Respi 3

• Respiratory and circulatory systems

  Function together to transport sufficient oxygen (O2) from the lungs to the tissues and to transport carbon dioxide (CO2) from the tissues to the lungs for expiration

  
• Forms of oxygen transport in blood

  • Dissolved in plasma (1.5%)
  • Combined with hemoglobin (98.5%)

  
• Under normal conditions, about 5 ml O2/ 100 ml blood are transported from the lungs to the tissue
• Dissolved oxygen


  Measured clinically in an ABG sample as PaO2, can become a significant factor in conditions of severe hypoxemia

  
• Oxygen bound to hemoglobin (oxyhemoglobin)


  Is the primary transport mechanism of O2, hemoglobin not bound to O2 is referred to as deoxyhemoglobin or reduced hemoglobin

  
• Reaction of hemoglobin and oxygen

  Hemoglobin + Oxygen ⇌ Oxyhemoglobin

  
• Hemoglobin


  • Has 4 subunits each of which contains a heme moiety attached to a polypeptide chain, each of the 4 iron atoms in hemoglobin can reversibly bind one O2 molecule, binding of O2 to hemoglobin is rapid and loose/reversible
• Binding of O2 to hemoglobin

  Alters the ability of hemoglobin to absorb light, responsible for the change in color between oxygenated arterial blood (bright red) and deoxygenated venous blood (dark-red bluish)

  
• Oxygen dissolved in plasma


  As O2 diffuses from the alveoli into the pulmonary capillary blood, it dissolves in the plasma of the blood, at normal body temperature ~0.003 ml of O2 will dissolve in 100 ml of blood for every 1 mmHg of PO2

  
• Hemoglobin


  • Each red blood cell contains about 280 million Hb molecules, which are highly specialized to transport O2 and CO2, normal hemoglobin value for males is 14-16 g% and for females is 12-15 g%
• Oxygen binding capacity


  Maximum amount of O2 that can be bound to hemoglobin per volume of blood, dependent on the hemoglobin concentration of the blood, limits the amount of O2 that can be carried in blood, 1 gram of Hb is capable of carrying approximately 1.34 ml of O2

  
• Normal oxygen binding capacity is 20 ml O2/ml blood
• Oxygen saturation (SO2)


  Refers to the amount of O2 bound to hemoglobin, at 100% O2 capacity the heme groups of the Hb molecules are fully saturated with O2, at 75% SO2 capacity three of the four heme groups are occupied, binding of O2 to each heme group increases the affinity of the Hb molecule to bind additional O2

  
• Oxygen content


  Sum of the O2 bound to hemoglobin and the dissolved O2, expressed as ml O2/ dl blood (vol%), decreases in the presence of increased CO2 and CO and in individuals with anemia

  
• Oxygen delivery to tissues

  Determined by blood flow and O2 content of the blood, normal cardiac output is 5-5.5 L/min so 50-55 dl are pumped by the heart, oxygen delivery = cardiac output x O2 blood content, normal oxygen delivery is 250 to 275 ml O2/min

  
• Oxygen dissociation curve


  Relates percentage saturation of the O2 carrying power of hemoglobin to PO2, the curve is S-shaped with a steep slope between 10 and 60 mmHg and a flat portion between 70 and 100 mmHg, hemoglobin affinity for O2 increases as blood PO2 increases

  
• Significance of the sigmoid shape curve

  • Combination of the first heme in Hb molecule with O2 increases the affinity of the 2nd heme for O2, and oxygenation of the 2nd increases the affinity of the 3rd heme for the O2 and so on

  
• Significance of flat portion

  • Shows that the PO2 can fall from 100 to 60 mmHg and the hemoglobin will still be 90% saturated with O2
• Significance of steep portion

  • PO2 reductions below 60 mmHg produce a rapid decrease in the amount of O2 bound to hemoglobin, clinically when the PO2 falls below 60 mmHg, the quantity of O2 delivered to the tissue cells may be significantly reduced, as oxygen partial pressure decreases in this steep area of the curve, the oxygen is unloaded to peripheral tissue readily as the hemoglobin affinity diminishes

