SEMINAR
FEBRUARY DM 27, 2004
OXYGEN - CARBON DIOXIDE
TRANSPORT
NAVNEET SINGH
DEPARTMENT OF PULMONARY
AND CRITICAL CARE MEDICINE
PGIMER CHANDIGARH
HEADINGS
INTRODUCTION
OXYGEN TRANSPORT FROM LUNGS
TO CELLS
OXYGEN DELIVERY DURING
EXERCISE
OXYGEN DELIVERY DURING
CRITICAL ILLNESS
CARBON DIOXIDE TRANSPORT
INTRODUCTION TO PHYSIOLOGY OF
OXYGEN TRANSPORT
Substrate used by cells in max qty
Key factor for aerobic metabolism and cell
integrity
No storage system in tissues - req for continuous
supply
Tissue hypoxia anaerobic metabolism
Cascade for transport from environmental air to
mitochondria
OXYGEN TRANSPORT - CONVECTIVE
AND DIFFUSIVE
Convective - bulk movement
Active energy dependant process
Tracheobronchial tree and circulation
Diffusive - passive movement down concentration
gradient
Alveolo-capillary membrane and capillary-tissue
transport
REQUIREMENTS FOR OXYGEN
TRANSPORT SYSTEM
Energy efficient (avoid unnecessary
cardiorespiratory work)
Match O2 supply with demand
Efficient transportation of oxygen (minimal
wastage/ transmission losses)
ROLE OF HEMOGLOBIN
Increases oxygen transport capacity by
30-100 fold
Increases CO2 transport capacity 1520 fold
KEY STEPS IN OXYGEN CASCADE
Uptake in the lungs
Carrying capacity of blood
Delivery from lungs to tissue capillaries
Delivery from capillary blood to
interstitium
Delivery from interstitium to individual
cells
Cellular use of oxygen
OXYGEN UPTAKE IN LUNGS
DETERMINANTS OF PaO2
Inspired O2 concentration & barometric
pressure
Alveolar ventilation
V/Q distribution & matching
O2 diffusion from alveoli to pul capillaries
DIFFUSION FROM ALVEOLI TO
PULMONARY CAPILLARIES
PAO2 Driving Pressure for O2 Diffusion Into
Pul Capillary Bed and Main Determinant of PaO2
normally
PAO2-PaO2 reflects overall efficiency of O2
uptake from alveoli to arterial blood
Capillary blood fully oxygenated before traversing
1/3 distance of alveolo-capillary interface
Inadequate oxygenation due to reduced pul
capillary time occurs only with very high C.O. or
severe desaturation of mixed pul arterial blood
OXYGEN CARRYING CAPACITY OF
BLOOD
97-98% Carried in Combination With Hb (2-3%
Dissolved in Plasma)
O2 CONTENT = 1.31 x Hb x Sat + 0.0031 x PO2
1gm Hb Binds 1.31 Though Expected 1.39 Due to
Presence of Iron in non-heme form
O2 content in 100 ml blood (in normal adult with
Hb 15 gm/dl) ~ 20 ml
(19.4 ml as OxyHb + 0.3 ml in plasma)
Shift of Curve to Right Release of O2 to Tissues
& Improves O2 availability provided PaO2 > 60
mm Hg
FACTORS AFFECTING O2-Hb
DISSOCIATION CURVE
PCO2
TEMPERATURE
2,3 DIPHOSPHOGLYCERATE
PRESENCE/PERCENTAGE OF FETAL Hb
pH
EFFECT OF pH & TEMP
In pH from 7.4 to 7.2 causes shift of curve
to right by 15%
In pH by similar value causes shift of
curve to left by similar magnitude
Temp affinity of O2 to Hb and hence
shift of curve to right and more release of
O2 at a given PO2. Opposite changes occur
with temp
EFFECT OF PCO2
Shift of O2-Hb dissociation curve to right by
PCO2 (BOHR EFFECT) - Important to enhance
oxygenation of blood in lungs and to enhance
release of O2 in the tissues
In the lungs, CO2 diffuses out of the blood (H+
conc also due to in H2CO3 conc) Shift of
O2-Hb curve to left & more avid binding of O2 to
Hb in quantity of O2 bound to Hb O2
transport to tissues.
