Download Carbon Dioxide Transport

RESPIRATORY GAS
TRANSPORT
Biochemistry Departement
Medical Faculty Of Andalas
University
Padang
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Oxygen Transport
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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.
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:
Hb  O2  HbO2
HbO2  O2  Hb (O2 ) 2
Hb (O2 ) 2  O2  Hb (O2 )3
Hb (O2 ) 3  O2  Hb (O2 ) 4
Equilibrium constants for different reactions
different
Binding of first O2 relatively low affinity
2nd, 3rd and 4th - much higher affinity
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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.
Oxygen Saturation of Hb
O 2 combined with Hb
SHbO2 (% saturation ) 
 100
O 2 capacity of Hb
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Four (5-6?) Things Change
Oxyhemoglobin Affinity
1.
•
•
•
Hydrogen Ion Concentration, [H+]
Carbon Dioxide Partial Pressure, PCO2
Temperature
[2,3-DPG]
•
•
Special Case: Carbon Monoxide
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):
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– Increased temperature and 2,3-DPG reduces O2 affinity.
Effect of CO & Anemia on Hb-O2 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.
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-):
CA
CO2  H2O 
 H2CO3 
 H  HCO-3
• Amount of CO2 in HCO3- form at PCO2=40
mmHg is about 420 ml/L (90% of the total
arterial CO2).
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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 = 30 to 55 mmHg
and PO2 = 40 to 100 mmHg), the CO2 equilibrium curve is
nearly linear. But, O2 equilibrium curve is highly nonlinear.30
Bicarbonate in RBCs.
• Carbonic anhydrase is present in RBCs
• CO2 forms carbonic acid which
dissociates to H+ and HCO3CO 2  H 2 O       
 H 2 CO 3 
 H   HCO 3 
Carbonic Anhydrase
• Released H+ is buffered by histidine
residues (imidazole group)
• 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 2  CO2  R  NH  COO   H 
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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
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 where O2
is converted to CO2 and 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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Gas Transport in Cell
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Pelepasan CO2
• Dilakukan oleh:
1. isositrat dehidrogenase
2. α-ketoglutarat dehidrogenase
• Pelepasan CO2 tidak mengkonsumsi
oksaloasetat.
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Siklus ATP/ADP
•
•
•
Berperan untuk menghubungkan prosesproses yg menghasilkan P-berenergi-tinggi
dgn proses yg menggunakan P-berenergitinggi.
ATP dikonsumsi & dibentuk kembali secara
kontinu.
Depot ATP/ADP sangat kecil, sehingga
hanya cukup untuk mempertahankan
jaringan aktif dlm waktu beberapa detik
saja.
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Siklus ATP/ADP
ATP
CO2
Pernapasan:
pembentukan energi
dari; - karbohidrat
- lemak
- protein
Penggunaan energi:
- biosintesis makromolekul
- kontraksi otot
- transpor ion aktif
- termogenesis
O2
ADP + Pi
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Fosforilasi Oksidatif
•
Adalah sistem dalam mitokondria yang
memasangkan respirasi dengan proses
pembentukan intermediat berenergi tinggi,
ATP.
•
Sistem ini memungkinkan organisme
aerob menangkap energi bebas dari
substrat respiratorik dalam jumlah lebih
besar dibanding organisme anaerob.
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Peran Rantai Respirasi
asam lemak
+
gliserol
b-oksidasi
ATP
O2
glukosa
Asetil KoA
SAS
2H
H2O
rantai respirasi
ADP
Asam amino
mitokondria
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Produk ATP pada Fosforilasi Oksidatif
Berdasarkan hipotesis kimiosmotik dari Mitchell
yaitu;
rantai bekerja --> proton dipompa keluar
dari membran dlm mitokondria --> pH antar
membran turun --> proton balik ke dalam
matrik lewat tonjolan ATP-sintase-->
fosforilasi ADP menjadi ATP.
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Produk ATP pada Fosforilasi Oksidatif
•
•
•
Diperkirakan satu ATP disintesis setiap dua
proton melewati tonjolan tsb.
Hasilnya ialah;
- 3 mol. ATP utk oksidasi 1 mol. NADH
- 2 mol. ATP utk oksidasi 1 mol. FADH2
Laju fosforilasi oksidatif dikendalikan oleh;
NADH, oksigen, ADP
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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.
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