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Pathophysiology of Oxygen Transport

Pathophysiology of Oxygen Transport. V. Rentko VMD DACVIM. Is This Patient Oxygenated?. - Hct 13% - S a O 2 98 mm Hg - CRT = 1.5 sec - pale mucous membranes - tachycardia - tachypnea - strong peripheral pulses. Response to Decreased Oxygenation. Increased heart rate Vasoconstriction

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Pathophysiology of Oxygen Transport

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  1. Pathophysiology of Oxygen Transport V. Rentko VMD DACVIM

  2. Is This Patient Oxygenated? - Hct 13%- Sa O2 98 mm Hg - CRT = 1.5 sec - pale mucous membranes - tachycardia - tachypnea - strong peripheral pulses

  3. Response to Decreased Oxygenation Increased heart rate Vasoconstriction Increased respiratory rate RBC’s offload more oxygen Spleen releases stored RBCs

  4. Oxygen Delivery • Amount of oxygen entering lungs • Adequacy of pulmonary gas exchange • Blood flow to tissue • Oxygen carrying capacity of blood • Dissolved oxygen • Hemoglobin concentration • Oxygen affinity of hemoglobin

  5. Tissue hypoxia Release of inflammatory mediators Activation of endothelium Deplete ATP Platelet activation Activation of coagulation Increased vascular permeability Thrombosis Microcirculatory disturbance Vascular hyporeactivity Cell death

  6. Oxygen Delivery • Blood flow • Hemodynamics • Oxygen carrying ability of blood

  7. Oxygen Delivery BLOOD FLOW Viscosity ()  = PCV   = Viscosity  = Velocity

  8. Oxygen Delivery HEMODYNAMICS Q= ∆P/R Q= blood flow P= arterial blood pressure R= total peripheral resistance

  9. Hemoglobin and Oxygen Affinity Quarternary structure Reduced ferrous state 2+ (oxy and deoxyHb) Oxidized ferric state 3+ (metHb) Cooperativity Shifting of peptide chains: R and T state

  10. Tissue oxygenation after exchange transfusion with ultrahigh-molecular-weight tense- and relaxed-state polymerized bovine hemoglobins. Cabrales P, Zhou Y, Harris DR, Palmer AF. La Jolla Bioengineering Institute, CA, USA. pcabrales@ucsd.edu Hemoglobin (Hb)-based O(2) carriers (HBOCs) constitute a class of therapeutic agents designed to correct the O(2) deficit under conditions of anemia and traumatic blood loss. The O(2) transport capacity of ultrahigh-molecular-weight bovine Hb polymers (PolybHb), polymerized in the tense (T) state and relaxed (R) state, were investigated in the hamster chamber window model using microvascular measurements to determine O(2) delivery during extreme anemia. …… These results suggest that the extreme high O(2) affinity of R-state PolybHb prevented O(2) bound to PolybHb from been used by the tissues. The results presented here show that T-state PolybHb, a high-viscosity O(2) carrier, is a quintessential example of an appropriately engineered O(2) carrying solution, which preserves vascular mechanical stimuli (shear stress) lost during anemic conditions and reinstates oxygenation, without the hypertensive or vasoconstriction responses observed in previous generations of HBOCs. Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H1062-71. Epub 2010 Jan 8.

  11. Oxygen carrying ability of Hemoglobin

  12. CO2 Transport • CO2 = 20X more soluble than O2 • Unloading of O2 in capillaries facilitates loading of CO2 • In RBC: • CO2 → H2CO3 • H2CO3 →HCO3¯ + H+ • HCO3 ¯ exchanges with Cl ¯ • Buffering capacity of Hb • DeoxyHb (in capillaries) binds more H+ than oxyHb (Haldane effect) • Some CO2 binds amino groups→carbamino groups • DeoxyHb binds more carbamino groups than oxygHb • CO2 transport facilitated in venous blood

  13. Total CO2

  14. Oxygen Content Of Blood • Hemoglobin • Hb (red cell + plasma) x 1.35 x saturation • Normal: 20 ml oxygen per dL • Anemic: < 13 ml oxygen per dL • Plasma • 0.003 ml O2 per 100ml blood for each mmHg of PaO2 • Room air (PaO2 =100): 0.3 ml O2 per dL • 100 % O2: 1.5 ml O2 per dL

  15. Determinants of Oxygenation OxygenDelivery (DO2) OxygenContent(CaO2) Cardiac Output(CO) X Hemoglobin RBC Plasma CaO2 = (1.34 X (Hb) X SatX 10-2) +0.003 PaO2

  16. Oxygen Delivery Oxygen Carrying Ability of Blood 6 Factors: Hb, P50, SaO2, PaO2, CaO2 & VO2 • Uptake by lungs • Transport by blood • Extraction by tissue • Utilization by cells

  17. Oxygen Content Of Blood withVarious Diseases*

  18. Quick Facts • P50 = pO2 at which 50% Hb is saturated with oxygen (blood =25 mmHg) • DO2 = Cardiac output x arterial oxygen content • Cardiac output • Dog/cat: 2 L/min • Blood volume • Dog 85 ml/kg • Cat 75 ml/kg

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