFFUSION OF O2 FROM PERIPHERAL CAPILLARIES IN TO TISSUE FLUID

OXYGEN UTILIZATION

• Arterial Blood - 100 ml of blood combines with 19.4ml of O2

– Po2 95 mmHg– %Hb saturation 97%

• Venous Blood - 100 ml of blood combines with 14.4ml of O2

– Po2 40 mmHg – % Hb saturation 75%• Thus, 5ml of O2 is transported by each 100

ml of blood through tissues per cycle(250 ml/5L/ min).

Summary of Gas Exchange in Lungs & Tissues

THE OXYGEN DISSOCIATION CURVE(ODC)

• Reveals the amount of Haemoglobin saturation at different PO2 values.

CHARACTERISTICS OF THE CURVESigmoid Shaped Curve.The amount of oxygen that is saturated on the

hemoglobin (SO2) is dependent on the amount dissolved (PO2).

Amount of O2 carried by Hb rises rapidly upto PO2 of 60mmHg(Steep Slope) but above that curve becomes flatter(Flat Slope).

Combination Of 1st Heme with O2 increases affinity of 2nd Heme for the 2nd O2 and so on. It is known as “Positive Co-Operativity”.

THE OXYGEN DISSOCIATION CURVE

In the lungs the partial pressure is approximately 100mm Hg at this Partial Pressure haemoglobin has a high affinity to 02 and is 98% saturated.

In the tissues of other organs a typical PO2 is 40 mmHg here haemoglobin has a lower affinity for O2 and offloads O2 to the tissues.

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THE “P50”

• A common point of reference on the oxygen dissociation curve is the P50.

• The P50 represents the partial pressure at which the hemoglobin is 50% saturated with oxygen, typically 26.6 mm Hg in adults.

• The P50 is a conventional measure of hemoglobin affinity for oxygen.

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SHIFTS IN THE P50• In the presence of disease or other conditions

that change the hemoglobin’s oxygen affinity and, consequently, shift the curve to the right or left, the P50 changes accordingly.

• An increased P50 indicates a rightward shift of the standard curve, which means that a larger partial pressure is necessary to maintain a 50% oxygen saturation, indicating a decreased affinity.

• Conversely, a lower P50 indicates a leftward shift and a higher affinity.

FACTORS AFFECTING ODC

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RIGHT SHIFT

• Right shift decrease the loading of oxygen onto Hb at the Alveolo-Capillary membrane.

• The total oxygen delivery may be much lower than indicated by a particular Pao2 when the patient has some disease process that causes a right shift.

• Right shift curves enhance the unloading of oxygen at the tissue level.

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LEFT SHIFT

• Left shift curves enhance the loading capability of oxygen at the Alveolo-Capillary membrane.

• The total oxygen delivery may be higher than indicated by a particular PaO2 when the patient has some disease process that cause a left shift.

• Left shift curves decreases the unloading of oxygen at the tissue level.

FACTORS AFFECTING DISSSOCIATION BLOOD TEMPERATURE• increased blood temperature• reduces haemoglobin affinity for O2

• hence more O2 is delivered to warmed-up tissue

Respiratory Response to Exercise

BLOOD Ph• lowering of blood pH (making blood

more acidic)• caused by presence of H+ ions from

lactic acid or carbonic acid• reduces affinity of Hb for O2

• and more O2 is delivered to acidic sites which are working harder

CARBON DIOXIDE CONCENTRATION• the higher CO2 concentration in

tissue• the less the affinity of Hb for O2

• so the harder the tissue is working, the more O2 is released

HEMOGLOBIN & MYOGLOBIN• Myoglobin is single

chained heme pigment found in skeletal muscle.

• Myoglobin has an increased affinity for O2 (binds O2 at lower Po2)

• Mb stores O2 temporarily in muscles & acts as a reserve in muscles, which can be used during exercise.

ROLE OF 2,3-DPG (DiPhosphoGlycerate):

•2,3 DPG is an organic phosphate normallyfound in the RBC.

•Produced during Anaerobic glycolysis inRBCS.

CONTD..

• 2,3 DPG has a tendency to bind to β chains of Hb and thereby decrease the affinity of Hemoglobin for oxygen.

HbO2 + 2,3 DPG → Hb-2,3 DPG + O2• It promotes a rightward shift and enhances

oxygen unloading at the tissues.

• This shift is longer in duration than that due to [H+] or PCO2 or temperature.

The levels increase with:• Cellular hypoxia.• Anemia• Hypoxemia secondary to

COPD• Congenital Heart

Disease• Ascent to high altitudes

The levels decrease with:• Septic Shock• Acidemia• Stored blood has No

DPG after 2 weeks of storage.

• In banked blood,the 2,3-BPG level falls and the ability of this blood to release O2 to the tissues is reduced.

•

EFFECTS OF ANEMIA & CARBON MONOXIDE ONTHE OXYGEN DISSOCIATION CURVE

• ↓O2 content.• SaO2remains normal• Carbon Monoxide [CO]

affinity of Hb for CO is 250 fold relative to O2 competes with O2 binding

• L shift- interfere with O2 unloading at tissues causing severe tissue hypoxia.

