Oxygen and carbondioxide cascade

Oxygen and carbondioxide cascade - Dr Gyanendra Agrawal Dr...

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Unformatted text preview: Dr. Gyanendra Agrawal Dr Senior Resident Dept of Pulmonary Medicine OXYGEN AND CARBONDIOXIDE CASCADE Introduction Introduction Oxygen – indispensable for life Substrate used in the greatest quantity No storage system Continuous supply required Carbondioxide ‐ major by‐product of energy metabolism Mechanisms Mechanisms of oxygen transport Convection (bulk flow) Diffusion Chemical combination with hemoglobin 30‐100 fold increase in O2 transport 15‐20 fold increase in CO2 transport Oxygen Oxygen Cascade Uptake in the lungs Carrying capacity of blood Global delivery from lungs to tissue Regional distribution of oxygen delivery Diffusion from capillary to cell Cellular use of oxygen Oxygen Oxygen Cascade Uptake in the lungs Carrying capacity of blood Global delivery from lungs to tissue Regional distribution of oxygen delivery Diffusion from capillary to cell Cellular use of oxygen Oxygen Oxygen uptake in the lungs Inspired O2 concentration Barometric pressure Alveolar ventilation Diffusion of O2 from alveoli to pulm capillaries Distribution and matching of ventilation and perfusion Alveolar Alveolar ventilation Depends on rate of breathing and tidal volume (VT) Hyperbolic relationship between alveolar ventn and PAO2 Affected by disorders of respiratory centre and respiratory muscles High‐frequency ventilation allows lower tidal volumes while maintaining MV Third Third gas effect Administration of nitrous oxide ↓ Large quantities of more soluble gas replace smaller quantities of less soluble nitrogen ↓ Net transfer of ‘inert ’ gas from alveoli into body ↓ Temporary increase in O2 concentration FINK EFFECT Diffusion Diffusion from alveoli to pulmonary capillaries O2 diffusion = K x S/d x ΔP Diffusion Diffusion from alveoli to pulmonary capillaries PAO2 is main determinant of PaO2 (A‐a) gradient describes the overall efficiency of oxygen uptake Capillary blood is fully oxygenated before traversing ⅓ distance of alveolar capillary interface V/Q V/Q matching ‐‘True shunt’ v/s ‘effective ‘ shunt ‐Clinical correlates High PEEP strategy Prone ventilation BMJ 1998;317:1302‐6 Hypoxemia Hypoxemia BMJ 1998;317:1302‐6 Oxygen Oxygen Cascade Uptake in the lungs Carrying capacity of blood Global delivery from lungs to tissue Regional distribution of oxygen delivery Diffusion from capillary to cell Cellular use of oxygen Carriage Carriage of O2 in blood 2% in plasma 98% in hemoglobin Hemoglobin Hemoglobin saturation Extent to which the Hb is combined with O2 Depends on PO2 of the blood Phenomenon of “cooperativity” P50 ~ 28 mm Hg Rapid and reversible reaction Factors Factors affecting OEC • pH Oxygen hemoglobin dissociation curve (Oxyhemoglobin equilibrium curve) • PCO2 • Temperature • 2,3 DPG • Percentage of fetal Hb Chest 2005; 128:554S–560S Bohr Bohr Effect Christian Bohr (1855‐ 1911) Eff Effect of PCO2 on OEC Concept of permissive hypercapnia 2,3‐ Diphosphogleycerate Formed in the Rapoport‐Luebering shunt of the glycolytic pathway DPG mutase activity increased at high pH Decreased DPG – in stored blood Increased in – anemia ‐ high altitude Oxygen Oxygen content (CaO2) Total amount of O2 present in 100 ml of blood (1.34 x Hb x SaO2) + (0.003 x PaO2) CaO2 = 20 vol % CvO2 = 15 vol % O2 content decreased in Hypoxemia (low PO2) Anemia (low Hb) Hypercarbia, acidemia, hyperthermia (low SaO2) Effect Effect of anemia and CO Anemia → ↓Hb → ↓O2 carrying capacity of blood & ↓ O2 content Carbon Monoxide affinity for Hb 250 fold relative to O2 Competes with O2 binding L shift‐ interfere with O2 unloading at tissues Severe tissue hypoxia Oxygen Oxygen Cascade Uptake in the lungs Carrying capacity of blood Global delivery from lungs to tissue Regional distribution of oxygen delivery Diffusion from capillary to cell Cellular use of oxygen Oxygen Oxygen delivery (DO2) Quantity of O2 made available to body in one minute – O2 delivery or flux Equal to cardiac output X arterial oxygen content DO2 is approximately 1000 mL/min Oxygen Oxygen consumption (VO2) Total amount of O2 consumed by the tissues per unit of time VO2 = 10 x CO x (CaO2 ‐ CvO2) Normal resting O2 consumption ~250 mL/min in adult humans OER = VO2/DO2 DO DO2 – VO2 relationship Jindal SK, Agarwal R. Oxygen Therapy. 