1. V. Rentko VMD DACVIM

2. - Hct 13% - S a O 2 98 mm Hg - CRT = 1.5 sec - pale mucous membranes - tachycardia - tachypnea - strong peripheral pulses

3.  Increased heart rate  Vasoconstriction  Increased respiratory rate  RBC’s offload more oxygen  Spleen releases stored RBCs

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

6.  Blood flow  Hemodynamics  Oxygen carrying ability of blood

7. 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.  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 PCabrales P, Zhou Y, Harris DR, Palmer AF.Zhou YHarris DRPalmer 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.

12.  CO 2 = 20X more soluble than O 2  Unloading of O 2 in capillaries facilitates loading of CO 2  In RBC: CO 2 → H 2 CO3 H 2 CO3 → HCO3¯ + H+ HCO3 ¯ exchanges with Cl ¯  Buffering capacity of Hb DeoxyHb (in capillaries) binds more H+ than oxyHb (Haldane effect) Some CO 2 binds amino groups → carbamino groups DeoxyHb binds more carbamino groups than oxygHb CO 2 transport facilitated in venous blood

14. l Hemoglobin l Hb (red cell + plasma) x 1.35 x saturation l Normal: 20 ml oxygen per dL l Anemic: < 13 ml oxygen per dL l Plasma l 0.003 ml O 2 per 100ml blood for each mmHg of PaO 2 l Room air (PaO 2 =100) : 0.3 ml O 2 per dL l 100 % O 2 : 1.5 ml O 2 per dL

15. Oxygen Delivery (DO 2 ) Cardiac Output (CO) Hemoglobin RBCPlasma C a O 2 = (1.34 X (Hb) X Sat X 10 -2 ) +0.003 P a O 2 X Oxygen Content (C a O 2 )

16. Oxygen Carrying Ability of Blood 6 Factors: Hb, P 50, SaO 2, PaO 2, CaO 2 & VO 2 Uptake by lungs Transport by blood Extraction by tissue Utilization by cells

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