Download Gaseous transport in the blood

Gaseous transport in the
blood
By
Dr.M.B.Bhat.
Gaseous transport
• O2 consumption by body = 250ml/min
• CO2 excretion by body = 200ml/min
Oxygen transport
Oxygen transport Arterial blood Venous blood
Content
or
concentration
19.8 (ml/dl)
14.8(ml/dl)
Tension or partial
pressure
97.5 mm Hg
40 mm Hg
A-V O2 difference (O2 delivered to tissue) =
5ml/dl (in content) in 57.5 mm Hg (in tension)
Oxygen transport
• 2 forms
• Physical form –Dissolved form in plasma as
simple solution
• Chemical form –Combination with Hemoglobin
Physical form (or) Dissolved form in
plasma
• Account for about 1 to 2 % of O2 transport
• Solubility coefficient of O2 = 0.003 ml/dl/mm Hg
• O2 content in arterial blood (PO2100mm Hg) =
0.3ml/dl (15 ml in whole blood of 5Liter)
• O2 content in venous blood (PO2 40 mm Hg)
=0.12 ml /dl (6 ml in whole blood)
Significance of dissolved form
• Dissolved form determine PO2 in the blood;
which in turn determine O2 combining capacity
of Hb.
• When O2 carrying capacity of Hb is affected; as in
the case of CO poisoning, with Hyperbaric O2
treatment, this form content is increased and
provide necessary O2 for tissue
Chemical form (oxy-hemoglobin)
• Normal Hb level = 15gm/dl
• With full saturation (100%) O2 carrying capacity
of Hb = 1.34 ml/ gm of Hb
• O2 carrying capacity of 100ml blood =
• 1.34 x 15 = 20.1ml/dl (with 100% Hb sat.)
• Arterial blood (PO2 of 97mm Hg) with 97.5%
Hb saturation (due physiological shunt) = 19.8
ml/dl
Oxygen
transport
O2 content
O2 Tension
In plasma With Hb
% in Hb
Arterial O2
19.8 ml/dl
97.5 mm Hg
0.3 ml/dl
19.5 ml/dl
98.48
Venous O2
15.2 ml/dl
40 mm Hg
0.12 ml/dl
15.08 ml/dl
99.21
Out of O2 Delivery to tissue of 4.6 ml/dl --
0.17 ml/dl
4.43 ml/dl
96.3
Hemoglobin (Hb)
• Molecular weight = 68,000
• Consists of 4 Heme moieties (with a ferrous ion
in each) & conjugate with 4 polypeptide chains
• Each ferrous ion combine with a molecule of
Oxygen
• Each Hb molecule carry 4 molecule of O2 (Hb4O8)
• Combination of O2 with Hb is oxygenation (not
oxidation)
• This oxygenation & de oxygenation are so rapid
require <0.01sec
O2 dissociation curve
• Method of determination:
• 5 ml of blood placed in 250 ml of tonometer
• Fill the tonometer with known concentration of
O2.
• Shake for 20 minutes in water bath at 37.5oc
• After that measure % of Hb saturation in the
blood
• The result of saturation is plotted against that
ofPO2.
Oxygenation of Hb
• Combination of O2 with Hb depend on PO2.
• The relationship between PO2 & Hb saturation is
not linear but “sigmoid shape”.
• The curve obtained by plotting the Hb saturations
against their various PO2 is – Oxygen dissociation
curve
• (Or Oxy-Hb dissociation curve
• Or Hb dissociation curve)
O2 dissociation curve
• Sigmoid in shape
• Having three phases–
• Phase 1 -- Slow ascend (between 0 to 10 mm Hg of
PO2.)
• Phase 2 --Steep ascend (between 10 to 50 mm Hg) &
• Phase 3 -- Plateau (between 70 to 100 mm Hg of
PO2.)
• 3 important points in O2 dissociation curve are -• Arterial point -- PO2 of 100 mm Hg & Hb saturation
of 97,5%
• Venous point --PO2 of 40 mm Hg & Hb saturation of
75%
• P50 --PO2 of 28 mm Hg & Hb saturation of 50%
• P50 – is the partial pressure at which 50% Hb
saturation occur
• When P50 – increases O2 affinity decreases
Basis or Reason for sigmoid shape
• Heme to Heme interaction
• Configuration change of Hb
Heme to Heme interaction
• O2 combine with Hb in step by step involving each Heme
moiety with Ferrous iron one after another
• Oxy-form increases O2 affinity for Hb by 300 times
• In each stage, the kinetic velocity of formation of oxy-Hb
proportionately increases by 300 times in every step
• Hb4 +O2 Hb4 O2 K1 (Equilibrium constant)
• Hb4 +O2 Hb4 O4 K2
• Hb4 +O2 Hb4 O6 K3
• Hb4 +O2 Hb4 O8 K4
• K1 >K2 > K3>K4 (by 300 times in every step)
• So, initial slow combination become steep & when reaches
saturation becomes plateau
Effect of configuration change of Hb
• The configuration of Hb changes due to oxygenation &
deoxygenation
• In deoxygenated state –Hb is in tight form (& expel O2)
–Hence called “T” Hb
• In oxygenated state – Hb is relaxed form
(accommodate more O2) –called “R” Hb
• T-form is formed due to salt bridges connecting
opposite charged amino acids of the polypeptide chains
(with exposure of Histidine amino acids)
• These salt bridges are broken by O2.