2nd Ed. pp78 DO DO2 – VO2 relationship in critically ill Slope of maximum OER is less steep ↓ Reduced extraction of oxygen by tissues ↓ Does not plateau (consumption remains supply dependent even at “supranormal” levels of DO2) Critical level of DO2 range from 2.1 to 6.2 mL/min/kg BMJ 1998;317:1302‐6 Mechanisms Mechanisms causing failure of global oxygen delivery Reduction in cardiac output Fall in hemoglobin concentration Failure of oxygen uptake by blood Failure Failure of oxygen delivery Relative effects of changes in PaO2, Hb and CO on DO2 in a critically ill Thorax 2002; 57:170–177 DO DO2 during exercise During exercise O2 requirement may be 20 times Blood remains in capillary blood < ½ N time But saturation not affected Full saturation in first ⅓ of N time Increased diffusion capacity Additional capillaries open up V/Q ratio improves Dilatation of both alveoli and capillaries OEC shifts to right‐ ↑ CO2, ↓ pH, ↑ temp, ↑ 2,3 DPG Oxygen Oxygen Cascade Uptake in the lungs Carrying capacity of blood Global delivery from lungs to tissue Regional distribution of oxygen delivery Diffusion from capillary to cell Cellular use of oxygen Regional Regional distribution and Oxygen consumption Perfusion pressure is an important determinant Chest 2005; 128:554S–560S Oxygen Oxygen Cascade Uptake in the lungs Carrying capacity of blood Global delivery from lungs to tissue Regional distribution of oxygen delivery Diffusion from capillary to cell Cellular use of oxygen Cellular Cellular use of oxygen Important for aerobic metabolism EMP pathway Krebs’ cycle Can be inhibited by cellular metabolic poisons Exogenous (e.g. cyanide) or Endogenous (e.g. endotoxins in septic shock) Clinical Clinical features of tissue hypoxia Dyspnea Altered mental state Tachypnea or hypoventilation Arrhythmias Peripheral vasodilatation Systemic hypotension Coma Cyanosis (unreliable) Nausea, vomiting, and gastrointestinal disturbance Issues Issues in critically patient Disordered regional distribution of blood flow Both between and within organs Loss of autoregulation Use of vasopressors Capillary microthrombosis after endothelial damage Cytokines Cytokines induced disordered cellular O2 use Issues Issues in critically patient Decreased O2 carrying capacity of blood Phlebotomy Hemorrhage secondary to trauma / surgery Inflammation Nutritional deficiencies Decreased erythropoietin production Altered dissociation profile of OEC Acidosis, fever Decreased 2,3 DPG Issues Issues in critically patient Cardiac dysfunction in ICU patients Underlying organic heart disease Insufficient DO2 to the coronary circulation, precipitated by anemia Subendocardial ischemia from LVH Compromised myocardial contractility from the effects of inflammatory cytokines Inappropriate intravascular fluid status CARBONDIOXIDE CASCADE Blood Blood transports more CO2 than O2 CO2 is twenty fold more soluble than O2 in plasma CO2 content reflects the sum of CO2 in the blood in all three forms CaCO2= 48 vol % CvCO2=52 vol% Each time blood circulates through the body, 4 vol% of CO2 is removed from the tissues and delivered to the lungs to be exhaled Dissolved Dissolved CO2 Only ∼5% of total arterial content is present in the form of dissolved CO2 0.3 ml of CO2/100 ml in absolute terms During heavy exercise may increase up to sevenfold Carbonic Carbonic anhydrase (CA) Key enzyme in CO2 transport Catalyzes reaction in both direction (~5000 fold) Not present in plasma 7 isozymes CA II in RBCs and CA IV membrane bound isozyme present in pulmonary capillaries Inhibited by thiazides and acetazolamide Chloride Chloride shift Hamburger in 1918 HCO3‐ exchange with Cl‐ ions across RBC membrane Passive process Mediated by membrane bound protein ‘band 3’ Band 3 anchoring site for ankyrin and spectrin CO CO2 bound as carbamate CO2 reacts directly with Hb Reversible reaction with a loose bond Depends on O2 satn of Hb and 2,3 DPG (binding to Hb) H+ concn (both Hb & plasma proteins) However, ↑ Hb desat and ↑ in H+ concn work in opposite direction Haldane Haldane Effect JBS Haldane [1892‐1964] Christiansen J, Douglas CG, Haldane JS. J Physiol 1914;48:244‐71 Molecular Molecular basis for Haldane Effect Reduced Hb is better than oxygenated Hb in combining with‐‐ 1. H+ ions 2. CO2 to form carbamino compounds in turn assisting blood to load more CO2 from the tissues Haldane Haldane Effect Binding of O2 with hemoglobin tends to displace CO2 from the blood Leads to ↑ uptake of CO2 in the tissues and ↑ release of CO2 in the lungs Approximately doubles the amount of CO2 released from the blood in the lungs and that picked up in the tissues Coupled Coupled transport within the red cell in peripheral tissues N Eng J Med 1998;338:239‐47 Influence Influence of CO2 on blood pH Carbonic acid–bicarbonate buffer system resists blood pH changes If H+ concentrations in blood begin to rise, excess H+ removed by combining with HCO3‐ If H+ concentrations begin to drop, carbonic acid dissociates, releasing H+ Hypercapnia Hypercapnia Signs of ventilatory failure: Tachypnea Acidemia Increased pulsus paradoxus Hyperinflation Somnolence / Decreased mental status Hypercapnia ‐ Etiologies PaCO2 α VCO2 RR (VT – VD) ↑VCO2 (Hypermetabolism) ↓VT Fever Seizures Sepsis Hyperalimentation Skeletal muscle weakness Impaired neuromuscular transmission ↓ Lung / chest wall compliance Airway obstruction COPD Asthma Obstructive sleep apnea ↓RR (Central hypoventilation) Drugs Brainstem lesions Obesity‐hypoventilation syndrome ↑VD Excessive PEEP ...
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This note was uploaded on 12/03/2011 for the course MEDICINE 350 taught by Professor Dr.aslam during the Winter '07 term at Medical College.

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