OXIGEN & CARBON DIOXIDE OXIGEN & CARBON DIOXIDE TRANSPORTTRANSPORT

Biochemistry Departement Biochemistry Departement

Medical Faculty Of Andalas Medical Faculty Of Andalas University University

PadangPadang

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Oxygen Transport

Total Body Oxygen Stores

• Oxygen in the Lung (~500 ml O2).

• Oxygen in the Blood (~850 ml O2).

• Oxygen in the Cells (very little except Mb-bound).

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At the Lung Level

At the Tissue Level

Oxygen Is Carried in Blood in 2 Forms

• Bound to hemoglobin in red blood cells.

• Dissolved in plasma. Normally insignificant.

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Hemoglobin

• Each “heme” molecule is capable of binding with 1 O2 molecule and each “globin” molecule is capable of binding with 1 CO2 molecule.

• So, each molecule of Hb can bind to either 4 molecules of O2 and 1 molecule of CO2

• 100 ml of blood has about 15 gm of Hb, at Hct = 0.45

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• Binding of O2 to 4 heme sites given by:

42232

32222

2222

22

)()(

)()(

)(

OHbOOHb

OHbOOHb

OHbOHbO

HbOOHb

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Oxygen as Oxyhemoglobin

• Each gram of Hb can store about 1.34 ml of O2:

• 1 L of blood (150 gm of Hb) can store about 208 ml of O2 Oxygen Capacity of Hb.

• With normal cardiac output, about 1040 ml of O2 can be carried in blood per minute. (4 times of the metabolic demands).

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O2 Saturation.

• Units: percent.

• Fraction or percentage of all the hemoglobin binding sites that are currently occupied by oxygen.

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100Hb ofcapacity O

Hb with combined O )saturation (% S

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2HbO2

Oxygen Saturation of Hb

Four (5-6?) Things Change Oxyhemoglobin Affinity

1. Hydrogen Ion Concentration, [H+]

2. Carbon Dioxide Partial Pressure, PCO2

3. Temperature

4. [2,3-DPG]

5. Special Case: Carbon Monoxide

6. Hemoglobin variants

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Factors Affecting Hb-O2 Affinity: Summary

• Hydrogen Ion: – Increased H+ (decreased pH) increases H+ binding to Hb

and reduces O2 affinity (HbO2+H+HbH++O2).

• Carbon Dioxide (Bohr effect):– Increased PCO2 increases CO2 binding to Hb and reduces

O2 affinity (increased O2 delivery to tissue).

– Increased PCO2 increases H+ and reduces O2 affinity (fixed acid Bohr effect).

• Temperature and 2,3-DPG (diphosphoglycerate): – Increased temperature and 2,3-DPG reduces O2 affinity.

Effect of CO & Anemia on Hb-OEffect of CO & Anemia on Hb-O22 Affinity Affinity

Normal blood with Hb=15 gm/dl, anemia with Hb=7.5 gm/dl, and normal blood with 50% HbCO (carboxyhemoglobin).

Exercise

• Increase temperature

• Increased PCO2 and

• Decreased pH (acidosis)

2,3-DPG

• 2,3-DPG is a glycolytic intermediate– accumulates to uniquely high levels in RBCs

-Increased 2,3-DPG right shift

-Decreased 2,3-DPG left shift

• Increased 2,3-DPG associated with hypoxia.

Conditions with Increased 2,3-DPG

• acclimatization to high altitudes.

• chronic lung disease; emphysema.

• anemia.

• hyperthyroidism.

• right to left shunt.

• congenital heart disease.

• pulmonary vascular disease.

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Carbon Dioxide Transport

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At the Tissue Level

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At the Lung Level

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Carbon Dioxide Transport

• CO2 is transported in blood in dissolved form, as bicarbonate ions, and as protein-bound carbamino compound.

• Protein-bound CO2 (carbamino compounds):

• Amount of CO2 stored as carbamino compounds is about 21 ml/L (4% of the total art CO2).

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Carbon Dioxide Transport• A majority amount of CO2 is transported in the

form of bicarbonate ions (HCO3-):

• Amount of CO2 in HCO3- form at PCO2=40

mmHg is about 420 ml/L (90% of the total arterial CO2).

-HCOHCOH OH CO 332CA

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Carbon Dioxide Transport

• Haldane Effect: Increasing O2-saturation reduces CO2 content and shifts the CO2 dissociation curve to right. This is because, increasing PO2 leads to :– Decrease in the formation of carbamino compound.– Release of H+ ions from the hemoglobin and resulting

in dehydration of HCO3-.

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Carbon Dioxide Dissociation Curve

Over the normal physiological range (PCO2 CO2 = 30 to 55 mmHg and PO2 O2 = 40 to 100 mmHg), the CO22 equilibrium curve is nearly linear. But, O22 equilibrium curve is highly nonlinear.

Bicarbonate in RBCs.

• Carbonic anhydrase is present in RBCs• CO2 forms carbonic acid which

dissociates to H+ and HCO3-

• Released H+ is buffered by histidine residues (imidazole group)

CO H O H CO H HCO2 2 2 3 3 Carbonic Anhydrase

• Percent of the total PaCO2: 70%

Carbamino Compounds in RBCs.

• Approximately 30% of RBC contents is Hb

• CO2 forms carbamino hemoglobin

• Released H+ is buffered by histidine residues (imidazole group)

• Percent of the total PaCO2: 23 %

CO2 Formation in Plasma

• Carbamino compounds– CO2 binds the amine groups of plasma

proteins to form carbamino compounds.

R NH CO R NH COO H 2 2

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Chloride Shift (Hamburger Shift)

• Newly formed HCO3- passes out of RBC

• Cl- diffuses into RBC to maintain electroneutrality– Chloride shift is rapid– Complete before the RBCs exit capillary

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Tissue-Gas Exchange: Summary

• Gas exchange processes in the peripheral organs are essentially opposite those in the lungs.

• O2 is released from the capillary blood to the tissues and diffuses to the mitochondria energy (ATP) through cellular metabolism.

• CO2 diffuses from the tissues to the blood stream and is transported to the lungs for elimination.

• The exchange of O2 and CO2 in the blood-tissue exchange unit depends on PO2, PCO2, and also on O2 and CO2 saturation curves.

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Resources

• BIOEN 589: Integrative Physiology. Download 24 jan 05.

• Kennelly, PJ., Rodwell, V W. Proteins: Myoglobin & Hemoglobin. In: Harper’s Illustrated Biochemistry. 27th Ed. 41- 8.

• Miliefsky, M. Respiratory System Ch.23. Download 24 Nov 10.• Sheardown, H. Blood Biochemistry. McMaster University.

Download 20 Mei 07. • Irvin, CG. Respiratory Physiology. Lecture 4A CO2 Transport. In:

MEDICAL PHYSIOLOGY 30. Download 22 Jun 09.• Marks, DB., Marks, AD., Smith CM. Basic medical biochemistry: a

clinical approach. 1996. Dalam: B.U. Pendit, penerjemah. Biokimia Kedokteran Dasar: Sebuah Pendekatan Klinis. Eds. J. Suyono., V. Sadikin., L.I. Mandera. Jakarta: EGC, 2000

• R.K. Murray, D.K. Granner, P.A. Mayes, V.W. Rodwell Harper’s Biochemistry. 27th ed. McGraw-Hill Companies, New York. 2006.