• More & more entry of O2 brake more & more salt
bridges & consequently more & more relaxed and
accommodate more & more O2 till saturation occurs
Advantages of sigmoid shape curve
• Plateau phase –Helps to tide over atmospheric
pressure variations in different environmental
conditions
• Steep phase –Helps to deliver more O2 in case
of body’s requirement
Factors shifting O2 dissociation
curve to right (less O2 affinity)
In the blood level -1. Increase in temperature
2. Increase in H+ ion concentration ( pH)
3. Increase in CO2
4. Increase in 2,3-DPG level
Bohr’s effect
• Decrease O2 affinity due to decrease in pH of
blood is called Bohr’s effect
• Normally decrease in pH of blood occur due to
increase in CO2 content of blood –
Hence, increase in blood CO2 shifts the O2
dissociation curve to right can also be called
Bohr’s effect.
Significance of Bohr’s effect
• Takes place at tissue level
• Helps in unloading & O2 delivery to tissue
• Most of Hb unsaturation (O2 delivery) to tissue
occur due to decrease in PO2.
• Extra 1 to 2% of unsaturation of Hb (and
resulting O2 delivery) is due to increase in PCO2
2,3-Diphosphoglycerate (2,3-DPG)
• Metabolic byproduct of glycolysis via Embden
Meyerhof pathway in RBC itself
• It is a highly charged anion
• Bind with β-chain of Deoxy-Hb
• HbO2 + 2,3-DPG  Hb-2,3-DPG + O2
• Increase in concentration of 2,3-DPG causing
more & more O2 liberation
• Thereby decrease oxygen affinity with Hb
Factors decrease 2,3-DPG level
1. Acidosis (inhibit glycolysis)
2. Fetal Hb (γ-chain of fetal Hb has poor binding
capacity for 2,3,DPG)
3. Stored blood (due decrease in metabolism)
Factors increase 2,3-DPG level
1. Hormones –Thyroid hormone, GH &
androgen
2. Exercise –increase metabolism
3. High altitude –(secondary due to alkalosis with
half life of 6 hours)
4. Anemia
5. Diseases causing chronic hypoxia
Factors shift O2 dissociation curve to
left (increased affinity)
1.
2.
3.
4.
5.
Decrease in temperature
Decrease in H+ ion concentration ( pH)
Decrease in CO2 level
Fetal Hb
CO poisoning
Conclusion
• Speed of combination of Hb with O2 takes place
with half saturation of 0.07second
• Hb saturation with O2 complete in 0.3sec.
• RBC travel through pulmonary capillariesin
about 0.75second
• Reverse reaction of HbO2  Hb + O2 also
rapid with half saturation of 0.004sec in solution
& 0.038 second in RBC
CO2 Transport
•
•
•
•
•
•
•
Arterial blood –
CO2 content (concentration) – 50 ml/dl
CO2 tension -- PCO2 of 40 mm Hg
Venous blood–
CO2 content (concentration) – 54 ml/dl
CO2 tension -- PCO2 of 45 mm Hg
A-V CO2 difference = 4ml/dl
•
1.
2.
3.
CO2 present in the blood in 3 forms
Simple solution
-- 7%
Bicarbonate form (HCO3) – 70%
Carbamino-compound
-- 23%
(Carbamino-Hemoglobin)
Simple solution (Dissolved form in
plasma)
• Accounts for about 7% of CO2 transport
• Solubility of CO2 is 20 times of O2
• CO2 in arterial blood -with PCO2 of 40 mm Hg –2.4 ml/dl
• CO2 in venous blood -with PCO2 of 45 mm Hg –2.7 ml/dl
Chloride shift (Hamburger phenomena)
T
ti
• Account for 70% of CO2 transport
• Formation of HCO3 is very slow in plasma &
• Rapid in RBC due to presence of Carbonic anhydrase
(CA)
• 2/3rd of HCO3 formed in RBC enter into plasma by
chloride shift (occurs rapidly & completed within one
second)
• Accumulation of HCO3 & Chloride ions in RBC increases
the osmolality of RBC leads to endosmosis of water
• Henceii venous blood RBC is slightly bulged & Hct of
venous blood is slightly higher (about 3%) than arterial
blood.
Carbamino Hemoglobin
Carbamino-Hemoglobin (Carbamino
compound)
• In general CO2 combine with proteins in the blood are
called carbamino compound
• CO2 combine with protein of Hb alone called
carbamino hemoglobin
• Accounts for 15 to 25% of total CO2 transport
• CO2 combine with amino groups –as buffering
mechanism
• Hb is an effective buffer in pH range of 7 to 7.6
• Hb as protein has 6 times more buffering capacity than
plasma proteins
Haldane’s effect
• Binding of O2 with Hb reduces CO2 affinity for Hb is called
Haldane’s effect
• Takes place at lung level
• O2 tension at alveoli cause oxygenation of Hb and thereby
decrease CO2 affinity for Hb &
• Cause release of CO2 from blood into alveoli
• Haldane’s effect account for 50% of CO2 release from the
blood into alveoli
• Out of 4ml/dl expelled –
• 2ml due to P CO2 difference between blood & alveoli
• Another 2ml is due to Haldane’s effect
CO2-Dissociation curve
Conclusion of CO2 transport
•
•
•
•
•
•
In Arterial blood with pH 7.4 –
Out of total 50ml of CO2/dl –
Dissolved form accounts for –3ml (7%)
Carbamino compound –13ml (25%)
Bicarbonate form –34ml (68%)
In the venous blood with 54ml of CO2 & pH 7.36 -Out of 4ml of CO2/dl added into blood from tissue -• Dissolved form –0.4ml (10%)
• Carbamino compound –0.8ml (20%)
• Bicarbonate form –2.8ml (70%)
• In the lungs about 4 ml of CO2 from each
100 ml of blood discharged into the alveoli
• This amounts to 200 ml of CO2 /minute
expelled from the body
• This amount of CO2 is equivalent in 24
hours to over 12,500 meq. Of H+ ions.
END