GAS TRANSPORT & CONTROL OF RESPIRATION

1. GAS TRANSPORT &CONTROL OF RESPIRATION

2. GAS TRANSPORT • Blood transports Oxygen and Carbon dioxide between lungs and the tissues of the body • These gases are transported in different states • Dissolved in plasma • Chemically combined with hemoglobin • Converted to a different molecule

3. Due to low solubility, only 1.5 % of oxygen is dissolved in plasma 98.5 % of oxygen combines with hemoglobin Oxygen Transport

5. Each Hb consists of a globin portion composed of 4 polypeptide chains • Each Hb also contains 4 iron containing pigments called heme groups • Up to 4 molecules of O2 can bind one Hb molecule because each iron atom can bind one oxygen molecule • There are about 250 million Hb hemoglobin molecules in one Red Blood Cell • When 4 oxygen molecules are bound to Hb, it is 100% saturated, with fewer, it is partially saturated • Oxygen binding occurs in response to high partial pressure of Oxygen in the lungs

6. Oxygen + Hb  Oxyhemoglobin (Reversible) • Cooperative binding Hb’s affinity for O2 increases as its saturation increases (similarly its affinity decreases when saturation decreases) • In the lungs where the partial pressure of oxygen is high, the rxn proceeds to the right forming Oxyhemoglobin • In the tissues where the partial pressure of oxygen is low, the rxn reverses. OxyHb will release oxygen, forming again Hb (or properly said deoxyhemoglobin)

8. Oxygen-Hemoglobin Dissociation Curve • Hb saturation is determined by the partial pressure of Oxygen • @ High partial pressures of O2 – lungs – Hb is 98% saturated • @ Low partial pressures of Oxygen – tissues – Hb is only 75% saturated • “S” shape is a trademark of its cooperative binding interaction – the binding of one oxygen molecule increases Hb’s affinity for binding additional oxygen molecules

9. Other factors altering Hb saturation • Low pH (Carbonic Acid, Lactic Acid) • High Temperature • High 2,3 DiphosphoGlycerate concentration (DPG) • High partial pressure of Carbon Dioxide • These conditions decrease Hb’s affinity for oxygen, releasing more oxygen to active cells

10. Example: Vigorous physical exercise • Contracting muscles produce metabolic acids such as lactic acid which lower the pH, more heat and more carbon dioxide. • In addition 2,3 DPGA is produced during conditions of higher temperature and lower partial pressures of oxygen Acting together or individually, these conditions lead to a decrease in Hemoglobin’s activity for Oxygen, releasing more Oxygen to the tissues (muscles)

11. BOHR EFFECT

12. Bohr Effect • Bohr Effect refers to the changes in the affinity of Hemoglobin for oxygen • It is represented by shifts in the Hb-O2 dissociation curve • Three curves are shown with progressively decreasing oxygen affinity indicated by increasing P(50)

13. SHIFT to the RIGHT • Decreased affinity of Hb for Oxygen • Increased delivery of Oxygen to tissues • It is brought about by • Increased partial pressure of Carbon Dioxide • Lower pH (high [H+]) • Increased temperature • Increased levels of 2,3 DPGA • Ex: increased physical activity, high body temperature (hot weather as well), tissue hypoxia (lack of O2 in tissues)

14. SHIFT to the LEFT • Increased affinity of Hb for Oxygen • Decreased delivery of Oxygen to tissues • It is brought about by • Decreased partial pressure of Carbon Dioxide • Higher pH (low [H+]) • Decreased temperature • Decreased levels of 2,3 DPGA • Ex: decreased physical activity, low body temperature (cold weather as well), satisfactory tissue oxygenation

16. Carbon Dioxide Transport • Produced by cells thru-out the body • CO2 diffuses from tissue cells and into the capillaries • 7% dissolves in plasma • 93% diffuses into the Red Blood Cells • Within the RBC ~23% combines with Hb (to form carbamino hemoglobin) and ~ 70% is converted to Bicarbonate Ions which are then transported in the plasma

17. In the lungs, which have low Carbon Dioxide partial pressure, CO2 dissociates from CarbaminoHemoglobin, diffuses back into lungs and is exhaled • Within the RBC, CO2 combines with water and in the presence of carbonic anhydrase it transforms into Carbonic acid • Carbonic acid then dissociate into H+ and HCO3- • In the lungs CO2 diffuses out into the alveoli. This lowers the partial press. Of Co2 in blood, causing the chemical reactions to reverse

18. Other gases have different affinities for hemoglobin

19. CO carbon monoxide has more than 250 times the affinity for Hb than oxygen. It will quickly and almost irreversibly bind to Hb  CO poisoning • NO nitrogen oxide has more than 200,000 times the affinity for Hb than oxygen. Irreversible bind • CO and O2 bind to same site on Hb • CO2 and O2 bind to different sites on Hb • Myoglobin (in muscle cells) binds more tightly to oxygen than Hb but NOT cooperatively (Mb serves as temporary intracellular O2 storage mechanism useful in muscle contraction)

21. Llama and Vicuna • Llama & Vicuna live in the Andes Mts. South America • Oxygen dissociation curves are located to the left of other mammals • Higher oxygen affinity of the blood of these animals aids in oxygen uptake at the low pressure of high altitude

22. High Altitude Adaptations for us… • Chronic Mountain Sickness (ventilatory depression, polycythemia, heart failure) R.I.P. • At high altitude initially the person is hyperventilating • After some time however… • Hb/RBC production increases (more oxygen carrying capacity) • 2,3 DPGA concentration rises in RBCs shifting the curve to the right, improving O2 tissue delivery • Increased sensitivity to concentrations of [H+], CO2, pH and their respective variations

23. That’s exactly why sportsmen (real football players for instance- wrongfully called “soccer players” here) train in the mountainsTo improve physical performance !

24. At similar pH and Co2, small mammals have lower oxygen affinity. Improved delivery of oxygen in the tissues to sustain the high metabolic rate of a small animal

25. Higher oxygen affinity of the fetal blood helps in the transfer of oxygen to the fetal blood in the placenta • Fetus – higher affinity- shift left • Fetus [Hb]~200g/L • Mother [Hb]~135g/L • Normal [Hb]~150g/L

26. Control of Respiration • Basic rhythm is controlled by respiratory centers located in medulla and brainstem • An inspiratory center sends impulses via nerves to the effectors: diaphragm and intercostals muscles • Normal breathing rate @ rest is about 12 to 15 breaths a minute • Chemo receptors located thru out the body modify the breathing rhythm by responding to changes in partial pressures of Co2, O2, pH. • Central chemoreceptors  medulla  changes in pH • Peripheral chemoreceptors: carotid body, aortic bodies monitor values of arterial blood: Pco2, Po2, pH

28. Carbon dioxide is the most important factor controlling depth and rate of breathing For all other inquiries, please refer back to the BOHR Effect.

29. HYPERVENTILATION Increased rate and depth of breathing if Low pp. O2 High pp. CO2 Low pH, High [H+] High Temperature High 2,3 DPGA High metabolic requirements Shift to the RIGHT HYPOVENTILATION Decreased rate and depth of breathing if High pp O2 Low pp CO2 High pH, Low [H+] Low Temperature Low 2,3 DPGA Low metabolic requirements Shift to the LEFT

30. Other factors that affect respiration • Pain & strong emotion • Pulmonary Irritants (dust, smoke, noxious fumes, excess mucus) • Voluntary control (ALWAYS OVERIDDEN) • Lung Hyperinflation (stretch receptors in pleurae send inhibitory signals protecting against hyperinflation) • Exercise and ventilation