Transport Of Gases

TRANSPORT OF GASES prePARed by

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ON • One of the major events in

the process of ‘External respiration’. • The respiratory & circulatory systems function concurrently to transport O2 from lungs to the tissues & CO2 in the reverse direction. • Loading & Unloading of O2 & CO2 , not only occur simultaneously but also facilitate each other.

Gas movement throughout the respiratory system • occurs predominantly via diffusion . • A passive ,temp-dependent process where there is net movement of gas molecules from an area of higher partial pressure to an area of lower partial pressure & continues until an equilibrium is reached. • Similar whether occurring in a gaseous or liquid phase & follows basic diffusion laws.

To facilitate gas diffusion The respiratory and circulatory systems contain several unique anatomic and physiological features: • (1) large surface areas for gas exchange (alveolar to capillary and capillary to tissue membrane barriers) with short distances to travel, • (2) substantial partial pressure gradients & • (3) gases with advantageous diffusion properties.

OXYGEN TRANSPORT from the lungs to the tissues Acc. to differences in the partial pressure of Oxygen (PO2) at various sites : • Alveolar air PO2  104 mm of Hg • Arterial blood PO2  95 mm of Hg • Venous (or Pulmonary arterial) blood PO2  40 mm of Hg • Tissue interstitial fluid PO2  40 mm of Hg • Normal intracellular tissue PO2 avg. 23 mm Hg(an arbitrary range of 5-40 mm Hg)

3 Major Steps • A) Uptake of oxygen by pulmonary blood • B) Transport of oxygen in the arterial blood • C) Release of oxygen in the tissues

of oxygen by pulmonary blood: •Along the pressure gradient of 104-40 = 64 mm of Hg ,across the respiratory membrane. •oxygen readily diffuses from the alveoli into the blood.

B) Transport of oxygen in the arterial blood: • In 2 forms--I. Dissolved form (1.5%) II. Combined with Haemoglobin (98.5%) • Normal O2 content (per 100ml blood)-Arterial ~20 ml & Venous ~15 ml So,~5ml of O2 is transported per 100ml of blood from lungs to tissues.

I. OXYGEN TRANSPORT IN DISSOLVED FORM:

• relatively insoluble in water. • at the arterial PO2 value of 100 mm Hg, 100 ml of blood, contains only 0.3 ml of dissolved O2 , expressed as ‘volumes%’ . • measured clinically in an ABG-sample as P aO2. • product of the ‘oxygen solubility’(0.003 ml O2 /dl .Torr) & the oxygen tension (Torr).

Contd….. • Obeys Henry’s law---the amount of gas dissolved will be directly proportional to the partial pressure of the gas . • no limit to the amount of O2 that can be carried in dissolved form, provided the PO2 is sufficiently increased---a distinct advantage .

II.OXYGEN TRANSPORT IN COMBINATION WITH HAEMOGLOBIN:

Hbstructure: • each molecule consists of 4 nonprotein ‘haem’-groups & 4 polypeptide chains making up the ‘globin’component. • ‘Haem’ is an ironporphyrin compound, where iron is present in the ‘ferrous (Fe++ )’form & is the site of oxygen-binding.  

More About Hb • The ferrous O2 binding sites in Hb also bind NO, & an additional NO binding site is present on the beta chains. The affinity of this 2nd site is increased by O2, so Hb binds NO in the lungs and releases it in the tissues, where it promotes vasodilation. 

functions of Hb:

• it facilitates O2 & CO2 transport; • has an important role as a buffer ; • it transports NO.

Oxygenation of Hb: • most of the O2 quickly diffuses from the plasma into the RBCs • combines with Hb in a loose & readily reversible manner---rapidly (<0.01sec) • occupies the 6th coordination-position of the iron atom & does not become ionic oxygen . • accompanied by a conformational conversion in the Hb-molecule: deoxyhb(T) oxy-hb(R)

Reaction of Haem with Oxygen (M, V, and P stand for the groups shown on the molecule on the left)

Contd…….

