Oxygen transport

Oxygen transport

1. OXYGEN TRANSPORT AND OXY- Hb DISSASOCIATION CURVE

2. By mass, oxygen is the third-most abundant elemet   in the universe, after hydrogen and helium. Oxygen was discovered independently by   Carl Wilhelm Scheele , in 1773 or earlier, and   Joseph Priestly   in 1774, but Priestley is often given priority because his work was published first. Dr Albert Blodgett  -First use of continuous oxygen on 46 year old woman with pneumonia. The individual who built on their work and brought oxygen therapy to a rational and scientific basis was John Scott Haldane (1860–1936) -‘ The therapeutic administration of oxygen’

3. Oxygen Transport: Transfer of O2 from A tmosphere to lungs. Diffusion across Alveoli to Blood in lung. Diffusion from Blood to Tissue. Utilization of O2 in tissue(Mitochondria).

4. 1)Oxygen Transport From Atmosphere to Lungs

5. ALVEOLAR OXYGEN TENSION : With every breath, the inspired gas is humidified at 37°C in the upper airway. The inspired tension of oxygen (PIO2 ) is therefore reduced by the added water vapor . Water vapor pressure is 47 mm Hg at 37°C. In humidified air, in the trachea the normal partial pressure of O2 at sea level is 149.7 mm Hg:(760-47)0.21

6. Alveolar Gas Equation PAO2 = PiO2 -PACO2/R -where PIO2 is inspired oxygen tension, PACO2 is alveolar CO2 tension (assumed to equal arterial PCO2) R is the respiratory exchange ratio (normally in the range of 0.8 to 1.0). The alveolar oxygen tension is approximately 104mm of Hg . The factors that determine the precise value of alveolar PO2 are (1) the PO2 of atmospheric air, (2) the rate of alveolar ventilation, and (3) the rate of total body oxygen consumption

7. Diffusion of Gases Across Respiratory Membrane :

8. Exchange of Gases-Henry’s Law: When a liquid is exposed to air containing a particular gas, molecules of the gas will enter the liquid and dissolve in it. Henry’s law states that “the amount of gas dissolved in a liquid will be directly proportional to the partial pressure of the gas in the liquid-gas interface”. As long as the PO2 in the gas phase is higher than the PO2 in the liquid phase, there will be a net diffusion of O2 into the blood. Diffusion equilibrium will be reached only when the PO2 in the liquid phase is equal to the PO2 in the gas phase .

9. Factors affecting gas diffusion 1)Partial pressure gradient of the gas across the alveolarcapillary membrane. (60 mmHg for O2 & 6 mmHg for CO2 ). 2) Surface area of the alveolar-capillary membrane . 3)Thickness of the alveolar-capillary membrane . (about 0.5 μ). 4)Diffusion coefficient of the gas that depends on: - Gas solubility . (CO2 is 24 times soluble than O2). - Molecular weight of the gas . (CO2 M.W. is 1.4 times greater than O2). • Net effect: CO2 diffusion is 20 times faster than O2 2)

10. Rate of gas diffusion = Diffusion coefficient X Pressure gradient x Surface area of the membrane /Thickness of the membrane The volume of gas transfer across the alveolar-capillary membrane per unit time is: Directly proportional to : - The difference in the partial pressure of gas between alveoli and capillary blood. The surface area of the membrane . The solubility of the gas . Inversely proportional to: Thickness of the membrane . Molecular weight of the gas.

11. GAS EXCHANGE

12. Third Step-Transport in Blood

13. Physically dissolved O2 Only  1.5 % of total O2 in blood. Dissolved  in plasma and water  of RBC. (because solubility of  O2 is very  low) It  is about 0.3ml of O2 dissolved  in 100ml arterial blood (at PO2  100 mmHg).    Chemically combined O2 98.5  % of total O2 in blood. Transported  in combination with  Hb . It  is about 19.5 ml of O2 in 100  ml arterial blood. Can  satisfy tissue needs.

14. Hemoglobin Each  hemoglobin molecule is a protein made up of four subunits bound together.  Each subunit  consists of a molecular group know as  heme and a polypeptide attached to the  heme . The four polypeptides of a  hemoglobin   molecule  are,collectively  called  globin . Heme  is an  ironporphyrin  compound that is an  essential part of the O2binding sites; only the  divalent form (+2 charge) of iron can bind O2

15. Each of the four heme groups in a  hemoglobin  molecule  contains one atom of iron (Fe), to which oxygen binds. Thus  this chain can exist in one of two forms— deoxyhemoglobin ( Hb ) and oxyhemoglobin (HbO2).  