• Sigmoidal HbO2 curve becomes Hyperbolic.

HAEMOGLOBIN SATURATION AT HIGH ALTITUDES

Lungs at sea level: PO2 of 100mmHg haemoglobin is 98% SATURATED

Lungs at high elevations: PO2 of 80mmHg, haemoglobin 95% saturated At pressures above

60mm Hg, the standard dissociation curve is relatively flat.

This means the oxygen content does not change significantly even with large changes in the partial pressure of oxygen.

HAEMOGLOBIN SATURATION DURING EXERCISE

CARBON DIOXIDE• Volatile waste product of aerobic

metabolism.• Production averages 200 ml/min in resting

adult.• During exercise this amount may increase

6x.• Produced almost entirely in the

mitochondria.• Importance of CO2 elimination lies in the

fact that -Ventilatory control system is more responsive to PaCO2 changes

CARBON DIOXIDE TRANSPORT

• Carbon dioxide also relies on the blood for transportation. Once carbon dioxide is released from the cells, it is carried in the blood primarily in three ways..

Dissolved in plasma.As bicarbonate ions resulting from the

dissociation of carbonic acid.Bound to haemoglobin.

When CO2 molecules diffuse from the tissues into the blood

• 7% remains dissolved in plasma• 23% combines in the erythrocytes with

deoxyhemoglobin to form carbamino compounds.

• 70% combines in the erythrocytes with water to form carbonic acid, which then dissociates to yield bicarbonate and H+ ions.

MOST CO2 TRANSPORTEDAS BICARBONATE (HCO3-)*

CHLORIDE SHIFT ANDREVERSE CHLORIDE SHIFT

• Most of the bicarbonate then moves out of the erythrocytes into the plasma in exchange for Cl- ions & the excess H+ ions bind to deoxyhemoglobin,known as Chloride Shift.

• The reverse occurs in the pulmonary capillaries and CO2

moves down its concentration gradient from blood to alveoli,known as Reverse Chloride Shift.

• As a result of the shift of chloride ions into the red cell and the buffering of hydrogen ions onto reduced haemoglobin, the intercellular osmolarity increases slightly and→→ water enters causing the cell to swell →→ an increase in mean corpuscular volume (MCV)

• Hematocrit of venous blood is 3%>arterial• Venous RBC are more fragile• Cl content of RBCs V>A

CARBON DIOXIDE TRANSPORT

CARBON DIOXIDE DISSOCIATION CURVETotal CO2 carriage inthe blood depends onthe three blood-gasparameters:– PCO2– Plasma pH– PO2

Carbon dioxide dissociation curvesrelate PaCO2 to the amount ofcarbon dioxide carried in blood

Lower the saturation ofHb with O2 , larger theCO2 conc for a givenPaCO2.CO2 curve is shifted toright by increase in SpO2

Graph illustrates the differencebetween the content in blood ofoxygen and carbon dioxide withchange in partial pressure

•CO2 content rises throughoutthe increase in partialpressure.

• O2content rises more steeplyuntil a point at which the hb isfully saturated. After that, theincrease is small because ofthe small increased amount insolution.

• Consequently, the CO2 curveis more linear than the O2Hbdissociation curve.

Deoxygenation of Hb qty of CO2 bound to Hb.

For any given PCO2, the blood will hold more CO2 when the PO2 has been diminished.

Reflects the tendency for an increase in PO2 to diminish the affinity of hemoglobin for CO2.

HALDANE EFFECT

MECHANISM OF HALDANE EFFECT Combination of oxygen with hemoglobin in the lungs

causes the hemoglobin to become a stronger acid.

Therefore:

1) The more highly acidic hemoglobin has less tendency to combine with CO2 to form CO2 Hb

2) The increased acidity of the hemoglobin also causes it to release an excess of hydrogen ions thus causing a further rise in the ph and decreased tendency of CO2 to combine with hemoglobin in the presence of oxygen.

INTERACTION BETWEEN CO2 AND

O2 TRANSPORTATION

1. Bohr effect

2. Haldane effect

DIFFERENCES BETWEEN BOHR’S AND HALDANE’S

EFFECT• BOHR’S EFFECT1.It is the effect by

which the presence of CO2 decreases the affinity of Hb for O2

• HALDANE EFFECT1.It is the effect by

which combination of O2 with Hb displaces CO2 from Hb

2. Was postulated by Bohr in 1904.

3. Occurs at tissues and systemic capillaries.

4. In tissues, body metabolism causes ↑PCO2(45 mmHg) & ↓ PO2(40mmHg)

with respect to arterial PCO2 and PO2.

2. Described by John Scott Haldane in 1860.

3. Occurs at alveolar and pulmonary capillaries.

4. In lungs, Hb+O2HbO2 HbO2 has low

tendency to combine with CO2.

• CO2 enters the blood and O2 released from blood to tissues..

• Shifting O2 disosiciation curve to right and unloading O2 to the tissues.

• O2+HbH+ and CO2

• H+ + HCO3- H2CO3H2O +CO2..

• CO2 is thus released from blood to alveoli to be expelled out.

tissues