++  One O2-molecule combines with the ‘(Fe )’- of each

‘haem’-group. So, max four oxygen molecules can bind to each Hb-molecule.  Interaction & ‘Positive Co-operativity’  the reaction proceeds in following four steps-  • Hb4 + O2  Hb4O2 • Hb4O2 + O2  Hb4O4 • Hb4O4 +O2  Hb4O6 • Hb4O6 + O2  Hb4O8

*Some Related Concepts* Oxygen-carrying capacity :



• maximum amount of O2 that can be combined with Hb . • 1 gm of Hb can combine with avg.1.34 ml of O2 (max.1.39 ml ,if in chemically pure form) • as normal blood has about 15 gm of Hb/100 ml, the O2-carrying capacity is about 1.34 X 15,i.e. 20.1 ml O2 /100 ml= ~ “20 volumes%”

*Concepts Contd……… Oxygen-content of blood : • Vol. of O2 contained per unit vol. of blood. • Sum of the dissolved O2 (but is frequently ignored d/t its’ small contribution) & Hb-bound O2 . • Same unit as O2–carrying capacity. • Decreases with anemia & conditions with increased CO & CO2 .

*Concepts Contd……… Oxygen-saturation of haemoglobin

 (SO2 ):

•  the amount of O2 bound to Hb relative to the maximum amount of O2 that can bind with Hb. It is expressed as a % . • of systemic arterial blood with PO2 of 95 mm Hg is about 97% • of normal venous blood (returning from peripheral tissues) with PO2 of 40 mm Hg is about 75%

Oxyhaemoglobin Dissociation Curve(OHDC) :

OHDC

• can also be expressed in terms of ‘volume % of oxygen’, as shown by the far right scale. • Shows that, as the PO2 increases , SO2 % also increases. But the relation is sigmoid or Sshaped (i.e.not linear), reflecting the change of affinity of Hb for oxygen, with increased binding of O2 to haem. • Two distinct zones are recognized .

Oxyhaemoglobin Dissociation Curve(OHDC) :

(i) Loading or flat (plateau) part ----above P of 60mm Association Zone : Hg • Upper O2

• Related to the O2-uptake in the lungs • at a PO2 of 100 mm of Hg ,Hb is about 97.5 % saturated & even if PO2 falls to about 60 mm of Hg , Hb is still 90% saturated. • provides a ‘margin of safety’ --ensures adequate O2 uptake by the pulmonary blood even when alveolar PO2 is moderately decreased.

Oxyhaemoglobin Dissociation Curve(OHDC) :

(ii) Unloading or Dissociation Zone: • lower steep (almost linear) part. • Related to the O2 –delivery to the tissues. • Hb-saturation is significantly compromised when PO2 progressively falls below 60 mm Hg. • facilitates the O2 –delivery , keeping the PO2 in the capillary blood relatively high .

Concept of P50 : • The PO2 at which 50% of Hb is saturated. • At sea level, in a normal adult with 370C body temperature & arterial blood PCO2 of 40 mmHg, it is about 27 mm of Hg . • Index of affinity for O2 – inversely proportional.

P50 value is the most useful point on the ODC for specifying the curve’s position because it is on the steepest part of the curve. It is therefore the most sensitive point for detecting a shift of the curve & allows comparison with the position of other curves under different conditions. 

Other 2 imp. points: •Arterial pointpO2 =100 mmHg with SaO2 = 97.5% • Mixed venous pO2 =40 mmHg with SaO2 = 75%

Points on ODC of HbA •

•Factors that shift the OHDC:

Bohr Effect • Demonstrated by the danish physiologist Christian Bohr (father of Neils Bohr & grandfather of Aage Bohr —both got nobel prize in Physics) • A shift of the OHDC to the right in response to increases in blood CO2 and H+- ions(or decrease in pH)  a significant effect by enhancing the release of O2 from the blood in the tissues & conversely enhancing oxygenation of the blood in the lungs d/t exactly opposite environment . • Explains basic mech. of Hb-bound O2 –transport.

•At PO2 of 20 mm Hg, where HBA is only 35% saturated,HbF is ~60% saturated. •Because affinity of gammachains for 2,3-DPG is less than beta-chains, HbF(P50 = 18 mm Hg) has more affinity for O2 than HbA. •Such property helps HbF to take up adequate O2, inspite of the fact that it is exposed to rather low PO2 of the maternal blood in placenta.