16. Principle of Saturation(SpO2) monitoring: In a blood sample containing many  Hb  molecules, the  fraction of  all the  Hb  in the form of  OxyHb  is  expressedas  the percent Hb saturation

17. Hb-O2 Disassociation Curve  The oxygen– hemoglobin dissociation curve  plots the proportion of  Hb  in  its  saturated   form  on the vertical axis against the prevailing O2 tension on  the horizontal axis.  Important tool for understanding how blood  carries  and releases oxygen. It is an S-shaped curve that has 2 parts : - upper flat (plateau) part . - lower steep part.

18. The curve is  S shaped  because each  Hb  molecule  cont- ains  four  subunits.Each  binding of O2 to each subunit  facilitates  the  b- inding  of the next  on. Explanation The   globin  units of  DeoxyHb  are tightly held by electrostatic bonds in a  conformation with a relatively low affinity for oxygen.  The binding of oxygen to a  heme  molecule breaks some of these  bonbetween  the  globin  units, leading to a conformation change such that the  remaining oxygen-binding sites are more exposed.  Thus , the binding of one O2 molecule to  DeoxyHb  increases the affinity of the  remaining sites on the same  hemoglobin  molecule, and so on.

19. Physiologic significance: - Drop of arterial PO2 from 100 to 60 mmHg little decrease in Hb saturation to 90 % which will be sufficient to meet the body needs . This provides a good margin of safety against blood PO2 changes in pathological conditions and in abnormal situations. Increase arterial PO2 (by breathing pure O2 ) little increase in % Hb saturation (only 2.5%) and in total O2 content of blood.

20. The P50 : The PaO2 in the blood at which the hemoglobin is 50% saturated, typically about 26.6 mmHg for a healthy person. Increased P50 indicates a rightward shift of the standard curve, which means that a larger partial pressure is necessary to maintain a 50% oxygen saturation. This indicates a decreased affinity Conversely, a lower P50 indicates a leftward shift and a higher affinity

21. 2-3 DPG  It interacts with deoxygenated Hb beta subunits by decreasing their affinity for O2 It allosterically promotes the release of the remaining oxygen molecules bound to the hemoglobin , T hus enhancing the ability of RBCs to release oxygen near tissues that need it most. Increased by: exercise, at high altitude, thyroid hormone, growth hormone and androgens. Decreased by: acidosis and in stored blood.

22. Fetal Hb –O2 Disassociation Curve   Fetal Hb ( HbF ) contains 2α and 2γ polypeptide chains and has no β chain which is found in adult Hb ( HbA ). So , it cannot combine with 2, 3 DPG that binds only to β chains. So , fetal Hb has a dissociation curve to the left of that of adult Hb . So , its affinity to O2 is high increased O2 uptake by the fetus from the mother.

23. The Fourth Step Capillary Blood Within the Cell : The blood entering the capillary with a high PO2 begins to surrender its oxygen because it is surrounded by an immediate environment of lower PO2 I nitially giving off oxygen dissolved in plasma, and followed by release of oxygen bound to Hb . The principal force driving diffusion is the gradient in pO2 from blood to the cells The oxygen dissociation characteristics of Hb facilitate the rapid and efficient unloading of oxygen within the capillary. The O2ultimately diffuses from the microcirculation into the cells and finally into the mitochond

24. The oxygen cascade describes the process of declining oxygen tension from atmosphere to mitochondria. At sea level:159mmHg PIO2 : 140mmHg PAO2 : 105 mmHg PaO2 : 98 mmHg PvO2 : 47mmHg Intracellular : < 40 mmHg Mitochondria : < 5 mmHg * Any interference to the delivery of oxygen at any point in the cascade, significant injury can occur downstream.

25. Double Edged Sword O2 Toxicity:Neonatal Free Radical Disease Free radicals are molecules which have unpaired electron in their outermost orbit. Free radicals cause lipid peroxidations , especially in the cell membranes, inhibit nucleic acids and protein synthesis, and inactivate cellular enzymes

26. Oxygen derived free radicals , as being the probable aetiological factor in the development of these toxic effects .

27. Ischemic –Reperfusion Injury

28. THANK