When the blood reaches the tissue capillaries,
the opposite occurs ( CO2 and H+) and
hence greater release of O2 due to less avid
binding of O2 to Hb.
EFFECT OF 2,3 - DPG
levels shift curve to right & vice-versa with
levels.
Concentration 2,3 - DPG in RBCs affects the structure of
the Hb molecule and its affinity for O2.
Reduced concentrations (as found in old blood from
blood banks) reduce the P50 delivery to tissues
O2 DELIVERY FROM LUNGS
TO TISSUES
Major function of circulation to transport O2 from
lungs to peripheral tissues at a rate that satisfies
overall oxygen consumption.
Failure to supply sufficient O2 to meet metabolic
req of tissues defines circulatory shock.
Under normal resting conditions total or global
oxygen delivery (DO2 ) is more than adequate to
meet the total tissue oxygen requirements (VO2 )
for aerobic metabolism.
DO2 (ml/min) = Qt x CaO2
CaO2 = Hb x SaO2 x K
where K is coefficient for Hb-O2 binding capacity
DO2 = Qt x Hb x SaO2 x K
VO2 = Qt x (CaO2 - CvO2)
O2 Extraction ratio (VO2/DO2)
Normally ~ 25% but to 70-80% during maximal
exercise in well trained athletes
SvO2 in blood draining from diff organs varies widely
- hepatic SvO2 ~ 30-40%
- renal SvO2 ~ 80%
Reflects regional differences in DO2 and VO2
O2 not extracted by tissues returns to lungs
& mixed venous saturation (SvO2 )
measured in the pul A represents the pooled
venous saturation from all organs.
SvO2 influenced by changes in both DO2
and VO2
> 65% if supply matches demand (provided
regional perfusion and mechanisms for
cellular O2 uptake are normal).
As metabolic demand (VO2 ) or supply (DO2 )
O2 Extraction Ratio (VO2/DO2) to maintain
aerobic metabolism.
After max VO2/DO2 reached (60-70% for most
tissues) further in demand or in supply lead to
hypoxia
Under normal circumstances 5 ml of O2
transported to tissues by each 100 ml of blood
since the amount of O2 in blood reduces from 19.4
ml to 14.4 ml/100 ml of blood on passing though
the capillaries
This reflects a change in PO2 from 95 mm Hg to
40 mm Hg (O2 Sat of 97% and 75% respectively)
O2 DIFFUSION FROM
INTERSTITIUM TO CELLS
Intracellular PO2 < Interstitial fluid PO2
O2 constantly utilized by the cells
Considerable distance between capillaries
and cells in some tissues
N PcO2 ~ 5-40 mm Hg (average 23 mmHg)
N intracellular req for optimal maintenance of
metabolic pathways ~ 3 mm Hg
CELLULAR USE OF OXYGEN
Cellular metabolic rate determines overall
O2 consumption
Cellular use of O2 #- by metabolic poisons
(CN , Cellular toxins (e.g. endotoxins)
Relative effects of tissue hypoxia due to #of cellular use or excessive O2 consumption
not fully established
FACTORS AFFECTING VO2/DO2
FROM CAPILLARY BLOOD
Rate of O2 delivery to capillary
O2-Hb dissociation relation
PiO2 - PcO2
1/diffusion distance
Rate of use of oxygen by cells
O2 DELIVERY DURING EXERCISE
During strenuous exercise VO2 may to 20
times N
Blood also remains in the capillary for <1/2
N time due to C.O.
