V. Rentko VMD DACVIM

- Hct 13%- Sa O2 98 mm Hg- CRT = 1.5 sec- pale mucous membranes- tachycardia- tachypnea - strong peripheral pulses

Increased heart rate

Vasoconstriction

Increased respiratory rate

RBC’s offload more oxygen

Spleen releases stored RBCs

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

Activation of endotheliumActivation of endothelium

Platelet activationPlatelet activation

Tissue hypoxiaTissue hypoxia

Microcirculatory disturbanceVascular hyporeactivity

Microcirculatory disturbanceVascular hyporeactivity

Activation of coagulationActivation of coagulation

Deplete ATPDeplete ATP

Cell death Cell death

Increased vascular permeability

Increased vascular permeability

Release of inflammatory mediators

Release of inflammatory mediators

ThrombosisThrombosis

Blood flow

Hemodynamics

Oxygen carrying ability of blood

BLOOD FLOW

Viscosity ()

= PCV

= Viscosity = Velocity

Oxygen Delivery

HEMODYNAMICS

Q= ∆P/R

Q= blood flowP= arterial blood pressureR= total peripheral resistance

Quarternary structure Reduced ferrous state 2+ (oxy and

deoxyHb) Oxidized ferric state 3+ (metHb) Cooperativity Shifting of peptide chains: R and T

state

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.

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

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

OxygenOxygen

Delivery Delivery (DO(DO22))

Cardiac Output (CO)

Hemoglobin

RBC Plasma

CaO2 = (1.34 X (Hb) X Sat X 10-2) +0.003 PaO2

XOxygen Content (CaO2)

Oxygen Carrying Ability of Blood6 Factors: Hb, P50, SaO2, PaO2, CaO2 & VO2

•Uptake by lungs

•Transport by blood

•Extraction by tissue

•Utilization by cells

Parameter Normal Pneumonia Anemia

Pneumonia Anemia Alkalosis

Hct 45 15 15

PaO2 100 65 65

SaO2 100 100 100

Constant 0.003 0.003 <0.003

CaO2 (ml/ dl) 20 6.8 <6.8

Breathing room air CaO2 = 1.34 X (Hb) X S02 X 10-2

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