  
• P50


  PO2 at 50% saturation, represents the partial pressure at which the hemoglobin is 50% saturated with oxygen, typically 26.6% mmHg in adults, conventional measure of hemoglobin affinity for oxygen

  
• Shifts in the P50

  An increased P50 indicates rightward shift of the standard curve, which means that a larger partial pressure is necessary to maintain a 50% oxygen saturation indicating a decreased affinity, conversely, a lower P50 indicates a leftward shift and a higher affinity

  
• Factors shifting the oxyhemoglobin dissociation curve

  • pH (decrease)
  • pCO2 (increase)
  • Temperature (increase)
  • 2,3 DPG (increase)

  
• Bohr effect


  Reflects the effect of CO2 on affinity of O2 with hemoglobin, CO2 binding with hemoglobin reduces affinity of O2 with hemoglobin, releasing O2 for unloading to tissues for metabolism

  
• 2,3 Diphosphoglycerate (2,3 DPG)


  Although the binding sites of 2,3 DPG and O2 differ on the hemoglobin molecule, binding of 2-3, DPG creates an allosteric effect that inhibits the binding of O2
• Factors shifting the oxygen-hemoglobin dissociation curve to the right

  pH (more acidic), temperature, pCO2, 2,3 BPG, called Bohr effect

  
• Fetal hemoglobin


  Has greater affinity for O2 than adult hemoglobin, shifts the oxyhemoglobin dissociation curve to the left
• Myoglobin


  • A heme protein in muscle cells which combine chemically with a single molecule of oxygen, can transport and store oxygen in skeletal muscle and can be released when conditions cause lower PO2, has a higher affinity to O2

  
• Carboxyhemoglobin (HgbCO)


  Carbon monoxide (CO) binds to the heme group of the hemoglobin molecule at the same site as O2, CO has about 200x affinity to hemoglobin, shifts the hemoglobin dissociation curve to the left

  
• 2,3 DPG


  Binds with hemoglobin to reduce its affinity for oxygen, thus promoting oxygen delivery to tissues (right curve shift)

  
• 2,3 DPG


  Seen with exercise and hypoxia
• Decrease in body temperature, especially in extremities

  Shifts the O2 dissociation curve to the left (higher Hgb affinity)
• In cold weather, PaO2 may be normal but release of O2 in extremities is not facilitated, causing bluish coloration
• This situation is not compatible with life and is the case of death in individuals of CO poisoning
• Carbon Monoxide Poisoning


  • Odorless, colorless and non-irritating
  • Arterial PO2 is normal
  • HbCO2 gives a typical cherry-red color to tissues
  • 100% O2 administration as treatment
• Anemia


  • Most forms do not affect the oxyhemoglobin dissociation curve
  • It is the amount of hemoglobin that decreases, not the percent saturation or even the arterial PO2

  
• Myoglobin


  • Has lower P50 compared to P50 of Hgb
  • Has higher affinity to O2
• Nitric Oxide (NO)


  • Hgb within erythrocytes can rapidly scavenge it
  • Has great affinity (200,000 times greater than O2) for Hgb, and it binds irreversibly to Hgb at the same site as O2 does
  • Hypoxia-induced vasodilation
  • Hgb-bound CO and No is referred to as methemoglobin
  • Under normal conditions, about 1 to 2% of Hgb is bound to CO and NO

  
• Carbon Dioxide Transport


  • Under healthy conditions, CO2 is produced at a rate of approximately 200 mL/min
  • Typically, 80 molecules of CO2 will be expired by the lung for every 100 molecules of O2 that enter the capillary bed

  
• Chloride Shift


  • Exchange of chloride ions for bicarbonate ions by the bicarbonate-chloride protein
  • Occurs in both in the lungs and peripheral tissue
  • Maintains electrical neutrality between membranes
• Carbon Dioxide Dissociation Curve

  • The CO2 dissociation curve from blood is linear and directly related to PCO2
  • PCO2 is solely dependent on alveolar ventilation and CO2 production