O2 Sat not affected
Blood fully sat in first 1/3 of N time
available to pass through pul circulation
Diffusion capacity upto 3 fold since:
1.Additional capillaries open up no of
capillaries participating in diffusion process
2. Dilatation of both alveoli and capillaries
alveolo-capillary distance
3. Improved V/Q ratio in upper part of lungs
due to blood flow to upper part of lungs
Shift of O2-Hb dissociation curve to right
because of:
1. CO2 released from exercising muscles
2. H+ ions pH
3. Temp
4. Release phospates of 2,3 - DPG
OXYGEN DELIVERY IN
CRITICAL ILLNESS
Optimum Hb conc in critically ill patients is 10-11
gm/dL - represents balance between maximising
O2 content & adverse microcirculatory effects
associated with marked in viscosity at high PCV
In many critically ill pts tissue hypoxia is due to
disordered regional distribution of blood flow both
between and within organs
In critical illness, particularly sepsis, hypotension
and loss of normal autoregulation cause shunting
and tissue hypoxia in some organs despite high
DO2 and SvO2
Perfusion pressure is an imp determinant of
regional perfusion and drugs often used in
attempt to improve regional tissue perfusion
However :
Inotropes given to maintain Sys BP may
regional distribution, particularly to the
renal and splanchnic capillary beds.
Dopamine previously used to improve renal
blood flow but overall C.O. rather than
regional distribution.
During critical illness tissue hypoxia is
often caused by capillary microthrombosis
after endothelial damage and neutrophil
activation rather than by arterial
hypoxaemia
Ideally, individual tissue oxygenation needs
to be measured directly to assess and
manage organ hypoxia correctly
INTRODUCTION TO PHSYIOLOGY
OF CO2 TRANSPORT
1. CO2 is the end-product of aerobic
metabolism.
2. Produced almost entirely in the
mitochondria where the PCO2 is the
highest
3. Elimination of CO2 - one of major req of
body. Large but highly variable amount of
CO2 produced
CO2 in blood present in 3 forms:
Dissolved
Bound as bicarbonate
Bound as carbamate
Relative contribution of diff forms to overall CO2
transport changes markedly along the elimination
pathway of CO2
For diffusion across membrane barriers, gaseous form
more appropriate while for transport within intra- or
extracellular compartments, other forms more imp
Kinetics of interchange between diff forms very imp
Products of hydration reaction of CO2 ,
HCO3 , and H+ reqd for variety of other
cellular fx such as secretion of acid or base
and some reactions of intermediary
metabolism.
In exercising skeletal muscle, the other end
product of metabolism, lactic acid,
contributes huge amounts of H+ and affects
predominance of the three forms of CO2 ,
because HCO3 as well as carbamate are
critically dependent on concentration of H+.
CO2 DIFFUSION
At each point in gas transport chain, CO2
diffuses in exactly the opp direction to O2
diffusion.
CO2 diffuses 20 times as rapidly as O2.
Pressure differences reqd for CO2 diffusion
far less than those reqd to cause O2
diffusion
CO2 TRANSPORT IN BLOOD
Under N resting conditions av 4 ml CO2
transported from tissues to lungs/dL blood
CO2 diffuses out of tissue cells in gaseous
form but does not leave cells to any
significant extent in form of HCO3 since
cell memb almost impermeable to HCO3
Most of CO2 entering and leaving blood
also in gaseous form though amount carried
in sol very small
Within plasma little chemical combination of CO2
because:
No carbonic anhydrase in plasma
H2CO3 formed very slowly
Little buffering power in plasma to
promote dissociation of H2CO3
DISSOLVED CO2
CO2 belongs to group of gases with moderate
solubility in water
According to Henrys law of solubility:
PCO2 x = CO2 conc in sol
= Solubility Coefficient
Value dependant upon temp (inversely
proportional) more temp lesser amount of
CO2 dissolved
Only 5% of total arterial content of CO2
present in dissolved form
At rest, contribution of dissolved CO2 to total
A-V CO2 conc diff only 10%. In absolute
terms only 0.3 ml of CO2/dL transported in
dissolved form
During heavy exercise contribution of
dissolved CO2 can 7 fold 1/3 of total
CO2 exchange
During heavy work load of muscle, levels of
lactic acid present in addition to CO2
aggravating in pH fraction of HCO3 in
total CO2 diminished
CO2 BOUND AS HCO3
Resp for 70% of CO2 transport from
tissues to lungs.