HbF

A haem-containing oxygen binding protein that is present in skeletal muscle.acts as ‘temporary storehouse’ of O2 . Comparison with OHDC: •Rectangular Hyperbola •Takes up O2 at lower PO2 , much readily. •Does not show Bohr’s effect.

Myoglobin

Hb-affinity of CO is ~200 times than that of O2 •

Hb(HbCO)

•P50 value of CO= only 0.5 mm Hg •CO binds with Hb at the same site (as of O2 ) . •Interferes with O2 – transport by decreasing functional Hb-conc. •in the presence of CO as a modifying factor, OHDC Shifts to left as binding of CO causes a conformational change in the Hb causing increased affinity for O2 by the other subunits.

tissues: •O2 diffuses rapidly first from the peripheral capillary blood to the ISF along a PG of 95-40=55 mm Hg & then from the ISF into the tissue-cells along approx. PG of 40-23= 17 mm Hg. •Tissue Po2 is determined by a balance b/w (i)rate of O2 -transport to the tissues by the blood & (ii) rate at which the O2 is used by the tissues. • Only 1- 3 mm Hg of PO2 is normally required for the oxidative chemical processes in the cell. So this low intracellular PO2 is more than adequate and provides a large safety factor.

CO2 TRANSPORT From tissues to the lungs. Acc. to the differences in PCO2 at various sites: • Intracellular PCO2  46 mm Hg • Interstitial Fluid PCO2  45 mm Hg • Arterial blood(at the tissue capillaries)PCO2  40 mm Hg • Venous blood PCO2  45 mm Hg Alveolar Air P

 40 mm Hg

3 major steps

• A) Uptake of CO2 by the blood • B) Transport of CO2 in the blood • C) Release of CO2 in the lungs

A) Uptake of CO2 by the blood: •from the cells rapidly diffuse to ISF even if the PG is only 46-45=1 mm Hg •From the ISF, diffuse into the capillary blood(which flows in the systemic venous system)along a PG of 45-40=5 mm Hg. •Diffusivity of CO2 is ~20 times higher than O2 .

B) Transport of CO2 in the blood: In 3 forms— • I) Dissolved form (7%) • II) As Carbamino compounds (23%) • III) As Bicarbonate (70%) Normal CO2 content (per 100 ml blood)-• Venous ~ 52 ml & Arterial ~ 48 ml So, ~4ml of CO2 is transported per 100ml of blood from tissue cells to lungs .

I. CO2 TRANSPORT IN DISSOLVED FORM:

• Obeys Henry’s law. • Venous blood(at PCO2 =45mm Hg) & Arterial blood(at PCO2 = 40 mm Hg) contain respectively 2.7 vol % & 2.4 vol % of CO2 in dissolved state. Only 0.3 ml of CO2 is transported

II. CO2 TRANSPORT AS CARBAMINO COMPOUND: some CO combines with the • After entering the blood, 2

(-NH2) of proteins to form ‘carbamino-compounds’ In the Plasma: combines with plasma-proteins— CO2 + Pr.NH2  Pr.NH.COOH (relatively insignificant) In the RBC: with Hb, form carbamino-Hb— CO2 + Hb.NH2  Hb.NH.COOH  A loose,reversible binding—competed by 2,3-DPG  Much slower reaction than that of CO2 & water.

III. CO2 TRANSPORT AS BICARBONATE:

• From plasma most CO2 enters RBCs ,where in the presence of CA, reacts rapidly (within a very small fraction of a sec): H2O + CO2  H2CO3 + • H2CO3 dissociates  H + HCO3 HCO diffuse out into the plasma & transported as Sod.bicarbonate 3 • + • H are buffered by deoxygenated Hb(weaker acid than oxygenated Hb) • To maintain electrical neutrality,Cl ions diffuse into the RBCs to replace HCO3- --- “Chloride Shift”.