Dissolved CO2 in blood reacts with water to
form Carbonic Acid
CO2 + H2O H2CO3
Under physiological conditions, equilibrium
of equation to extreme left i.e. very
negligible amounts dissolved as H2CO3
(<1%)
Carbonic Anhydrase (C.A.) present inside
RBCs, pul capillary endo & other tissues
but not plasma catalyzes this RX - acc it
5000 fold both ways & markedly time
reqd for completion of RX
Other roles for C.A.:
Generation of H & HCO3 in secretory
organs esp kidney
Transfer of CO2 in skeletal & cardiac
muscle
Carbonic acid dissociates into H+ & HCO3
H2CO3 H + HCO3
Most of H+ combine with Hb (powerful buffer)
& HCO3 diffuse out of RBCs into plasma in
exchange for Cl - Band 3 HCO3/Cl carrier
protein in RBC memb
Cl content of RBCs V>A HAMBURGER (CHLORIDE) SHIFT
Ping-pong mech (1st ion moves out of cell
before 2nd ion moves inwards - most other ion
pumps simultaneous exchange 2 ions)
Related to proteins ankyrin & spectrin involved in maint of cell shape & memb
stability.
Genetically altered Band 3 protein asso with
small fragile spherical RBCs in exp animals
#- C.A. by acetazolamide PiCO2 from 45
upto 80 mm Hg
At pH 7.4 qty of CO2 as HCO3 20-fold that as
dissolved CO2 13-fold at pH 7.2 (N inside
RBCs), ratio further as plasma pH during
max exercise. Absolute A-V diff is during
exercise compared to that at rest, relative
contribution of HCO3 to overall exchange less.
CO2 BOUND AS CARBAMATE
Resp for 15-25% of total CO2 transport
CO2 reacts directly with Hb to form the
carbaminoHb (Hgb.CO)
Reversible RX - very loose bond CO2 easily
released into alveoli where PACO2<PCO2 of pul
cap
Small qty of CO2 reacts with plasma proteins - less
significant (qty of proteins 1/4th that of Hb)
Amount of CO2 bound as carbamate to Hb or
plasma proteins depends on:
1) O2 Sat of Hb (RBCs)
2) H+ conc (RBCs & plasma)
During passage of blood thru muscle &
tissues, O2 Sat and H+ conc change
considerably, in particular during exercise.
in Hb Sat & in H+ conc in RBCs in
capillary affect qty of CO2 bound to Hb in
opp directions
H+ conc - Acidification qty of carbamate
formed by Hb (Avoided to some extent by
buffering of H+ produced with imidazole
groups on the histidine residues of Hb
O2 Sat of Hb - Deoxygenation of Hb qty of
CO2 bound to Hb (HALDANE EFFECT)
HALDANE EFFECT
Binding of O2 with Hb tends to displace
CO2 from blood
Quantitatively more imp in promoting CO2
transport than is Bohr effect in promoting
O2 transport
Haldane effect ~ doubles qty of CO2
released from blood in lungs and that picked
up in tissues.
Oxygenation of Hb
acidity of Hb
tendency to combine with
CO2 to form Hgb.CO
Displacement of CO2 from Hb
LUNGS
H+ binding to Hb
Release of H+ from Hb
formation of H2CO3
release of CO2
Reduction of Hb ( oxygenation of heme)
TISSUES basicity of Hb
H+ binding to reduced Hb
dissociation of H2CO3
carriage of CO2 as HCO3