Summary of changes that occur in a RBC on addition of CO2 to blood.For each CO2 molecule that enters the RBC, there is an additional HCO3– or Cl– ion in the cell.

Hamburger Phenomena: • by the presence of a special ‘bicarbonatechloride carrier protein’ in RBC membrane that shuttles these two ions in opposite directions at rapid velocities. • As a result, the chloride content of venous RBCs is greater than that of arterial RBCs, l/t osmotic absorption of fluid into these RBCs-- ‘water shift’. Fluid content is greater in Venous RBCs. Size of venous RBCs are larger than arterial RBCs. Venous RBCs are more fragile than arterial RBCs.

Schematic Representation of uptake & transport of CO2 in blood from peripheral tissues

In comparison with typical OHDC: • total CO2 -content on Y-axis 

•Nearly linear over the wider range of PCO2 • Practically ,in the body PCO2 varies within a narrow range (40-45 mm Hg) in contrast to PO2 (40-100) •So, this full range shown here is an experimental theoretical phenomena. Factors affecting CDC: • O2 – deoxy-Hb binds more CO2, shifts CDC to left.aka ‘Haldane or CDH Effect’. •2,3-DPG – decrease carbamino-Hb formation esp in deoxygenated blood---shifts to right •Body temp– increased temp cause release of O2 from blood—left shift

CURVE:

•Deoxygenated Hb is capable of loading more CO2 than oxygenated Hb. i.e.for any given PCO2, the blood will hold more CO2 when the PO2 has been diminished.

CDH effect depicts that: • Blood reaching the tissues(PCO2 = 4o mm Hg) is capable of drawing CO2 more at PO2 =4o mm Hg,than at PO2 =100 mm Hg left shift of CDC •Blood reaching lungs (PcO2 =45 mm Hg) is capable of releasing more CO2 at PO2 =100 mm Hg, than at PO2 = 40 mm Hg  right shift of CDC **The line AB is called ‘Physiological CDC’

Effect:

C) Release of CO2 in the lungs: Following changes occur in venous blood on reaching pulmonary capillaries: Release of CO2 from carbamino-Hb into plasma:  O enters the capillary blood & in RBC, converts deoxy-Hb to oxy-Hb  released CO2 • 2 diffuse out. Release of CO2 from bicarbonate into plasma:  Strong acidity of oxy-Hb HCO3- diffuse into RBCs to neutralize H+ form • H2CO3dissociates(in CA-presence)H2O + CO2 CO2 diffuse out. •

Ingoing of HCO3- outgoing of Cl- to maintain electrical neutralityreversal of Cl- shift

to alveoli: •All the dissolved & released CO2 diffuses into the alveoli along a PG of 45-40=5 mm Hg. •D/t constant ventilation this CO2 is then transported to the atmosphere.

Schematic Representation of blood transport & release of CO2 in Lungs

Outline of summary of the Blood Gas Transport

Gas Content of Blood

2 Special Related Terminologies Utilization Co-efficient:

• percentage of the ratio of O2 consumption rate(N=250 ml/min) & O2 -delivery rate (N=1000ml/min) in the tissue.

Respiratory Quotient:

• Ratio of rate of CO2 excretion(N=4ml/1 00 ml) & rate of O2 consumption(N=5 ml/100 ml) per min.

Normal avg. UC = 250/1000 X 100% = 25  Normal avg. RQ = %

4/5= 0.8

Till Death.........

SOME PONDERABLE FACTS Think before You Move…

Combination oxygen with Hb is called ‘oxygenation’ but not oxidation.

Almost flat bottom portion of the initial OHDC is a safety measure, esp for persons with Chronic lung disease.

Stored blood(esp with ACD as anticoagulant) is not safe to be transfused in a severely hypoxic patient.

The high RBC count in foetus is basically d/t the characteristic ODC of HbF.

The Hct value of venous blood is about 3% higher than that of arterial blood.

Hypoxemia occur much earlier than hypercapnia in patients with ‘Diffusiondefects of lungs’.

Hyperbaric oxygen is therapeutically utilised in CO poisoning.

The point on OHDC representing PO2 = 60 mm Hg & SO2 %=90, is called the ‘ICU Point’.

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